Imfinzi With Chemo Produces Inconclusive Outcomes in Phase 3 Mesothelioma Study

In the phase 3 DREAM3R study, first-line treatment with Imfinzi (durvalumab) plus chemotherapy demonstrated consistent improvements in overall survival, progression-free survival, and objective response rates among patients with advanced pleural mesothelioma, echoing findings from earlier phase 2 trials. Despite these positive trends, slow patient enrollment and evolving standards of care led to inconclusive results, leaving several key questions unresolved.

Data from the trial were presented at the 2025 ESMO Congress. In patients treated with Imfinzi and chemotherapy, the median overall survival was 21 months compared with 18 months for patients receiving chemotherapy alone. Median progression-free survival was 8 months with the combination versus 7 months with chemotherapy alone. The objective response rate, which measures the proportion of patients who experienced tumor shrinkage, was 58% with Imfinzi plus chemotherapy versus 35% with chemotherapy alone.

The safety profile of chemotherapy, with or without Imfinzi, was consistent with the known effects of these treatments. Fatigue, nausea, and anemia were the most commonly reported side effects in both treatment groups, consistent with what has been seen in previous studies of these therapies.

Rationale and Design of the DREAM3R Trial

Imfinzi was previously evaluated in the phase 2 DREAM and PrE0505 trials, in which it demonstrated promising activity when combined with pemetrexed and either cisplatin or carboplatin chemotherapy. The phase 3 DREAM3R study enrolled patients with advanced pleural mesothelioma and patient enrollment began in February 2021.

The trial design was influenced by findings from the CheckMate 743 study in 2021, which demonstrated that nivolumab (Opdivo) combined with ipilimumab (Yervoy) significantly improved overall survival compared with chemotherapy alone. This change in standard treatment led to modifications in the DREAM3R trial, including the addition of a nivolumab/ipilimumab arm and adjusting the randomization to 1:1 for Imfinzi plus chemotherapy versus physician’s choice of nivolumab/ipilimumab or chemotherapy. At the 2025 ESMO Congress, only data from the Imfinzi and chemotherapy cohorts were presented.

A total of 114 patients received chemotherapy with Imfinzi, while 60 patients received chemotherapy alone. The trial’s primary end point was overall survival. Secondary end points included progression-free survival, objective response rate, and side effects.

Next Steps and Implications After the DREAM3R Study

Dr. Anna Nowak, deputy vice chancellor at the University of Western Australia, noted that although DREAM3R was a well-designed study, early trial termination due to slow enrollment makes it unlikely that the primary study question will ever be definitively answered. She explained that slow patient enrollment was influenced by the global pandemic and by changes in clinical practice following the CheckMate 743 study, which complicates interpretation of the findings. Chemotherapy alone is no longer considered standard treatment.

Despite this, Nowak emphasized that the high tumor response and disease control observed with Imfinzi plus chemotherapy suggest potential for future testing in the neoadjuvant setting, which is treatment given before surgery. Correlative biomarker analyses from DREAM3R are ongoing and may provide insights into which patients are most likely to benefit. She highlighted the importance of initiating randomized phase 3 trials promptly after positive phase 2 results to maximize enrollment and generate reliable evidence, noting that delays in starting the trial were due to multiple factors.

Overall, the DREAM3R trial provides valuable insights into the potential role of Imfinzi in combination with chemotherapy for advanced pleural mesothelioma, even though the study’s early termination limits definitive conclusions. The observed improvements in survival outcomes, tumor response, and disease control highlight the promise of this approach, particularly for patients who may benefit from earlier or neoadjuvant therapy. Ongoing analyses of correlative biomarkers and patient subgroups may further refine understanding of which patients are most likely to respond.

References:

1. "Primary results of DREAM3R: DuRvalumab (MEDI4736) with chemotherapy as first line treatment in advanced pleural Mesothelioma: A phase 3 Randomised trial," by Dr. Anna Nowak, et al. Presented at: 2025 ESMO Congress; October 17–20, 2025; Berlin, Germany. Abstract LBA104.
2. "First-line nivolumab plus ipilimumab in unresectable malignant pleural mesothelioma (CheckMate 743): a multicentre, randomised, open-label, phase 3 trial," by Paul Baas. et al. Lancet.

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