Neoplasms

Respiratory Tract (Lung and Bronchial) Diseases

All Conditions

Carcinoma, Non-Small-Cell Lung

Lung Neoplasms

Carcinoma

Respiratory Tract Neoplasms

Thoracic Neoplasms

Lung Diseases

Respiratory Tract Diseases

Carcinoma, Bronchogenic

Bronchial Neoplasms

Antineoplastic Agents

All Drugs and Chemicals

Atezolizumab

Antibodies

Immunoglobulins

Anetumab ravtansine

Maytansine

Antibodies, Monoclonal

Immune Checkpoint Inhibitors

Antineoplastic Agents, Immunological

Immunologic Factors

Tubulin Modulators

Antimitotic Agents

Immunoconjugates

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.

Anetumab Ravtansine

Laboratory Biomarker Analysis

Alex Adjei

This phase I/II trial studies the best dose and side effects of anetumab ravtansine when given together with atezolizumab and how well they work in treating participants with non-small cell lung cancer that has spread to other places in the body. Monoclonal antibodies, such as anetumab ravtansine and atezolizumab, may interfere with the ability of tumor cells to grow and spread.

PRIMARY OBJECTIVES:

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)

SECONDARY OBJECTIVES:

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)

CORRELATIVE OBJECTIVES:

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.

Anetumab Ravtansine and Atezolizumab in Treating Participants With Advanced Non-small Cell Lung Cancer

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

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)

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.

Will be summarized by simple descriptive summary statistics delineating complete and partial responses as well as stable and progressive disease in this patient population.

The number and severity of all adverse events (overall and by dose-level) will be tabulated and summarized in this patient population.

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.

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).

National Cancer Institute (NCI)

Mayo Clinic

Since only one patient was accrued, patient confidentiality prevents the reporting of this patient.

Participants receive 5.5 mg/kg anetumab ravtansine IV over 60 minutes and 1200 mg atezolizumab IV over 30-60 minutes on day 1. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

Treatment (Anetumab Ravtansine, Atezolizumab)

Age, Categorical

Sex: Female, Male

Race (NIH/OMB)

Histologic type

Alex A Adjei, MD, PhD

Maximum Tolerated Dose (MTD) (Phase I)

Rate of Confirmed Response (Phase II)

Clinical Activity (Phase I)

Incidence of Adverse Events According to Common Terminology Criteria for Adverse Events Version 4.0 (Phase I)

Overall Survival (Phase II)

Progression-free Survival (Phase II)

Overall Study

Spots Global Cancer Trial Database for mesothelin positive