"Durvalumab plus standard chemotherapy delivered a promising median overall survival rate for patients with previously untreated, inoperable malignant pleural mesothelioma."
The addition of durvalumab (Imfinzi) to the only FDA-approved chemotherapy regimen of pemetrexed and cisplatin (Pem-Cis) improved overall survival (OS) in patients with malignant pleural mesothelioma, meeting the primary end point if the phase II PrE0505 study, announced PrECOG, LLC, in a press release.
“Durvalumab plus standard chemotherapy delivered a promising median overall survival rate for patients with previously untreated, inoperable malignant pleural mesothelioma,” said lead investigator Patrick Forde, MD, of Johns Hopkins University. “The data signal us to move forward with a phase three study.”
Data from PrE0505 will be highlighted during an oral presentation at the upcoming American Society of Oncology (ASCO) Virtual Annual Meeting, which will be held from May 29 to May 31.
The median OS in the durvalumab combination arm was 20.4 months compared with 12.2 months in the historical chemotherapy control arm (P =.0014). At 12 months, the OS rate was 70.4%, and at 24 months, the OS rate was 44.2%.
At 6 months, the progression-free survival (PFS) was 69.1% with the addition of durvalumab. For 56.4% of patients (n = 31), the best response was a partial response, and 40% of participants (n = 22) had stable disease. There was 1 patient who progressed on treatment.
Durvalumab in combination with Pem-Cis was also well-tolerated in patients, and no new toxicities were observed. Most of the adverse events observed in the trial were grade 1 or 2 in severity.
In an exploratory analysis, tumor samples were examined for an association between PD-L1 expression and response, but no statistically significant associations were seen. The assessment did find a neoantigen-specific T-cell response in some patients.
PrE0505 is an interventional, non-randomized study ongoing at 15 clinical sites in the United States. The target enrollment of 55 patients has been reached. In the study, patients receive durvalumab at 1120 mg doses every 3 weeks for up to 6 cycles. Cisplatin is administered at 75 mg/m2 and pemetrexed is administered at 500 mg/ m2.
In some cases, cisplatin can be substituted with carboplatin in the event of toxicity. Patients have the option to switch to durvalumab until disease progression after completing 6 cycles of concurrent chemotherapy. Twelve months is the maximum duration allowed for treatment with durvalumab.
The secondary end points being explored in PrE0505 include safety and tolerability, PFS, and objective response rate.
To be eligible for the trial, patients are required to have histologically or cytologically confirmed malignant pleural mesothelioma, untestable disease, measurable disease with at least 1 lesion, and available archived tumor tissue samples. Fitness criteria included an ECOG performance status of 0 to 1 and adequate organ function.
Based on data from this study, the combination of durvalumab with Pem-Cis may advance to a phase III clinical trial.
“This is a remarkable result in mesothelioma, and warrants confirmation in a randomized phase three trial, which is already in the planning,” stated Peter J. O’Dwyer, MD, chief executive officer and chair, PrECOG, LLC.
Durvalumab added to standard chemotherapy improved overall survival in mesothelioma [new release]. Philadelphia, PA: PrECOG, LLC; May 20, 2020. https://bit.ly/2LPWYg1. Accessed May 21, 2020.