First presentation of data from Phase 3 KRYSTAL-12 study showed statistically significant and clinically meaningful improvement in progression-free survival with KRAZATI compared to standard of care chemotherapy

Late-breaking data featured in an oral presentation at the 2024 American Society of Clinical Oncology (ASCO) Annual Meeting

Bristol Myers Squibb (NYSE: BMY) today announced results from the Phase 3 KRYSTAL-12 study evaluating KRAZATI^® (adagrasib) compared to standard of care chemotherapy in patients with locally advanced or metastatic KRAS^G12C-mutated non-small cell lung cancer (NSCLC) who had previously received platinum-based chemotherapy, concurrently or sequentially with anti-PD-(L)1 therapy. At a median follow-up of 9.4 months, KRAZATI demonstrated a statistically significant and clinically meaningful improvement in progression-free survival (PFS), the study’s primary endpoint, as assessed by Blinded Independent Central Review (BICR) compared to docetaxel (HR: 0.58; [95% CI, 0.45-0.76]; P <0.0001). Median PFS was 5.5 months for KRAZATI compared to 3.8 months for docetaxel. Overall response rate (ORR) as assessed by BICR was also significantly higher with KRAZATI compared to docetaxel (32% vs 9%; odds ratio, 4.68; P < 0.0001). The median duration of response (mDOR) was 8.31 months (95% CI, 6.05–10.35) versus 5.36 months (95% CI, 2.86–8.54), respectively.

KRAZATI demonstrated intracranial response among patients with central nervous system (CNS) metastases at baseline, with a response rate per BICR that was more than double that observed with docetaxel (24% with KRAZATI vs. 11% with docetaxel).

The KRYSTAL-12 study remains ongoing to assess the additional key secondary endpoint of overall survival.

No new safety signals were identified for KRAZATI, and the safety data were consistent with the known safety profile. Treatment-related adverse events (TRAEs) of any grade were reported in 94% of patients treated with KRAZATI and 86.4% with docetaxel. Grade ≥3 TRAEs occurred in 47% and 46% of patients, respectively.

These data will be presented in a late-breaking oral presentation during the 2024 American Society of Clinical Oncology (ASCO) Annual Meeting on June 1 at 1:27 p.m. CDT (Abstract LBA8509).

“Approximately 14% of all patients with advanced non-small cell lung cancer carry the KRAS^G12C mutation, impacting thousands of people worldwide,” said Tony Mok, M.D., Chairman of the Department of Clinical Oncology and Li Shu Fan Medical Foundation Professor of Clinical Oncology of the Faculty of Medicine at The Chinese University of Hong Kong (CU Medicine). “These results from the Phase 3 KRYSTAL-12 study reinforce adagrasib as a targeted option for patients with KRAS^G12C-positive lung cancer after failing standard first-line treatment.”

“The accelerated approval of KRAZATI from the FDA in 2022 was welcome news for patients with KRAS^G12C-mutated locally advanced or metastatic NSCLC. These confirmatory results further support KRAZATI as an efficacious, targeted treatment option for these patients,” said Abderrahim Oukessou, M.D., vice president, global program lead, KRAZATI, Bristol Myers Squibb. “We look forward to further sharing these results, while also continuing to evaluate KRAZATI in other advanced KRAS^G12C-mutated solid tumors.”

In addition to KRAS^G12C-mutated NSCLC, KRAZATI and KRAZATI-based combinations have shown encouraging, meaningful benefit in Phase 2 clinical trials across several tumors, including advanced colorectal cancer, pancreatic cancer, and other solid tumors.

Bristol Myers Squibb thanks the patients and investigators involved in the KRYSTAL-12 clinical trial.

This study was funded by Mirati Therapeutics, Inc., a Bristol Myers Squibb company. KRAZATI is a registered trademark of Mirati Therapeutics, Inc., a Bristol Myers Squibb company.

About KRYSTAL-12

KRYSTAL-12 is an open-label, multicenter, randomized Phase 3 study evaluating KRAZATI compared to standard-of-care chemotherapy alone, in patients with KRAS^G12C-mutated non-small cell lung cancer. The primary endpoint of the study is progression-free survival (PFS) as assessed by Blinded Independent Central Review (BICR). Secondary endpoints included overall survival (OS), overall response rate (ORR), duration of response (DOR), and safety.

About KRAS^G12C -Mutated Non-Small Cell Lung Cancer

Lung cancer is the leading cause of cancer deaths globally. The two main types of lung cancer are non-small cell and small cell. Non-small cell lung cancer (NSCLC) is one of the most common types of lung cancer, representing up to 84% of diagnoses. KRAS^G12C is the most common KRAS mutation in NSCLC, present in approximately 14% of patients with lung adenocarcinoma, and is a biomarker of poor prognosis.

About KRAZATI^® (adagrasib)

KRAZATI (adagrasib) is a highly selective and potent oral small-molecule inhibitor of KRAS^G12C that is optimized to sustain target inhibition, an attribute that could be important to treat KRAS^G12C-mutated cancers, as the KRAS^G12C protein regenerates every 24-48 hours. KRAS^G12C mutations act as oncogenic drivers and occur in approximately 14% of non-small cell lung cancer, 3-4% of colorectal cancer, and 1-2% of several other cancers.

In 2022, the U.S. Food and Drug Administration (FDA) granted KRAZATI accelerated approval for treatment of adult patients with KRAS^G12C-mutated locally advanced or metastatic 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).

KRAZATI continues to be evaluated as a monotherapy and in combination with other anti-cancer therapies in patients with advanced KRAS^G12C-mutated solid tumors, including NSCLC and colorectal cancer (CRC).

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

INDICATION

KRAZATI is indicated for the treatment of adult patients with KRAS^G12C-mutated locally advanced or metastatic non-small cell lung cancer, 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 (eg, 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.

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 platforms 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 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 results of future post-marketing studies will not be consistent with the results of this study, that KRAZATI (adagrasib) may not be commercially successful, that any marketing approvals, if granted, may have significant limitations on their use, and, that continued approval of KRAZATI may be contingent upon verification and description of clinical benefit in additional confirmatory trials. 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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$BMY announces results being presented at ASCO from the Phase 3 KRYSTAL-12 clinical trial in patients with previously treated metastatic KRASG12C-mutated non-small cell lung cancer