Paige Britt

In phase 3 DREAM3R, first-line Imfinzi plus chemotherapy showed survival and response benefits in advanced mesothelioma, but results were inconclusive.

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 

. 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.

Overall survival (OS): The length of time patients remain alive after starting treatment.

Progression-free survival (PFS): The length of time patients live without the cancer getting worse.

Objective response rate (ORR): The percentage of patients whose tumors shrink or disappear after treatment.

Neoadjuvant setting: Treatment given before the main therapy (such as surgery) to shrink a tumor.

Randomized trial: A study in which patients are assigned by chance to different treatment groups to compare outcomes.

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.

"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.

"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. 

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Articles

The phase 3 DREAM3R study evaluated the efficacy of Imfinzi (durvalumab) combined with chemotherapy in treating advanced pleural mesothelioma. Results showed improved overall survival, progression-free survival, and objective response rates compared to chemotherapy alone. However, slow patient enrollment and evolving treatment standards led to inconclusive results. The trial's early termination limits definitive conclusions, but the combination therapy's potential in neoadjuvant settings remains promising. Ongoing biomarker analyses may identify patients who benefit most, emphasizing the need for timely phase 3 trials following positive phase 2 outcomes.

Imfinzi With Chemo Produces Inconclusive Outcomes in Phase 3 Mesothelioma Study

Adding Imfinzi to Bacillus Calmette-Guérin therapy improved disease-free survival for patients with high-risk, non-muscle invasive bladder cancer.

Adding Imfinzi (durvalumab) to Bacillus Calmette-Guérin (BCG) therapy helped patients with high-risk, non-muscle invasive bladder cancer live longer without their cancer returning compared with BCG alone, according to results from a phase 3 study presented at the 2025 ESMO Congress.

The findings were presented by Dr. Maria De Santis, associate professor at the University of Warwick Medical School in Coventry, England, and simultaneously published in The Lancet.

The open-label, randomized study included 1,018 patients who were assigned in 3 cohorts: 339 received 1 year of Imfinzi with BCG induction and maintenance therapy, 339 received one year of Imfinzi with BCG induction only, and 340 received BCG induction and maintenance therapy alone.

The primary end point of DFS was achieved, with a 32% reduction in risk of a DFS event with the addition of Imfinzi to BCG induction and maintenance. Early and sustained DFS benefit with Imfinzi was observed starting as early as four months. The median follow-up was 60.7 months.

However, the difference in DFS for Imfinzi plus BCG induction only versus BCG induction and maintenance was not statistically significant.

While overall survival (OS) data were immature, there was no detriment to OS with the addition of Imfinzi to BCG induction and maintenance therapy.

Disease-free survival (DFS): time after treatment during which a patient lives without any signs or symptoms of cancer returning.

Overall survival (OS): time from treatment start or diagnosis until death from any cause.

The addition of Imfinzi to BCG induction and maintenance therapy had no major impact on patient-reported quality of life, one of the secondary end points of the trial.

Regarding safety, another key secondary end point, results showed that the Imfinzi/BCG regimen was tolerable and manageable with no unexpected side effects, and there were no deaths possibly related to the study treatment. Grade 3 (severe) or 4 (life-threatening) side effects possibly related to any treatment occurred in 21% of the Imfinzi/BCG induction and maintenance arm, 15% of the Imfinzi/BCG induction arm, and 4% of the BCG induction and maintenance arm.

The most frequently reported any-grade side effects in the Imfinzi/BCG induction and maintenance and BCG-only arms included dysuria (37% versus 36%, respectively), hematuria (32% versus 30%), pollakiuria (26% versus 25%), urinary tract infection (21% versus 18%), cystitis (19% versus 19%), and pyrexia (16% versus 20%).

“Overall, these events were consistent with what we expected for Imfinzi and BCG therapy with dysuria, hematuria, and pollakiuria being the three most commonly reported in both arms,” said De Santis during the presentation.

Most patients were male, and the median age was 68. Approximately 64% of patients had papillary disease only. Patients also had high-risk tumors, defined as being either T1, high grade, carcinoma in situ, or multiple and recurrent and large.

Patients received a median of six BCG induction instillations and 14 BCG maintenance instillations, with a maximum of 15 in both arms. More than half of patients received BCG for 18 months.

“In conclusion, these results support one year of Imfinzi with BCG induction and maintenance therapy as a potential new treatment in BCG-naive, high-risk NMIBC,” De Santis said during the presentation.

According to the National Cancer Institute, NMIBC refers to bladder cancers that have not grown into the muscle layer of the bladder wall. These cancers are confined to the inner lining (urothelium) or the connective tissue just beneath it. NMIBC includes stage 0 and stage 1 disease, meaning the tumor is limited to the surface or shallow layers of the bladder and has not invaded the deeper muscular wall.

“Durvalumab in combination with BCG for BCG-naive, high-risk, non-muscle-invasive bladder cancer” by Dr. Maria De Santis, et al., The Lancet.

The integration of Imfinzi (durvalumab) with BCG therapy in high-risk, non-muscle invasive bladder cancer (NMIBC) patients demonstrated a significant improvement in disease-free survival (DFS) compared to BCG alone, as per a phase 3 study. The study involved 1,018 patients and showed a 32% reduction in DFS events with Imfinzi addition. While overall survival data remain immature, no adverse impact on survival was noted. The treatment was well-tolerated, with manageable side effects, and no significant quality of life detriment was observed.

Paige Britt

Imfinzi With Chemo Produces Inconclusive Outcomes in Phase 3 Mesothelioma Study

Imfinzi Plus BCG Improves Disease-Free Survival in High-Risk NMIBC

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