Pembrolizumab With or Without Anetumab Ravtansine in Treating Patients With Mesothelin-Positive Pleural Mesothelioma

Official Title

Phase 1 Safety Run-In and Phase 2 Randomized Clinical Trial of Anetumab Ravtansine and Pembrolizumab (MK-3475) Compared to Pembrolizumab (MK-3475) Alone for Mesothelin-Positive Malignant Pleural Mesothelioma

Summary:

This phase I/II trial studies the side effects and how well pembrolizumab with or without anetumab ravtansine works in treating patients with mesothelin-positive pleural mesothelioma. Monoclonal antibodies, such as anetumab ravtansine, may interfere with the ability of tumour cells to grow and spread. Immunotherapy with monoclonal antibodies, such as pembrolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumour cells to grow and spread.

Trial Description

Primary Outcome:

• Recommended phase 2 dose of anetumab ravtansine with combination of pembrolizumab
• Confirmed tumour response rate (Phase II)

Secondary Outcome:

• Duration of response
• Overall survival
• Progression free survival
• Incidence of adverse events
• Pharmacokinetics of anetumab ravtansine
• Change in megakaryocyte potentiating factor levels assessed in tumour
• Mononuclear phagocyte system -FcgammaRs and chemokine mediators of mononuclear phagocyte system

PRIMARY OBJECTIVES:
I. Determine the dose of anetumab ravtansine that is safe in combination with pembrolizumab to be used in the randomized phase 2 study. (Phase I safety lead-in) II. Determine if the overall response rate of the combination of anetumab ravtansine and pembrolizumab is superior to pembrolizumab alone. (Phase II) SECONDARY OBJECTIVES:
I. To determine the progression free survival of anetumab ravtansine and pembrolizumab compared to MK-3475 (pembrolizumab) alone. II. To evaluate the pharmacodynamic effects of anetumab ravtansine and pembrolizumab on soluble megakaryocyte potentiating factor (MPF). III. To evaluate the pharmacokinetics of anetumab ravtansine and pembrolizumab. IV. To evaluate mononuclear phagocyte system (MPS) function, FcgammaRs, hormone and chemokine mediators as methods to evaluate factors affecting the pharmacokinetics and pharmacodynamics of these agents. V. To determine the incidence of antibodies directed against anetumab ravtansine. CORRELATIVE STUDY OBJECTIVES:
I. To determine whether elevations in Bim in TTR predict responses to treatment and whether its detection is dynamic with treatment. II. To determine whether soluble PD-L1 predicts responses to treatment and whether its detection is dynamic with treatment. III. To evaluate PD-L1 expression in archival tissue as a predictive marker of response to pembrolizumab-based therapy. IV. To explore the symptomatic adverse events (AE) for tolerability of each treatment group using patient reported outcomes (PRO)-Common Terminology Criteria for Adverse Events (CTCAE). OUTLINE:

Patients are randomized to 1 of 2 groups. GROUP I: Patients receive pembrolizumab intravenously (IV) over 30 minutes on day 1. Cycles repeat every 21 days for up to 2 years in the absence of disease progression or unacceptable toxicity. Upon radiologic documentation of disease progression, patients may cross over to Group II. GROUP II: Patients receive anetumab ravtansine IV over 1 hour and pembrolizumab IV over 30 minutes on day 1. Cycles repeat every 21 days for up to 2 years in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up for 12 months.

View this trial on ClinicalTrials.gov