This was a multi-center, single-arm, open-label phase 2 trial of men with mCRPC who received testosterone cypionate 400mg intramuscular (BAT) every 28 days and nivolumab 480mg IV every 28 days, during which time LHRH agonist treatment was continued. All patients received BAT as single-agent therapy for a 12-week lead-in prior to the addition of nivolumab. Eligible patients were those with asymptomatic mCRPC who had soft tissue disease amenable to biopsy and progressed on at least one prior novel AR targeted therapy. Up to one line of chemotherapy was allowed for the treatment of mCRPC disease. The trial design for this study is as follows:
The primary endpoint for this trial was confirmed PSA50 response rate. Key secondary endpoints included safety, objective response rate, and radiographic progression-free survival (rPFS). The trial was designed to detect a 20% absolute increase in PSA50 response rate from the null of 25%.
There were 45 patients enrolled on study and treated. The confirmed PSA50 response rate was 40.0% (n = 18/45, 95% CI: 26-56%, p = 0.02 against the 25% null hypothesis). For patients with measureable disease, the objective response rate was 23.8% (n = 10/42):
Median rPFS on BAT and nivolumab was estimated at 5.7 months (95% CI 4.9-7.8 months), and 11.1% (n = 5/45) of patients were free from radiographic progression for 11 or more months. One patient achieved a complete radiographic response, which is ongoing (>13 months):
The majority of adverse events were Grade <2. The most common adverse events were edema (20%), nausea (20%), and back pain (13%). Immune-related adverse events were generally mild (Grade <2) with only two grade 3 immune-related adverse events observed (pericarditis, lipase elevation).
Dr. Markowski concluded his presentation of this phase 2 trial assessing BAT plus nivolumab with the following take-home points:
- BAT plus nivolumab was well-tolerated without concerning safety signals
- The combination met the pre-specified primary endpoint of confirmed PSA50response in a heavily treated population
- Durable responses were observed in a subset of patients
- Biomarker analysis is ongoing to identify a molecular signature predictive of response
Clinical trial information: NCT03554317
Presented by: Mark C. Markowski, MD, PhD, The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins University, Baltimore, MD
Written by: Zachary Klaassen, MD, MSc – Urologic Oncologist, Assistant Professor of Urology, Georgia Cancer Center, Augusta University/Medical College of Georgia Twitter: @zklaassen_md at the 2021 American Society of Clinical Oncology (ASCO) Annual Meeting, Virtual Annual Meeting #ASCO21, June, 4-8, 2021