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Approval based on Phase 2 CheckMate -142 trial results showing nearly two-thirds of patients responded to the Opdivo plus Yervoy combination with durable responses observed
Opdivo plus Yervoy is the first dual immunotherapy regimen approved in the European Union for colorectal cancer
Opdivo plus Yervoy-based combinations now indicated in the European Union for five different advanced cancer types: mesothelioma, non-small cell lung cancer, melanoma, renal cell carcinoma and colorectal cancer
PRINCETON, N.J.--(BUSINESS WIRE)-- Bristol Myers Squibb (NYSE: BMY) announced that the European Commission (EC) has approved Opdivo (nivolumab) plus Yervoy (ipilimumab) for the treatment of adult patients with mismatch repair deficient (dMMR) or microsatellite instability-high (MSI-H) metastatic colorectal cancer (mCRC) after prior fluoropyrimidine-based combination chemotherapy. The EC’s decision is based on results from the Phase 2 CheckMate -142 trial in which Opdivo plus Yervoy demonstrated a clinically meaningful improvement in objective response rate (ORR) in patients with MSI-H/dMMR mCRC who received prior treatment with fluoropyridine, oxaliplatin and irinotecan. The safety profile for Opdivo plus Yervoy was consistent with previous studies of the combination in other tumor types.
“Metastatic colorectal cancer is an aggressive disease with a poor prognosis, leaving patients with a critical need for additional treatment options beyond standard chemotherapy,” said Ian M. Waxman, M.D., development lead, gastrointestinal cancers, Bristol Myers Squibb. “With this approval, patients in the EU with mismatch repair deficient or microsatellite instability-high metastatic colorectal cancer will now have the first dual immunotherapy treatment available to them, and we look forward to working with stakeholders to advance this rational combination.”
The combination of Opdivo plus Yervoy is the first approved dual immunotherapy treatment option for any GI tumor in the European Union (EU). This combination is also approved in the EU for non-small cell lung cancer and renal cell carcinoma. The Marketing Authorization approves use of Opdivo plus Yervoy in all EU member states, as well as Norway, Iceland and Liechtenstein.
Opdivo plus Yervoy received approval from the U.S. Food and Drug Administration (FDA) in July 2018 for the treatment of adult and pediatric patients 12 years and older with MSI-H or dMMR mCRC that has progressed following treatment with fluoropyrimidine, oxaliplatin and irinotecan. Opdivo plus Yervoy was also approved in Japan by the Ministry of Health, Labour and Welfare (MHLW) in September 2020 for the treatment of MSI-H unresectable advanced or recurrent colorectal cancer progressing after cancer chemotherapy.
CheckMate -142 Efficacy and Safety Results
Results from the CheckMate -142 trial at minimum follow-up of 46.9 months include:
About CheckMate -142
CheckMate -142 included a multicenter, non-randomized, open-label cohort investigating Opdivo plus Yervoy in patients with mismatch repair deficient (dMMR) or microsatellite instability–high (MSI-H) metastatic colorectal cancer (mCRC) whose disease had progressed during or after prior treatment with a fluoropyrimidine, oxaliplatin- or irinotecan-based chemotherapy.
In this combination cohort, patients received Opdivo 3 mg/kg with Yervoy 1 mg/kg every three weeks for four doses, followed by Opdivo 3 mg/kg as a single agent every two weeks until disease progression, death or unacceptable toxicity. Efficacy outcome measures included objective response rate (ORR) as assessed by blinded independent central review using Response Evaluation Criteria in Solid Tumors (RECIST v1.1) and duration of response (DOR).
About dMMR or MSI-H Colorectal Cancer
Colorectal cancer (CRC) is cancer that develops in the colon or the rectum, which are part of the body’s digestive or gastrointestinal system. Globally, CRC is the third most commonly diagnosed cancer in the world. In 2020, it is estimated that there were approximately 1,931,000 new cases of the disease and that it will be the second leading cause of cancer-related deaths among men and women combined.
Mismatch repair deficiency (dMMR) occurs when the proteins that repair mismatch errors in DNA replication are missing or non-functional, leading to microsatellite instability-high (MSI-H) tumors. Approximately 5% of metastatic CRC patients have dMMR or MSI-H tumors. Patients with these biomarkers are less likely to benefit from conventional chemotherapy and typically have a poor prognosis.
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.
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.
INDICATIONS
OPDIVO® (nivolumab), as a single agent, is indicated for the treatment of patients with unresectable or metastatic melanoma.
OPDIVO® (nivolumab), in combination with YERVOY® (ipilimumab), is indicated for the treatment of patients with unresectable or metastatic melanoma.
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 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 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 patients with advanced renal cell carcinoma (RCC).
OPDIVO® (nivolumab) is indicated for the treatment of 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 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 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. This indication is approved under accelerated approval based on tumor 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), 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) is indicated for the treatment of 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), in combination with YERVOY® (ipilimumab), is indicated for the treatment of 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 adjuvant treatment of patients with melanoma with involvement of lymph nodes or metastatic disease who have undergone complete resection.
OPDIVO® (nivolumab) is indicated for the treatment of 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 patients who have received neoadjuvant chemoradiotherapy (CRT).
OPDIVO® (nivolumab), in combination with fluoropyrimidine- and platinum-containing chemotherapy, is indicated for the treatment of patients with advanced or metastatic gastric cancer, gastroesophageal junction cancer, and esophageal adenocarcinoma.
IMPORTANT SAFETY INFORMATION
Severe and Fatal Immune-Mediated Adverse Reactions
Immune-mediated adverse reactions listed herein may not include all possible severe and fatal immune-mediated adverse reactions.
Immune-mediated adverse reactions, which may be severe or fatal, can occur in any organ system or tissue. While immune-mediated adverse reactions usually manifest during treatment, they can also occur after discontinuation of OPDIVO or YERVOY. Early identification and management are essential to ensure safe use of OPDIVO and YERVOY. Monitor for signs and symptoms that may be clinical manifestations of underlying immune-mediated adverse reactions. Evaluate clinical chemistries including liver enzymes, creatinine, adrenocorticotropic hormone (ACTH) level, and thyroid function at baseline and periodically during treatment with OPDIVO and before each dose of YERVOY. In cases of suspected immune-mediated adverse reactions, initiate appropriate workup to exclude alternative etiologies, including infection. Institute medical management promptly, including specialty consultation as appropriate.
Withhold or permanently discontinue OPDIVO and YERVOY depending on severity (please see section 2 Dosage and Administration in the accompanying Full Prescribing Information). In general, if OPDIVO or YERVOY interruption or discontinuation is required, 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 immune-mediated adverse reactions 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
OPDIVO and YERVOY can cause immune-mediated pneumonitis. The incidence of pneumonitis is higher in patients who have received prior thoracic radiation. In patients receiving OPDIVO monotherapy, immune-mediated pneumonitis occurred in 3.1% (61/1994) of patients, including Grade 4 (
