Immunotherapy Trial: Phase 1 Study for Mesothelioma
Baylor College of Medicine PHASE1/PHASE2 clinical trial testing immunotherapy for people with mesothelioma. Trial NCT05932199 is now recruiting.
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:
- 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.
- 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:
- Discuss eligibility with their oncologist
- Review the full eligibility criteria on ClinicalTrials.gov
- Contact the study coordinator for screening
Reader Q&A
Frequently Asked Questions
What is the life expectancy of someone with immunotherapy for mesothelioma?
People with mesothelioma treated with immunotherapy, such as Opdivo plus Yervoy, have a median survival of 18.1 months, compared to 14.1 months with chemotherapy alone, per the CheckMate 743 trial. Keytruda combined with chemotherapy yields a median survival of 17.3-19.8 months. The DREAM trial reported 20.4 months median overall survival with durvalumab plus chemotherapy, rising to 24.3 months for epithelioid pleural mesothelioma. Overall, 3-year survival rates reach 23-25% with these treatments.
Is cancer caused by asbestos curable?
There is no known cure for asbestos-related cancers, including lung cancer and mesothelioma. However, treatment can extend survival and improve quality of life, particularly when cancer is detected early. For non-small cell lung cancer treated with surgery in early stages, people with asbestos-related lung cancer lived an average of 35 months. Recent clinical trials show that combining immunotherapy with chemotherapy extended median overall survival to 15 months compared to less than 13 months with chemotherapy alone. Some people with asbestos-related lung cancer have achieved remission, and individual outcomes vary based on factors like stage at diagnosis, treatment type, and overall health.
Where does mesothelioma cancer usually start?
Mesothelioma most commonly starts in the pleura, the thin membrane lining the lungs, accounting for the majority of cases. The cancer can also develop in the peritoneum, the lining of the abdominal cavity, or more rarely in the pericardium (heart lining) or tunica vaginalis testis. Asbestos fibers that are inhaled travel to the ends of small air passages and reach the pleura, where they can cause inflammation, scarring, and DNA damage that leads to uncontrolled cell growth. If asbestos fibers are swallowed, they can reach the abdominal lining and contribute to peritoneal mesothelioma.
Is Keytruda alone for peritoneal mesothelioma?
Keytruda (pembrolizumab) is not FDA-approved as monotherapy for peritoneal mesothelioma, unlike its approval in September 2024 combined with chemotherapy for unresectable pleural mesothelioma. Case reports document complete responses or prolonged survival in individual people with peritoneal mesothelioma treated with Keytruda alone, including one patient cancer-free for nearly 4 years as of 2024. Peer-reviewed studies show promising off-label use but call for larger clinical trials to confirm efficacy. About 20% of mesothelioma tumors express PD-L1 levels that may predict better response to Keytruda. Ongoing trials explore its role in peritoneal cases.