Ipilimumab

The Application is based on Phase 3 CheckMate – 9DW trial results demonstrating improved survival with Opdivo plus Yervoy compared to investigator’s choice of lenvatinib or sorafenib in this patient population PRINCETON, NJ, USA I July 19, 2024 I Bristol Myers Squibb (NYSE: BMY) today announced that the European Medicines Agency (EMA) validated its Type II variation application for Opdivo ® (nivolumab) plus Yervoy ® (ipilimumab) as a potential first-line treatment option for adult patients with unresectable or advanced hepatocellular carcinoma (HCC) who have not received prior systemic therapy. The application was based on results from the Phase 3 CheckMate -9DW trial and validation of the application confirms the submission is complete and begins the EMA’s centralized procedure review. “Approximately 62,000 cases of liver cancer are diagnosed annually in the European Union, with HCC being the predominant type. Despite recent treatment advances, the prognosis remains poor for patients in more advanced stages which highlights the need for therapies with better clinical outcomes,” said Dana Walker, M.D., M.S.C.E., vice president, global program lead, gastrointestinal and genitourinary cancers, Bristol Myers Squibb. “ We look forward to working with the EMA to advance our application for Opdivo plus Yervoy to provide a new first-line dual immunotherapy combination treatment optionfor adult patients with unresectable or advanced hepatocellular carcinoma in the European Union.” In the Phase 3 CheckMate -9DW trial, Opdivo plus Yervoy demonstrated statistically significant and clinically meaningful improvement in overall survival (OS) compared to investigator’s choice of lenvatinib or sorafenib, which showed the clinical benefit of the combination treatment option when provided in the first-line setting. The safety profile for the combination of Opdivo plus Yervoy remained consistent with previously reported data and was manageable with established protocols, with no new safety signals identified. Results were presented at the 2024 American Society of Clinical Oncology (ASCO) Annual Meeting . Bristol Myers Squibb thanks the patients and investigators involved with the Phase 3 CheckMate -9DW clinical trial. About CheckMate -9DW CheckMate -9DW is a Phase 3 randomized, open-label trial evaluating the combination of Opdivo plus Yervoy compared to investigator’s choice of lenvatinib or sorafenib monotherapy in patients with unresectable or advanced hepatocellular carcinoma who have not received prior systemic therapy. Approximately 668 patients were randomized to receive Opdivo plus Yervoy ( Opdivo 1mg/kg plus Yervoy 3 mg/kg Q3W for up to four doses, followed by Opdivo monotherapy 480 mg for a maximum duration of 2 years) infusion, or single agent lenvatinib or sorafenib as oral capsules in the control arm. The primary endpoint of the trial is overall survival and key secondary endpoints include objective response rate and time to symptom deterioration. About Hepatocellular Carcinoma Liver cancer is the third most frequent cause of cancer death worldwide. Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer and accounts for 75% – 85% of all liver cancers. HCC is often diagnosed in an advanced stage, where effective treatment options are limited and are usually associated with poor outcomes. Up to 70% of patients experience recurrence within five years, particularly those still considered to be at high risk after surgery or ablation. While most cases of HCC are caused by hepatitis B virus (HBV) or hepatitis C virus (HCV) infections, metabolic syndrome and nonalcoholic steatohepatitis (NASH) are rising in prevalence and expected to contribute to increased rates of HCC. 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 understanding of causal human biology, cutting-edge capabilities and differentiated research programs uniquely position the company to approach 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. As a leader in cancer care, Bristol Myers Squibb is working to empower all people with cancer to have a better future. About Opdivo Opdivo is a programmed death-1 (PD-1) immune checkpoint inhibitor that is designed to uniquely harness the body’s own immune system to help restore anti-tumor immune response. By harnessing the body’s own immune system to fight cancer, Opdivo has become an important treatment option across multiple cancers. Opdivo ’s leading global development program is based on Bristol Myers Squibb’s scientific expertise in the field of Immuno-Oncology and includes a broad range of clinical trials across all phases, including Phase 3, in a variety of tumor types. To date, the Opdivo clinical development program has treated more than 35,000 patients. The Opdivo trials have contributed to gaining a deeper understanding of the potential role of biomarkers in patient care, particularly regarding how patients may benefit from Opdivo across the continuum of PD-L1 expression. In July 2014, Opdivo was the first PD-1 immune checkpoint inhibitor to receive regulatory approval anywhere in the world. Opdivo is currently approved in more than 65 countries, including the United States, the European Union, Japan and China. In October 2015, the Company’s Opdivo and Yervoy combination regimen was the first Immuno-Oncology combination to receive regulatory approval for the treatment of metastatic melanoma and is currently approved in more than 50 countries, including the United States and the European Union. About Yervoy Yervoy is a recombinant, human monoclonal antibody that binds to the cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4). CTLA-4 is a negative regulator of T-cell activity. Yervoy binds to CTLA-4 and blocks the interaction of CTLA-4 with its ligands, CD80/CD86. Blockade of CTLA-4 has been shown to augment T-cell activation and proliferation, including the activation and proliferation of tumor infiltrating T-effector cells. Inhibition of CTLA-4 signaling can also reduce T-regulatory cell function, which may contribute to a general increase in T-cell responsiveness, including the anti-tumor immune response. On March 25, 2011, the U.S. Food and Drug Administration (FDA) approved Yervoy 3 mg/kg monotherapy for patients with unresectable or metastatic melanoma. Yervoy is approved for unresectable or metastatic melanoma in more than 50 countries. There is a broad, ongoing development program in place for Yervoy spanning multiple tumor types. INDICATIONS OPDIVO® (nivolumab), as a single agent, is indicated for the treatment of adult and pediatric patients 12 years and older with unresectable or metastatic melanoma. OPDIVO® (nivolumab), in combination with YERVOY® (ipilimumab), is indicated for the treatment of adult and pediatric patients 12 years and older with unresectable or metastatic melanoma. OPDIVO® is indicated for the adjuvant treatment of adult and pediatric patients 12 years and older with completely resected Stage IIB, Stage IIC, Stage III, or Stage IV melanoma. 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. This indication is approved under accelerated approval based on overall response rate. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials. OPDIVO® (nivolumab) is indicated for the treatment of adult patients with recurrent or metastatic squamous cell carcinoma of the head and neck (SCCHN) with disease progression on or after platinum-based therapy. OPDIVO® (nivolumab) is indicated for the treatment of adult patients with locally advanced or metastatic urothelial carcinoma who have disease progression during or following platinum-containing chemotherapy or have disease progression within 12 months of neoadjuvant or adjuvant treatment with platinum-containing chemotherapy. OPDIVO® (nivolumab), as a single agent, is indicated for the adjuvant treatment of adult patients with urothelial carcinoma (UC) who are at high risk of recurrence after undergoing radical resection of UC. OPDIVO® (nivolumab), in combination with cisplatin and gemcitabine, is indicated as first-line treatment for adult patients with unresectable or metastatic urothelial carcinoma. OPDIVO® (nivolumab), as a single agent, is indicated for the treatment of adult and pediatric (12 years and older) patients with microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) metastatic colorectal cancer (CRC) that has progressed following treatment with a fluoropyrimidine, oxaliplatin, and irinotecan. This indication is approved under accelerated approval based on overall response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials. OPDIVO® (nivolumab), in combination with YERVOY® (ipilimumab), is indicated for the treatment of adults and pediatric patients 12 years and older with microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) metastatic colorectal cancer (CRC) that has progressed following treatment with a fluoropyrimidine, oxaliplatin, and irinotecan. This indication is approved under accelerated approval based on overall response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials. OPDIVO® (nivolumab), in combination with YERVOY® (ipilimumab), is indicated for the treatment of adult patients with hepatocellular carcinoma (HCC) who have been previously treated with sorafenib. This indication is approved under accelerated approval based on overall response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials. OPDIVO® (nivolumab) is indicated for the treatment of adult patients with unresectable advanced, recurrent or metastatic esophageal squamous cell carcinoma (ESCC) after prior fluoropyrimidine- and platinum-based chemotherapy. OPDIVO® (nivolumab) is indicated for the adjuvant treatment of completely resected esophageal or gastroesophageal junction cancer with residual pathologic disease in adult patients who have received neoadjuvant chemoradiotherapy (CRT). OPDIVO® (nivolumab), in combination with fluoropyrimidine- and platinum-containing chemotherapy, is indicated for the first-line treatment of adult patients with unresectable advanced or metastatic esophageal squamous cell carcinoma (ESCC). OPDIVO® (nivolumab), in combination with YERVOY® (ipilimumab), is indicated for the first-line treatment of adult patients with unresectable advanced or metastatic esophageal squamous cell carcinoma (ESCC). OPDIVO® (nivolumab), in combination with fluoropyrimidine- and platinum- containing chemotherapy, is indicated for the treatment of adult patients with advanced or metastatic gastric cancer, gastroesophageal junction cancer, and esophageal adenocarcinoma. Please see US Full Prescribing Information for OPDIVO and YERVOY . Clinical Trials and Patient Populations Checkmate 227–previously untreated metastatic non-small cell lung cancer, in combination with YERVOY; Checkmate 9LA–previously untreated recurrent or metastatic non-small cell lung cancer in combination with YERVOY and 2 cycles of platinum-doublet chemotherapy by histology; Checkmate 649–previously untreated advanced or metastatic gastric cancer, gastroesophageal junction and esophageal adenocarcinoma; Checkmate 577–adjuvant treatment of esophageal or gastroesophageal junction cancer; Checkmate 238– adjuvant treatment of patients with completely resected Stage III or Stage IV melanoma; Checkmate 76K–adjuvant treatment of patients 12 years of age and older with completely resected Stage IIB or Stage IIC melanoma; Checkmate 274–adjuvant treatment of urothelial carcinoma; Checkmate 275–previously treated advanced or metastatic urothelial carcinoma; Checkmate 142–MSI-H or dMMR metastatic colorectal cancer, as a single agent or in combination with YERVOY; Checkmate 142–MSI-H or dMMR metastatic colorectal cancer, as a single agent or in combination with YERVOY; Attraction-3–esophageal squamous cell carcinoma; Checkmate 648–previously untreated, unresectable advanced recurrent or metastatic esophageal squamous cell carcinoma; Checkmate 648–previously untreated, unresectable advanced recurrent or metastatic esophageal squamous cell carcinoma; Checkmate 040–hepatocellular carcinoma, in combination with YERVOY; Checkmate 743–previously untreated unresectable malignant pleural mesothelioma, in combination with YERVOY; Checkmate 037–previously treated metastatic melanoma; Checkmate 066–previously untreated metastatic melanoma; Checkmate 067–previously untreated metastatic melanoma, as a single agent or in combination with YERVOY; Checkmate 017–second-line treatment of metastatic squamous non-small cell lung cancer; Checkmate 057–second-line treatment of metastatic non-squamous non-small cell lung cancer; Checkmate 816–neoadjuvant non-small cell lung cancer, in combination with platinum-doublet chemotherapy; Checkmate 901–Adult patients with unresectable or metastatic urothelial carcinoma; Checkmate 141–recurrent or metastatic squamous cell carcinoma of the head and neck; Checkmate 025–previously treated renal cell carcinoma; Checkmate 214–previously untreated renal cell carcinoma, in combination with YERVOY; Checkmate 9ER–previously untreated renal cell carcinoma, in combination with cabozantinib; Checkmate 205/039–classical Hodgkin lymphoma. About the Bristol Myers Squibb and Ono Pharmaceutical Collaboration In 2011, through a collaboration agreement with Ono Pharmaceutical Co., Bristol Myers Squibb expanded its territorial rights to develop and commercialize Opdivo globally, except in Japan, South Korea and Taiwan, where Ono had retained all rights to the compound at the time. On July 23, 2014, Ono and Bristol Myers Squibb further expanded the companies’ strategic collaboration agreement to jointly develop and commercialize multiple immunotherapies – as single agents and combination regimens – for patients with cancer in Japan, South Korea and Taiwan. About Bristol Myers Squibb Bristol Myers Squibb is a global biopharmaceutical company whose mission is to discover, develop and deliver innovative medicines that help patients prevail over serious diseases. For more information about Bristol Myers Squibb, visit us at BMS.com or follow us on LinkedIn , Twitter , YouTube , Facebook and Instagram . SOURCE: Bristol Myers Squibb

Agenus shares plunged over 54% on Thursday after the company revealed that the FDA "discouraged" its pursuit of accelerated approval for an immunotherapy combination in microsatellite stable colorectal cancer (MSS CRC), the most prevalent form of the disease. The setback affects the company's dual approach combining botensilimab, an Fc-enhanced anti-CTLA-4 antibody, with the PD-1 inhibitor balstilimab for patients with relapsed or refractory disease.The negative market reaction came as Agenus revealed outcomes of its end-of-Phase II meeting with the FDA, where the agency advised against submitting recent trial results in a bid to secure a speedy approval for the regimen. The FDA's stance was based on the view that the objective response rates (ORRs) observed may not necessarily translate to a survival benefit.Topline interim data from the ongoing Phase II trial showed trends consistent with earlier Phase I results, according to the company. In the cohort receiving the agreed-upon Phase III dose (BOT 75 mg/BAL 240 mg), Agenus said the ORR was 19.4% after a median 9.5 months of follow-up, with a six-month survival rate 90% and data continuing to mature. At the increased BOT dose of 150 mg, the combination was associated with an 8.2% ORR.Results of a 77-patient Phase I study reported earlier this year, had shown a 23% ORR with the regimen after a median follow-up of 13.6 months. The estimated median overall survival was 21.2 months. Like the Phase II trial, the earlier study also included refractory MSS CRC patients with no active liver metastases.Open to partnershipsSteven O'Day, the company's chief medical officer, indicated Thursday that Agenus was still committed to the programme despite the regulatory hurdle."Based on the high level of enthusiasm from significant numbers of global clinical experts and the promising clinical activity we have seen in the Phase I and II studies, our commitment to seek all possible pathways to make BOT/BAL available to patients is unwavering," O'Day stated, adding "this includes exploring opportunities to partner in the US to accomplish a successful Phase III trial."The company noted that FDA has recommended the inclusion of a BOT monotherapy arm "at Agenus' discretion" in the Phase III study. The toplined mid-stage results unveiled Tuesday showed an ORR of 7.5% for BOT monotherapy at 150 mg, but no response at the 75-mg dose.In the meantime, Agenus says it is ploughing ahead with efforts to bring BOT/BAL to patients in Europe, where discussions to explore registration paths are scheduled for later this summer.