Category: Healthcare

Opdualag is a first-in-class, fixed-dose dual immunotherapy combination treatment of the PD-1 inhibitor nivolumab and novel LAG-3-blocking antibody relatlimab

In RELATIVITY-047, Opdualag more than doubled median progression-free survival compared to nivolumab monotherapy

PRINCETON, N.J. — (BUSINESS WIRE) — $BMY #EMA—Bristol Myers Squibb (NYSE: BMY) today announced that the European Commission (EC) has approved the fixed-dose combination of Opdualag (nivolumab and relatlimab) for the first-line treatment of advanced (unresectable or metastatic) melanoma in adults and adolescents 12 years of age and older with tumor cell PD-L1 expression < 1%.

The EC’s decision is based upon an exploratory analysis of results from the Phase 2/3 RELATIVITY-047 trial in patients with tumor cell expression < 1%, which demonstrated that treatment with the fixed-dose combination of the PD-1 inhibitor nivolumab and novel LAG-3-blocking antibody relatlimab more than doubled the median progression-free survival (PFS) compared to nivolumab monotherapy – an established standard of care. No new safety events were identified with the combination when compared to nivolumab monotherapy.

“Opdualag is now the first approved LAG-3-blocking antibody combination for advanced melanoma in the European Union. The RELATIVITY-047 study demonstrated the important benefit of inhibiting both LAG-3 and PD-L1 with our novel immunotherapy combination,” said Samit Hirawat, M.D., executive vice president, chief medical officer, Global Drug Development, Bristol Myers Squibb. “This is a continuation of our work in bringing innovative medicines to adults and adolescents living with melanoma. Thank you to all of the patients, researchers and physicians who contributed to these advancements and made today’s approval possible.”

The EC decision allows for the use of Opdualag for the first-line treatment of adults and adolescents 12 years of age and older with advanced melanoma and tumor cell PD-L1 expression < 1% in all European Union member states*, as well as Iceland, Liechtenstein, and Norway.

RELATIVITY -047 Efficacy and Safety Results

The indication in the European Union is based upon an exploratory analysis of the RELATIVITY-047 data in patients with tumor cell PD-L1 expression < 1%:

• Efficacy: Median PFS was 6.7 months in patients receiving Opdualag (95% Confidence Interval [CI]: 4.7 to 12.0); (Hazard Ratio [HR] 0.68 (0.53, 0.86)) compared to 3.0 months in patients receiving nivolumab monotherapy (95% CI: 2.8 to 4.5). Median overall survival in the Opdualag arm of the trial has not yet been reached (HR 0.78 (0.59, 1.04)).
• Safety: The most common adverse reactions were fatigue (41%), musculoskeletal pain (32%), rash (29%), arthralgia (26%), diarrhea (26%), pruritus (26%), headache (20%), nausea (19%), cough (16%), decreased appetite (16%), hypothyroidism (16%), abdominal pain (14%), vitiligo (13%), pyrexia (12%), constipation (11%), urinary tract infection (11%), dyspnea (10%), and vomiting (10%). The most common serious adverse reactions were adrenal insufficiency (1.4%), anemia (1.4%), back pain (1.1%), colitis (1.1%), diarrhea (1.1%), myocarditis (1.1%), pneumonia (1.1%), and urinary tract infection (1.1%). The incidence of Grade 3-5 adverse reactions was 43% among patients treated with Opdualag compared to 35% among patients receiving nivolumab monotherapy.

The RELATIVITY-047 trial also met its primary endpoint of PFS in the all-comer population.

*Centralized Marketing Authorization does not include approval in Great Britain (England, Scotland, Wales).

About RELATIVITY-047

RELATIVITY-047 is a global, randomized, double-blind Phase 2/3 study evaluating the fixed-dose combination of nivolumab and relatlimab versus nivolumab alone in patients with previously untreated metastatic or unresectable melanoma. Patients were enrolled regardless of tumor cell PD-L1 expression. The trial excluded patients with active autoimmune disease, medical conditions requiring systemic treatment with moderate or high dose corticosteroids or immunosuppressive medications, uveal melanoma, and active or untreated brain or leptomeningeal metastases. The primary endpoint of the trial is progression-free survival (PFS) determined by Blinded Independent Central Review (BICR) using Response Evaluation Criteria in Solid Tumors (RECIST v1.1) in the all-comer population. The secondary endpoints are overall survival (OS) and objective response rate (ORR) in the all-comer population. A total of 714 patients were randomized 1:1 to receive a fixed-dose combination of nivolumab (480 mg) and relatlimab (160 mg) or nivolumab (480 mg) by intravenous infusion every four weeks until disease progression, unacceptable toxicity or withdrawal of consent.

About LAG-3

Lymphocyte-activation gene 3 (LAG-3) is a cell-surface molecule expressed on effector T cells and regulatory T cells (Tregs) and functions to control T-cell response, activation and growth. Preclinical studies indicate that inhibition of LAG-3 may restore effector function of exhausted T cells and potentially promote an anti-tumor response. Early research demonstrates that targeting LAG-3 in combination with other potentially complementary immune checkpoints may be a key strategy to more effectively potentiate anti-tumor immune activity.

Bristol Myers Squibb is evaluating relatlimab, its LAG-3-blocking antibody, in clinical trials in combination with other agents in a variety of tumor types.

About Melanoma

Melanoma is a form of skin cancer characterized by the uncontrolled growth of pigment-producing cells (melanocytes) located in the skin. Metastatic melanoma is the deadliest form of the disease and occurs when cancer spreads beyond the surface of the skin to other organs. The incidence of melanoma has been increasing steadily for the last 30 years. In the United States, 106,110 new diagnoses of melanoma and about 7,180 related deaths are estimated for 2021. Globally, the World Health Organization estimates that by 2035, melanoma incidence will reach 424,102, with 94,308 related deaths. Melanoma can be mostly treatable when caught in its very early stages; however, survival rates can decrease as the disease progresses.

Bristol Myers Squibb: Creating a Better Future for People with Cancer

Bristol Myers Squibb is inspired by a single vision — transforming patients’ lives through science. The goal of the company’s cancer research is to deliver medicines that offer each patient a better, healthier life and to make cure a possibility. Building on a legacy across a broad range of cancers that have changed survival expectations for many, Bristol Myers Squibb researchers are exploring new frontiers in personalized medicine, and through innovative digital platforms, are turning data into insights that sharpen their focus. Deep scientific expertise, cutting-edge capabilities and discovery platforms enable the company to look at cancer from every angle. Cancer can have a relentless grasp on many parts of a patient’s life, and Bristol Myers Squibb is committed to taking actions to address all aspects of care, from diagnosis to survivorship. Because as a leader in cancer care, Bristol Myers Squibb is working to empower all people with cancer to have a better future.

OPDUALAG U.S. INDICATION

Opdualag™ (nivolumab and relatlimab-rmbw) is indicated for the treatment of adult and pediatric patients 12 years of age or older with unresectable or metastatic melanoma.

OPDUALAG IMPORTANT SAFETY INFORMATION

Severe and Fatal Immune-Mediated Adverse Reactions

Immune-mediated adverse reactions (IMARs) listed herein may not include all possible severe and fatal immune-mediated adverse reactions.

IMARs which may be severe or fatal, can occur in any organ system or tissue. IMARs can occur at any time after starting treatment with a LAG-3 and PD-1/PD-L1 blocking antibodies. While IMARs usually manifest during treatment, they can also occur after discontinuation of Opdualag. Early identification and management of IMARs are essential to ensure safe use. Monitor patients closely for symptoms and signs that may be clinical manifestations of underlying IMARs. Evaluate clinical chemistries including liver enzymes, creatinine, and thyroid function at baseline and periodically during treatment. In cases of suspected IMARs, initiate appropriate workup to exclude alternative etiologies, including infection. Institute medical management promptly, including specialty consultation as appropriate.

Withhold or permanently discontinue Opdualag depending on severity (please see section 2 Dosage and Administration in the accompanying Full Prescribing Information). In general, if Opdualag requires interruption or discontinuation, administer systemic corticosteroid therapy (1 to 2 mg/kg/day prednisone or equivalent) until improvement to Grade 1 or less. Upon improvement to Grade 1 or less, initiate corticosteroid taper and continue to taper over at least 1 month. Consider administration of other systemic immunosuppressants in patients whose IMARs are not controlled with corticosteroid therapy. Toxicity management guidelines for adverse reactions that do not necessarily require systemic steroids (e.g., endocrinopathies and dermatologic reactions) are discussed below.

Immune-Mediated Pneumonitis

Opdualag can cause immune-mediated pneumonitis, which may be fatal. In patients treated with other PD-1/PD-L1 blocking antibodies, the incidence of pneumonitis is higher in patients who have received prior thoracic radiation. Immune-mediated pneumonitis occurred in 3.7% (13/355) of patients receiving Opdualag, including Grade 3 (0.6%), and Grade 2 (2.3%) adverse reactions. Pneumonitis led to permanent discontinuation of Opdualag in 0.8% and withholding of Opdualag in 1.4% of patients.

Immune-Mediated Colitis

Opdualag can cause immune-mediated colitis, defined as requiring use of corticosteroids and no clear alternate etiology. A common symptom included in the definition of colitis was diarrhea. Cytomegalovirus infection/reactivation has been reported in patients with corticosteroid-refractory immune-mediated colitis. In cases of corticosteroid-refractory colitis, consider repeating infectious workup to exclude alternative etiologies.

Immune-mediated diarrhea or colitis occurred in 7% (24/355) of patients receiving Opdualag, including Grade 3 (1.1%) and Grade 2 (4.5%) adverse reactions. Colitis led to permanent discontinuation of Opdualag in 2% and withholding of Opdualag in 2.8% of patients.

Immune-Mediated Hepatitis

Opdualag can cause immune-mediated hepatitis, defined as requiring the use of corticosteroids and no clear alternate etiology.

Immune-mediated hepatitis occurred in 6% (20/355) of patients receiving Opdualag, including Grade 4 (0.6%), Grade 3 (3.4%), and Grade 2 (1.4%) adverse reactions. Hepatitis led to permanent discontinuation of Opdualag in 1.7% and withholding of Opdualag in 2.3% of patients.

Immune-Mediated Endocrinopathies

Opdualag can cause primary or secondary adrenal insufficiency, hypophysitis, thyroid disorders, and Type 1 diabetes mellitus, which can be present with diabetic ketoacidosis. Withhold or permanently discontinue Opdualag depending on severity (please see section 2 Dosage and Administration in the accompanying Full Prescribing Information).

For Grade 2 or higher adrenal insufficiency, initiate symptomatic treatment, including hormone replacement as clinically indicated. In patients receiving Opdualag, adrenal insufficiency occurred in 4.2% (15/355) of patients receiving Opdualag, including Grade 3 (1.4%) and Grade 2 (2.5%) adverse reactions. Adrenal insufficiency led to permanent discontinuation of Opdualag in 1.1% and withholding of Opdualag in 0.8% of patients.

Hypophysitis can present with acute symptoms associated with mass effect such as headache, photophobia, or visual field defects. Hypophysitis can cause hypopituitarism; initiate hormone replacement as clinically indicated. Hypophysitis occurred in 2.5% (9/355) of patients receiving Opdualag, including Grade 3 (0.3%) and Grade 2 (1.4%) adverse reactions. Hypophysitis led to permanent discontinuation of Opdualag in 0.3% and withholding of Opdualag in 0.6% of patients.

Thyroiditis can present with or without endocrinopathy. Hypothyroidism can follow hyperthyroidism; initiate hormone replacement or medical management as clinically indicated. Thyroiditis occurred in 2.8% (10/355) of patients receiving Opdualag, including Grade 2 (1.1%) adverse reactions. Thyroiditis did not lead to permanent discontinuation of Opdualag. Thyroiditis led to withholding of Opdualag in 0.3% of patients. Hyperthyroidism occurred in 6% (22/355) of patients receiving Opdualag, including Grade 2 (1.4%) adverse reactions. Hyperthyroidism did not lead to permanent discontinuation of Opdualag. Hyperthyroidism led to withholding of Opdualag in 0.3% of patients. Hypothyroidism occurred in 17% (59/355) of patients receiving Opdualag, including Grade 2 (11%) adverse reactions. Hypothyroidism led to the permanent discontinuation of Opdualag in 0.3% and withholding of Opdualag in 2.5% of patients.

Monitor patients for hyperglycemia or other signs and symptoms of diabetes; initiate treatment with insulin as clinically indicated. Diabetes occurred in 0.3% (1/355) of patients receiving Opdualag, a Grade 3 (0.3%) adverse reaction, and no cases of diabetic ketoacidosis. Diabetes did not lead to the permanent discontinuation or withholding of Opdualag in any patient.

Immune-Mediated Nephritis with Renal Dysfunction

Opdualag can cause immune-mediated nephritis, which is defined as requiring use of steroids and no clear etiology. In patients receiving Opdualag, immune-mediated nephritis and renal dysfunction occurred in 2% (7/355) of patients, including Grade 3 (1.1%) and Grade 2 (0.8%) adverse reactions. Immune-mediated nephritis and renal dysfunction led to permanent discontinuation of Opdualag in 0.8% and withholding of Opdualag in 0.6% of patients.

Withhold or permanently discontinue Opdualag depending on severity (please see section 2 Dosage and Administration in the accompanying Full Prescribing Information).

Immune-Mediated Dermatologic Adverse Reactions

Opdualag can cause immune-mediated rash or dermatitis, defined as requiring use of steroids and no clear alternate etiology. Exfoliative dermatitis, including Stevens-Johnson syndrome, toxic epidermal necrolysis, and Drug Rash with eosinophilia and systemic symptoms has occurred with PD-1/L-1 blocking antibodies. Topical emollients and/or topical corticosteroids may be adequate to treat mild to moderate non-exfoliative rashes.

Withhold or permanently discontinue Opdualag depending on severity (please see section 2 Dosage and Administration in the accompanying Full Prescribing Information).

Immune-mediated rash occurred in 9% (33/355) of patients, including Grade 3 (0.6%) and Grade 2 (3.4%) adverse reactions. Immune-mediated rash did not lead to permanent discontinuation of Opdualag. Immune-mediated rash led to withholding of Opdualag in 1.4% of patients.

Immune-Mediated Myocarditis

Opdualag can cause immune-mediated myocarditis, which is defined as requiring use of steroids and no clear alternate etiology. The diagnosis of immune-mediated myocarditis requires a high index of suspicion. Patients with cardiac or cardio-pulmonary symptoms should be assessed for potential myocarditis. If myocarditis is suspected, withhold dose, promptly initiate high dose steroids (prednisone or methylprednisolone 1 to 2 mg/kg/day) and promptly arrange cardiology consultation with diagnostic workup. If clinically confirmed, permanently discontinue Opdualag for Grade 2-4 myocarditis.

Myocarditis occurred in 1.7% (6/355) of patients receiving Opdualag, including Grade 3 (0.6%), and Grade 2 (1.1%) adverse reactions. Myocarditis led to permanent discontinuation of Opdualag in 1.7% of patients.

Other Immune-Mediated Adverse Reactions

The following clinically significant IMARs occurred at an incidence of <1% (unless otherwise noted) in patients who received Opdualag or were reported with the use of other PD-1/PD-L1 blocking antibodies. Severe or fatal cases have been reported for some of these adverse reactions: Cardiac/Vascular: pericarditis, vasculitis; Nervous System: meningitis, encephalitis, myelitis and demyelination, myasthenic syndrome/myasthenia gravis (including exacerbation), Guillain-Barré syndrome, nerve paresis, autoimmune neuropathy; Ocular: uveitis, iritis, and other ocular inflammatory toxicities can occur. Some cases can be associated with retinal detachment. Various grades of visual impairment, including blindness, can occur. If uveitis occurs in combination with other IMARs, consider a Vogt-Koyanagi-Harada–like syndrome, as this may require treatment with systemic steroids to reduce the risk of permanent vision loss; Gastrointestinal: pancreatitis including increases in serum amylase and lipase levels, gastritis, duodenitis; Musculoskeletal and Connective Tissue: myositis/polymyositis, rhabdomyolysis (and associated sequelae including renal failure), arthritis, polymyalgia rheumatica; Endocrine: hypoparathyroidism; Other (Hematologic/Immune): hemolytic anemia, aplastic anemia, hemophagocytic lymphohistiocytosis, systemic inflammatory response syndrome, histiocytic necrotizing lymphadenitis (Kikuchi lymphadenitis), sarcoidosis, immune thrombocytopenic purpura, solid organ transplant rejection.

Infusion-Related Reactions

Opdualag can cause severe infusion-related reactions. Discontinue Opdualag in patients with severe or life-threatening infusion-related reactions. Interrupt or slow the rate of infusion in patients with mild to moderate infusion-related reactions. In patients who received Opdualag as a 60-minute intravenous infusion, infusion-related reactions occurred in 7% (23/355) of patients.

Complications of Allogeneic Hematopoietic Stem Cell Transplantation (HSCT)

Fatal and other serious complications can occur in patients who receive allogeneic hematopoietic stem cell transplantation (HSCT) before or after being treated with a PD-1/PD-L1 receptor blocking antibody. Transplant-related complications include hyperacute graft-versus-host disease (GVHD), acute GVHD, chronic GVHD, hepatic veno-occlusive disease after reduced intensity conditioning, and steroid-requiring febrile syndrome (without an identified infectious cause). These complications may occur despite intervening therapy between PD-1/PD-L1 blockade and allogeneic HSCT.

Follow patients closely for evidence of transplant-related complications and intervene promptly. Consider the benefit versus risks of treatment with a PD-1/PD-L1 receptor blocking antibody prior to or after an allogeneic HSCT.

Embryo-Fetal Toxicity

Based on its mechanism of action and data from animal studies, Opdualag can cause fetal harm when administered to a pregnant woman. Advise pregnant women of the potential risk to a fetus. Advise females of reproductive potential to use effective contraception during treatment with Opdualag for at least 5 months after the last dose of Opdualag.

Lactation

There are no data on the presence of Opdualag in human milk, the effects on the breastfed child, or the effect on milk production. Because nivolumab and relatlimab may be excreted in human milk and because of the potential for serious adverse reactions in a breastfed child, advise patients not to breastfeed during treatment with Opdualag and for at least 5 months after the last dose.

Serious Adverse Reactions

In Relativity-047, fatal adverse reaction occurred in 3 (0.8%) patients who were treated with Opdualag; these included hemophagocytic lymphohistiocytosis, acute edema of the lung, and pneumonitis. Serious adverse reactions occurred in 36% of patients treated with Opdualag. The most frequent serious adverse reactions reported in ≥1% of patients treated with Opdualag were adrenal insufficiency (1.4%), anemia (1.4%), colitis (1.4%), pneumonia (1.4%), acute myocardial infarction (1.1%), back pain (1.1%), diarrhea (1.1%), myocarditis (1.1%), and pneumonitis (1.1%).

Common Adverse Reactions and Laboratory Abnormalities

The most common adverse reactions reported in ≥20% of the patients treated with Opdualag were musculoskeletal pain (45%), fatigue (39%), rash (28%), pruritus (25%), and diarrhea (24%).

The most common laboratory abnormalities that occurred in ≥20% of patients treated with Opdualag were decreased hemoglobin (37%), decreased lymphocytes (32%), increased AST (30%), increased ALT (26%), and decreased sodium (24%).

Please see U.S. Full Prescribing Information for OPDUALAG.

OPDIVO U.S. INDICATIONS

OPDIVO^® (nivolumab), as a single agent, is indicated for the treatment of adult patients with unresectable or metastatic melanoma.

OPDIVO^® (nivolumab), in combination with YERVOY^® (ipilimumab), is indicated for the treatment of adult patients with unresectable or metastatic melanoma.

OPDIVO^® (nivolumab) is indicated for the adjuvant treatment of adult patients with melanoma with involvement of lymph nodes or metastatic disease who have undergone complete resection.

OPDIVO^® (nivolumab), in combination with platinum-doublet chemotherapy, is indicated as neoadjuvant treatment of adult patients with resectable (tumors ≥4 cm or node positive) non-small cell lung cancer (NSCLC).

OPDIVO^® (nivolumab), in combination with YERVOY^® (ipilimumab), is indicated for the first-line treatment of adult patients with metastatic non-small cell lung cancer (NSCLC) whose tumors express PD-L1 (≥1%) as determined by an FDA-approved test, with no EGFR or ALK genomic tumor aberrations.

OPDIVO^® (nivolumab), in combination with YERVOY^® (ipilimumab) and 2 cycles of platinum-doublet chemotherapy, is indicated for the first-line treatment of adult patients with metastatic or recurrent non-small cell lung cancer (NSCLC), with no EGFR or ALK genomic tumor aberrations.

OPDIVO^® (nivolumab) is indicated for the treatment of adult patients with metastatic non-small cell lung cancer (NSCLC) with progression on or after platinum-based chemotherapy. Patients with EGFR or ALK genomic tumor aberrations should have disease progression on FDA-approved therapy for these aberrations prior to receiving OPDIVO.

OPDIVO^® (nivolumab), in combination with YERVOY^® (ipilimumab), is indicated for the first-line treatment of adult patients with unresectable malignant pleural mesothelioma (MPM).

OPDIVO^® (nivolumab), in combination with YERVOY^® (ipilimumab), is indicated for the first-line treatment of adult patients with intermediate or poor risk advanced renal cell carcinoma (RCC).

OPDIVO^® (nivolumab), in combination with cabozantinib, is indicated for the first-line treatment of adult patients with advanced renal cell carcinoma (RCC).

OPDIVO^® (nivolumab) is indicated for the treatment of adult patients with advanced renal cell carcinoma (RCC) who have received prior anti-angiogenic therapy.

OPDIVO^® (nivolumab) is indicated for the treatment of adult patients with classical Hodgkin lymphoma (cHL) that has relapsed or progressed after autologous hematopoietic stem cell transplantation (HSCT) and brentuximab vedotin or after 3 or more lines of systemic therapy that includes autologous HSCT.

Contacts

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• DESTINY-Lung02 phase 2 trial shows clinically meaningful efficacy and favorable safety at 5.4 mg/kg dose versus 6.4 mg/kg dose of Daiichi Sankyo and AstraZeneca’s ENHERTU in HER2 mutant disease
• Updated results from DESTINY-Lung01 phase 2 trial demonstrate continued durable activity across patient subtypes

TOKYO & BASKING RIDGE, N.J. — (BUSINESS WIRE) — Detailed positive results from an interim analysis of the DESTINY-Lung02 phase 2 trial showed ENHERTU^® (trastuzumab deruxtecan) demonstrated clinically meaningful tumor responses in previously treated patients with HER2 mutant unresectable and/or metastatic non-squamous non-small cell lung cancer (NSCLC). Results will be presented today as a late breaking presentation (LBA55) at the European Society for Medical Oncology (#ESMO22) 2022 Congress.

ENHERTU is a specifically engineered HER2 directed antibody drug conjugate (ADC) being jointly developed and commercialized by Daiichi Sankyo (TSE:4568) and AstraZeneca (LSE/STO/Nasdaq: AZN).

At a pre-specified interim analysis of DESTINY-Lung02, with a data cutoff of March 24, 2022, patients receiving ENHERTU at a dose of 5.4 mg/kg (n=52) or 6.4 mg/kg (n=28) demonstrated clinically meaningful activity. The safety profile for both doses also was consistent with the overall safety profile of ENHERTU with the 5.4 mg/kg dose demonstrating a favorable safety profile in this patient population. A confirmed objective response rate (ORR) of 53.8% (95% confidence interval [CI], 39.5-67.8) and 42.9% (95% CI, 24.5-62.8) was seen in the 5.4 mg/kg and 6.4 mg/kg arms, respectively, as assessed by blinded independent central review (BICR). One complete response (CR) was observed in each arm (5.4 mg/kg: 1.9%, 6.4 mg/kg: 3.6%) with 27 (51.9%) partial responses (PR) observed in the 5.4 mg/kg arm and 11 (39.3%) PRs observed in the 6.4 mg/kg arm. At the pre-specified interim analysis, a median duration of response (DoR) was not reached in the 5.4 mg/kg arm and a median DoR of 5.9 months (95% CI: 2.8-NE) was seen in the 6.4 mg/kg arm. As median DoR was not reached in the 5.4 mg/kg arm, an additional 90-day follow-up response analysis was conducted, with a data cutoff of June 22, 2022, where ENHERTU demonstrated a confirmed ORR of 57.7% (95% CI, 43.2-71.3) and a median DoR of 8.7 months (95% CI: 7.1-NE) with CRs seen in 1.9% of patients and PRs in 55.8% of patients.

“DESTINY-Lung02 reinforces HER2 as an actionable mutation in patients with metastatic non-small cell lung cancer and further demonstrates that ENHERTU provides a clinically meaningful tumor response for these patients who have historically had limited treatment options,” said Koichi Goto, MD, Medical Oncologist and Investigator at National Cancer Center Hospital East, Kashiwa, Japan. “The response seen in this trial along with the disease control observed support ENHERTU as a potential treatment option in this type of non-small cell lung cancer.”

In DESTINY-Lung02, a favorable safety profile was observed in patients treated with ENHERTU 5.4 mg/kg with no new safety signals identified at either dose. Grade 3 treatment-emergent adverse events (TEAEs) were higher with ENHERTU 6.4 mg/kg versus 5.4 mg/kg (n=151). Grade 3 or higher treatment-related TEAEs occurred in 31.7% and 58.0% of all patients receiving ENHERTU 5.4 mg/kg or 6.4 mg/kg, respectively. The most common grade 3 or higher treatment-related TEAEs occurring in >10% of patients were neutropenia (11.9% (5.4 mg/kg), 34.0% (6.4 mg/kg)), anemia (8.9% (5.4 mg/kg), 14.0% (6.4 mg/kg)) and leukopenia (2.0% (5.4 mg/kg), 14.0% (6.4 mg/kg)). There were 13 cases (5.9% in the 5.4 mg/kg arm and 14% in the 6.4 mg/kg arm) of treatment-related ILD or pneumonitis reported as determined by an independent adjudication committee. The majority (5.4 mg/kg: 5.0%, 6.4 mg/kg: 14.0%) were low grade (grade 1 or 2), with one grade 3 event (5.4 mg/kg: 1.0%) reported. No grade 4 or grade 5 ILD or pneumonitis events occurred.

“The DESTINY-Lung02 results are consistent with the data previously seen with ENHERTU in non-small cell lung cancer and the efficacy demonstrated in this interim analysis, which supported the recent U.S. FDA accelerated approval of ENHERTU in patients with HER2 mutant non-small cell lung cancer, reinforces the potential to establish this medicine as a treatment option for these patients,” said Ken Takeshita, MD, Global Head, R&D, Daiichi Sankyo. “These data will help inform future regulatory submissions worldwide with the goal of continuing to offer this innovative medicine to as many patients as possible.”

“The clinically meaningful activity, together with the favorable safety profile seen in the DESTINY-Lung02 trial helps establish the optimal dose of ENHERTU at 5.4 milligrams per kilogram in previously treated HER2 mutant non-small cell lung cancer,” said Cristian Massacesi, MD, Chief Medical Officer and Oncology Chief Development Officer, AstraZeneca. “As we continue to explore the potential of this important medicine across multiple HER2 targetable tumor types, these data reaffirm the need to undertake HER2 testing in patients diagnosed with lung cancer.”

All patients in DESTINY-Lung02 received at least one prior cancer therapy, including platinum-based chemotherapy. In the pre-specified early cohort, 71.2% and 78.6% of patients received prior anti-PD-1 therapy in the 5.4 mg/kg and 6.4 mg/kg arms, respectively. Median follow-up was 5.6 months (1.1-11.7) in the 5.4 mg/kg arm and 5.4 months (0.6-12.1) in the 6.4 mg/kg arm.

Summary of DESTINY-Lung02 Results

DESTINY-Lung01 Updated Results

Updated results from the DESTINY-Lung01 phase 2 trial, which evaluated ENHERTU in HER2 mutant (cohort 2) or HER2 overexpressing (cohort 1 and cohort 1a) NSCLC, also were presented at ESMO and showed that ENHERTU continues to demonstrate consistent efficacy, safety and survival with longer follow-up.

After a median follow-up of 16.7 months, results of previously-treated patients with HER2 mutant NSCLC (cohort 2) showed the median duration of response (DoR) for ENHERTU in the overall patient population increased to 10.6 months (95% CI: 5.6-18.3) with median overall survival (OS) increasing to 18.6 months (95% CI: 13.8-25.8). Subgroup analyses of patients with or without a presence of baseline asymptomatic brain metastases showed that treatment with ENHERTU resulted in a median PFS of 7.1 months (95% CI: 5.5-9.8) and 9.7 months (95% CI: 4.5-16.9), respectively and a median OS of 14.0 months (95% CI: 9.8-19.5) and 27.0 months (95% CI: 15.3-NE), respectively. The subgroup analysis of patients who had received either two or fewer prior therapies or more than two prior therapies showed a median PFS of 8.3 months (95% CI: 5.8-15.2) and 6.8 months (95% CI: 4.4-9.8), respectively and a median OS of 22.1 months (95% CI: 14.0-31.3) and 13.8 months (95% CI: 7.1-18.6), respectively.

Additionally, updated results from cohort 1 (ENHERTU 6.4 mg/kg; n=49) and cohort 1a (ENHERTU 5.4 mg/kg; n=41), which evaluated patients with previously-treated metastatic HER2 overexpressing NSCLC, highlight encouraging anti-tumor activity. At the data cutoff of December 3, 2021, in cohort 1, a confirmed ORR of 26.5% (95% CI: 15.0-41.1) was seen in patients receiving ENHERTU 6.4 mg/kg with a median PFS of 5.7 months (95% CI: 2.8-7.2) and a median OS of 12.4 months (95% CI: 7.8-17.2). In cohort 1a, a confirmed ORR of 34.1% (95% CI: 20.1-50.6) was seen in patients receiving ENHERTU 5.4 mg/kg, with a median PFS of 6.7 months (95% CI: 4.2-8.4) and a median OS of 11.2 months (95% CI: 8.4-NE). Median duration of follow-up was 12.0 months (95% CI: 0.4-36.0) and 10.6 months (95% CI: 0.6-16.9) in the 6.4 mg/kg and 5.4 mg/kg treatment groups, respectively.

The overall safety profile of ENHERTU in DESTINY-Lung01 was consistent with previous data, with no new safety signals identified with the longer follow-up. In the HER2 mutant NSCLC patient cohort, there was one additional case of treatment-related ILD or pneumonitis observed, as determined by an independent adjudication committee. ILD has been observed in 27.5% of patients treated with ENHERTU 6.4 mg/kg in the HER2 mutant cohort with the majority identified as low-grade and two grade 5 events occurring. In the HER2 overexpressing NSCLC patient cohorts, there were two additional cases of treatment-related ILD or pneumonitis observed in the 6.4 mg/kg dose arm and two cases observed in the 5.4 mg/kg dose cohort, as determined by an independent adjudication committee. ILD has been observed in 20.4% and 4.9% of patients treated with ENHERTU at the 6.4 mg/kg and 5.4 mg/kg doses, respectively, in the HER2 overexpressing cohort with the majority identified as low-grade and four grade 5 events occurring. Data from the DESTINY-Lung01 phase 2 trial were previously published in The New England Journal of Medicine.

ENHERTU is not approved outside the U.S. for the treatment of patients with metastatic HER2 mutant NSCLC.

About DESTINY-Lung02

DESTINY-Lung02 is a global, randomized phase 2 trial evaluating the safety and efficacy of ENHERTU in patients with HER2 mutant metastatic NSCLC with disease recurrence or progression during or after at least one regimen of prior anticancer therapy that must have contained a platinum-based chemotherapy. Patients were randomized 2:1 to receive ENHERTU 5.4 mg/kg (Cohort 1; n=102) or ENHERTU 6.4 mg/kg (Cohort 2; n=50). The primary endpoint of the study is confirmed ORR as assessed by BICR. Secondary endpoints include confirmed disease control rate (DCR), DoR and PFS assessed by investigator and BICR, investigator-assessed OS and safety. DESTINY-Lung02 enrolled 152 patients at multiple sites, including Asia, Europe and North America. For more information about the trial, visit ClinicalTrials.gov.

About DESTINY-Lung01

DESTINY-Lung01 is a global phase 2, open-label, two-cohort trial evaluating the efficacy and safety of ENHERTU (5.4 mg/kg or 6.4 mg/kg) in patients with HER2 mutant (cohort 2, n=91) or HER2 overexpressing (cohort 1 and 1a, n=90) (defined as IHC 3+ or IHC 2+) unresectable or metastatic non-squamous NSCLC who had progressed after one or more systemic therapies. The primary endpoint is confirmed ORR by independent central review (ICR). Key secondary endpoints include DoR, DCR, PFS, OS and safety. DESTINY-Lung01 enrolled 181 patients at multiple sites, including Asia, Europe and North America. For more information about the trial, visit ClinicalTrials.gov.

About HER2 Mutant and HER2 Overexpressing NSCLC

Lung cancer is the second most common form of cancer globally, with more than two million patients diagnosed in 2020.¹ For patients with metastatic NSCLC, prognosis is particularly poor, as only approximately 8% will live beyond five years after diagnosis.²

HER2 is a tyrosine kinase receptor growth-promoting protein expressed on the surface of many types of tumors, including lung, breast, gastric and colorectal cancers. Certain HER2 (ERBB2) gene alterations (called HER2 mutations) have been identified in patients with non-squamous NSCLC as a distinct molecular target, and occur in approximately 2 to 4% of patients with this type of lung cancer.^3,4 While HER2 gene mutations can occur in a range of patients, they are more commonly found in patients with NSCLC who are younger, female and have never smoked.⁵ HER2 gene mutations have been independently associated with cancer cell growth and poor prognosis, with an increased incidence of brain metastases.⁶

Although the role of anti-HER2 treatment is well established in breast and gastric cancers, there were no approved HER2 directed therapies in NSCLC prior to the accelerated U.S. FDA approval of ENHERTU in unresectable or metastatic HER2 mutant NSCLC.⁷ Next-generation sequencing has been utilized in the identification of HER2 (ERBB2) mutations.⁸

HER2 overexpression is associated with a specific HER2 gene alteration known as HER2 amplification and is often associated with aggressive disease and poorer prognosis.⁹ It has been reported in approximately 10% to 15% of patients with NSCLC, with an incidence as high as 30% in those with adenocarcinoma (a subtype of cancer that grows in the glands that line the insides of organs).^10,11,12,13

About ENHERTU

ENHERTU^® (trastuzumab deruxtecan; fam-trastuzumab deruxtecan-nxki in the U.S. only) is a HER2 directed ADC. Designed using Daiichi Sankyo’s proprietary DXd ADC technology, ENHERTU is the lead ADC in the oncology portfolio of Daiichi Sankyo and the most advanced program in AstraZeneca’s ADC scientific platform. ENHERTU consists of a HER2 monoclonal antibody attached to a topoisomerase I inhibitor payload, an exatecan derivative, via a stable tetrapeptide-based cleavable linker.

ENHERTU (5.4 mg/kg) is approved in more than 30 countries for the treatment of adult patients with unresectable or metastatic HER2 positive breast cancer who have received a (or one or more) prior anti-HER2-based regimen, either in the metastatic setting or in the neoadjuvant or adjuvant setting, and have developed disease recurrence during or within six months of completing therapy based on the results from the DESTINY-Breast03 trial. ENHERTU also is approved in several countries for the treatment of adult patients with unresectable or metastatic HER2 positive breast cancer who have received two or more prior anti-HER2-based regimens based on the results from the DESTINY-Breast01 trial.

ENHERTU (5.4 mg/kg) is approved in the U.S. for the treatment of adult patients with unresectable or metastatic HER2 low (immunohistochemistry (IHC) 1+ or IHC 2+/in-situ hybridization (ISH)-) breast cancer who have received a prior chemotherapy in the metastatic setting or developed disease recurrence during or within six months of completing adjuvant chemotherapy based on the results from the DESTINY-Breast04 trial.

ENHERTU (5.4 mg/kg) is approved under accelerated approval in the U.S. for the treatment of adult patients with unresectable or metastatic non-small cell lung cancer (NSCLC) whose tumors have activating HER2 (ERBB2) mutations, as detected by an FDA-approved test, and who have received a prior systemic therapy based on the results from the DESTINY-Lung02 trial. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial.

ENHERTU (6.4 mg/kg) is approved in several countries for the treatment of adult patients with locally advanced or metastatic HER2 positive gastric or gastroesophageal junction (GEJ) adenocarcinoma who have received a prior trastuzumab-based regimen based on the results from the DESTINY-Gastric01 trial.

ENHERTU is approved in the U.S. with Boxed WARNINGS for Interstitial Lung Disease and Embryo-Fetal Toxicity. For more information, please see the accompanying full Prescribing Information, including Boxed WARNINGS, and Medication Guide.

About the ENHERTU Clinical Development Program

A comprehensive global development program is underway evaluating the efficacy and safety of ENHERTU monotherapy across multiple HER2 targetable cancers including breast, gastric, lung and colorectal cancers. Trials in combination with other anticancer treatments, such as immunotherapy, are also underway.

Regulatory applications for ENHERTU in breast and gastric cancer are currently under review in several countries based on the DESTINY-Breast01, DESTINY-Breast03, DESTINY-Breast04, DESTINY-Gastric01 and DESTINY-Gastric02 trials, respectively.

About the Daiichi Sankyo and AstraZeneca Collaboration

Daiichi Sankyo and AstraZeneca entered into a global collaboration to jointly develop and commercialize ENHERTU in March 2019 and datopotamab deruxtecan (Dato-DXd) in July 2020, except in Japan where Daiichi Sankyo maintains exclusive rights for each ADC. Daiichi Sankyo is responsible for the manufacturing and supply of ENHERTU and datopotamab deruxtecan.

U.S. Important Safety Information

Indications

ENHERTU is a HER2-directed antibody and topoisomerase inhibitor conjugate indicated for the treatment of adult patients with:

• Unresectable or metastatic HER2-positive breast cancer who have received a prior anti-HER2-based regimen either:

  – In the metastatic setting, or

  – In the neoadjuvant or adjuvant setting and have developed disease recurrence during or within six months of completing therapy

• Unresectable or metastatic HER2-low (IHC 1+ or IHC 2+/ISH-) breast cancer who have received a prior chemotherapy in the metastatic setting or developed disease recurrence during or within 6 months of completing adjuvant chemotherapy

• Unresectable or metastatic non-small cell lung cancer (NSCLC) whose tumors have activating HER2 (ERBB2) mutations, as detected by an FDA-approved test, and who have received a prior systemic therapy

• This indication is approved under accelerated approval based on objective response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial.

• Locally advanced or metastatic HER2-positive gastric or gastroesophageal junction adenocarcinoma who have received a prior trastuzumab-based regimen

Contraindications

None.

Warnings and Precautions

Interstitial Lung Disease / Pneumonitis

Severe, life-threatening, or fatal interstitial lung disease (ILD), including pneumonitis, can occur in patients treated with ENHERTU. A higher incidence of Grade 1 and 2 ILD/pneumonitis has been observed in patients with moderate renal impairment. Advise patients to immediately report cough, dyspnea, fever, and/or any new or worsening respiratory symptoms. Monitor patients for signs and symptoms of ILD. Promptly investigate evidence of ILD. Evaluate patients with suspected ILD by radiographic imaging. Consider consultation with a pulmonologist. For asymptomatic ILD/pneumonitis (Grade 1), interrupt ENHERTU until resolved to Grade 0, then if resolved in ≤28 days from date of onset, maintain dose. If resolved in >28 days from date of onset, reduce dose one level. Consider corticosteroid treatment as soon as ILD/pneumonitis is suspected (e.g., ≥0.5 mg/kg/day prednisolone or equivalent). For symptomatic ILD/pneumonitis (Grade 2 or greater), permanently discontinue ENHERTU. Promptly initiate systemic corticosteroid treatment as soon as ILD/pneumonitis is suspected (e.g., ≥1 mg/kg/day prednisolone or equivalent) and continue for at least 14 days followed by gradual taper for at least 4 weeks.

Metastatic Breast Cancer and HER2-Mutant NSCLC (5.4 mg/kg)

In patients with metastatic breast cancer and HER2-mutant NSCLC treated with ENHERTU 5.4 mg/kg, ILD occurred in 12% of patients. Fatal outcomes due to ILD and/or pneumonitis occurred in 1.0% of patients treated with ENHERTU. Median time to first onset was 5 months (range: 0.9 to 23).

Locally Advanced or Metastatic Gastric Cancer (6.4 mg/kg)

In patients with locally advanced or metastatic HER2-positive gastric or GEJ adenocarcinoma treated with ENHERTU 6.4 mg/kg, ILD occurred in 10% of patients. Median time to first onset was 2.8 months (range: 1.2 to 21).

Neutropenia

Severe neutropenia, including febrile neutropenia, can occur in patients treated with ENHERTU. Monitor complete blood counts prior to initiation of ENHERTU and prior to each dose, and as clinically indicated. For Grade 3 neutropenia (Absolute Neutrophil Count [ANC] <1.0 to 0.5 x 10⁹/L), interrupt ENHERTU until resolved to Grade 2 or less, then maintain dose. For Grade 4 neutropenia (ANC <0.5 x 10⁹/L), interrupt ENHERTU until resolved to Grade 2 or less, then reduce dose by one level. For febrile neutropenia (ANC <1.0 x 10⁹/L and temperature >38.3º C or a sustained temperature of ≥38º C for more than 1 hour), interrupt ENHERTU until resolved, then reduce dose by one level.

Metastatic Breast Cancer and HER2-Mutant NSCLC (5.4 mg/kg)

In patients with metastatic breast cancer and HER2-mutant NSCLC treated with ENHERTU 5.4 mg/kg, a decrease in neutrophil count was reported in 65% of patients. Sixteen percent had Grade 3 or 4 decreased neutrophil count. Median time to first onset of decreased neutrophil count was 22 days (range: 2 to 664). Febrile neutropenia was reported in 1.1% of patients.

Locally Advanced or Metastatic Gastric Cancer (6.4 mg/kg)

In patients with locally advanced or metastatic HER2-positive gastric or GEJ adenocarcinoma treated with ENHERTU 6.4 mg/kg, a decrease in neutrophil count was reported in 72% of patients. Fifty-one percent had Grade 3 or 4 decreased neutrophil count. Median time to first onset of decreased neutrophil count was 16 days (range: 4 to 187). Febrile neutropenia was reported in 4.8% of patients.

Left Ventricular Dysfunction

Patients treated with ENHERTU may be at increased risk of developing left ventricular dysfunction. Left ventricular ejection fraction (LVEF) decrease has been observed with anti-HER2 therapies, including ENHERTU. Assess LVEF prior to initiation of ENHERTU and at regular intervals during treatment as clinically indicated. Manage LVEF decrease through treatment interruption. When LVEF is >45% and absolute decrease from baseline is 10-20%, continue treatment with ENHERTU. When LVEF is 40-45% and absolute decrease from baseline is <10%, continue treatment with ENHERTU and repeat LVEF assessment within 3 weeks. When LVEF is 40-45% and absolute decrease from baseline is 10-20%, interrupt ENHERTU and repeat LVEF assessment within 3 weeks. If LVEF has not recovered to within 10% from baseline, permanently discontinue ENHERTU.

Contacts

Global:
Victoria Amari

Daiichi Sankyo, Inc.

vamari@dsi.com
+1 908 900 3010 (mobile)

Japan:
Masashi Kawase

Daiichi Sankyo Co., Ltd.

kawase.masashi.a2@daiichisankyo.co.jp
+81 3 6225 1126 (office)

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• Extended follow-up data from phase 1/2 trial of DS-7300 in patients with metastatic lung, prostate or esophageal cancer to be featured in Proffered Paper session at ESMO

TOKYO, BASKING RIDGE, N.J. & NASHVILLE, Tenn. — (BUSINESS WIRE) — Daiichi Sankyo (TSE: 4568) and Sarah Cannon Research Institute (SCRI) announced that extended follow-up data from a phase 1/2 trial of DS-7300, a specifically designed potential first-in-class B7-H3 directed DXd antibody drug conjugate (ADC), continues to show promising durable tumor response in patients with several types of heavily pretreated cancers including lung, prostate or esophageal cancer. These data were presented today in a Proffered Paper session (Abstract #453O) at the European Society of Medical Oncology (#ESMO22) Congress.

B7-H3 is overexpressed in a wide range of cancer types, including lung, prostate and esophageal, and its overexpression has been shown to correlate with poor prognosis in some cancers, making B7-H3 a promising therapeutic target.^1,2,3,4,5,6

A response rate of 32% (95% CI: 24-41) was observed with 38 responses (33 confirmed; 28%; 95% CI: 20-37) in 118 patients with various solid tumors including small cell lung cancer (SCLC), squamous non-small cell lung cancer (NSCLC), metastatic castration-resistant prostate cancer (CRPC), esophageal squamous cell carcinoma (ESCC), head and neck squamous cell carcinoma (HNSCC) or endometrial cancer receiving doses of DS-7300 ranging from 4.8 mg/kg to 16.0 mg/kg.

“These results represent important progress in the development of DS-7300, which is continuing to show promising durable efficacy in patients with several different types of advanced cancers, including lung, prostate or esophageal cancer,” said Ken Takeshita, MD, Global Head, R&D, Daiichi Sankyo. “Based on these results, we are evaluating next steps for the clinical development of DS-7300 beyond the phase 2 trial recently initiated in patients with extensive-stage small cell lung cancer.”

Lung Cancer Subset Efficacy Analyses

In two subsets of patients with advanced lung cancer, response rates of 58% (95% CI: 33-80) and 40% (95% CI: 5-85) were observed in patients with SCLC (n=19) and squamous NSCLC (n=5), respectively. Eleven responses (10 confirmed; 53%; 95% CI: 29-76) were seen in patients with SCLC and two confirmed responses (40%; 95% CI: 5-85) were seen in patients with squamous NSCLC. Median duration of response (DOR) was 5.5 months (95% CI: 2.8-NR) in patients with SCLC and 4.3 months (95% CI: 3.1-NR) in patients with squamous NSCLC. Median follow-up was 4.9 months (95% CI: 3.3-8.8) in patients with SCLC and 1.7 months (95% CI: 0.3-5.2) in patients with squamous NSCLC.

“All lung cancer patients except for one with squamous non-small cell lung cancer experienced a reduction in tumor size with DS-7300, which is potentially promising for patients looking beyond standard chemotherapy and immunotherapy options,” said Melissa L. Johnson, MD, Director, Lung Cancer Research, Sarah Cannon Research Institute at Tennessee Oncology. “We are eager to confirm the encouraging efficacy and safety results in patients with small cell lung cancer in an ongoing phase 2 trial currently enrolling patients with extensive-stage disease.”

Prostate Subset Efficacy Analysis

A response rate of 33% (95% CI: 21-47) was observed in a subset of patients in the dose escalation and expansion cohorts with metastatic CRPC (n=54). Eighteen responses (15 confirmed; 28%; 95% CI: 17-42) were seen in patients with metastatic CRPC and median DOR was 4.4 months (95% CI: 2.7-NR). Median follow-up was 9.3 months (95% CI: 7.5-10.6). For metastatic CRPC, 46% of patients had baseline liver metastases of which 40% of patients had a response.

Esophageal Subset Efficacy Analysis

A response rate of 23% (95% CI: 8-45) was observed in a subset of patients in the dose escalation and expansion cohorts with ESCC (n=22). Five responses (four confirmed; 18%; 95% CI: 5-40) were seen in patients with ESCC and median DOR was 2.8 months (95% CI: 2.6-NR). Median follow-up was 7.7 months (95% CI: 3.3-10.9).

Overall Safety

The safety and tolerability of DS-7300 was consistent with that previously reported from the trial. The most common treatment emergent adverse events (TEAEs) reported in >10% of all patients (n=147) were nausea (63%), anemia (33%), infusion-related reaction (32%), decreased appetite (31%), fatigue (30%), vomiting (30%), diarrhea (16%), pyrexia (16%), constipation (14%), chills (13%) and dehydration (11%). Grade ≥ 3 TEAEs occurred in 66 patients (45%), the most common of which were anemia (19%), neutropenia (4%), nausea (3%), pneumonia (3%) and decreased neutrophil count (3%). Two grade 1 and four grade 2 treatment-related interstitial lung disease (ILD)/pneumonitis events were reported at the 12.0 mg/kg dose and one grade 5 ILD event previously reported at the 16.0 mg/kg dose, which was discontinued due to safety concerns. These ILD events were adjudicated as drug-related by an independent adjudication committee. Two ILD/pneumonitis events are currently pending adjudication. Treatment discontinuations due to TEAEs occurred in 8% of patients.

“Prostate and esophageal cancer are two types of cancer that remain difficult to treat in advanced stages, where many patients experience repeated disease recurrence,” said Toshihiko Doi, MD, PhD, Director of Exploratory Oncology Research, Director of Clinical Trial Center and Center of Promotion of Translational Research, and Chief of Department of Experimental Therapeutics, National Cancer Center Hospital East. “Targeting the B7-H3 protein in both prostate and esophageal cancer with DS-7300 may be an encouraging treatment strategy for these patients who have limited treatment options in the metastatic setting.”

Patients enrolled in both the dose escalation and dose expansion parts of the trial across the 4.8 mg/kg to 16.0 mg/kg doses of DS-7300 received a median of five prior lines of therapies (range, 0-14). As of the data cut-off on June 30, 2022, 35 patients (24%) were still being treated with DS-7300 including eight patients (40%) with SCLC, 17 patients (23%) with metastatic CRPC, four patients (15%) with ESCC and five patients (56%) with squamous NSCLC. The expansion cohort in patients with squamous NSCLC remains open for enrollment.

About the DS-7300 Phase 1/2 Trial

This first-in-human, open-label phase 1/2 trial is evaluating the safety, tolerability and preliminary activity of DS-7300 in adult patients with advanced/unresectable or metastatic solid tumors that are refractory or intolerable to standard treatment or for whom no standard treatment exists.

The phase 1 part of the trial (dose escalation) is assessing the safety and tolerability of increasing doses of DS-7300 to determine the maximum tolerated dose (MTD) or recommended dose for expansion (RDE). This portion of the trial enrolled 81 patients with advanced/unresectable or metastatic SCLC, squamous NSCLC, metastatic CRPC, ESCC, HNSCC, bladder cancer, sarcoma, endometrial cancer, melanoma or breast cancer.

The phase 2 part of the trial (dose expansion) is evaluating the safety, tolerability and preliminary activity of DS-7300 at the RDE of 12.0 mg/kg in patients with squamous NSCLC, metastatic CRPC or ESCC.

The dose escalation part of the trial is evaluating dose-limiting toxicity and safety. The dose expansion part of the trial is evaluating ORR, DOR, disease control rate, progression-free survival, overall survival and safety. Pharmacokinetic endpoints, exploratory biomarker and immunogenicity endpoints also will be assessed.

Patient enrollment into the squamous NSCLC cohort of the dose expansion part of the trial remains underway in Asia and North America. For more information, please visit ClinicalTrials.gov.

About B7-H3

B7-H3 is a transmembrane protein that belongs to the B7 family, which also includes PD-L1.⁶ B7-H3 is overexpressed in a wide range of cancer types, including lung, prostate and esophageal, and its overexpression has been shown to correlate with poor prognosis in some cancers, making B7-H3 a promising therapeutic target.^1,2,3,4,5,6 Currently, no B7-H3 directed medicines are approved for the treatment of any cancer.

About Lung, Prostate and Esophageal Cancer

Lung cancer is the second most common cancer and the leading cause of cancer-related mortality worldwide with more than 2.2 million new cases and 1.7 million deaths in 2020.⁷ The two main types of lung cancer include NSCLC, which represents more than 80 to 85% of all cases, and SCLC, which comprises about 15% of cases.⁸ NSCLC is further divided into three subtypes including squamous cell carcinoma, which represents about 25% of cases and originates in squamous cells that line the inside of the airways in the lungs.⁸ More than half of patients with lung cancer are diagnosed in the metastatic stage.⁹ The five-year survival rate is only 8% and 3% for patients diagnosed with advanced NSCLC and SCLC, respectively.^10,11

Prostate cancer is the second most frequent cancer and the fifth leading cause of cancer death among men with an estimated 1.4 million new cases and 375,000 deaths worldwide in 2020.⁷ The five-year survival rate is only 32.3% for patients with metastatic prostate cancer.^12,13

Esophageal cancer is the tenth most common cancer worldwide and the sixth leading cause of cancer mortality with an estimated 604,000 new cases and 544,000 deaths reported in 2020.⁷ The majority of patients with esophageal cancer are diagnosed at advanced stage where the five-year survival rate is only 5.7%.^{14, 15}

About DS-7300

DS-7300 is an investigational B7-H3 directed ADC and is one of five ADCs currently in clinical development in the oncology pipeline of Daiichi Sankyo. Designed using Daiichi Sankyo’s proprietary DXd ADC technology, DS-7300 is comprised of a humanized anti-B7-H3 IgG1 monoclonal antibody attached to a number of topoisomerase I inhibitor payloads (an exatecan derivative, DXd) via tetrapeptide-based cleavable linkers.

In addition to the phase 1/2 trial in collaboration with Sarah Cannon Research Institute, DS-7300 also is being evaluated by Daiichi Sankyo in a phase 2 trial in patients with extensive-stage SCLC.

DS-7300 is an investigational medicine that has not been approved for any indication in any country. Safety and efficacy have not been established.

About Daiichi Sankyo

Daiichi Sankyo is dedicated to creating new modalities and innovative medicines by leveraging our world-class science and technology for our purpose “to contribute to the enrichment of quality of life around the world.” In addition to our current portfolio of medicines for cancer and cardiovascular disease, Daiichi Sankyo is primarily focused on developing novel therapies for people with cancer as well as other diseases with high unmet medical needs. With more than 100 years of scientific expertise and a presence in more than 20 countries, Daiichi Sankyo and its 16,000 employees around the world draw upon a rich legacy of innovation to realize our 2030 Vision to become an “Innovative Global Healthcare Company Contributing to the Sustainable Development of Society.” For more information, please visit: www.daiichisankyo.com.

About Sarah Cannon Research Institute

Sarah Cannon Research Institute is the research arm of HCA Healthcare’s Cancer Institute, Sarah Cannon. Focused on advancing therapies for patients, it is one of the world’s leading clinical research organizations conducting community-based clinical trials. A leader in drug development, Sarah Cannon has led more than 600 first-in-human clinical trials since its inception in 1993, and has been a clinical trial leader in the majority of approved cancer therapies for more than a decade. Additionally, Sarah Cannon offers management, regulatory, and other research support services for drug development and industry sponsors through its contract research organization (CRO), Sarah Cannon Development Innovations.

_________________________

References:

¹ Yamato M, et al. Mol Cancer Ther. 2022;21:635–46.

² Dong P, et al. Front Oncol. 2018;8:264.

³ Picarda E, et al. Clin Cancer Res. 2016;22(14):3425-3431.

⁴ Bendell JC, et al. J Clin Oncol. 2020;39(15 suppl 1). Abstract TPS3646.

⁵ Kontos F, et al. Clin Cancer Res. 2021;27(5):1227-1235.

⁶ Qiu M-j, et al. Front. Oncol. 2021;11:600238.

⁷ Sung H, et al. CA Cancer J Clin . 2021;71(3): 209-249

⁸ Schabath MB and Cote ML. Cancer Epidemiol Biomarkers Prev. 2019 Oct;28(10):1563-1579

⁹ Chen R, et al. J Hematol Oncol. 2020;13(1):58

¹⁰American Cancer Society. NSCLC Survival Rates (SEER Data). Updated March 2022

¹¹ SEER. Small Cell Carcinoma of the Lung and Bronchus SEER 5-Year Relative Survival Rates. 2012-2018. Accessed September 2022

¹² NCI Seer Cancer Stats Prostate Cancer
¹³ NCI Seer Cancer Stat Facts Prostate Cancer by Stage
¹⁴ Yang J et al. Front Oncol. 2020; 10: 1727

¹⁵ NCI Seer Cancer Stat Facts: Esophageal Cancer

Contacts

Media Contacts:
Global:
Sarah McGovern

Daiichi Sankyo, Inc.

smcgovern@dsi.com
+1 908 821 7376 (mobile)

Investor Relations Contact:
DaiichiSankyoIR@daiichisankyo.co.jp

Japan:
Masashi Kawase

Daiichi Sankyo Co., Ltd.

kawase.masashi.a2@daiichisankyo.co.jp
+81 3 6225 1126 (office)

Late-Breaking presentation of phase 2 results from a clinical trial of GX-188E in combination with KEYTRUDA^® (pembrolizumab) demonstrates anti-tumor benefit in heavily pre-treated, recurrent and advanced cervical cancer

SEOUL, South Korea — (BUSINESS WIRE) — Genexine (KOSDAQ: 095700), a publicly traded, clinical-stage Korean biopharmaceutical company committed to the discovery and development of novel biologics for the treatment of unmet medical needs, today announced that GX-188E, its first-in-class proprietary DNA vaccine, demonstrated potent efficacy and favorable safety in patients with advanced cervical cancer in a phase 2 study when given in combination with KEYTRUDA^® (pembrolizumab), MSD’s (Merck & Co., Inc., Rahway, NJ, USA) anti-PD-1 therapy.

A total of 60 patients with HPV 16- and/or 18- positive advanced cervical cancer were analyzed in the phase 2 treatment group. Top line results showed a Best Overall Response Rate (BORR) of 31.7% (19 of 60 patients). 6 patients (10.0%) had a complete response and 13 patients (21.7%) had a partial response. Median duration of response (DOR) was 12.3 months and overall survival (OS) was 17.2 months.

The BORR increased to 38.5% in PD-L1 positive patients with HPV 16+ and Squamous Cell Carcinoma. Importantly, PD-L1 negative patients showed an ORR of 25.0%, which is extremely encouraging for this patient population, as it demonstrates potential improvement in efficacy compared to monotherapy of immune checkpoint inhibitors, suggesting a beneficial effect of the combination therapy.

In the safety analysis (n=65) 22 of 65 patients (33.8%) had treatment-related adverse events (TRAEs) of any grade and three (4.6%) had grade 3 or 4 TRAEs. The combination therapy was found to be safe and tolerable with a similar safety profile to that of pembrolizumab monotherapy.

“There is an urgent need for better therapies for patients with advanced cervical cancer and the combination of a therapeutic DNA vaccine together with checkpoint inhibition could be a strong alternative,” said professor Sung-Jong Lee of the Catholic University of Korea, College of Medicine and Investigator in the trial. “The data are very encouraging and appear to show a clear efficacy signal and the product appears safe and well tolerated. I am particularly pleased to see a clear efficacy signal in all patients, regardless of PD-L1 expression. Genexine’s combination therapy has strong appeal from a mechanistic perspective. This approach of using checkpoint inhibition to restore immune system function combined with the vaccine’s effect of upregulating and increasing the influx of CD8+ and other immune cells into the tumor microenvironment, appears to result in a strong, beneficial effect as demonstrated by major outcome measures such as BORR (31.7%) and OS (17.2 months) through the elimination of tumor cells and tumors.”

“We are very pleased to have been invited to present our phase 2 top-line data at ESMO and encouraged by the efficacy and safety shown in this study,” said Neil Warma, President and CEO of Genexine. “The combination of GX-188E, our unique DNA vaccine, with pembrolizumab could represent a new standard of care for patients with HPV 16/18 related recurrent or metastatic cervical cancer, regardless of PD-L1 expression. We are encouraged by the ORR of over 31% but particularly excited by the efficacy signal observed in PD-L1 negative patients. This could open the door to a new therapy for this patient population that previously had limited treatment options available.”

The clinical trial was an open-label, single-arm, phase 2 trial conducted in South Korea in patients with HPV-16 or HPV-18 positive advanced cervical cancer, and who had progressed after standard-of-care therapy. Patients received intramuscular 2 mg GX-188E at weeks 1, 2, 4, 7, 13, 19, and optional dose at week 46, and intravenous pembrolizumab 200 mg every 3 weeks for up to 2 years or until disease progression. The primary endpoint was ORR assessed by the blinded independent central reviewers (BICR) using RECIST version 1.1.

KEYTRUDA^® is a registered trademark of Merck Sharp & Dohme LLC., a subsidiary of Merck & Co., Inc., Rahway, NJ.

About Genexine

Genexine, Inc. is a publicly traded, clinical-stage biotechnology company focused on the development and commercialization of immunotherapeutics and next-generation long-acting biologics. Primary technology platforms are Therapeutic DNA vaccine technology and hyFc^® fusion technology. The company has multiple products in clinical development, including several undergoing phase 3 registration trials. The company’s proprietary pipeline includes GX-188E for cervical cancer and head and neck cancer, GX-I7 (efineptakin alfa) for multiple cancers, GX-H9 (eftansomatropin alfa) for Growth Hormone Deficiency and GX-E4 for CKD-induced anemia, among others. Genexine has established multiple partnerships with global companies in order to expedite product development and commercialization and create significant value. Genexine is listed on the Korean stock exchange (KOSDAQ: 095700) and is headquartered in Seoul, Korea. Genexine is committed to the well-being and care of patients worldwide.

About GX-188E

GX-188E is a novel DNA-based therapeutic vaccine discovered by Genexine and being jointly developed with the National Cancer Center Korea Onco-Innovation Unit (NOIU). It has a mechanism of inducing an antigen-specific T-cell immune response to E6/E7, a cancer-causing protein produced by HPV types 16 and 18, which are the main causes of cervical cancer. The T cells with activated immune response have an immune-anticancer mechanism that effectively eliminates cervical cancer cells by inducing a cytotoxic T lymphocyte response. Genexine is currently developing GX-188E in cervical cancer and is also conducting two on-going combination trials with GX-188E in Squamous Cell Carcinoma of the Head and Neck (SCCHN).

About Cervical Cancer

Cervical cancer is a cancer arising from the cervix and is due to the abnormal growth of cells that have the ability to invade or spread to other parts of the body. Human Papilloma Virus (HPV) causes more than 90% of cases and HPV 16 and 18 strains are responsible for the majority of high grade cervical cancers. According to WHO, cervical cancer is the fourth most common cancer among women globally, with an estimated 604,000 new cases and 342,000 deaths in 2020. A recent Arizton research report estimated that the cervical cancer therapeutics market was $5.5 billion in 2021 and expected to grow at a CAGR of 4.14% during 2021-2027 to reach $7.1 billion with targeted therapies expected to be the fastest-growing segment during the forecast period.

Forward Looking Statements

This press release contains forward-looking statements regarding the business of Genexine, Inc. (“Genexine”). Any statement describing Genexine’s goals, expectations, financial or other projections, intentions or beliefs, development plans and the commercial potential of Genexine’s drug development pipeline, including without limitation GX-I7 (efineptakin alfa), GX-188E, GX-H9 (eftansomatropin alfa), GX-E4 is a forward-looking statement and should be considered an at-risk statement. Such statements are subject to risks and uncertainties, particularly those challenges inherent in the process of discovering, developing and commercialization of new drug products that are safe and effective for use as human therapeutics and in the endeavor of building a business around such drugs.

Genexine’s forward-looking statements also involve assumptions that, if they never materialize or prove correct, could cause its results to differ materially from those expressed or implied by such forward-looking statements. Although Genexine’s forward-looking statements reflect the good faith judgment of its management, these statements are based only on facts and factors currently known by Genexine. As a result, you are cautioned not to rely on these forward-looking statements. These and other risks concerning Genexine’s programs are described in additional detail in Genexine’s annual reports on DART (Data Analysis, Retrieval and Transfer System) internet site (https://dart.fss.or.kr/) of the Korean Financial Supervisory Service. Genexine assumes no obligation to update the forward-looking statements or to update the reasons why actual results could differ from those projected in the forward-looking statements, except as required by law.

Contacts

For further information, please contact Genexine Investor Relations:

Mr. Edward Shin

edward.shin@genexine.com

Mr. Jongsoo Lee

jongsoo.lee@genexine.com

JEFFERSON, N.J. — (BUSINESS WIRE) — #3DMammogram–A pioneering, state-of-the-art radiology center in New Jersey has officially announced its opening date to the public this month.

Set to improve and redefine the medical diagnostic imaging experience for its patients, the new ImageCare Radiology location in Jefferson was launched on September 1, 2022 and will provide the most advanced medical diagnostic imaging to date.

Launching initially with their newly-introduced 10-minute 3T MRI scans, those working at the radiology center are excited to be offering patients the fastest medical scans on the market, along with other useful and innovative services that are beyond anything they have been able to offer patients before.

“We’ll soon be launching a number of new image and radiology services, but in particular, the introduction of 10-minute MRI scans will be groundbreaking,” said Dr. Clay Hinrichs, President of ImageCare Radiology. “Not only will our patients continue to receive the highest possible service and advanced diagnostic imaging, but they will also be able to take advantage of the fastest 3T scans available. This is useful in many ways, but particularly for patients that are children, are claustrophobic, or living with disabilities. It’s going to make them feel much more comfortable knowing they can still receive detailed and advanced image quality, but will take much less time.”

“Many people have previously avoided such scans due to feeling uneasy about tight spaces or being uncomfortable about remaining still for long periods of time, which isn’t ideal because we want to ensure our patients get the best possible service and early diagnosis. Now though, patients no longer need to worry about this and can now also receive accurate imaging within a shorter timeframe,” added Dr. Hinrichs.

Alongside the initial 3T MRI scans, the site will also offer the highest resolution of Siemens PET/CT Scans, sedation services with anesthesiologists for all modalities, and Nuclear Medicine – offering bone scans, thyroid function tests, HIDA scans, renal scans and tumor workups. The center is also expected to launch an interventional suite, which will offer lower cost outpatient solutions for procedures including nephrostomy tubes, peripheral vascular studies, MediPorts for cancer therapy, tumor embolizations, and vertebroplasty for spinal fractures.

Dr. Clay Hinrichs said that each of the services will be launched gradually, but patient experience will be improved from the very first day of its opening.

He concluded, “Following the initial launch of our 10-minute 3T MRI scans, we will also offer mammography, ultrasound with Echocardiography, and X-rays. We will have the first full-service non-hospital nuclear scanner in Northern NJ , and be able to offer lower cost outpatient solutions with our interventional suite. We’re proud to say that our mammograms will be ‘PINK Better Mammo’ with Artificial Intelligence, which is the first FDA approved AI Technology for improved breast cancer detection. We’re also excited for our future opening of CT/PET scanners and sedation for all our services, which is expected to be available to everyone by the end of summer.”

Patients looking to book appointments can use the new services starting September 1.

Notes to Editors

ImageCare Radiology has centers conveniently located throughout North and Central New Jersey in Bergen, Essex, Hunterdon, Middlesex, Monmouth, Morris, Passaic, Sussex, and Warren Counties.

ImageCare is committed to providing the most advanced medical diagnostic imaging to their patients, working to ensure everyone who uses their services are comfortable and at ease. Only recruiting caring and compassionate staff members, and skilled radiologists, they are renowned for their state-of the-art Radiology services including Open and Closed MRIs, Sedation MRIs, Ultrasounds, X-rays, DEXA Bone Density Scans, 3D Mammograms with Artificial Intelligence, Pediatric Radiology, Nuclear Imaging, PET/CT Scans, and Interventional Radiology.

For more information on the center or to book an appointment, please visit: www.imagecarecenters.com

To contact ImageCare or to organize any interviews regarding the new center, please contact Thomas Wood, Director of Marketing, here: twood@imagecarecenters.com

Contacts

ImageCare

Thomas Wood, Director of Marketing

twood@imagecarecenters.com