Durvalumab Mesothelioma Trial Shows Promise But Lacks Definitive Answers

Promising but Inconclusive Findings for Durvalumab

Recent findings from the phase 3 DREAM3R trial suggest that adding durvalumab (Imfinzi) to chemotherapy shows promise for patients with advanced pleural mesothelioma. The combination led to favorable trends in overall survival (OS), progression-free survival (PFS), and a significantly better objective response rate (ORR). However, as presented at the 2025 ESMO Congress, challenges with patient enrollment and a shifting standard-of-care landscape ultimately rendered the results inconclusive.

A Closer Look at the DREAM3R Trial Data

The study compared durvalumab combined with chemotherapy against chemotherapy alone. The key outcomes reported were:

• Overall Survival (OS): The median OS was 21 months for the durvalumab combination group, compared to 18 months for the chemotherapy-only group.
• Progression-Free Survival (PFS): Patients receiving the combination therapy had a median PFS of 8 months, versus 7 months for those on chemotherapy alone.
• Objective Response Rate (ORR): The combination achieved a significantly higher ORR of 58%, while the chemotherapy arm had an ORR of 35%.

The safety profile of the combination therapy was consistent with the known side effects of the individual drugs. The most frequently reported adverse events in both arms of the study included fatigue, nausea, and anemia.

Why the Trial's Design Was Challenged

The DREAM3R trial was initially designed based on promising results from earlier phase 2 studies. Patients were randomized to receive either the durvalumab-chemotherapy combination or just chemotherapy. However, the trial, which began enrollment in February 2021, soon faced a major hurdle.

The landscape of mesothelioma treatment was transformed by the 2021 publication of the CheckMate 743 study. This trial established a new standard of care with the immunotherapy combination of nivolumab (Opdivo) and ipilimumab (Yervoy), which showed a significant survival benefit over chemotherapy. This development, along with the global pandemic, led to slow patient accrual for DREAM3R. Consequently, the study's design was modified, and it was ultimately stopped early, making it difficult to draw definitive conclusions from the data.

Expert Insights on Future Directions

During her presentation, Dr. Anna Nowak of the University of Western Australia acknowledged that while the trial was well-designed, its early termination means the primary research question remains unanswered. She explained, "Slow accrual was no doubt, an artifact, partly of the global pandemic, but also then of a change of clinical practice as a result of the of the CheckMate 743 study."

Despite the limitations, Dr. Nowak highlighted that the high tumor response rate seen with the durvalumab and chemotherapy combination could open doors for future research, particularly in the neoadjuvant setting before surgery. Furthermore, valuable biomarker data collected from trial participants is currently under analysis.

Dr. Nowak stressed a critical lesson from this experience: the timely activation of phase 3 trials after positive phase 2 results is essential "to seize the window of opportunity for accrual and provide reliable answers."

References

1. Nowak A. Primary results of DREAM3R: DuRvalumab (MEDI4736) with chemotherapy as first line treatment in advanced pleural Mesothelioma – A phase 3 Randomised trial. Presented at: 2025 ESMO Congress; October 17–20, 2025; Berlin, Germany. Abstract LBA104.
2. Baas P, Scherpereel A, Nowak AK, et al. First-line nivolumab plus ipilimumab in unresectable malignant pleural mesothelioma (CheckMate 743): a multicentre, randomised, open-label, phase 3 trial. Lancet. 2021 Jan 30;397(10272):375-386. doi: 10.1016/S0140-6736(20)32714-8. Epub 2021 Jan 21.