Zai Lab Announces The New England Journal of Medicine Publication Demonstrating Durable Clinical Activity of Repotrectinib in Patients with Advanced ROS1 Fusion-Positive NSCLC

Rhea-AI Summary

Zai Lab Limited (ZLAB) announced Phase 1/2 TRIDENT-1 study data published in The New England Journal of Medicine demonstrate the potential of repotrectinib (TPX-0005) to overcome limitations of first-generation TKIs in terms of durability of responses and activity in ROS1 resistance mutations. The study showed robust intracranial activity in patients with ROS1-positive non-small cell lung cancer, with repotrectinib demonstrating high response rates and durable activity, including in patients with TKI-naïve and TKI-pretreated tumors, ROS1 G2032R resistance mutations, and brain metastases. The findings suggest repotrectinib as a next-generation treatment for ROS1+ NSCLC. The Center for Drug Evaluation of the National Medical Products Administration accepted the New Drug Application for repotrectinib for the treatment of adult patients with locally advanced or metastatic ROS1-positive NSCLC after granting priority review in May 2023.

Oncology Doctor

The introduction of repotrectinib, a novel tyrosine kinase inhibitor (TKI), into the treatment landscape for ROS1-positive non-small cell lung cancer (NSCLC) represents a significant advancement in oncology. The Phase 1/2 TRIDENT-1 study's findings suggest that repotrectinib may offer substantial benefits over first-generation TKIs, particularly in addressing resistance mutations and providing intracranial activity, which is crucial given the prevalence of brain metastases in this patient population.

From a clinical perspective, the high response rates and durable activity in both TKI-naïve and TKI-pretreated patients underscore the potential of repotrectinib to serve as a first-line treatment and as a subsequent therapy following the development of resistance to initial treatment. The tolerability and safety profile of repotrectinib also indicate its suitability for long-term administration, which is vital for managing a chronic disease like NSCLC.

Medical Research Analyst

The data from the TRIDENT-1 study, as published in The New England Journal of Medicine, provide a robust evidence base for the efficacy of repotrectinib in ROS1 fusion-positive NSCLC. The study's design, including its primary endpoints of maximum tolerated dose (MTD), recommended Phase 2 dose (RP2D) and confirmed objective response rate (ORR), as well as secondary endpoints like duration of response (DOR) and progression-free survival (PFS), are well-aligned with regulatory requirements for new oncology drugs.

The acceptance of the New Drug Application (NDA) by the National Medical Products Administration (NMPA) with priority review status and the subsequent approval by the U.S. Food and Drug Administration (FDA), are indicative of repotrectinib's potential to meet an unmet medical need. The study's international scope, including patient enrollment in Greater China by Zai Lab, emphasizes the global relevance of this treatment option.

Market Research Analyst

The approval of repotrectinib for ROS1-positive NSCLC is poised to impact the market dynamics within the oncology sector. Given the high incidence of lung cancer in China and the fact that NSCLC represents the majority of these cases, the market potential for repotrectinib in Greater China is significant. The collaboration between Zai Lab and Turning Point Therapeutics, now a subsidiary of Bristol-Myers Squibb, is strategically important as it leverages local expertise to navigate the Chinese regulatory environment and healthcare market.

For investors, the approval and commercialization of repotrectinib in a large market such as China, coupled with the FDA's approval in the United States, may signal potential revenue growth for the involved companies. However, market uptake will depend on factors such as pricing, reimbursement policies and competition from other TKIs. The long-term market success of repotrectinib will also hinge on continued positive outcomes from ongoing and future clinical trials.

Phase 1/2 TRIDENT-1 study data demonstrate repotrectinib’s clinically meaningful response rates and durable clinical activity in patients with ROS1-positive non-small cell lung cancer

Data show robust intracranial activity both in TKI naïve and pretreated settings in patients with ROS1-positive NSCLC

Findings demonstrate potential of repotrectinib to overcome limitations of first-generation TKIs in terms of durability of responses and activity in ROS1 resistance mutations

TRIDENT-1 study ongoing globally; Zai Lab leading execution in Greater China

SHANGHAI & CAMBRIDGE, Mass.--(BUSINESS WIRE)-- Zai Lab Limited (NASDAQ: ZLAB; HKEX: 9688) today announced The New England Journal of Medicine (NEJM) has published data from the registrational Phase 1/2 TRIDENT-1 study evaluating repotrectinib (TPX-0005) in patients with ROS1 fusion-positive (ROS1+) non-small cell lung cancers (NSCLCs). Repotrectinib is a tyrosine kinase inhibitor (TKI) that has shown robust anti-tumor activity against ROS1+ cancers in preclinical models. In the TRIDENT-1 study, repotrectinib demonstrated high response rates and durable activity in patients with ROS1+ NSCLC, including patients with TKI-naïve and TKI-pretreated tumors, ROS1 G2032R resistance mutations and brain metastases. Treatment with repotrectinib was generally well tolerated with a manageable safety profile compatible with long-term administration.

Turning Point Therapeutics, a wholly owned subsidiary of the Bristol-Myers Squibb Company, sponsored and designed the global, registrational TRIDENT-1 study. In August 2022, Bristol Myers Squibb acquired the company, including its asset repotrectinib. As part of its exclusive license agreement with Turning Point Therapeutics to develop and commercialize repotrectinib in Greater China (mainland China, Hong Kong, Taiwan, and Macau), Zai Lab participated and enrolled 81 patients for this trial.

Every year in China, more than 800,000 people are newly diagnosed with lung cancer, and NSCLC accounts for approximately 85% of the cases. ROS1 rearrangements occur in ≤2% of patients with NSCLC¹. Brain metastases are common among patients with ROS1+ NSCLC and intracranial activity of approved ROS1 TKIs can be suboptimal.

“The results from the TRIDENT-1 study suggest repotrectinib results in high and durable response rates in patients with ROS1+ NSCLC, in the settings of both treatment naïve, treatment resistant, and intracranial disease, which may address the limitations of first-generation TKIs,” said Rafael G. Amado, M.D., president, head of Global Oncology Research and Development, Zai Lab. “We look forward to advancing the development of repotrectinib in Greater China as a next generation treatment in this clinical setting.”

TRIDENT-1 is a registrational, first-in-human Phase 1/2 study assessing the efficacy and safety of repotrectinib in patients with advanced solid tumors, including ROS1+ NSCLC. In the study, 519 patients received one or more doses of repotrectinib, with 103 treated in Phase 1 and 416 treated in Phase 2. Primary endpoints were maximum tolerated dose (MTD) and/or recommended Phase 2 dose (RP2D) and confirmed objective response rate (ORR), as assessed by blinded independent central review (BICR) using RECIST v1.1 (Phase 2). Secondary endpoints included duration of response (DOR), progression-free survival (PFS) and safety.

Based on the results of this trial, the Center for Drug Evaluation (CDE) of the National Medical Products Administration (NMPA) accepted the New Drug Application (NDA) for repotrectinib submitted by Zai Lab for the treatment of adult patients with locally advanced or metastatic ROS1-positive NSCLC, after granting priority review in May 2023. In November 2023, the U.S. Food and Drug Administration approved repotrectinib for use in adult patients with locally advanced or metastatic ROS1+ NSCLC in the United States.

About Repotrectinib

Repotrectinib is a next-generation tyrosine kinase inhibitor (TKI) targeting the ROS1 and NTRK oncogenic drivers of advanced solid tumors, including non-small cell lung cancer (NSCLC). Patients with tumor harboring ROS1 and NTRK gene fusions treated with approved targeted therapies often develop resistance mutations, eventually leading to tumor progression. Repotrectinib is the first next-generation TKI for ROS1-positive metastatic NSCLC and tumors with NTRK fusions, uniquely designed to address key drivers of disease progression.

In China, repotrectinib has been granted four Breakthrough Therapy Designations from the Center for Drug Evaluation (CDE) of the National Medical Products Administration (NMPA) in ROS1-positive metastatic NSCLC patients who have not been treated with a ROS1 TKI; ROS1-positive metastatic NSCLC patients who have previously been treated with a ROS1 TKI and who have not received prior platinum-based chemotherapy; ROS1-positive metastatic NSCLC patients who have previously been treated with a ROS1 TKI and one prior line of platinum-based chemotherapy; and patients with advanced solid tumors that have an NTRK gene fusion who have progressed following treatment with prior TRK tyrosine kinase inhibitors (TKIs).

Zai Lab has an exclusive license agreement with Turning Point Therapeutics, a wholly owned subsidiary of the Bristol-Myers Squibb Company, to develop and commercialize repotrectinib in Greater China (mainland China, Hong Kong, Taiwan and Macau).

About Zai Lab

Zai Lab (NASDAQ: ZLAB; HKEX: 9688) is an innovative, research-based, commercial-stage biopharmaceutical company based in China and the United States. We are focused on discovering, developing, and commercializing innovative products that address medical conditions with significant unmet needs in the areas of oncology, autoimmune disorders, infectious diseases, and neuroscience. Our goal is to leverage our competencies and resources to positively impact human health in China and worldwide.

For additional information about Zai Lab, including our products, business activities and partnerships, research, and other events or developments, please visit www.zailaboratory.com or follow us at www.twitter.com/ZaiLab_Global.

Zai Lab Forward-Looking Statements

This press release contains forward-looking statements about future expectations, plans, and prospects for Zai Lab, including, without limitation, statements relating to the prospects of repotrectinib and the potential treatment of NSCLC and NTRK-positive solid tumors in Greater China. These forward-looking statements may contain words such as “aim,” “anticipate,” “believe,” “could,” “estimate,” “expect,” “forecast,” “goal,” “intend,” “may,” “plan,” “possible,” “potential,” “will,” “would,” and other similar expressions. Such statements constitute forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. Forward-looking statements are not statements of historical fact or guarantees or assurances of future performance. Forward-looking statements are based on our expectations and assumptions as of the date of this press release and are subject to inherent uncertainties, risks and changes in circumstances that may differ materially from those contemplated by the forward-looking statements. Actual results may differ materially from those indicated by such forward-looking statements as a result of various important factors, including but not limited to (1) our ability to successfully commercialize and generate revenue from our approved products; (2) our ability to obtain funding for our operations and business initiatives, (3) the results of our clinical and pre-clinical development of our product candidates, (4) the content and timing of decisions made by the relevant regulatory authorities regarding regulatory approvals of our product candidates, (5) risks related to doing business in China, and (6) other factors identified in our most recent annual and quarterly reports and in other reports we have filed with the U.S. Securities and Exchange Commission. We anticipate that subsequent events and developments will cause our expectations and assumptions to change, and we undertake no obligation to update or revise any forward-looking statements, whether as a result of new information, future events or otherwise, except as may be required by law. These forward-looking statements should not be relied upon as representing our views as of any date subsequent to the date of this press release.

Our SEC filings can be found on our website at www.zailaboratory.com and on the SEC’s website at www.sec.gov.

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¹Zhang et al. Prevalence of ROS1 fusion in Chinese patients with non-small cell lung cancer, Thoracic Cancer January 2019.

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Source: Zai Lab Limited

FAQ

What are the key findings of the Phase 1/2 TRIDENT-1 study published in The New England Journal of Medicine for Zai Lab Limited (ZLAB)?

The key findings demonstrate the potential of repotrectinib (TPX-0005) to overcome limitations of first-generation TKIs in terms of durability of responses and activity in ROS1 resistance mutations. The study showed robust intracranial activity in patients with ROS1-positive non-small cell lung cancer, with repotrectinib demonstrating high response rates and durable activity, including in patients with TKI-naïve and TKI-pretreated tumors, ROS1 G2032R resistance mutations, and brain metastases.

What is the significance of the Phase 1/2 TRIDENT-1 study for Zai Lab Limited (ZLAB) and repotrectinib (TPX-0005)?

The Phase 1/2 TRIDENT-1 study demonstrates the potential of repotrectinib as a next-generation treatment for ROS1+ NSCLC, addressing the limitations of first-generation TKIs and showing high response rates and durable activity in patients with ROS1-positive non-small cell lung cancer.

What is the status of the New Drug Application (NDA) for repotrectinib for the treatment of adult patients with locally advanced or metastatic ROS1-positive NSCLC?

The Center for Drug Evaluation of the National Medical Products Administration accepted the New Drug Application for repotrectinib for the treatment of adult patients with locally advanced or metastatic ROS1-positive NSCLC after granting priority review in May 2023.