Phase 1/2 Study of Ensartinib and Durvalumab, in ALK-rearranged Non-small Cell Lung Cancer
|The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.|
|ClinicalTrials.gov Identifier: NCT02898116|
Recruitment Status : Completed
First Posted : September 13, 2016
Results First Posted : August 21, 2018
Last Update Posted : November 21, 2018
|Condition or disease||Intervention/treatment||Phase|
|Non-small Cell Lung Cancer Carcinoma NSCLC||Drug: Ensartinib Drug: Durvalumab||Phase 1 Phase 2|
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.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||2 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||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)|
|Actual Study Start Date :||May 10, 2017|
|Actual Primary Completion Date :||August 4, 2017|
|Actual Study Completion Date :||August 4, 2017|
Experimental: Ensartinib ± Durvalumab
Subjects were to receive ensartinib monotherapy during a pre-immunotherapy Run-in Period for one to two 28-day cycles, followed by combination therapy with ensartinib plus durvalumab for subjects with no DLTs during the Run-in Period.
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).
Other Name: X-396
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.
Other Name: MEDI4736
- Number of Subjects With Treatment-emergent Adverse Events [ Time Frame: up to 3 months ]Toxicity was graded in accordance with the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE), version 4.03. Treatment-emergent adverse events (TEAEs) were reported based on clinical laboratory tests, physical examinations, and vital signs from pre-treatment through the end of the study period. Dose-limiting toxicity (DLT) during the Run-in Period was defined as ≥ Grade 2 rash or other toxicity requiring discontinuation of ensartinib dosing.
- Number of Subjects With Best Overall Tumor Response at the Last Assessment [ Time Frame: up to 3 months ]Tumor response was evaluated using computed tomography and categorized according to the Response Evaluation Criteria in Solid Tumors (RECIST) (version 1.1) at Baseline, every 2 cycles, and at the end of the study. Per RECIST, target lesions are categorized as follows: Complete Response (CR): Disappearance of all target lesions; Partial Response (PR): ≥ 30% decrease in the sum of the longest diameter of target lesions; Progressive Disease (PD): ≥ 20% increase in the sum of the longest diameter of target lesions; Stable Disease (SD): small changes that do not meet above criteria.
- Number of Subjects With Immune-related Tumor Response at the Last Assessment [ Time Frame: up to 3 months ]Immune-related tumor response was evaluated by computed tomography at Baseline, every 2 cycles, and at the end of the study. Tumor response was designated according to the immune-related Response Criteria (irRC) (Wolchok et al. Clin Cancer Res 2009;15:7412-20) into the following categories: immune-related complete response (irCR) requires disappearance of all lesions in two consecutive observations not less than 4 weeks apart; immune-related partial response (irPR) requires ≥ 50% decrease in tumor burden compared with baseline in two observations at least 4 weeks apart; immune-related stable disease (irSD) is assigned when neither a 50% decrease from baseline tumor burden nor a 25% increase in tumor burden from nadir can be established; immune-related progressive disease (irPD) requires a ≥ 25% increase from nadir in tumor burden at any single time point in two consecutive observations at least 4 weeks apart.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02898116
|United States, New York|
|New York, New York, United States, 10016|
|Study Chair:||Leena Gandhi, MD, PhD||Laura & Isaac Perlmutter Cancer Center|