Data from clinical efficacy and biomarker analyses conducted for the single-arm phase II PrE0505 study of the initial treatment of patients with malignant pleural mesothelioma were presented by Patrick Forde, MB, BCh, and colleagues during the Lung Cancer Oral Abstract Session at the ASCO20 Virtual Scientific Program (Abstract 9003). The trial evaluated the addition of durvalumab, an immune checkpoint inhibitor targeting programmed cell death ligand 1 (PD-L1), to chemotherapy consisting of pemetrexed and cisplatin in 55 patients with mesothelioma of any histologic subtype.
Patrick Forde, MD
“Durvalumab plus standard chemotherapy delivered a promising median overall survival rate for patients with previously untreated, inoperable malignant pleural mesothelioma,” said lead investigator Dr. Forde, of Johns Hopkins University. “The data signal us to move forward with a phase III study.”
Study Background
PrE0505 study investigators at 15 U.S. clinical sites enrolled 55 patients into the study between June 2017 and June 2018. Eligible patients received the combination of pemetrexed (500 mg/m2) and cisplatin (75 mg/m2) with durvalumab (1,120 mg) every 3 weeks for up to six cycles. Substitution of carboplatin (AUC 5) for cisplatin was permitted if toxicity occurred during the initial treatment.
After up to six cycles of concurrent chemotherapy with durvalumab, patients who had a partial response or stable disease could continue on durvalumab until disease progression. The maximum duration of durvalumab treatment was 12 months from the start of therapy.
Results
The study met its primary endpoint with a median overall survival of 20.4 months (one-sided P = .0014) as compared to the historical control of 12.1 months. Overall survival rates at 12 and 24 months were 70.4% and 44.2%, respectively. The combination was well tolerated with no unexpected toxicities.
KEY POINTS
- The study met its primary endpoint with a median overall survival of 20.4 months (one-sided P = .0014) as compared to the historical control of 12.1 months.
- Overall survival rates at 12 and 24 months were 70.4% and 44.2%, respectively.
The secondary endpoints in the PrE0505 trial are safety and tolerability, progression-free survival, and objective response rate. Progression-free survival at 6 months in those treated with the durvalumab combination was 69.1%. Best responses to treatment were measured by Response Evaluation Criteria in Solid Tumors and included 31 patients (56.4%) with a partial response, 22 (40%) with stable disease, and 1 (1.8%) whose disease progressed during the evaluation period. One patient was not evaluable for response.
All patients were evaluated for safety, and there were no unexpected toxicities. Adverse events reported by investigators as associated with durvalumab were generally mild in severity (grade 1 and 2).
In analyses of exploratory objectives, researchers saw no statistically significant associations between tumor sample expression of PD-L1 or tumor mutational burden and progression or survival. They observed neoantigen-specific T-cell responses in some selected cases. Analytic work for the study is ongoing.
The study authors concluded, “The combination of chemotherapy with durvalumab delivered a promising median overall survival for previously untreated patients with unresectable malignant pleural mesothelioma. Full results from the study along with the extensive correlative analyses performed will be reported. The phase III PrE0506/DREAM3R trial evaluating cisplatin/pemetrexed/durvalumab vs cisplatin/pemetrexed alone will commence enrollment in the United States and Australia in 2020.”
Disclosure: For full disclosures of the study authors, visit coi.asco.org.
