The announcement comes in light of serious adverse events reported in the phase 1/2 clinical trials for BPX-601.
Another serious adverse event (AE) and dose-limiting toxicity is the latest blow to Bellicum Pharmaceuticals, who accounced it would halt progress on its clinical trials for its 2 GoCAR-T cell therapy candidates, BPX-601 and BPX-603.1
The news, which is just the latest in what has been a few rocky years for the biotech, has the company considering "strategic alternatives" for the path forward.
The most recent adverse event ocurred in a patient enrolled in the phase 1/2 clinical trial of BPX-601 (NCT02744287), which was being evaluated in previously treated patients with prostate stem cell antigen (PSCA)-positive, metastatic castration-resistant advanced prostate cancer. The patient experienced serious immune-mediated AEs that included grade 4 cytokine release syndrome (CRS), which was the second dose-limiting toxicity recorded in this dose escalation cohort.
Despite some observed efficacy, the company said "it does not have the necessary resources to optimize either the clinical dose and schedule of BPX-601 cells and the activating agent rimiducid, or the design of the BPX-601 cell construct to achieve a favorable risk/benefit profile."1
The clinical trial was examining the feasibility, safety, and clinical activity of PSCA-specific CAR-T cells co-administered with rimiducid. BPX-601 CAR-T cells are genetically engineered to express a CAR that targets the PSCA antigen and a signaling domain induced by rimiducid that acts as a 'go-switch' to activate and proliferate the cells. The target enrollment for the trial was 151 participants and it had an estimated primary completion date of October 2025.
Bellicum recently presented data from its phase 1 portion of the clinical trial at the 2023 American Society of Clinical Oncology Genitourinary Cancers Symposium.2
The 2 cohorts included 8 patients who received lymphodepleting chemotherapy followed by a single dose of 5x106 BPX-601 cells/kg and single (n=3) or weekly (n=5) doses of 0.4 mg/kg rimiducid beginning 7 days following the cell infusion. Following dosing, 50% of patients achieved a PSA50 response, and 3 of those patients achieved a PSA90 response. Among the 6 patients with soft tissue disease, 2 achieved a partial response. Among the 2 patients with bone-only disease, 1 achieved a PSA90 response with decreased enhancement of bone lesions on bone scan.2
The most common AE grade 3 or higher was myelosuppression. Two patients experienced grade 3 CRS, and 1 patient experienced grade 4 immune effector cell neurotoxicity syndrome with concurrent hemophagocytic lymphohistiocytosis, which did result in patient death.
The trial discontinuation also includes Bellicum's phase 1/2 clinical trial of BPX-603 (NCT04650451), which was investigating the safety, tolerability, and clinical activity of HER2-specific dual-switch CAR-T cells co-administered with rimiducid in patients with heavily pretreated, locally advanced or metastatic HER2-positive solid tumors.
Bellicum president and CEO, Rick Fair, spoke with CGTLive in 2021 about the company's next-generation CAR-T cell therapies, that included technologies that could act as a go-switch as well as a represser in the event of AEs. Watch the interview here.