CHICAGO—The novel anti-PD-L1 agent avelumab showed some promising clinical activity and was generally well tolerated in a phase I trial of patients with unresectable, previously treated mesothelioma. Results of the trial were presented at the American Society of Clinical Oncology (ASCO) Annual Meeting, held June 3–7 in Chicago.
“Approximately 3,000 new cases of malignant mesothelioma are diagnosed each year in the United States,” said Raffit Hassan, MD, of the National Cancer Institute in Bethesda, Maryland, who presented the study. The current standard treatment of pemetrexed and cisplatin yields a median overall survival of 12.1 months, and there is no US Food and Drug Administration (FDA)-approved therapy for patients progressing after first-line chemotherapy.
Avelumab is a fully human anti-PD-L1 IgG1 antibody; it is under investigation in multiple malignancies. PD-L1 is expressed on the surface of mesothelioma cells, providing a rationale for avelumab’s use in this malignancy. In the new JAVELIN study, more than 1,600 patients have been treated with the drug across a variety of malignancies; in this analysis, 53 patients with unresectable pleural or peritoneal mesothelioma were included. All patients had progressed after a platinum/pemetrexed-containing regimen; they were unselected for PD-L1 expression.
The median treatment duration was 12 weeks, and the median age of patients was 66 years. Most patients (73.6%) had an ECOG performance status of 1, and the median number of prior treatments was 1.5.
The unconfirmed objective response rate (ORR) was 9.4%, with five partial responses (four confirmed); response was ongoing in four of five of those patients, and the median duration of response was not reached. Twenty-five patients had stable disease (47.2%), and the disease control rate was 56.6%. The median progression-free survival (PFS) was 17.1 weeks; at 24 weeks, the PFS rate was 38.4%.
Of 39 evaluable patients, 14 (35.9%) were found to be PD-L1–positive based on a staining cut-off of ≥ 5% of positive cells. The ORR was 14.3% in those patients, compared with 8% in PD-L1–negative patients. The median PFS was 17.1 weeks in PD-L1–positive patients, and 7.4 weeks in the PD-L1–negative patients. That advantage was not evident in terms of PFS rate at 24 weeks, however, at 39.2% in PD-L1–positive patients and 40.7% in PD-L1–negative patients.
Treatment-related adverse events (AEs) occurred in 41 patients (77.4%). The most common AEs included infusion-related reaction (37.7% of patients), fatigue (15.1%), chills (15.1%), and pyrexia (11.3%); all of those were grade 1 or 2 AEs. There were grade 3 or higher AEs in four patients (7.5%); these included colitis, decreased lymphocytes, and increased GGT or CPK. The study had no treatment-related deaths.
“Ongoing follow-up will further characterize durability of the clinical benefit,” Hassan said. “This dataset is the largest study to date of patients with mesothelioma treated with an anti–PD-1 or anti–PD-L1 antibody.”