Repotrectinib Receives NMPA Approval in China for ROS1+ NSCLC

Shun Lu, MD, PhD

China’s National Medical Products Administration (NMPA) has approved repotrectinib (Augtyro) for the treatment of patients with ROS1-positive non–small cell lung cancer (NSCLC).¹

This regulatory decision was based on data from the open-label, single-arm, phase 1/2 TRIDENT-1 trial (NCT03093116), in which repotrectinib produced an overall response rate (ORR) of 79% (95% CI, 68%-88%) in treatment-naive patients with ROS1-positive NSCLC (n = 71).^1,2 In this patient cohort, the median duration of response (DOR) was 34.1 months (95% CI, 25.6-not estimable [NE]), and the median progression-free survival (PFS) was 35.7 months (95% CI, 27.4-NE).2 Furthermore, in the population of patients who had received 1 prior ROS1 TKI and had never received chemotherapy (n = 56), the ORR was 38% (95% CI, 25%-52%), the median DOR was 14.8 months (95% CI, 7.6-NE), and the median PFS was 9.0 months (95% CI, 6.8-19.6).

“Despite existing earlier-generation TKIs for ROS1-positive NSCLC, there remains an unmet need for new treatment options that support important clinical goals, such as durable therapeutic response,” Shun Lu, MD, PhD, chief of the Lung Cancer Center at Shanghai Chest Hospital, Shanghai Jiaotong University in China, stated in a press release.¹ “The TRIDENT-1 study showed that treatment with repotrectinib results in high response rates with promising durability in patients with ROS1-positive NSCLC, across TKI-naive and TKI-pretreated settings, including in the presence of intracranial disease. Based on this study, repotrectinib has the potential to become a new standard of care for these patients.”

“We are pleased with the NMPA’s approval of [repotrectinib] for the treatment of patients with ROS1-positive NSCLC in China,” Rafael G. Amado, MD, president and head of Global Oncology Research and Development at Zai Lab, added in the press release. “There is a significant unmet need for these patients given the limited durability of benefit due to the emergence of resistance with existing therapies, eventually leading to tumor progression. We appreciate the NMPA for their thorough assessment of [repotrectinib], recognizing its potential to address the unmet medical need in China.”

Repotrectinib is a next-generation TKI that targets ROS1 and NTRK oncogenic drivers. In 2021, the first patient in Greater China was dosed in TRIDENT-1.

Among the patients enrolled in TRIDENT-1 with measurable baseline brain metastases who were ROS1 TKI–naive (n = 9), this agent elicited an intracranial ORR (IC-ORR) of 89% (95% CI, 52%-100%).² The IC-ORR with repotrectinib was 38% (95% CI, 14%-68%) in ROS1 TKI–pretreated patients with measurable baseline brain metastases (n = 13). The estimated rate of IC-ORR lasting at least 12 months was 83% (95% CI, 54%-100%) in ROS1 TKI–naive patients and 60% (95% CI, 17%-100%) in ROS1 TKI–pretreated patients. Of the patients without baseline brain metastases, the estimated 12-month intracranial PFS rates were 91% (95% CI, 83%-100%) and 82% (95% CI, 65%-98%), in these respectively, in ROS1 TKI–naive and –pretreated patientsrespective populations.

Treatment with repotrectinib was generally well tolerated, and the agent had a manageable safety profile, according to the press release.1 The most common treatment-related adverse effects were dizziness (58%), dysgeusia (50%), and paresthesia (30%).²

Previously, Rrepotrectinib previously received FDA approval for the treatment of adult patients with locally advanced or metastatic ROS1-positive NSCLC in November 2023.1 Additionally, in 2021, the agent received breakthrough therapy designation from the FDA in 2021 for patients with NTRK gene fusion–positive advanced solid tumors who have progressed after exposure to 1 or 2 prior TRK TKIs, with or without chemotherapy, who have no satisfactory alternative treatment options.

Repotrectinib is currently under FDA priority review for adult and pediatric patients at least 12 years of age with NTRK-positive locally advanced or metastatic solid tumors for whom surgical resection may result in severe morbidity.³

References

1. Zai Lab announces approval of AUGTYRO (repotrectinib) for patients with ROS1-positive NSCLC by China’s NMPA. News release. Zai Lab Limited. May 12, 2024. Accessed May 13, 2024. https://ir.zailaboratory.com/news-releases/news-release-details/zai-lab-announces-approval-augtyrotm-repotrectinib-patients-ros1
2. Drilon A, Camidge DR, Lin JJ, et al. Repotrectinib in ROS1 fusion-positive non-small-cell lung cancer. N Engl J Med. 2024;390(2):118-131. doi:10.1056/NEJMoa2302299
3. U.S. Food and Drug Administration accepts for priority review Bristol Myers Squibb’s application for Augtyro™ (repotrectinib) for the treatment of patients with NTRK-positive locally advanced or metastatic solid tumors. News release. Bristol Myers Squibb. February 14, 2024. Accessed February 14, 2024. https://news.bms.com/news/corporate-financial/2024/U.S.-Food-and-Drug-Administration-Accepts-for-Priority-Review-Bristol-Myers-Squibbs-Application-for-Augtyro-repotrectinib-for-the-Treatment-of-Patients-with-NTRK-Positive-Locally-Advanced-or-Metastatic-Solid-Tumors/default.aspx