Two Chemo-Combo Trials, Two Very Different Signals

Two chemotherapy-plus-immunotherapy combinations for mesothelioma delivered data in the past year. One was a Phase 3 trial that never reached full enrollment and ended with inconclusive results. The other was a small Phase 2 that reported striking numbers in a specific subgroup, but with a sample too small to reshape care on its own.

Read together, the two readouts show how uneven the current research pipeline is, and why patients and clinicians have to weigh each new trial on its own terms rather than on headlines.

DREAM3R: Stopped Early, Inconclusive

MesoWatch previously reported on the DREAM3R Phase 3 results presented at ESMO 2025. The trial tested whether adding durvalumab (Imfinzi), a PD-L1 checkpoint inhibitor, to standard platinum and pemetrexed chemotherapy would improve survival in people with unresectable pleural mesothelioma.

DREAM3R opened for enrollment in February 2021, directly into the COVID-19 pandemic. Of the 480 patients needed for statistical power, only 174 were enrolled across the combination arm (n=114) and the chemotherapy-only control arm (n=60). Enrollment was further undercut in October 2020 when the FDA approved nivolumab plus ipilimumab as the first immunotherapy combination for mesothelioma, making the chemotherapy-only control arm harder to fill.

The median overall survival was 21 months in the combination arm versus 18 months in the chemotherapy arm. The objective response rate was 58% with the combination versus 35% with chemotherapy alone. The hazard ratio for overall survival was 0.92, with a wide 95% confidence interval of 0.63 to 1.36. None of the differences reached statistical significance.

Dr. Anna Nowak of the University of Western Australia, who presented the results, put it plainly: “Due to the early stopping of DREAM3R, it is unlikely that the study question will ever be answered.”

BNT327: A Small Phase 2 With a Large Peritoneal Signal

BNT327, also known as PM8002, is a bispecific antibody that binds two targets at once. One arm blocks PD-L1, an immune checkpoint that tumors use to avoid detection. The other arm blocks VEGF-A, a protein that tumors use to grow new blood vessels.

At the 2025 ASCO Annual Meeting, researchers reported Phase 2 data from a single-arm Chinese trial that gave BNT327 plus chemotherapy to 31 patients with untreated unresectable mesothelioma. Twenty-three had pleural disease and eight had peritoneal disease.

The overall confirmed objective response rate was 51.6%. The disease control rate reached 90.3%. In the peritoneal subgroup of eight patients, the response rate was 75% and every patient reached disease control at a median follow-up of 20.3 months.

Those numbers are unusual in a cancer with limited treatment options. They are also drawn from eight people. No randomized comparator arm was included. Grade 3 or higher adverse events occurred in 93.5% of patients, largely driven by the chemotherapy backbone. No treatment-related deaths were reported.

Side by Side

How to Read These Results

The two trials sit at opposite ends of the research pipeline. DREAM3R was the kind of large, randomized study needed to change first-line care. It could not enroll enough patients to answer its question, and the numbers it did produce were directionally favorable but statistically silent.

BNT327 is earlier work. The peritoneal response figures are notable because peritoneal mesothelioma has no FDA-approved systemic therapies, and a 2026 preclinical study in Scientific Reports found that the peritoneal cavity creates an immune-suppressive microenvironment resistant to checkpoint therapy alone. A drug that pairs PD-L1 blockade with VEGF-A blockade has a plausible mechanism for that setting. Eight patients is still eight patients.

What to Watch Next

BNT327 is now partnered between BioNTech and Bristol Myers Squibb. The drug is advancing more rapidly in lung cancer and triple-negative breast cancer, where larger patient populations make trials faster to complete. No Phase 3 mesothelioma trial timeline has been announced.

DREAM3R will not be re-run. Dr. Nowak suggested the 58% response rate from DREAM3R could be explored in the neoadjuvant (pre-surgery) setting, where tumor shrinkage before an operation could improve outcomes. Whether any sponsor takes that idea forward is not yet public.