NCT02898116

Phase 1/2 Study of Ensartinib and Durvalumab, in ALK-rearranged Non-small Cell Lung Cancer

A Phase 1/2 Study of ALK Inhibitor, Ensartinib (X-396), and Anti-PD-L1, Durvalumab (MEDI4736), in Subjects With ALK-rearranged (ALK-positive) Non-small Cell Lung Cancer (NSCLC)

• Status: Completed
• Phase: Phase 1 / Phase 2
• Study type: Interventional
• Enrollment: 2 (actual)
• Sponsor: Ludwig Institute for Cancer Research · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

This was a Phase 1/2, open-label, multicenter, single-arm study of combination therapy with ensartinib, an anaplastic lymphoma kinase (ALK) inhibitor, and durvalumab, an anti-programmed cell death ligand 1 (PD-L1) antibody, in subjects with ALK-rearranged (ALK-positive) non-small cell lung cancer (NSCLC). Primary study objectives were to determine the recommended combination dose (RCD) and safety and tolerability of the combination. Further objectives were to evaluate the clinical efficacy and biologic activity of the combination.

Detailed description

Prior to initiation of combination therapy with ensartinib plus durvalumab, subjects were enrolled sequentially to receive ensartinib monotherapy (orally once daily) during a pre-immunotherapy Run-in Period for one to two 28-day cycles. The purpose of the Run-in Period was to determine whether any safety signals might compromise combination therapy and to determine the effect of ALK inhibitor therapy on the immune tumor microenvironment. For subjects with no dose-limiting toxicity (DLT) during the Run-in Period, combination therapy was then initiated during a dose-finding phase using a standard 3 + 3 design until determination of the RCD, which was defined as the highest dose level at which ≤ 1 of 6 subjects (i.e., \< 33%) experienced DLTs during the first 2 cycles of combination treatment. A fixed dose of durvalumab (1500 mg by intravenous \[IV\] infusion every 4 weeks) was administered in all cohorts. Ensartinib dosing started at 200 mg, with subsequent cohorts receiving a reduced (150 mg) or escalated (225 mg) ensartinib dose depending upon observed toxicity. The study was then designed to include an expansion phase, in which the RCD cohort would be expanded to a total of 20 subjects. Subjects were monitored for safety (including immune-related adverse events), disease status (using the Response Evaluation Criteria in Solid Tumors \[RECIST\] version 1.1 and immune-related RECIST), and biologic activity (peripheral blood assays and immunological changes in the tumor microenvironment) for the duration of study participation.

Conditions

• Non-small Cell Lung Cancer
• Carcinoma
• NSCLC

Interventions

Type	Name	Description
DRUG	Ensartinib	Ensartinib was administered orally once daily at a dose of 200 mg during the Run-in Period. During combination therapy, the ensartinib starting dose was to be 200 mg. Based on observed toxicity at the starting dose level, the ensartinib dose may have been escalated to the recommended single-agent dose (225 mg) or de-escalated to the minimum effective dose (150 mg).
DRUG	Durvalumab	During combination therapy, durvalumab was to be administered as an IV infusion over 60 (± 5) minutes every 4 weeks at a dose of 1500 mg.

Timeline

• Start date: 2017-05-10
• Primary completion: 2017-08-04
• Completion: 2017-08-04
• First posted: 2016-09-13
• Last updated: 2022-10-10
• Results posted: 2018-08-21

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study