Tislelizumab Meets Overall Survival End Point in Phase 3 Study of Advanced NSCLC

The primary end point of overall survival (OS) with tislelizumab compared with docetaxel as the second- or third-line treatment of patients with locally advanced or metastatic non–small cell lung cancer (NSCLC) who progressed on previous platinum-based chemotherapy, according to findings from the intention-to-treat (ITT) population in a planned interim analysis of the phase 3 RATIONALE 303 clinical trial.

“The RATIONALE 303 trial is the third phase 3 trial of tislelizumab in NSCLC that has achieved a positive outcome at interim analysis, and more importantly, marks the first global pivotal trial with a positive outcome in the tislelizumab clinical program,” said Yong Ben, MD, chief medical officer, Immuno-Oncology at BeiGene, in a statement. “We look forward to sharing the full results at an upcoming medical conference and providing additional updates on our lung cancer program in the future.”

The safety profile of this anti-PD-1 monoclonal antibody observed in this study was consistent with the known risks of this agent, and no new safety signals were identified.

“As we continue to advance tislelizumab in its broad clinical program, which targets a wide range of prevalent cancer types, we expect to see a growing body of clinical evidence that we believe will help further evaluate this potentially differentiated checkpoint inhibitor and support potential regulatory filings in China and globally,” Ben stated.

The global open-label multicenter study (NCT03358875) randomized patients to receive either tislelizumab or docetaxel in order to evaluate the safety and efficacy of this therapy. Patients with locally advanced or metastatic NSCLC were able to receive therapy in either the second- or third-line setting following progression on a platinum-based chemotherapy regimen.

OS of both the ITT population and in patients with high PD-L1 expression served as the co-primary end points, and secondary end points in the study include objective response rate, duration of response, progression-free survival, and safety. In total, 805 patients have been randomized 2:1 to receive either tislelizumab or docetaxel across 10 different countries. The anti-PD-1 monoclonal antibody was given intravenously (IV) at 200 mg every 3 weeks, while docetaxel was given at a dose of 75 mg/m2 IV every 3 weeks.

To be included in the study, patients had to have a histologically confirmed diagnosis of either locally advanced or metastatic (stage IIIB or IV) NSCLC, and either squamous or non-squamous histologies were included following progression during or after treatment with at least 1 prior platinum-based chemotherapy. They also had to have an ECOG performance status of ≤ 1, adequate hematologic and end-organ function, and an expected life span > 12 weeks. Patients could not have received more than 2 lines of systemic therapy, and they couldn’t harbor an EGFR mutation or ALK gene translocation.

Tislelizumab is under evaluation in clinical trials both as a monotherapy and in combination with other therapies for the treatment of a variety of solid tumors, as well as hematologic malignancies. The China National Medical Products Administration approved this therapy as treatment of patients with locally advanced or metastatic urothelial carcinoma with high PD-L1 expression who had progression during or after a platinum-based chemotherapy or within 12 months of neoadjuvant/adjuvant treatment with a platinum-based regimen.

Three supplemental New Drug Applications have been submitted in China and remain under review for combination use with chemotherapy in the frontline setting for patients with advanced squamous NSCLC, for the frontline treatment of those with advanced non-squamous NSCLC, and as monotherapy for previously treated patients with unresectable hepatocellular carcinoma.

These agent is not currently approved in the United States, nor any other countries outside of China. The agent remains under investigation in a dozen phase 3 clinical trials across a variety of cancer types, as well as 2 phase 2 clinical trials.

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_{Beigene announces that rationale 303 trial of tislelizumab in non-small cell lung cancer met the primary endpoint of overall survival at interim analysis. News Release. BeiGene, Ltd. November 17, 2020. Accessed November 17, 2020. https://bwnews.pr/2Ke7Bf7}