On August 16, 2023 Bristol Myers Squibb (NYSE: BMY) reported 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) (Press release, Bristol-Myers Squibb, AUG 16, 2023, View Source [SID1234634446]). 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.

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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.