Anetumab Ravtansine and Atezolizumab in Treating Participants With Advanced Non-small Cell Lung Cancer
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|ClinicalTrials.gov Identifier: NCT03455556|
Recruitment Status : Recruiting
First Posted : March 6, 2018
Last Update Posted : August 14, 2018
|Condition or disease||Intervention/treatment||Phase|
|Mesothelin Positive Stage III Non-Small Cell Lung Cancer AJCC v7 Stage IIIA Non-Small Cell Lung Cancer AJCC v7 Stage IIIB Non-Small Cell Lung Cancer AJCC v7 Stage IV Non-Small Cell Lung Cancer AJCC v7||Biological: Anetumab Ravtansine Biological: Atezolizumab Other: Laboratory Biomarker Analysis||Phase 1 Phase 2|
I. To identify the recommended phase II dose of anetumab ravtansine combined with atezolizumab in advanced MSLN+ non-small cell lung cancer (NSCLC). (Phase I) II. To determine the confirmed response rate for the combination of anetumab ravtansine and atezolizumab in MSLN+ 2nd line NSCLC. (Phase II)
I. To describe adverse events and toxicities of the combination treatment of anetumab ravtansine and atezolizumab. (Phase I) II. To identify preliminary evidence of clinical activity (i.e. response, timed endpoints, etc.) (Phase I) III. To determine the progression-free survival (PFS) and the 1-year PFS rate for the combination of anetumab ravtansine and atezolizumab in 2nd-line NSCLC. (Phase II) IV. To determine the overall survival of anetumab ravtansine combined with atezolizumab in second-line therapy of NSCLC. (Phase II) V. Adverse events will also be summarized as well. (Phase II)
I. To determine using flow cytometry the levels of Bcl-2 interacting mediator of cell death (BIM) in circulating CD8+ CD11a+ PD-1+ T-cells, in peripheral blood samples collected from patients prior to initiation of therapy (baseline) and correlating these with confirmed response rate during and following treatment with the combination regimen.
II. To determine tissue MSLN and PD-L1 expression and correlate with response to combination therapy with atezolizumab and anetumab ravtansine.
III. To correlate baseline serum soluble PDL-1 (sPDL-1) with response to therapy.
OUTLINE: This is a phase I, dose-escalation study of anetumab ravtansine followed by a phase II study.
Participants receive anetumab ravtansine intravenously (IV) over 60 minutes and atezolizumab IV over 30-60 minutes on day 1. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, participants are followed up every 3 months for up to 2 years.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||49 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Phase I/II Study of the Human Anti-Mesothelin Antibody Drug Conjugate Anetumab Ravtansine (AR), Combined With the PD-L1 Inhibitor Atezolizumab in Non-Small Cell Lung Cancer|
|Actual Study Start Date :||August 10, 2018|
|Estimated Primary Completion Date :||October 23, 2020|
|Estimated Study Completion Date :||October 23, 2020|
Experimental: Treatment (anetumab ravtansine, atezolizumab)
Participants receive anetumab ravtansine IV over 60 minutes and atezolizumab IV over 30-60 minutes on day 1. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Biological: Anetumab Ravtansine
Other Name: BAY 94-9343
Other: Laboratory Biomarker Analysis
- Maximum tolerated dose (MTD) of anetumab ravtansine combined with atezolizumab defined as the dose level below the lowest dose that induces dose-limiting toxicity in at least one-third of patients (at least 2 of a maximum of 6 new patients) (Phase I) [ Time Frame: Up to 21 days ]Will be examined in an exploratory and hypothesis-generating fashion.
- Rate of confirmed response (Phase II) [ Time Frame: 6 months ]Defined as a patient who has achieved a partial response (PR) or complete response (CR) on two consecutive evaluations at least 4 weeks apart. Will be estimated by the number of successes divided by the total number of evaluable patients. Exact binomial 95% confidence intervals for the true success proportion will be calculated.
- Clinical activity (Phase I) [ Time Frame: Up to 6 months ]Will be summarized by simple descriptive summary statistics delineating complete and partial responses as well as stable and progressive disease in this patient population.
- Incidence of adverse events according to Common Terminology Criteria for Adverse Events version 4.0 (Phase I) [ Time Frame: Up to 21 days after last dose ]The number and severity of all adverse events (overall and by dose-level) will be tabulated and summarized in this patient population.
- Overall survival (Phase II) [ Time Frame: Up to 2 years ]Defined as the time from registration to death due to any cause. The distribution of overall survival will be estimated using the method of Kaplan-Meier.
- Progression-free survival (Phase II) [ Time Frame: 1 year and up to 2 years ]Defined as the time from registration to the earliest date of documentation of disease progression or death due to any cause. The distribution of progression-free survival will be estimated using the method of Kaplan Meier. Will also report the 1-year progression free survival (PFS) rate for the combination of anetumab ravtansine and atezolizumab in 2nd-line non-small cell lung cancer (NSCLC).
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03455556
|United States, Arizona|
|Mayo Clinic Hospital||Recruiting|
|Phoenix, Arizona, United States, 85054|
|Contact: Clinicial Trials Referral Office 855-776-0015|
|Principal Investigator: Helen J. Ross|
|United States, Florida|
|Mayo Clinic in Florida||Recruiting|
|Jacksonville, Florida, United States, 32224-9980|
|Contact: Clinical Trials Referral Office 855-776-0015|
|Principal Investigator: Yanyan Lou|
|United States, Minnesota|
|Rochester, Minnesota, United States, 55905|
|Contact: Clinical Trials Referral Office 855-776-0015|
|Principal Investigator: Alex A. Adjei|
|Principal Investigator:||Alex Adjei||Mayo Clinic|