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Bristol-Myers Squibb Receives FDA Approval for Opdivo (nivolumab) in MSI-H or dMMR Metastatic Colorectal Cancer That Has Progressed Following Treatment

PRINCETON, N.J.--(BUSINESS WIRE) August 1, 2017 -- Bristol-Myers Squibb Company (NYSE:BMY) today announced the U.S. Food and Drug Administration (FDA) has approved Opdivo (nivolumab) injection for intravenous use 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 (mCRC) that has progressed following treatment with a fluoropyrimidine, oxaliplatin, and irinotecan.2 Approval for this indication has been granted under accelerated approval based on overall response rate (ORR) and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials. The recommended dose is 240 milligrams administered as an intravenous infusion over 60 minutes every two weeks until disease progression or unacceptable toxicity.2 In the CheckMate -142 trial, among patients (53/74) who received prior treatment with a fluoropyrimidine, oxaliplatin, and irinotecan, 28% (95% CI: 17-42; 15/53) responded to treatment with Opdivo. The percentage of patients with a complete response was 1.9% (1/53) and the percentage of patients with a partial response was 26% (14/53). Among these responders, the median duration of response was not reached (range: 2.8+-22.1+ months).2 Among all enrolled patients, 32% (95% CI: 22-44; 24/74) responded to treatment with Opdivo; 2.7% (2/74) experienced a complete response, 30% (22/74) experienced a partial response.2

Opdivo is associated with the following Warnings and Precautions including immune-mediated: pneumonitis, colitis, hepatitis, endocrinopathies, nephritis and renal dysfunction, skin adverse reactions, encephalitis, other adverse reactions; infusion reactions; and embryo-fetal toxicity.2

“As part of our commitment to address hard-to-treat cancers, with today’s approval, Opdivo provides a new treatment option for these patients who have historically faced a poor prognosis,”3,4,5 said Chris Boerner, president, U.S. Commercial, Bristol-Myers Squibb. “This approval is one example of how our commitment to translational medicine and investigating predictive biomarkers may help us discover treatment approaches to address different patients’ unique needs.”

“Patients with metastatic colorectal cancer who have dMMR or MSI-H tumors are less likely to respond to conventional chemotherapy,”3,4,5 said Heinz-Josef Lenz, M.D., FACP, J. Terrence Lanni Chair in Gastrointestinal Cancer Research, University of Southern California. “While the challenges of treating these patients have been significant, tumors characterized by these biomarkers are immunogenic.3,6 Therefore, advances in immunotherapy research are encouraging in presenting new treatment options for appropriate patients with MSI-H metastatic colorectal cancer.”

NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) recommend universal MMR or MSI testing for all patients with a personal history of colon or rectal cancer to inform use of immunotherapy in patients with metastatic disease. The National Comprehensive Cancer Network® (NCCN®) panel recommends nivolumab (OPDIVO) as a category 2A treatment option in patients with metastatic deficient mismatch repair (dMMR) or microsatellite instability-high (MSI-H) colorectal cancer in second- or third-line therapy.7

Approval Based on Notable Tumor Response Rate and Duration of Response

CheckMate -142 is a Phase 2, multicenter, open-label, single-arm study evaluating Opdivo in patients with locally determined dMMR or MSI-H mCRC whose disease had progressed during, after, or were intolerant to, prior treatment with fluoropyrimidine-, oxaliplatin-, or irinotecan-based chemotherapy.1,2 In this study, 74 patients received Opdivo 3 mg/kg administered intravenously every two weeks.2 The recommended dose is 240 mg administered as an intravenous infusion over 60 minutes every two weeks until disease progression or unacceptable toxicity.2 Across the 74 patients, 72% received prior treatment with a fluoropyrimidine, oxaliplatin, and irinotecan.2 Efficacy outcome measures included independent radiographic review committee-assessed confirmed ORR per RECIST 1.1, and duration of response.2 More than half of patients (51%) had a BRAF (16%) or KRAS (35%) mutation.1

In this trial, Opdivo demonstrated an ORR of 28% (95% CI: 17-42; 15/53) in patients who received prior treatment with a fluoropyrimidine, oxaliplatin, and irinotecan, including a 1.9% complete response rate (1/53) and a 26% partial response rate (14/53). Median duration of response in these patients was not reached (range: 2.8+-22.1+ months).2 Among all enrolled patients, 32% (95% CI: 22-44; 24/74) responded to treatment with Opdivo, including a 2.7% complete response rate (2/74) and a 30% partial response rate (22/74). The median duration of response was not reached (range: 1.4+-26.5+ months).2 Data from CheckMate -142 were published in The Lancet Oncology in July.

“As the third most common type of cancer in the United States, our view is that colorectal cancer – particularly for those with dMMR or MSI-H metastatic disease – has been in need of new research and treatments.8 The approval of Opdivo for appropriate patients with this disease gives the community more hope,” said Michael Sapienza, chief executive officer of the Colon Cancer Alliance.

Select Safety Profile

The most common adverse reactions (≥20%) in patients who received Opdivo as a single agent were fatigue, rash, musculoskeletal pain, pruritus, diarrhea, nausea, asthenia, cough, dyspnea, constipation, decreased appetite, back pain, arthralgia, upper respiratory tract infection, pyrexia.2

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.9 In the United States, CRC is the third most common cancer, in 2017 it is estimated that there will be approximately 135,000 new cases of the disease and that it will be the second leading cause of cancer-related deaths among men and women combined.8,10 Approximately 5% of metastatic CRC patients have mismatch repair deficient (dMMR) or microsatellite instability-high (MSI-H) tumors.3

Mismatch repair deficiency occurs when the proteins that repair mismatch errors in DNA replication are missing or non-functional, which leads to MSI-H tumors in certain types of cancer, including CRC.5,11 Patients with dMMR or MSI-H metastatic CRC are less likely to benefit from conventional chemotherapy and typically have a poor prognosis.3,4,5 Routine testing to confirm dMMR or MSI-H status should be conducted for all metastatic CRC patients.7

INDICATION

OPDIVO® (nivolumab) is indicated for the treatment of adults 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.

About the Opdivo Clinical Development Program

Bristol-Myers Squibb’s global development program founded on scientific expertise in the field of Immuno-Oncology includes a broad range of clinical trials studying Opdivo, across all phases, including Phase 3, in a variety of tumor types. To date, the Opdivo clinical development program has enrolled more than 25,000 patients.

About Bristol-Myers Squibb’s Patient Access Support

Bristol-Myers Squibb remains committed to providing a comprehensive set of programs and services so that cancer patients who need our medicines can access them and expedite time to therapy.

BMS Access Support®, the Bristol-Myers Squibb Patient Access and Reimbursement Services program, is designed to help appropriate patients initiate and maintain access to BMS medicines during their treatment journey. BMS Access Support offers benefit investigation, prior authorization assistance and co-pay assistance for eligible, commercially insured patients. More information about our access and reimbursement support services can be obtained by calling BMS Access Support® at 1-800-861-0048 or by visiting www.bmsaccesssupport.com.

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 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 and Facebook.

Bristol-Myers Squibb Forward-Looking Statement

This press release contains “forward-looking statements” as that term is defined in the Private Securities Litigation Reform Act of 1995 regarding the research, development and commercialization of pharmaceutical products. Such forward-looking statements are based on current expectations and involve inherent risks and uncertainties, including factors that could delay, divert or change any of them, and could cause actual outcomes and results to differ materially from current expectations. No forward-looking statement can be guaranteed. Forward-looking statements in this press release should be evaluated together with the many uncertainties that affect Bristol-Myers Squibb’s business, particularly those identified in the cautionary factors discussion in Bristol-Myers Squibb’s Annual Report on Form 10-K for the year ended December 31, 2016 in our Quarterly Reports on Form 10-Q and our Current Reports on Form 8-K. Bristol-Myers Squibb undertakes no obligation to publicly update any forward-looking statement, whether as a result of new information, future events or otherwise.

The National Comprehensive Cancer Network makes no warranties of any kind whatsoever regarding their content, use or application and disclaims any responsibility for their application or use in any way.

References

1. Data on file. NIVO 287. Princeton, NJ: Bristol-Myers Squibb.
2. Opdivo Prescribing Information. Opdivo U.S. Product Information. Last updated: July 31, 2017. Princeton, NJ: Bristol-Myers Squibb Company.
3. Venderbosch S, Nagteagaal ID, Maughan TS, et al. Mismatch repair status and BRAF mutation status in metastatic colorectal cancer patients: A pooled analysis of the CAIRO, CAIRO2, COIN, and FOCUS studies. Clin Cancer Res. 2014;20:5322-5330.
4. Müller CI, Schulmann K, Reinacher-Schick A, et al. Predictive and prognostic value of microsatellite instability in patients with advanced colorectal cancer treated with a fluoropyrimidine and oxaliplatin containing first-line chemotherapy. A report of the AIO Colorectal Study Group. Int J Colorectal Dis. 2008;23:1033-1039
5. Koopman M, Kortman G, Mekenkamp L, et al. Deficient mismatch repair system in patients with sporadic advanced colorectal cancer. Brit J Cancer. 2009;100:266-273.
6. Llosa NJ, Cruise M, Tam A, et al. The vigorous immune microenvironment of microsatellite instable colon cancer is balanced by multiple counter-inhibitory checkpoints. Cancer Discov. 2015;5(1):43-51
7. Benson AB 3rd, Venook AP, Cederquist L, et al. Colon Cancer, Version 2.2017, NCCN Clinical Practice Guidelines in Oncology. J Natl Compr Canc Netw. 2017;15(3):370-398.
8. American Cancer Society. Colorectal Cancer Facts & Figures 2017-2019. Atlanta: American Cancer Society; 2017.
9. American Cancer Society. Key Statistics for Colorectal Cancer.https://www.cancer.org/cancer/colon-rectal-cancer/about/key-statistics.html. Accessed March 9, 2017.
10. National Cancer Institute. Cancer Stat Facts: Colon and Rectum Cancer. Surveillance, Epidemiology, and End Results Program. https://seer.cancer.gov/statfacts/html/colorect.html. Accessed March 9, 2017.
11. Yacoub, George, Srikanth Nagalla, Mebea Aklilu. Oncologic Management of Hereditary Colorectal Cancer. Clin Colon Rectal Surg. 2012;25:118–122.

Source: Bristol-Myers Squibb Company

Posted: August 2017

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