• Repotrectinib continued to demonstrate high response rates and durable responses, including robust intracranial responses, in patients with ROS1-positive locally advanced or metastatic non-small cell lung cancer who were TKI-naïve or previously treated with one TKI and no chemotherapy
• Median duration of response and progression-free survival to be disclosed for the first time in the pooled Phase 1/2 population alongside updated results at the IASLC 2023 World Conference on Lung Cancer hosted by the International Association for the Study of Lung Cancer

PRINCETON, N.J. / Aug 16, 2023 / Business Wire / Bristol Myers Squibb (NYSE: BMY) today announced updated results from the registrational TRIDENT-1 study, demonstrating that repotrectinib, a next-generation ROS1/TRK tyrosine kinase inhibitor (TKI), continued to show high response rates and durable responses in patients with ROS1-positive locally advanced or metastatic non-small cell lung cancer (NSCLC). Updated results will be featured in an oral presentation (Abstract #OA03.06) at the IASLC 2023 World Conference on Lung Cancer (#WCLC23) hosted by the International Association for the Study of Lung Cancer on September 10, 2023, from 1:02 a.m. to 1:12 a.m. EDT / 1:02 p.m. to 1:12 p.m. SGT.

Based on results from the TRIDENT-1 trial, the U.S. Food and Drug Administration accepted the New Drug Application for repotrectinib for the treatment of patients with ROS1-positive locally advanced or metastatic NSCLC and granted Priority Review; a Prescription Drug User Fee Act goal date of November 27, 2023 was assigned.

In this updated analysis, repotrectinib continued to demonstrate durable efficacy in patients with ROS1-positive NSCLC, including intracranial activity, in patients who were TKI-naïve or previously treated with one TKI and no chemotherapy. Median duration of response (DOR) and median progression-free survival (PFS) will also be disclosed for the first time in the pooled Phase 1 and Phase 2 population of patients with ROS1-positive NSCLC:

• In TKI-naïve patients (n=71) with median follow-up of 24.0 months, confirmed objective response rate (cORR) by Blinded Independent Central Review (BICR) was 79%, median DOR and PFS were 34.1 months and 35.7 months, respectively. In patients with measurable brain metastases at baseline (n=9), intracranial ORR per BICR was 89% and responses were prolonged.
• In patients who had been previously treated with one TKI and no chemotherapy (n=56) with median follow-up of 21.5 months, cORR by BICR was 38%, and median DOR and PFS were 14.8 months and 9.0 months, respectively. In this subset of patients with measurable brain metastases at baseline (n=13), intracranial ORR per BICR was 38%.
• At the recommended dose for Phase 2, the safety profile of repotrectinib was manageable and remained consistent with previous reports.

“The data from the TRIDENT-1 trial hold great significance in the field of non-small cell lung cancer research, as they add to the growing body of evidence pointing toward durable results with repotrectinib in patients who test positive for ROS1 gene fusions,” said Byoung Chul Cho, M.D., Ph.D., Yonsei Cancer Center, Yonsei University College of Medicine, DAAN Cancer Laboratory. “With these results, we are seeing durable benefit, including in the brain, in patients with ROS1-positive NSCLC that differentiates repotrectinib from existing agents and is especially impressive in the context of historic data with current ROS1 TKIs. This targeted therapy has true potential to change the treatment landscape and become a new standard of care for patients with ROS1-positive NSCLC.”

“These updated results reflect the potential of repotrectinib as a best-in-class ROS1 inhibitor. Furthermore, the data offer hope for the patients with ROS1-positive non-small cell lung cancer who still face high remaining unmet needs,” said Joseph Fiore, executive director, global program lead, repotrectinib, Bristol Myers Squibb. “Building on our heritage of transformational science with immunotherapy in the treatment of NSCLC, we are excited to advance this next-generation precision medicine, which has shown an unprecedented level of durability of responses and robust intracranial responses in patients with ROS1-positive NSCLC, so that it can hopefully help patients in their fight against cancer.”

The study remains ongoing to assess long-term outcomes and additional endpoints across patient populations with ROS1-positive locally advanced or metastatic NSCLC and NTRK-positive advanced solid tumors. Bristol Myers Squibb thanks the patients and investigators involved with the TRIDENT-1 clinical trial.

Turning Point Therapeutics is a wholly owned subsidiary of the Bristol-Myers Squibb Company. As of August 2022, Bristol Myers Squibb acquired the leading clinical stage precision oncology company and its pipeline of investigational drugs across precision oncology and advanced solid tumors, including repotrectinib.

About TRIDENT-1

TRIDENT-1 is a Phase 1/2 open-label, global, multi-center, first-in-human clinical trial evaluating the safety, tolerability, pharmacokinetics and anti-tumor activity of repotrectinib (TPX-0005, BMS-986472) in patients with advanced solid tumors, including non-small cell lung cancer (NSCLC). Phase 1 of the trial includes several primary and secondary safety and pharmacokinetics endpoints. Phase 2 of the trial has a primary endpoint of overall response rate (ORR) as assessed by Blinded Independent Central Review (BICR) using RECIST v1.1 and key secondary endpoints including duration of response (DOR), time to response (TTR), progression-free survival (PFS), overall survival (OS) and clinical benefit rate (CBR) in six distinct expansion cohorts, including tyrosine kinase inhibitor (TKI)-naïve and TKI-pretreated patients with ROS1-positive locally advanced or metastatic NSCLC and NTRK-positive advanced solid tumors.

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. Survival rates vary depending on the stage and type of the cancer when diagnosed. ROS1 fusions are rare and occur in about 1-2% of patients with NSCLC. Patients with tumors that are ROS1-positive tend to be younger than the average patient with lung cancer, more often female and may have little to no smoking history. Per international treatment guidelines, ROS1 targeted agents are preferred in patients with a tumor harboring this alteration.

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.

About Repotrectinib

Repotrectinib (TPX-0005, BMS-986472) is a next-generation, potential best-in-class tyrosine kinase inhibitor (TKI) targeting ROS1- 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. Repotrectinib was designed to improve durability of response and with favorable properties to enhance intracranial activity. It is being studied in a registrational Phase 1/2 trial primarily in adults and a Phase 1/2 trial in pediatric patients.

In June 2017, repotrectinib was granted an Orphan Drug designation by the U.S. Food and Drug Administration (FDA). Since then, repotrectinib 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.

Repotrectinib 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.

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 results to date, that repotrectinib may not receive regulatory approval for the indication described in this release in the currently anticipated timeline or at all, that any marketing approvals, if granted, may have significant limitations on their use, and, if approved, whether such product candidate for such indication 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, 2022, 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.