Approval marks the first-and-only immunotherapy-based treatment for use before surgery for non-small cell lung cancer1
In the Phase 3 CheckMate -816 trial, Opdivo plus platinum-doublet chemotherapy significantly improved event-free survival and pathologic complete response compared to platinum-doublet chemotherapy alone1
Opdivo-based combinations now approved in both metastatic and earlier stages of non-small cell lung cancer
PRINCETON, NJ, USA I March 04, 2022 IBristol Myers Squibb (NYSE: BMY) today announced that the U.S. Food and Drug Administration (FDA) approved Opdivo® (nivolumab) 360 mg (injection for intravenous use) in combination with platinum-doublet chemotherapy every three weeks for three cycles for adult patients with resectable (tumors ≥4 cm or node positive) non-small cell lung cancer (NSCLC) in the neoadjuvant setting.1 Opdivo plus chemotherapy is approved regardless of PD-L1 status.1 The approval is based on the CheckMate -816 trial, the first positive Phase 3 trial of an immunotherapy-based combination used before surgery for resectable NSCLC. The primary endpoints included event-free survival (EFS) and pathologic complete response (pCR), which were evaluated using independent blinded review, and an additional efficacy outcome measure was overall survival (OS).1 The study compared Opdivo plus platinum-doublet chemotherapy (n=179) to platinum-doublet chemotherapy alone (n=179).1
In the trial, when given before surgery, Opdivo plus chemotherapy showed a statistically significant improvement in EFS with a 37% reduction in the risk of progression, recurrence or death (Hazard Ratio [HR] 0.63; 95% Confidence Interval [CI]: 0.45 to 0.87; P=0.0052) compared to chemotherapy alone.1 Opdivo plus chemotherapy showed a median EFS of 31.6 months (95% CI: 30.2 to Not Reached [NR]) compared to 20.8 months for patients treated with chemotherapy alone (95% CI: 14.0 to 26.7).1 Additionally, 24% of patients treated with Opdivo plus chemotherapy achieved pCR (95% CI: 18.0 to 31.0), compared to 2.2% of patients treated with chemotherapy alone (95% CI: 0.6 to 5.6; estimated treatment difference 21.6; 95% CI: 15.1 to 28.2; P<0.0001).1 A prespecified interim analysis for OS resulted in a HR of 0.57 (95% CI: 0.38 to 0.87), which did not cross the boundary for statistical significance.1
“Given the rates of disease recurrence in patients with resectable NSCLC, additional treatment options are needed that can be given before surgery to help improve the chance of successful surgical treatment and support the goal of reducing the risk of cancer returning,” said Mark Awad, MD, PhD, CheckMate -816 study investigator and clinical director of the Lowe Center for Thoracic Oncology at Dana-Farber Cancer Institute.2,3 “The approval of nivolumab with platinum-doublet chemotherapy marks a turning point in how we treat resectable NSCLC and it enables us to use immunotherapy and chemotherapy as neoadjuvant treatment for patients before surgery. Today’s announcement reinforces the need to increase the rates of NSCLC screening and early detection, and for patients to discuss treatment options with their providers.”1
Opdivo is associated with the following Warnings & Precautions: severe and fatal immune-mediated adverse reactions including pneumonitis, colitis, hepatitis and hepatotoxicity, endocrinopathies, dermatologic adverse reactions, nephritis with renal dysfunction, other immune-mediated adverse reactions; infusion-related reactions; complications of allogeneic hematopoietic stem cell transplantation (HSCT); embryo-fetal toxicity; and increased mortality in patients with multiple myeloma when Opdivo is added to a thalidomide analogue and dexamethasone, which is not recommended outside of controlled clinical trials.1 Please see Important Safety Information below.
“At Bristol Myers Squibb, we are leading innovative science in the use of immunotherapy in earlier stages of cancer and are committed to bringing these options to patients,” said Adam Lenkowsky, senior vice president and general manager, U.S. Cardiovascular, Immunology and Oncology at Bristol Myers Squibb. “Today’s approval builds on that commitment and expands the role of Opdivo-based treatment in NSCLC, the most common form of lung cancer, so patients may benefit earlier in the course of their disease.”1,4
This application was approved 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.5 The review was also conducted under the FDA’s Project Orbis initiative, which enabled concurrent review by the health authorities in Australia, Canada and the United Kingdom, where the application remains under review. The EFS data from the Phase 3 CheckMate -816 trial will be presented at the American Association for Cancer Research Annual Meeting 2022 in April.
About CheckMate -816
CheckMate -816 is a randomized, open label trial evaluating Opdivo plus platinum-doublet chemotherapy compared to chemotherapy alone as neoadjuvant treatment in adult patients with resectable non-small cell lung cancer, regardless of PD-L1 expression.1 The trial included patients with histologically confirmed Stage IB (≥4 cm), II or IIIA NSCLC (per the 7th edition American Joint Committee on Cancer/Union for International Cancer Control [AJCC/UICC] staging criteria), ECOG performance status 0 or 1, and measurable disease (per RECIST version 1.1).1 Patients with unresectable or metastatic NSCLC, known EGFR mutations or ALK translocations, Grade 2 or greater peripheral neuropathy, active autoimmune disease, or medical conditions requiring systemic immunosuppression were excluded from the study.1 For the primary analysis, 358 patients were randomized to receive either Opdivo 360 mg plus histology-based platinum doublet chemotherapy on the same day every three weeks for up to three cycles, or platinum doublet chemotherapy every three weeks for up to three cycles, followed by surgery.1
The primary endpoints of the trial were EFS determined by Blinded Independent Central Review (BICR) and pCR determined by Blinded Independent Pathology Review (BIPR).1 EFS is defined as the length of time from randomization to any of the following events: any progression of disease precluding surgery, progression, or recurrence of disease after surgery, or death due to any cause.1 In addition, pCR was defined as 0% residual viable tumor cells in both primary tumor and sampled lymph nodes as assessed by BIPR.1 Additional efficacy outcome measures included OS.1
Select Safety Profile from CheckMate -816 Study
Adverse reactions leading to the discontinuation of Opdivo plus platinum-doublet chemotherapy occurred in 10% of patients and 30% had at least one treatment withheld for an adverse reaction.1 Serious adverse reactions occurred in 30% of patients receiving Opdivo plus platinum-doublet chemotherapy.1 Serious adverse reactions in >2% of patients included pneumonia and vomiting.1 No fatal adverse reactions occurred in patients who received Opdivo in combination with platinum-doublet chemotherapy.1 The most common (>20%) adverse reactions were nausea (38%), constipation (34%), fatigue (26%), decreased appetite (20%), and rash (20%).1
About Lung Cancer
Lung cancer is the leading cause of cancer deaths in the United States.4 The two main types of lung cancer are non-small cell and small cell.4 Non-small cell lung cancer is the most common type of lung cancer and accounts for up to 84% of diagnoses.4 Surgery (resection) remains the standard of care for resectable NSCLC and while many patients with NSCLC are treated with surgery, between 30% to 55% of patients develop recurrence and die of their disease despite resection.2,3
INDICATIONS
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) 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 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), 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) 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).
Please see US Full Prescribing Information for OPDIVO and YERVOY.
Clinical Trials and Patient Populations
Checkmate 238-adjuvant treatment of melanoma; Checkmate 816-neoadjuvant non-small cell lung cancer, in combination with platinum-doublet chemotherapy; 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 274-adjuvant treatment of urothelial carcinoma; Checkmate 577-adjuvant treatment of esophageal or gastroesophageal junction cancer.
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. 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.
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.
References
- Opdivo Prescribing Information. Opdivo U.S. Product Information. Last Updated: March 2022. Princeton, NJ: Bristol-Myers Squibb Company.
- Uramoto H, Tanaka F. Recurrence after surgery in patients with NSCLC. Translational Lung Cancer Research. 2014;3(4).
- Sekihara K, Hishida T, Yoshida J, et al. Long-term survival outcome after postoperative recurrence of non-small-cell lung cancer: who is “cured” from postoperative recurrence? European Journal of Cardio-Thoracic Surgery. 2017;52(3):522-528.
- American Cancer Society. Key Statistics for Lung Cancer. https://www.cancer.org/cancer/lung-cancer/about/key-statistics.html. Accessed February 16, 2022.
- U.S. Food and Drug Administration. Real-Time Oncology Review Pilot Program. https://www.fda.gov/about-fda/oncology-center-excellence/real-time-oncology-review. Accessed February 16, 2022.
SOURCE: Bristol Myers Squibb
Post Views: 158
Approval marks the first-and-only immunotherapy-based treatment for use before surgery for non-small cell lung cancer1
In the Phase 3 CheckMate -816 trial, Opdivo plus platinum-doublet chemotherapy significantly improved event-free survival and pathologic complete response compared to platinum-doublet chemotherapy alone1
Opdivo-based combinations now approved in both metastatic and earlier stages of non-small cell lung cancer
PRINCETON, NJ, USA I March 04, 2022 IBristol Myers Squibb (NYSE: BMY) today announced that the U.S. Food and Drug Administration (FDA) approved Opdivo® (nivolumab) 360 mg (injection for intravenous use) in combination with platinum-doublet chemotherapy every three weeks for three cycles for adult patients with resectable (tumors ≥4 cm or node positive) non-small cell lung cancer (NSCLC) in the neoadjuvant setting.1 Opdivo plus chemotherapy is approved regardless of PD-L1 status.1 The approval is based on the CheckMate -816 trial, the first positive Phase 3 trial of an immunotherapy-based combination used before surgery for resectable NSCLC. The primary endpoints included event-free survival (EFS) and pathologic complete response (pCR), which were evaluated using independent blinded review, and an additional efficacy outcome measure was overall survival (OS).1 The study compared Opdivo plus platinum-doublet chemotherapy (n=179) to platinum-doublet chemotherapy alone (n=179).1
In the trial, when given before surgery, Opdivo plus chemotherapy showed a statistically significant improvement in EFS with a 37% reduction in the risk of progression, recurrence or death (Hazard Ratio [HR] 0.63; 95% Confidence Interval [CI]: 0.45 to 0.87; P=0.0052) compared to chemotherapy alone.1 Opdivo plus chemotherapy showed a median EFS of 31.6 months (95% CI: 30.2 to Not Reached [NR]) compared to 20.8 months for patients treated with chemotherapy alone (95% CI: 14.0 to 26.7).1 Additionally, 24% of patients treated with Opdivo plus chemotherapy achieved pCR (95% CI: 18.0 to 31.0), compared to 2.2% of patients treated with chemotherapy alone (95% CI: 0.6 to 5.6; estimated treatment difference 21.6; 95% CI: 15.1 to 28.2; P<0.0001).1 A prespecified interim analysis for OS resulted in a HR of 0.57 (95% CI: 0.38 to 0.87), which did not cross the boundary for statistical significance.1
“Given the rates of disease recurrence in patients with resectable NSCLC, additional treatment options are needed that can be given before surgery to help improve the chance of successful surgical treatment and support the goal of reducing the risk of cancer returning,” said Mark Awad, MD, PhD, CheckMate -816 study investigator and clinical director of the Lowe Center for Thoracic Oncology at Dana-Farber Cancer Institute.2,3 “The approval of nivolumab with platinum-doublet chemotherapy marks a turning point in how we treat resectable NSCLC and it enables us to use immunotherapy and chemotherapy as neoadjuvant treatment for patients before surgery. Today’s announcement reinforces the need to increase the rates of NSCLC screening and early detection, and for patients to discuss treatment options with their providers.”1
Opdivo is associated with the following Warnings & Precautions: severe and fatal immune-mediated adverse reactions including pneumonitis, colitis, hepatitis and hepatotoxicity, endocrinopathies, dermatologic adverse reactions, nephritis with renal dysfunction, other immune-mediated adverse reactions; infusion-related reactions; complications of allogeneic hematopoietic stem cell transplantation (HSCT); embryo-fetal toxicity; and increased mortality in patients with multiple myeloma when Opdivo is added to a thalidomide analogue and dexamethasone, which is not recommended outside of controlled clinical trials.1 Please see Important Safety Information below.
“At Bristol Myers Squibb, we are leading innovative science in the use of immunotherapy in earlier stages of cancer and are committed to bringing these options to patients,” said Adam Lenkowsky, senior vice president and general manager, U.S. Cardiovascular, Immunology and Oncology at Bristol Myers Squibb. “Today’s approval builds on that commitment and expands the role of Opdivo-based treatment in NSCLC, the most common form of lung cancer, so patients may benefit earlier in the course of their disease.”1,4
This application was approved 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.5 The review was also conducted under the FDA’s Project Orbis initiative, which enabled concurrent review by the health authorities in Australia, Canada and the United Kingdom, where the application remains under review. The EFS data from the Phase 3 CheckMate -816 trial will be presented at the American Association for Cancer Research Annual Meeting 2022 in April.
About CheckMate -816
CheckMate -816 is a randomized, open label trial evaluating Opdivo plus platinum-doublet chemotherapy compared to chemotherapy alone as neoadjuvant treatment in adult patients with resectable non-small cell lung cancer, regardless of PD-L1 expression.1 The trial included patients with histologically confirmed Stage IB (≥4 cm), II or IIIA NSCLC (per the 7th edition American Joint Committee on Cancer/Union for International Cancer Control [AJCC/UICC] staging criteria), ECOG performance status 0 or 1, and measurable disease (per RECIST version 1.1).1 Patients with unresectable or metastatic NSCLC, known EGFR mutations or ALK translocations, Grade 2 or greater peripheral neuropathy, active autoimmune disease, or medical conditions requiring systemic immunosuppression were excluded from the study.1 For the primary analysis, 358 patients were randomized to receive either Opdivo 360 mg plus histology-based platinum doublet chemotherapy on the same day every three weeks for up to three cycles, or platinum doublet chemotherapy every three weeks for up to three cycles, followed by surgery.1
The primary endpoints of the trial were EFS determined by Blinded Independent Central Review (BICR) and pCR determined by Blinded Independent Pathology Review (BIPR).1 EFS is defined as the length of time from randomization to any of the following events: any progression of disease precluding surgery, progression, or recurrence of disease after surgery, or death due to any cause.1 In addition, pCR was defined as 0% residual viable tumor cells in both primary tumor and sampled lymph nodes as assessed by BIPR.1 Additional efficacy outcome measures included OS.1
Select Safety Profile from CheckMate -816 Study
Adverse reactions leading to the discontinuation of Opdivo plus platinum-doublet chemotherapy occurred in 10% of patients and 30% had at least one treatment withheld for an adverse reaction.1 Serious adverse reactions occurred in 30% of patients receiving Opdivo plus platinum-doublet chemotherapy.1 Serious adverse reactions in >2% of patients included pneumonia and vomiting.1 No fatal adverse reactions occurred in patients who received Opdivo in combination with platinum-doublet chemotherapy.1 The most common (>20%) adverse reactions were nausea (38%), constipation (34%), fatigue (26%), decreased appetite (20%), and rash (20%).1
About Lung Cancer
Lung cancer is the leading cause of cancer deaths in the United States.4 The two main types of lung cancer are non-small cell and small cell.4 Non-small cell lung cancer is the most common type of lung cancer and accounts for up to 84% of diagnoses.4 Surgery (resection) remains the standard of care for resectable NSCLC and while many patients with NSCLC are treated with surgery, between 30% to 55% of patients develop recurrence and die of their disease despite resection.2,3
INDICATIONS
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) 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 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), 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) 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).
Please see US Full Prescribing Information for OPDIVO and YERVOY.
Clinical Trials and Patient Populations
Checkmate 238-adjuvant treatment of melanoma; Checkmate 816-neoadjuvant non-small cell lung cancer, in combination with platinum-doublet chemotherapy; 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 274-adjuvant treatment of urothelial carcinoma; Checkmate 577-adjuvant treatment of esophageal or gastroesophageal junction cancer.
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. 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.
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.
References
- Opdivo Prescribing Information. Opdivo U.S. Product Information. Last Updated: March 2022. Princeton, NJ: Bristol-Myers Squibb Company.
- Uramoto H, Tanaka F. Recurrence after surgery in patients with NSCLC. Translational Lung Cancer Research. 2014;3(4).
- Sekihara K, Hishida T, Yoshida J, et al. Long-term survival outcome after postoperative recurrence of non-small-cell lung cancer: who is “cured” from postoperative recurrence? European Journal of Cardio-Thoracic Surgery. 2017;52(3):522-528.
- American Cancer Society. Key Statistics for Lung Cancer. https://www.cancer.org/cancer/lung-cancer/about/key-statistics.html. Accessed February 16, 2022.
- U.S. Food and Drug Administration. Real-Time Oncology Review Pilot Program. https://www.fda.gov/about-fda/oncology-center-excellence/real-time-oncology-review. Accessed February 16, 2022.
SOURCE: Bristol Myers Squibb
Post Views: 158
