Avelumab was shown to induce durable responses in patients with metastatic Merkel cell carcinoma (MCC), whose cancer had progressed after chemotherapy, according to results from a cohort of patients in a Phase 2 clinical trial. The results were recently presented at the ASCO Annual Meeting in Chicago, Illinois.
MCC is an aggressive and rare form of skin cancer, mostly caused by the human viral pathogen Merkel cell polyomavirus. The tumor often expresses a protein, called PD-L1, that upon interaction with its receptor PD-1 (present on the surface of T-cells) can suppress immune attacks against the tumor itself.
Avelumab, by Merck KGaA and Pfizer, is an anti–PD-L1 fully human monoclonal antibody being evaluated in the treatment of MCC, as well as others types of cancers. PD-1 inhibitors are currently being developed as novel chemotherapeutic and immunotherapeutic options, and some patients with advanced metastatic MCC have responded to such treatment.
“Avelumab offers a new treatment option for patients with this disease,” Howard L. Kaufman, MD, a professor of surgery at Robert Wood Johnson Medical School, said in the June presentation, according to a press release. “The recent advances with PD-L1– and PD-1–targeted agents has an opportunity to change the standard of care for patients with this disease.”
For these Phase 2 study (NCT02155647, JAVELIN) results, a group of 88 MCC patients, mostly males ages 33–88 (median age, 73) were identified by Kaufman and his colleagues to receive 10 mg/kg avelumab every two weeks, until confirmed disease progression, unacceptable toxicity, or withdrawal. Their tumors were examined every six weeks, and the primary endpoint was defined as response rate, while secondary endpoints were progression free survival (PFS), safety, tolerability, and duration of response.
Among these 88, a subgroup of 61 MCC patients — unresponsive to prior therapies — were selected and followed for at least 24 weeks. The presentation reported that patients in this subgroup had an overall response rate (ORR) of 32%, with six complete responses. Twelve other patients had partial responses, with seven achieving stable disease. Most of the responses (n=14) were noted by week seven, and the group was found to have a six-month durable response rate of 29.1%.
In terms of progression free survival, the recorded median for the cohort was 2.7 months, with a six-month PFS rate of 40%.
Anti–PD-L1 therapy was, overall, well-tolerated, with the most common side effects reported being fatigue (21.6%) and infusion-related reactions (13.6%).
JAVELIN is continuing, and is expected to conclude in September 2017. Patients with metastatic MCC, ages 18 and above, are still being recruited for the study, which is taking place at 52 sites in the U.S., Australia, and Europe. More information is available on the trial’s clinical trial.gov website.