Positive Data from the ChecMate 650 Immunotherapy Study

Prostate cancer, unlike other cancers, has not been nearly as responsive to immunotherapies, especially in monotherapy approaches, then other cancers. 

A recent phase II clinical trial described at the 2019 ASCO GU meeting using a combination of two immunotherapy drugs in metastatic prostate cancer has shown some positive activity.

The trial, the CheckMate 650 Study, evaluated the combination of ipilimumab (Yervoy) and nivolumab (Opdivo) in 90 men with mCRPC who were divided into two cohorts based on their prior treatment. Cohort 1 was comprised of both symptomatic and minimally symptomatic men who progressed after treatment with second-generation hormone therapy (Zytiga or Xtandi) and had not received taxane based chemotherapy for mCRPC, and cohort 2 which included men who had also progressed after taxane-based chemotherapy.

The study data showed that "In a malignancy where immune checkpoint monotherapy has shown limited activity, nivolumab plus ipilimumab demonstrated antitumor activity in patients with metastatic castration-resistant prostate cancer (mCRPC)," said study author Padmanee Sharma, MD, PhD, professor of Genitourinary Medical Oncology and Immunology at the University of Texas MD Anderson Cancer Center in Houston.

Subjects experienced, "Deep and durable object responses, as well as falls in prostate-specific antigen (PSA < 2 ng/mL) levels, were observed in a subgroup of patients," said Sharma, adding that the "preliminary data suggest that biomarkers have a role in identifying patients with mCRPC likely to respond to immunotherapy. "However, treatment tolerability was an issue.

Study subjects received nivolumab 1 mg/kg plus ipilimumab 3 mg/kg every 3 weeks for four doses, and then they received a maintenance therapy with nivolumab 480 mg every 4 weeks.

The combination showed an objective response rate of 25% in cohort 1 and 10% in cohort 2. There were two complete responses in each cohort, and partial responses were observed in six men in cohort 1 and one man in cohort 2. Additionally, 13 men achieved stable disease in cohort 1 and 11 men in cohort 2.

The authors concluded that there was a benefit regardless of prior exposure to chemotherapy, but the benefits appeared to be more pronounced in men who had not received prior chemotherapy.

Median time to response was 1.9 months in the first cohort and 2.1 months in the second cohort.

Prostate cancer needs more immunotherapy options.  Prior research shows us that the best approach to improve this option will be using combination therapy approaches.  This trial also reinforces the concept that we need better biomarker development so that we can know which men will be responsive before our spending money on treatments that will not have a positive result but will cause unnecessary side effects.