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 MK-3475 (Pembrolizumab) Compared to MK-3475 (Pembrolizumab) Alone for Mesothelin-Positive Malignant Pleural Mesothelioma

Summary:

This randomized phase I/II trial studies the side effects and how well pembrolizumab with or without anetumab ravtansine work in treating patients with mesothelin-positive pleural mesothelioma. Monoclonal antibodies, such as anetumab ravtansine and pembrolizumab, 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 assessed using Response Evaluation Criteria in Solid Tumours (RECIST) version 1.1 criteria (Phase II)

Secondary Outcome:

• Duration of response defined as evaluable patients who achieved noted to be a partial response or complete response based Response Evaluation Criteria in Solid Tumours version 1.1 criteria
• Overall survival
• Progression free survival
• Incidence of adverse events assessed by National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0
• 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:

• Determine the dose of anetumab ravtansine that is safe in combination with MK-3475 (pembrolizumab) to be used in the randomized phase 2 study. (Phase I safety lead-in)
• Determine if the overall response rate of the combination of anetumab ravtansine and MK-3475 (pembrolizumab) is superior to MK-3475 (pembrolizumab) alone. (Phase II)

SECONDARY OBJECTIVE:

• To determine the progression free survival of anetumab ravtansine and MK-3475 (pembrolizumab) compared to MK-3475 (pembrolizumab) alone.
• To evaluate the pharmacodynamic effects of anetumab ravtansine and MK-3475 (pembrolizumab) on soluble megakaryocyte potentiating factor (MPF).
• To evaluate the pharmacokinetics of anetumab ravtansine and MK-3475 (pembrolizumab).
• 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.
• To determine the incidence of antibodies directed against anetumab ravtansine.

TERTIARY OBJECTIVE:

• To determine whether elevations in Bim in TTR predict responses to treatment and whether its detection is dynamic with treatment.
• To determine whether soluble PD-L1 predicts responses to treatment and whether its detection is dynamic with treatment.
• To evaluate PD-L1 expression in archival tissue as a predictive marker of response to MK-3475 (pembrolizumab)-based therapy.
• 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. Courses 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. Courses 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