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

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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)-- 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% of patients were somnolence (8%), insomnia (6%) and hypersomnia (1.1%). Dose interruption was required in 0.9% of patients, and 0.3% required a dose reduction due to sleep disorders.

  • The incidences of CNS adverse reactions reported were similar in patients with and without CNS metastases.
  • Advise patients not to drive or use machines if they are experiencing CNS adverse reactions. Withhold and then resume at same or reduced dose upon improvement, or permanently discontinue AUGTYRO based on severity.
  • Interstitial Lung Disease (ILD)/Pneumonitis

    • Among the 351 patients treated with AUGTYRO, ILD/pneumonitis (pneumonitis [2.6%] and interstitial lung disease [0.3%]) occurred in 2.9%; Grade 3 ILD/pneumonitis occurred in 1.1%. The median time to onset was 45 days (19 days to 0.9 years). Dose interruption was required in 1.4% of patients, 0.6% required dose reduction, and 1.1% permanently discontinued AUGTYRO due to ILD/pneumonitis.
    • Monitor patients for new or worsening pulmonary symptoms indicative of ILD/pneumonitis. Immediately withhold AUGTYRO in patients with suspected ILD/pneumonitis and permanently discontinue AUGTYRO if ILD/pneumonitis is confirmed.

    Hepatotoxicity

    • Among the 351 patients treated with AUGTYRO, increased alanine transaminase (ALT) occurred in 35%, increased aspartate aminotransferase (AST) occurred in 40%, including Grade 3 or 4 increased ALT in 2% and increased AST in 2.6%. The median time to onset of increased ALT or AST was 15 days (range: 1 day to 1.9 years). Increased ALT or AST leading to dose interruptions or reductions occurred in 2.8% and 1.4% of patients, respectively. Hyperbilirubinemia leading to dose interruptions occurred in 0.6%.
    • Monitor liver function tests, including ALT, AST and bilirubin, every 2 weeks during the first month of treatment, then monthly thereafter and as clinically indicated. Withhold and then resume at same or reduced dose upon improvement or permanently discontinue AUGTYRO based on the severity.

    Myalgia with Creatine Phosphokinase (CPK) Elevation

    • Among the 351 patients treated with AUGTYRO, myalgia occurred in 13% of patients, with Grade 3 in 0.6%. Median time to onset of myalgia was 19 days (range: 1 day to 2 years). Concurrent increased CPK within a 7-day window was observed in 3.7% of patients. AUGTYRO was interrupted in one patient with myalgia and concurrent CPK elevation.
    • Advise patients to report any unexplained muscle pain, tenderness, or weakness. Monitor serum CPK levels during AUGTYRO treatment and monitor CPK levels every 2 weeks during the first month of treatment and as needed in patients reporting unexplained muscle pain, tenderness, or weakness. Initiate supportive care as clinically indicated. Based on severity, withhold and then resume AUGTYRO at same or reduced dose upon improvement.

    Hyperuricemia

    • Among the 351 patients treated with AUGTYRO, 18 patients (5%) experienced hyperuricemia reported as an adverse reaction, 0.9% experienced Grade 3 or 4 hyperuricemia. One patient without pre-existing gout required urate-lowering medication.
    • Monitor serum uric acid levels prior to initiating AUGTYRO and periodically during treatment. Initiate treatment with urate-lowering medications as clinically indicated. Withhold and then resume at same or reduced dose upon improvement, or permanently discontinue AUGTYRO based on severity.

    Skeletal Fractures

    • Among 351 adult patients who received AUGTYRO, fractures occurred in 2.3%. Fractures involved the ribs (0.6%), feet (0.6%), spine (0.3%), acetabulum (0.3%), sternum (0.3%), and ankles (0.3%). Some fractures occurred at sites of disease and prior radiation therapy. The median time to fracture was 71 days (range: 31 days to 1.4 years). AUGTYRO was interrupted in 0.3% of patients.
    • Promptly evaluate patients with signs or symptoms (e.g., pain, changes in mobility, deformity) of fractures. There are no data on the effects of AUGTYRO on healing of known fractures and risk of future fractures.

    Embryo-Fetal Toxicity

    • Based on literature reports in humans with congenital mutations leading to changes in tropomyosin receptor tyrosine kinase (TRK) signaling, findings from animal studies, and its mechanism of action, AUGTYRO can cause fetal harm when administered to a pregnant woman.
    • Advise pregnant women of the potential risk to a fetus. Advise females of reproductive potential to use effective non-hormonal contraception during treatment with AUGTYRO and for 2 months following the last dose, since AUGTYRO can render some hormonal contraceptives ineffective.
    • Advise male patients with female partners of reproductive potential to use effective contraception during treatment with AUGTYRO and for 4 months after the last dose.

    Adverse Reactions

    • Among 351 patients who received AUGTYRO for ROS1-positive NSCLC and other solid tumors in the TRIDENT-1 trial, the most common (>20%) adverse reactions were dizziness (64%), dysgeusia (50%), peripheral neuropathy (47%), constipation (37%), dyspnea (30%), ataxia (29%), fatigue (29%), cognitive disorders (23%), and nausea (20%).
    • In a subset of 264 patients who received AUGTYRO for ROS1-positive NSCLC, the most common (≥20%) adverse reactions were dizziness (63%), dysgeusia (48%), peripheral neuropathy (47%), constipation (36%), dyspnea (30%), ataxia (28%), fatigue (24%), cognitive disorders (23%), and muscular weakness (21%).

    Drug Interactions

    Effects of Other Drugs on AUGTYRO

    Strong and Moderate CYP3A Inhibitors

    • Avoid concomitant use with strong or moderate CYP3A inhibitors. Concomitant use of AUGTYRO with a strong or a moderate CYP3A inhibitor may increase repotrectinib exposure, which may increase the incidence and severity of adverse reactions of AUGTYRO. Discontinue CYP3A inhibitors for 3 to 5 elimination half-lives of the CYP3A inhibitor prior to initiating AUGTYRO.

    P-gp Inhibitors

    • Avoid concomitant use with P-gp inhibitors. Concomitant use of AUGTYRO with a P-gp inhibitor may increase repotrectinib exposure, which may increase the incidence and severity of adverse reactions of AUGTYRO.

    Strong and Moderate CYP3A Inducers

    • Avoid concomitant use with strong or moderate CYP3A inducers. Concomitant use of AUGTYRO with a strong or moderate CYP3A inducer may decrease repotrectinib plasma concentrations, which may decrease efficacy of AUGTYRO.

    Effects of AUGTYRO on other Drugs

    Certain CYP3A4 Substrates

    • Avoid concomitant use unless otherwise recommended in the Prescribing Information for CYP3A substrates, where minimal concentration changes can cause reduced efficacy. If concomitant use is unavoidable, increase the CYP3A4 substrate dosage in accordance with approved product labeling.
    • Repotrectinib is a CYP3A4 inducer. Concomitant use of repotrectinib decreases the concentration of CYP3A4 substrates, which can reduce the efficacy of these substrates.

    Contraceptives

    • Repotrectinib is a CYP3A4 inducer, which can decrease progestin or estrogen exposure to an extent that could reduce the effectiveness of hormonal contraceptives.
    • Avoid concomitant use of AUGTYRO with hormonal contraceptives. Advise females to use an effective nonhormonal contraceptive.

    Please see U.S. Full Prescribing Information for AUGTYRO.

    KRAZATI

    INDICATION

    KRAZATI is indicated for the 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).

    IMPORTANT SAFETY INFORMATION

    GASTROINTESTINAL ADVERSE REACTIONS

    • In the pooled safety population, serious gastrointestinal adverse reactions observed were gastrointestinal obstruction in 1.6%, including 1.4% grade 3 or 4, gastrointestinal bleeding in 0.5% of patients, including 0.5% grade 3, and colitis in 0.3%, including 0.3% grade 3. In addition, nausea, diarrhea, or vomiting occurred in 89% of 366 patients, including 9% grade 3. Nausea, diarrhea, or vomiting led to dosage interruption or dose reduction in 29% of patients and permanent discontinuation of KRAZATI in 0.3%
    • Monitor and manage patients using supportive care, including antidiarrheals, antiemetics, or fluid replacement, as indicated. Withhold, reduce the dose, or permanently discontinue KRAZATI based on severity

    QTC INTERVAL PROLONGATION

    • KRAZATI can cause QTc interval prolongation, which can increase the risk for ventricular tachyarrhythmias (e.g., torsades de pointes) or sudden death
    • In the pooled safety population, 6% of 366 patients with at least one post-baseline electrocardiogram (ECG) assessment had an average QTc ≥501 ms, and 11% of patients had an increase from baseline of QTc >60 msec. KRAZATI causes concentration-dependent increases in the QTc interval
    • Avoid concomitant use of KRAZATI with other products with a known potential to prolong the QTc interval. Avoid use of KRAZATI in patients with congenital long QT syndrome and in patients with concurrent QTc prolongation
    • Monitor ECGs and electrolytes prior to starting KRAZATI, during concomitant use, and as clinically indicated in patients with congestive heart failure, bradyarrhythmias, electrolyte abnormalities, and in patients who are taking medications that are known to prolong the QT interval. Withhold, reduce the dose, or permanently discontinue KRAZATI, depending on severity

    HEPATOTOXICITY

    • KRAZATI can cause hepatotoxicity
    • In the pooled safety population, hepatotoxicity occurred in 37%, and 7% were grade 3 or 4. A total of 32% of patients who received KRAZATI had increased alanine aminotransferase (ALT)/increased aspartate aminotransferase (AST); 5% were grade 3 and 0.5% were grade 4. Increased ALT/AST leading to dose interruption or reduction occurred in 11% of patients. KRAZATI was discontinued due to increased ALT/AST in 0.5% of patients
    • Monitor liver laboratory tests (AST, ALT, alkaline phosphatase, and total bilirubin) prior to the start of KRAZATI, and monthly for 3 months or as clinically indicated, with more frequent testing in patients who develop transaminase elevations. Reduce the dose, withhold, or permanently discontinue KRAZATI based on severity

    INTERSTITIAL LUNG DISEASE /PNEUMONITIS

    • KRAZATI can cause interstitial lung disease (ILD)/pneumonitis, which can be fatal. In the pooled safety population, ILD/pneumonitis occurred in 4.1% of patients, 1.4% were grade 3 or 4, and 1 case was fatal. The median time to first onset for ILD/pneumonitis was 12 weeks (range: 5 to 31 weeks). KRAZATI was discontinued due to ILD/pneumonitis in 0.8% of patients
    • Monitor patients for new or worsening respiratory symptoms indicative of ILD/pneumonitis (eg, dyspnea, cough, fever). Withhold KRAZATI in patients with suspected ILD/pneumonitis and permanently discontinue KRAZATI if no other potential causes of ILD/pneumonitis are identified

    ADVERSE REACTIONS

    • The most common adverse reactions (≥25%) are nausea, diarrhea, vomiting, fatigue, musculoskeletal pain, hepatotoxicity, renal impairment, edema, dyspnea, decreased appetite

    FEMALES AND MALES OF REPRODUCTIVE POTENTIAL

    • Infertility: Based on findings from animal studies, KRAZATI may impair fertility in females and males of reproductive potential

    Please see U.S. Full Prescribing Information for KRAZATI.

    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.

    Cautionary Statement Regarding Forward-Looking Statements

    This press release contains “forward-looking statements” within the meaning of the Private Securities Litigation Reform Act of 1995 regarding, among other things, the research, development and commercialization of pharmaceutical products. All statements that are not statements of historical facts are, or may be deemed to be, forward-looking statements. Such forward-looking statements are based on current expectations and projections about our future financial results, goals, plans and objectives and involve inherent risks, assumptions and uncertainties, including internal or external factors that could delay, divert or change any of them in the next several years, that are difficult to predict, may be beyond our control and could cause our future financial results, goals, plans and objectives to differ materially from those expressed in, or implied by, the statements. These risks, assumptions, uncertainties and other factors include, among others, that future study results may not be consistent with the results to date, that the treatments and combination treatments may not receive regulatory approval for the indications described in this release any marketing approvals, if granted, may have significant limitations on their use, and, if approved, whether the treatments and combination treatments for such indications described in this release will be commercially successful. No forward-looking statement can be guaranteed. Forward-looking statements in this press release should be evaluated together with the many risks and uncertainties that affect Bristol Myers Squibb’s business and market, particularly those identified in the cautionary statement and risk factors discussion in Bristol Myers Squibb’s Annual Report on Form 10-K for the year ended December 31, 2023, as updated by our subsequent Quarterly Reports on Form 10-Q, Current Reports on Form 8-K and other filings with the Securities and Exchange Commission. The forward-looking statements included in this document are made only as of the date of this document and except as otherwise required by applicable law, Bristol Myers Squibb undertakes no obligation to publicly update or revise any forward-looking statement, whether as a result of new information, future events, changed circumstances or otherwise.

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