Bristol Myers Squibb Presents Multiple New Analyses at 2024 ASCO® Annual Meeting Highlighting Opdivo and Opdivo-based Combinations in Early and Advanced Stages of Non-Small Cell Lung Cancer
Late-breaking exploratory analysis of the CheckMate -77T study of perioperative Opdivo shows improved event-free survival and pathologic complete response in stage III resectable NSCLC patients regardless of nodal status
Four-year follow-up data from the CheckMate -816 study reinforce neoadjuvant Opdivo plus chemotherapy in patients with resectable NSCLC, presented in late-breaking session June 2
Five-year follow-up data from the CheckMate -9LA study showed Opdivo plus Yervoy and chemotherapy improves survival in patients with previously untreated metastatic NSCLC versus chemotherapy alone
PRINCETON, N.J.–(BUSINESS WIRE)–$BMY #ASCO—Bristol Myers Squibb (NYSE: BMY) today announced results from three updated analyses from the CheckMate -77T, CheckMate -816, and CheckMate -9LA studies supporting Opdivo® (nivolumab) and Opdivo-based combinations in early stage and advanced non-small cell lung cancer (NSCLC). Data are being presented at the 2024 American Society of Clinical Oncology (ASCO®) Annual Meeting from May 31 to June 4, 2024, in Chicago, IL.
“Our research and development efforts in NSCLC are marked both by our continuing strength in immunotherapy and by targeted approaches that offer new options for patients with challenging mutations,” said Ian M. Waxman, M.D., vice president, senior global program lead, late development, oncology, Bristol Myers Squibb. “At ASCO, we are presenting studies that demonstrate the impact of immunotherapy earlier in the course of disease, including for those whose tumors may be removed by surgery, to help prevent recurrence. These studies, in addition to updates for patients with advanced disease, are reinforcing the growing body of evidence around our thoracic portfolio and our progress toward delivering options that improve the hope of survival.”
The immunotherapy analyses were presented as part of a larger collection of studies across the company’s lung cancer portfolio. Other presentations include an updated analysis of the Phase 1/2 TRIDENT-1 study which shows Augtyro™ (repotrectinib) continued to demonstrate durable responses in ROS1-positive TKI-naive NSCLC patients at a follow-up of approximately three years. Additionally, data from the Phase 3 KRYSTAL-12 study of KRAZATI® (adagrasib) showed a statistically significant improvement in progression-free survival (PFS) compared to docetaxel in patients with previously treated KRASG12C-mutated NSCLC.
CheckMate -77T Results
A late-breaking exploratory analysis from the Phase 3 CheckMate -77T study evaluating the perioperative regimen of neoadjuvant Opdivo with chemotherapy followed by surgery and adjuvant Opdivo in patients with stage III resectable NSCLC was presented today in an oral presentation (Abstract #LBA8007). In the analysis, the perioperative Opdivo regimen improved median event-free survival (EFS) regardless of nodal status, including in the N2 subgroup (30.2 vs. 10.0 months; HR, 0.46; 95% CI, 0.30–0.70) and non-N2 subgroup (NR vs. 17.0 months; HR, 0.60; 95% CI, 0.33-1.08) versus neoadjuvant chemotherapy and placebo followed by surgery and adjuvant placebo. One-year EFS rates were higher in both subgroups with the perioperative Opdivo regimen (N2 70% vs. 45%, and non-N2 74% vs. 62%, respectively). Surgical feasibility was similar between patients with N2 and non-N2 disease and was also similar between the Opdivo and placebo arms (77% vs. 73% among patients with N2 status; 82% vs. 79% among patients with non-N2). After surgery, a higher proportion of patients in the Opdivo arm had a pathologic complete response compared with placebo in both N2 (28.6% vs. 7.6%) and non-N2 (31.1% vs. 6.7%) subgroups. Grade 3–4 treatment-related adverse events (TRAEs) occurred in 34% and 26% in patients with N2 disease and 29% and 21% of patients with non-N2 disease with the perioperative Opdivo regimen and placebo regimen, respectively. These data represent a comprehensive analysis by nodal status among patients with stage III resectable NSCLC from a global Phase 3 study of perioperative immunotherapy.
CheckMate -77T is the company’s second positive randomized Phase 3 trial with an immunotherapy-based combination for the treatment of resectable non-metastatic NSCLC. Data from CheckMate –77T’s primary analysis supported the regulatory filing acceptances for the perioperative Opdivo-based regimen by the U.S. Food and Drug Administration and European Medicines Agency in February 2024.
CheckMate -816 Results
Four-year survival data from the Phase 3 CheckMate -816 study, representing the longest follow-up among all global Phase 3 studies evaluating neoadjuvant or perioperative immunotherapy-based treatments for stage IB-IIIA resectable NSCLC, were also presented in a rapid oral session on June 2 (Abstract #LBA8010). With a median follow up of 57.6 months, neoadjuvant Opdivo with chemotherapy continued to improve EFS versus chemotherapy alone (median: 43.8 months vs. 18.4 months; HR, 0.66; 95% CI, 0.49 to 0.90). Four-year EFS rates were higher in the neoadjuvant Opdivo with chemotherapy arm (49% vs. 38%). While overall survival (OS) did not meet statistical significance at this analysis, neoadjuvant Opdivo with chemotherapy continued to show a clinically important OS improvement trend over chemotherapy alone (HR, 0.71; 98.36% CI, 0.47 to 1.07). At four years, 71% of patients treated with neoadjuvant Opdivo and chemotherapy were alive, compared to 58% with chemotherapy alone. OS will continue to be followed. An exploratory analysis of lung cancer-specific survival in this study also showed a consistent trend with OS, favoring neoadjuvant Opdivo with chemotherapy (HR, 0.62; 95% CI, 0.41-0.93). No new safety signals were observed with neoadjuvant Opdivo with chemotherapy at the extended follow-up.
CheckMate -9LA Results
Finally, five-year follow-up results from the Phase 3 CheckMate -9LA study, showing durable, long-term survival benefits with Opdivo plus Yervoy® (ipilimumab) combined with two cycles of chemotherapy compared to chemotherapy alone as a first-line treatment in patients with metastatic NSCLC were presented. With a minimum follow-up of 57.3 months, the dual immunotherapy-based combination continued to improve OS, with 18% of patients treated with Opdivo plus Yervoy with two cycles of chemotherapy alive at five years compared to 11% of patients treated with chemotherapy alone (HR, 0.73, 95% CI, 0.62 to 0.85). The five-year survival rate for patients with tumor PD-L1 <1% (a patient population with high unmet need) who were treated with Opdivo plus Yervoy with two cycles of chemotherapy was more pronounced at 22% compared to 8% for patients treated with chemotherapy alone (HR, 0.63; 95% CI, 0.49 to 0.83).
At the 5-year landmark analysis, responses were more durable in the Opdivo plus Yervoy plus chemotherapy arm with 19% of patients still in response compared to 8% for chemotherapy alone. The benefit of Opdivo plus Yervoy with two cycles of chemotherapy was maintained across all secondary endpoints and subgroups of interest.
No new safety signals were observed with Opdivo plus Yervoy with two cycles of chemotherapy with this extended follow-up.
Opdivo and Opdivo-based combinations are approved in four indications in NSCLC, including in neoadjuvant and metastatic treatment settings.
Bristol Myers Squibb thanks the patients and investigators participating in the CheckMate -816, CheckMate -77T and CheckMate -9LA clinical trials.
About CheckMate -77T
CheckMate -77T is a Phase 3 randomized, double-blind, placebo-controlled, multi-center trial evaluating neoadjuvant Opdivo with chemotherapy followed by surgery and adjuvant Opdivo versus neoadjuvant placebo plus chemotherapy followed by surgery and adjuvant placebo in 461 patients with resectable stage IIA to IIIB NSCLC. The primary endpoint of the trial is EFS. Secondary endpoints include OS, pathologic complete response and major pathologic response.
About CheckMate -816
CheckMate -816 is a Phase 3 randomized, open label, multi-center trial evaluating Opdivo with chemotherapy compared to chemotherapy alone as neoadjuvant treatment in patients with resectable stage IB to IIIA NSCLC (per the 7th edition American Joint Committee on Cancer/Union for International Cancer Control staging criteria), regardless of PD-L1 expression. For the primary analysis, 358 patients were randomized to receive either Opdivo 360 mg plus histology-based platinum doublet chemotherapy every three weeks for three cycles, or platinum doublet chemotherapy every three weeks for three cycles, followed by surgery. The primary endpoints of the trial are EFS and pathologic complete response. Secondary endpoints include OS, major pathologic response, and time to death or distant metastases.
About CheckMate -9LA
CheckMate -9LA is an open-label, global, multi-center, randomized Phase 3 trial evaluating Opdivo (360 mg Q3W) plus Yervoy (1 mg/kg Q6W) combined with chemotherapy (two cycles) compared to chemotherapy alone (up to four cycles followed by optional pemetrexed maintenance therapy if eligible) as a first-line treatment in patients with metastatic NSCLC regardless of PD-L1 expression and histology. Patients in the experimental arm (n=361) were treated with immunotherapy for up to two years or until disease progression or unacceptable toxicity. Patients in the control arm (n=358) were treated with up to four cycles of chemotherapy and optional pemetrexed maintenance (if eligible) until disease progression or unacceptable toxicity. The primary endpoint of the trial was OS in the intent-to-treat population. Secondary hierarchical endpoints included PFS and overall response rate, and the study also evaluated efficacy measures according to biomarkers.
About Lung Cancer
Lung cancer is the leading cause of cancer deaths globally. Non-small cell lung cancer (NSCLC) is one of the most common types of lung cancer, representing up to 84% of diagnoses. Non-metastatic cases account for the majority of NSCLC diagnoses (approximately 60%, with up to half of these being resectable), and the proportion is expected to grow over time with enhanced screening programs. While many non-metastatic NSCLC patients are cured by surgery, 30% to 55% develop recurrence and die of their disease despite resection, contributing to a need for treatment options administered before surgery (neoadjuvant) and/or after surgery (adjuvant) to improve long-term outcomes.
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 Augtyro
Augtyro (TPX-0005, BMS-986472) is a next-generation tyrosine kinase inhibitor (TKI) targeting ROS1-positive or NTRK-positive locally advanced or metastatic solid tumors, including non-small cell lung cancer (NSCLC), where there remain significant unmet medical needs for patients. Augtyro was designed to improve durability of response and with favorable properties for human brain penetration to enhance intracranial activity. It is being studied in a registrational Phase 1/2 trial in adults (TRIDENT-1) and a Phase 1/2 trial in pediatric patients (CARE).
Augtyro has demonstrated clinically meaningful results and was granted three Breakthrough Therapy Designations (BTDs) by the FDA for the treatment of patients with: ROS1-positive metastatic NSCLC who have not been treated with a ROS1 TKI; ROS1-positive metastatic NSCLC who have been previously treated with one ROS1 TKI and who have not received prior platinum-based chemotherapy; and advanced solid tumors that have an NTRK gene fusion who have progressed following treatment with one or two prior tropomyosin receptor kinase (TRK) TKIs (with or without prior chemotherapy) and have no satisfactory alternative treatments.
Augtyro was also previously granted four fast-track designations in patients with: ROS1-positive advanced NSCLC who have been treated with disease progression following one prior line of platinum-based chemotherapy and one prior line of a ROS1 TKI; ROS1-positive advanced NSCLC who have not been treated with a ROS1 TKI; ROS1-positive advanced NSCLC who have been previously treated with one ROS1 TKI and who have not received prior platinum-based chemotherapy; and advanced solid tumors that have an NTRK gene fusion who have progressed following treatment with at least one prior line of chemotherapy and one or two prior TRK TKIs and have no satisfactory alternative treatments. Augtyro was also granted an Orphan Drug designation by the U.S. Food and Drug Administration (FDA).
About KRAZATI® (adagrasib)
KRAZATI (adagrasib) is highly selective and potent oral small-molecule inhibitor of KRASG12C that is optimized to sustain target inhibition, an attribute that could be important to treat KRASG12C-mutated cancers, as the KRASG12C protein regenerates every 24-48 hours. KRASG12C mutations act as oncogenic drivers and occur in approximately 14% of NSCLC (adenocarcinoma), 3-4% of colorectal cancers, and 1-2% of several other cancers.
In 2022, KRAZATI was granted accelerated approval for treatment of adult patients with KRASG12C-mutated locally advanced or metastatic non-small cell lung cancer (NSCLC), as determined by an FDA-approved test, who have received at least one prior systemic therapy. This indication is approved under accelerated approval based on objective response rate (ORR) and duration of response (DOR). Continued approval for this indication may be contingent upon verification and description of a clinical benefit in a confirmatory trial(s). In 2024, the European Commission (EC) granted conditional marketing authorization for KRAZATI as a targeted treatment option for adult patients with KRASG12C-mutated advanced NSCLC and disease progression after at least one prior systemic therapy.
KRAZATI continues to be evaluated as monotherapy and in combination with other anti-cancer therapies in patients with advanced KRASG12C-mutated solid tumors, including NSCLC and colorectal cancer.
In 2022, the FDA granted breakthrough therapy designation for KRAZATI in combination with cetuximab in patients with KRASG12C-mutated advanced colorectal cancer (CRC) whose cancer has progressed following prior treatment with chemotherapy and an anti-VEGF therapy.
Please see U.S. Full Prescribing Information for KRAZATI.
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.
OPDIVO
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).
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