Immunotherapy Trial: Phase 1 Study for Mesothelioma

Baylor College of Medicine is recruiting for a Phase 1/2 clinical trial testing neoadjuvant durvalumab plus tremelimumab, with or without chemotherapy, for people with potentially resectable pleural mesothelioma.

The trial, designated NCT05932199, aims to enroll 52 participants at two sites: Baylor St Luke’s in Houston, Texas, and Duke Cancer Institute in Durham, North Carolina. The principal investigator is Dr. Robert Taylor Ripley of Baylor College of Medicine. The trial began enrolling in July 2024 and is scheduled to run through May 2028.

About the Study

Objectives: The investigators will test whether combination of chemoimmunotherapy or dual agent immunotherapy alone improves efficacy for patients with MPM.

Primary Objectives:

The primary objective is to test whether the combination of platinum-based chemotherapy and pemetrexed with durvalumab / tremelimumab or durvalumab / tremelimumab alone improves recurrence-free survival for patients with resectable MPM compared to historical, published data for surgery with chemotherapy.

Secondary Objective(s):

The secondary objectives are to determine the safety of and whether the platinum-based chemotherapy and pemetrexed with durvalumab / tremelimumab or durvalumab / tremelimumab alone improves response rate, resectability, major pathological response, and complete pathological response.

Exploratory Objective(s):

The exploratory objectives are to determine the safety of and whether the platinum-based chemotherapy and pemetrexed with durvalumab / tremelimumab or durvalumab / tremelimumab alone improves response rate, resectability, major pathological response, and complete pathological response for patients with epithelioid and non-epithelioid histologies.

The scientific exploratory objectives include:

1. Develop an NGS plasma assay of common mutations identified from our previous grant cycle to prospectively measure minimal residual disease (MRD) after resection as a potential, novel biomarker test in mesothelioma.
2. Determine the predictive role of BH3 profiling in patients undergoing neoadjuvant ICI followed by surgery: With patient samples collected from our neoadjuvant ICI trial, the investigators will test whether BH3 profiling from pre-treatment tumor biopsies and PBMC predicts clinical, radiological, and pathological responses to ICIs. The investigators will identify TAMs from the TiME in MPM tumor samples before and after treatment to compare differences in polarization induced by ICI in clinical and pathologically responding versus non-responding patients.

Treatment Approach

This trial combines two checkpoint inhibitors: durvalumab (anti-PD-L1) and tremelimumab (anti-CTLA-4). One arm receives the dual immunotherapy combined with platinum-based chemotherapy plus pemetrexed before surgery. The other arm receives dual immunotherapy alone. The goal is to identify which approach produces better recurrence-free survival after surgery.

Key trial details:

• Phase: Phase 1/2
• Sponsor: Baylor College of Medicine
• Collaborator: Duke Cancer Institute
• Principal investigator: Dr. Robert Taylor Ripley
• Enrollment target: 52
• Status: Recruiting
• Study start: July 2024
• Estimated completion: May 2028

Why This Trial Matters

Study Locations

The trial is recruiting at:

• Baylor St Luke’s Medical Center, Houston, Texas
• Duke Cancer Institute, Durham, North Carolina

How to Enroll

Patients interested in this trial should:

1. Discuss eligibility with their oncologist
2. Review the full eligibility criteria on ClinicalTrials.gov
3. Contact the study coordinator for screening