A new phase 2 clinical trial in metastatic castration-resistant prostate cancer (mCRPC) with a combination treatment of nivolumab plus ipilimumab has published preliminary results.

The publication in Cancer Cell1 reporting on the CheckMate 650 Trial (ClinicalTrials.gov Identifier: NCT02985957) features 90 patients divided into 2 equal cohorts. One group where patients have been pretreated with cytotoxic chemotherapies and the other where patients had only previously received hormone therapy, but no chemotherapy.

There have been multiple clinical trials with immune checkpoint inhibitors (ICIs) in mCRPC, including trials with ipilimumab2 or atezolizumab, but none have met their primary endpoint. The CheckMate 650 trial combining anti–prgrammed cell death 1 (PD-1) therapy nivolumab and anti–cytotoxic T-lymphocyte antigen 4 (CTLA-4) drug ipilimumab was introduced as a “signal-seeking” trial with a primary goal of the researchers being to identify the best dosing and dosing schedule for each of the drugs.

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“We wanted to acknowledge that we were starting with these doses and schedule,” said Padmanee Sharma, MD, PhD, professor of genitourinary medical oncology and immunology at MD Anderson Cancer Center in Houston, Texas, and senior author of the study. “Did we have it right initially? Possibly, but we wanted to have an open mind and be able to amend the trial as we learned more because we were also getting biopsy samples and looking at biomarkers and clinical factors where we might find things to guide us,” added Dr Sharma.

“With the combination we are trying, we need to find the best dosing and scheduling. Ipilimumab is approved at 1 mg/kg or 3 mg/kg depending on type of cancer, with the dosing schedule every 3 to 4 weeks or 6 weeks in lung cancer.”

The nivolumab and ipilimumab combination has been trialed in several cancers including metastatic melanoma, non-small cell lung cancer, and renal cell carcinoma and several different doses and dosing strategies have been used. The CheckMate 650 trial used nivolumab at 1 mg/kg and ipilimumab at 3 mg/kg every 3 weeks.

In the study, cohort 1, which included patients who were not pretreated with chemotherapy, seemed to respond more favorably on all metrics tested (progression-free survival [PFS], overall survival [OS], response rate, and prostate-specific antigen [PSA] level) than those pretreated with non-chemotherapy agents.

“The cohorts are small, so it’s hard to say much from this, but patients who have received less treatments in any tumor type tend to tolerate ICI better and have less toxicities. They can often stay on treatment a bit longer, and hence get better outcomes,” said Dr Sharma.

It has been suggested that patients not heavily pretreated with chemotherapy may respond more favorably to ICIs, as they may be able to mount a more robust immune response. However, recent results have not been able to fully support this hypothesis.