Dr Aggarwal on the Activity of BXCL701 Plus Pembrolizumab in SCNC mCRPC

Rahul Aggarwal, MD, associate director for Clinical Sciences, University of California, San Francisco (UCSF) Helen Diller Family Comprehensive Cancer Center, associate professor of hematology/oncology, UCSF, discusses key findings from a phase 2a trial (NCT03910660) evaluating the combination of BXCL701 and pembrolizumab (Keytruda) in patients with metastatic castration-resistant prostate cancer (mCRPC) with the small cell neuroendocrine cancer (SCNC) phenotype.

De novo and treatment-emergent SCNC mCRPC is associated with poor survival outcomes. BXCL701 operates by activating innate immunity and adaptive immunity leading to cancer cell death. The oral agent was evaluated at a twice-daily dose of 0.3 mg on days 1 through 14 of each 21-day cycle in combination with 200 mg of intravenous pembrolizumab given once every 3 weeks.

The primary end point of the trial was composite response rate, which comprised the objective response rate (ORR) in patients with measurable disease per RECIST v1.1 criteria, circulating tumor cell (CTC) conversion from at least 5/7.5 mL to less than 5/7.5 mL, and at least a 50% reduction in prostate-specific antigen (PSA50) from baseline. Among the 34 patients enrolled to the phase 2a cohort, 28 were evaluable and 25 were evaluable per RECIST v1.1 criteria. In this population, the composite response rate was 25% and the ORR was 20% (n = 5). Of the 5 responders, 4 had received prior platinum-based chemotherapy.

Notably, the median duration of response was more than 6 months (range, 1.3-17.4). Several additional responders were identified when investigators evaluated responses including CTC and PSA50, leading to a composite ORR of 25%, Aggarwal says. Investigators are encouraged by this efficacy signal in this heavily pretreated population with aggressive disease biology who had received a median of 3 (range, 1-8) prior lines of therapy. 

The safety profile of the combination was also evaluated, and proved to be manageable, Aggarwal says. Forty-seven percent (n = 16) and 3% (n = 1) of patients experienced a grade 3 and 5 treatment-emergent adverse effect (AE), respectively. The addition of pembrolizumab to BXCL701 did not result in a significant increase in immune-related AEs, with only 1 case of grade 3 colitis having occurred. Moreover, cytokine release, hypotension (grade 3, n = 2), and hypoxia were largely grade 1 and 2 and did not lead to treatment discontinuation, Aggarwal concludes.