Vous n'êtes pas encore inscrit ?
Inscription
In CheckMate -9LA, nivolumab + ipilimumab combined with two cycles of chemotherapy demonstrated superior overall survival versus chemotherapy, regardless of PD-L1 expression or tumor histology1
Approval marks sixth indication for nivolumab + ipilimumab-based combinations across five types of cancer
Two nivolumab + ipilimumab-based combinations are now approved in first-line lung cancer
(PRINCETON, N.J., May 26, 2020) – Bristol Myers Squibb (NYSE: BMY) today announced that nivolumab 360 mg plus ipilimumab 1 mg/kg (injections for intravenous use) given with two cycles of platinum-doublet chemotherapy was approved by the U.S. Food and Drug Administration (FDA) 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.1 The therapy is approved for patients with squamous or nonsquamous disease and regardless of PD-L1 expression.1 This application was reviewed under the FDA’s Real-Time Oncology Review (RTOR) pilot program, which aims to ensure that safe and effective treatments are available to patients as early as possible.2 On May 15, the FDA approved nivolumab + ipilimumab as a first-line treatment for certain patients with metastatic NSCLC whose tumors express PD-L1?1% as determined by an FDA-approved test. Approval for nivolumab + ipilimumab with limited chemotherapy is based on the pre-specified interim analysis from the Phase 3 CheckMate -9LA trial in which nivolumab + ipilimumab combined with two cycles of platinum-doublet chemotherapy demonstrated superior overall survival (OS) versus chemotherapy (hazard ratio [HR] 0.69; 96.71% confidence interval [CI]: 0.55 to 0.87; P=0.0006) regardless of PD-L1 expression or tumor histology (minimum 8.1 months follow up).1,3 Median overall survival (mOS) was 14.1 months (95% CI: 13.2 to 16.2) versus 10.7 months (95% CI: 9.5 to 12.5), respectively.1 In a follow-up analysis at 12.7 months, the hazard ratio improved numerically to 0.66 (95% CI: 0.55 to 0.80), with mOS of 15.6 months (95% CI: 13.9 to 20.0) and 10.9 months (95% CI: 9.5 to 12.5).1,3 At one year, 63% of patients treated with nivolumab + ipilimumab with limited chemotherapy and 47% of those treated with chemotherapy were still alive.3
Nivolumab 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; infusionrelated reactions; embryo-fetal toxicity; and increased mortality in patients with multiple myeloma when nivolumab is added to a thalidomide analogue and dexamethasone, which is not recommended outside of controlled clinical trials.1,4
“We have come a long way in understanding the role of dual immunotherapybased approaches in cancer and the potential impact on patients’ long-term outcomes,” said David P. Carbone, MD, PhD, CheckMate -9LA investigator and Director of the James Thoracic Oncology Center at The Ohio State University. “The positive findings from CheckMate -9LA demonstrate the benefit of combining dual immunotherapy with limited chemotherapy for NSCLC patients regardless of PD-L1 status. With today’s approval, more patients now have access to a nivolumab + ipilimumab-based option and a chance at a longer life.”1 In the trial, the overall response rate (ORR) per Blinded Independent Central Review (BICR) was 38% (95% CI: 33 to 43) for patients treated with nivolumab + ipilimumab with limited chemotherapy and 25% (95% CI: 21 to 30) for patients treated with chemotherapy. “Non-small cell lung cancer is a complex disease that requires multiple treatment options to address the needs of different patient populations,”5 said Adam Lenkowsky, general manager and head, U.S., Oncology, Immunology, Cardiovascular, Bristol Myers Squibb. “This second approval of a nivolumab + ipilimumab -based combination for the first-line treatment of advanced NSCLC now gives more patients access to a dual immunotherapy approach that can be administered with or without limited chemotherapy, depending on the patient and their PD-L1 status, and the possibility of a chance to live longer.”1
Nivolumab + ipilimumab is a unique combination of immune checkpoint inhibitors, featuring a potentially synergistic mechanism of action that targets two different checkpoints (PD-1 and CTLA-4) to help destroy tumor cells: ipilimumab helps activate and proliferate T cells, while nivolumab helps existing T cells discover the tumor.1,4,6 Some of the T cells stimulated by ipilimumab can become memory T cells, which may allow for a long-term immune response.6,7,8,9,10,11 Targeting of normal cells can also occur and result in immune-mediated adverse reactions, which can be severe and potentially fatal.1 “Receiving a diagnosis of advanced lung cancer is devastating,”12 said Andrea Ferris, president and chief executive officer, LUNGevity. “Today’s announcement is welcome news as it provides a new dual immunotherapy-based option for previously untreated patients searching for a treatment that may help extend their lives.”1 This application is part of the FDA’s Project Orbis initiative, enabling concurrent review by the FDA and the health authorities in Australia, Canada and Singapore.
About CheckMate -9LA CheckMate -9LA (NCT03215706) is a Phase 3, randomized open-label, multi-center study evaluating nivolumab + ipilimumab combined with two cycles of platinum-doublet chemotherapy versus platinum-doublet chemotherapy (four cycles followed by optional pemetrexed maintenance therapy if eligible) as a first-line treatment in patients with metastatic or recurrent NSCLC regardless of PD-L1 expression and histology.1 A total of 361 patients were treated with nivolumab + ipilimumab with platinum-doublet chemotherapy until disease progression, unacceptable toxicity or for up to two years.1 A total of 358 patients were treated with platinum-doublet chemotherapy for four cycles and optional pemetrexed maintenance for non-squamous patients (if eligible) until disease progression or toxicity.1 The primary efficacy outcome measure of the trial was OS.1 Additional efficacy outcome measures included progression-free survival, ORR and duration of response as assessed by BICR.1
Select Safety Profile from CheckMate -9LA Study Serious adverse reactions occurred in 57% of patients.1 Nivolumab + ipilimumab in combination with platinum-doublet chemotherapy were discontinued for adverse reactions in 24% of patients and 56% had at least one treatment withheld for an adverse reaction.1 The most frequent (>2%) serious adverse reactions were pneumonia, diarrhea, febrile neutropenia, anemia, acute kidney injury, musculoskeletal pain, dyspnea, pneumonitis and respiratory failure.1 Fatal adverse reactions occurred in 7 (2%) patients, and included hepatic toxicity, acute renal failure, sepsis, pneumonitis, diarrhea with hypokalemia and massive hemoptysis in the setting of thrombocytopenia.1 The most common (>20%) adverse reactions were fatigue (49%), musculoskeletal pain (39%), nausea (32%), diarrhea (31%), rash (30%), decreased appetite (28%), constipation (21%) and pruritus (21%).1
About Lung Cancer
Lung cancer is the leading cause of cancer death in the United States.12 The two main types of lung cancer are non-small cell and small cell.13 Non-small cell lung cancer is one of the most common types of lung cancer, and accounts for approximately 84% of diagnoses.13 Survival rates vary depending on the stage and type of the cancer when diagnosed.12
Bristol Myers Squibb: Advancing Cancer Research
At Bristol Myers Squibb, patients are at the center of everything we do. The goal of our cancer research is to increase patients’ quality of life, long-term survival and make cure a possibility. We harness our deep scientific experience, cutting-edge technologies and discovery platforms to discover, develop and deliver novel treatments for patients. Building upon our transformative work and legacy in hematology and ImmunoOncology that has changed survival expectations for many cancers, our researchers are advancing a deep and diverse pipeline across multiple modalities. In the field of immune cell therapy, this includes registrational CAR T cell agents for numerous diseases, and a growing early-stage pipeline that expands cell and gene therapy targets, and technologies. We are developing cancer treatments directed at key biological pathways using our protein homeostasis platform, a research capability that has been the basis of our approved therapies for multiple myeloma and several promising compounds in early- to mid-stage development. Our scientists are targeting different immune system pathways to address interactions between tumors, the microenvironment and the immune system to further expand upon the progress we have made and help more patients respond to treatment. Combining these approaches is key to delivering potential new options for the treatment of cancer and addressing the growing issue of resistance to immunotherapy. We source innovation internally, and in collaboration with academia, government, advocacy groups and biotechnology companies, to help make the promise of transformational medicines a reality for patients.
About Bristol Myers Squibb’s Patient Access Support
Bristol Myers Squibb remains committed to providing assistance 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 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, as well as co-pay assistance for eligible, commercially insured patients. More information about our access and reimbursement support 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 nivolumab 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.6
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. Celgene and Juno Therapeutics are wholly owned subsidiaries of Bristol-Myers Squibb Company. In certain countries outside the U.S., due to local laws, Celgene and Juno Therapeutics are referred to as, Celgene, a Bristol Myers Squibb company and Juno Therapeutics, a Bristol Myers Squibb company.
References
1. Opdivo Prescribing Information. Opdivo U.S. Product Information. Last updated: May 2020. Princeton, NJ: Bristol Myers Squibb Company.
2. U.S. Food & Drug Administration. Real-Time Oncology Review Pilot Program. https://www.fda.gov/about-fda/oncology-center-excellence/real-time-oncology-reviewpilot-program. Accessed May 18, 2019.
3. Reck M, Tudor-Eilade C, Cobo Dols M, et al. Nivolumab (NIVO) + ipilimumab (IPI) + 2 cycles of platinum-doublet chemotherapy (chemo) vs 4 cycles of chemo as first-line (1L) treatment (tx) for stage IV/recurrent non-small cell lung cancer (NSCLC): CheckMate 9LA [abstract]. In: American Society of Clinical Oncology (ASCO) Annual Meeting; May 29 – June 2, 2020; Virtual.
4. Yervoy Prescribing Information. Yervoy U.S. Product Information. Last updated: May 2020. Princeton, NJ: Bristol Myers Squibb Company.
5. National Cancer Institute. Non-Small Cell Lung Cancer Treatment (PDQ®) – Health Professional Version. https://www.cancer.gov/types/lung/hp/non-small-cell-lungtreatment-pdq. Updated May 7, 2020. Accessed May 18, 2020.
6. Weber J, Hamid Omid, Chasalow S, et al. Ipilimumab Increases Activated T Cells and Enhances Humoral Immunity in Patients with Advanced Melanoma. Journal of Immunotherapy. 2012;35(1):89-97.
7. Farber D, Yudanin N, Restifo N. Human Memory T Cells: Generation, Compartmentalization and Homeostatsis. Nature Reviews Immunology. 2014;14:24-35.
8. Ansell S, Hurvitz S, Keonig P, et al. Phase I Study of Ipilimumab, an Anti–CTLA-4 Monoclonal Antibody, in Patients with Relapsed and Refractory B-Cell Non–Hodgkin Lymphoma. American Association for Cancer Research. 2009;15(20):6446-6453.
9. Felix J, Lambert J, Roelens M, et al. Ipilimumab reshapes T cell memory subsets in melanoma patients with clinical response. Oncoimmunology. 2016;5(7):1-10.
10. Pedicord V, Montalvo W, Leiner I, et al. Single dose of anti-CTLA-4 enhances CD8+ T-cell memory formation, function, and maintenance. Proceedings of the National Academy of Sciences of the United States of America. 2011;8(1):266-271.
11. Pico de Coana Y, Wolodarski M, Poschke I, et al. Ipilimumab treatment decreases monocytic MDSCs and increases CD8 effector memory T cell sin long-term survivors with advanced melanoma. Oncotarget. 2017; 8(13):21539-21553.
12. SEER. Lung and Bronchus Cancer, CSR 1975-2016. https://seer.cancer.gov/statfacts/html/lungb.html Accessed May 18, 2020.
13. American Cancer Society. Key Statistics for Lung Cancer. https://www.cancer.org/cancer/lung-cancer/about/key-statistics.html. Accessed May 18, 2020.
