Two groundbreaking clinical trials are advancing treatment options for mesothelioma patients, targeting both resectable and unresectable forms of this aggressive cancer that has historically carried a five-year survival rate of less than 10%. The parallel studies represent significant progress in addressing an urgent medical need, as recent immunotherapy advances have only extended three-year survival to 23% for some patients.
Baylor-Duke Trial Tests Combined Approach for Surgical Candidates
Baylor College of Medicine and Duke University have launched a clinical trial exploring the effectiveness of combining chemotherapy and immunotherapy both before and after surgery for patients with resectable mesothelioma. The study is enrolling 52 patients across both institutions, with participants randomly assigned to receive either immunotherapy alone or a combination of chemotherapy and immunotherapy prior to surgery.
"We assess the disease stage and ensure patients are physically fit for treatment," explained Dr. R. Taylor Ripley, professor of surgery and Meyer-DeBakey Chair in Investigative Research in the David J. Sugarbaker Division of Thoracic Surgery at Baylor. "Those with operable disease will be randomized into one of the two groups. They will undergo three cycles of treatment and then have surgery. Post-surgery, they will continue immunotherapy for one year."
The trial protocol involves ongoing evaluations before enrollment, before surgery, and throughout follow-up. After surgical intervention, all participants continue immunotherapy for one year. Ripley is leading the trial alongside Dr. Jeff Clarke and Dr. David Harpole from Duke University, with the team hoping this innovative treatment combination will improve recurrence-free survival and achieve the highest survival rates yet seen in mesothelioma care.
Patient Experience Highlights Treatment Journey
William Donchig, a participant in the Baylor-Duke trial, shared his experience with the disease and treatment protocol. "I felt good, except my right lung kept filling up with fluid," Donchig said. "I couldn't breathe well, and an X-ray confirmed the problem."
Diagnosed with stage 3 mesothelioma, Donchig underwent three rounds of chemotherapy every few weeks, followed by surgery. He is now receiving immunotherapy every three weeks for one year as part of the trial protocol.
AstraZeneca's Global Trial Tests Dual-Protein Blocking Approach
Simultaneously, AstraZeneca is conducting the eVOLVE-Meso Phase III clinical trial, a global study testing Volrustomig (MEDI5752) in combination with standard chemotherapy for patients with unresectable pleural mesothelioma. The randomized trial includes 600 participants worldwide, including 40 from the UK, comparing the new treatment against either standard chemotherapy or the immunotherapy combination of ipilimumab and nivolumab.
Volrustomig represents a novel approach to mesothelioma treatment, working differently from existing immunotherapy options. While current treatments block a single pathway of cancer progression, Volrustomig simultaneously blocks two different proteins on cancer cells. Scientists behind the drug theorize that this dual-blocking approach will boost the immune system's ability to detect and fight cancer more effectively than single-target treatments.
Treatment Protocol and Timeline
In the eVOLVE-Meso study, participants are randomly assigned to receive either the new combination of Volrustomig plus the chemotherapy drugs pemetrexed and carboplatin, or one of two current standard treatments: nivolumab with ipilimumab or chemotherapy alone. Patients receive treatment through IV drips every three weeks, with chemotherapy lasting approximately 18 weeks and Volrustomig continuing for up to two years based on initial results.
The eVOLVE-Meso trial began in November 2023 and is expected to be completed in 2025. Beyond testing effectiveness, researchers are evaluating how the treatment affects patients' quality of life to better measure both therapeutic efficacy and impact on daily living.
Addressing Critical Medical Need
Mesothelioma is a rare and aggressive cancer that develops in the lining of the lungs, abdomen, or heart, most commonly caused by exposure to asbestos. Because symptoms often appear decades after exposure and mimic other illnesses, mesothelioma is typically diagnosed at an advanced stage with limited treatment options available.
The dual-protein blocking approach being tested in the AstraZeneca trial has been described by scientists as being akin to having two locks on a door instead of one. Researchers hope that Volrustomig will improve the immune system's ability to find and destroy mesothelioma cells more effectively than current single-target treatments, potentially revolutionizing treatment for this challenging disease.
