Immune checkpoint inhibitor Bavencio (avelumab) shows durable clinical activity and long-term disease control among heavily pretreated malignant mesothelioma patients, according to a Phase 1 clinical trial.
The treatment — jointly developed by Merck KGaA (operating as EMD Serono in the U.S. and Canada) and Pfizer — controlled the disease in 58% of patients, with 17% living without disease worsening for one year or longer.
Findings were recently published in JAMA Oncology, in the study, “Efficacy and Safety of Avelumab Treatment in Patients With Advanced Unresectable Mesothelioma: Phase 1b Results From the JAVELIN Solid Tumor Trial.”
Malignant mesothelioma is a cancer that arises in the membranes lining certain parts of the body, especially the lungs or the abdomen. The disease has a very poor prognosis, with patients living only for a median of 12.1 months after their initial treatment.
Immune checkpoint inhibitors such as Opdivo (nivolumab) and Keytruda (pembrolizumab) have been added to the National Comprehensive Cancer Network guidelines for the second-line treatment of malignant pleural mesothelioma – cancer affecting the pleura, which are the two membranes that cover the lungs.
While not yet approved for mesothelioma, these therapies extended patients’ lives when given as second- or third-line treatments in Phase 1 and Phase 2 studies. However, Bavencio, which targets the same immune pathway as Opdivo and Keytruda — the PD-1/PD-L1 pathway — seems to cause a broader activation of the immune system.
The open-label Phase 1 JAVELIN Solid Tumor trial (NCT01772004) was designed to study the safety and efficacy of Bavencio across multiple cancer types. In the first part, patients received ascending doses of the treatment to determine a safe dose with the best efficacy. Then, the selected dose was tested across multiple expansion groups.
The malignant mesothelioma group included 53 patients, with a median age of 67 years, who had received prior Alimta (pemetrexed) and platinum chemotherapy. Patients had received a median of two prior lines of treatment, and a group of 38% had received three or more lines.
A response to treatment was seen in 9% of patients, including one (2%) complete response. Responses lasted for a median of 15.2 months. Patients who had received two prior lines of therapy had a better response rate (13%), compared with those who had one (6%) or three prior lines (10%).
In addition to the responders, 49% of patients also saw their disease stabilize, amounting to a total disease control rate of 58%.
Patients lived without disease worsening for a median of 4.1 months and remained alive for 10.7 months. At one year, 43.8% of patients were alive, and 17.4% were alive and progression-free.
Patients whose tumors produced the PD-L1 factor — a biomarker that usually predicts responses to PD-1 inhibitors — had the best responses to treatment, with a response rate of 19%, a median time without disease worsening of 5.3 months, and a median survival of 20.2 months.
However, those whose tumors were negative for the factor also benefited from Bavencio, with 7% responding to treatment, a median time without disease progression or death of 1.7 months, and a median survival of 10.2 months.
Bavencio was overall safe and well-tolerated, with its safety profile comparing favorably to chemotherapy. The treatment caused adverse events in 83% of patients, most of which were mild or moderate infusion-related reactions during the first and second infusions. However, 9% of patients experienced severe or life-threatening adverse events.
“In this phase 1b cohort of patients with unresectable mesothelioma who were heavily pretreated, including receipt of previous platinum and pemetrexed treatment in all patients, avelumab showed durable clinical activity and long-term disease control,” the researchers wrote.
“Although the study and its findings should be interpreted in context as a small phase 1b cohort, the level of long-term disease control, the duration of OS, and the safety profile suggest that avelumab could be a potential new therapeutic option for patients with mesothelioma,” they concluded.