BPX-601

Notably, radionuclide drug conjugates (RDC), specifically 177Lu/111In-J591 and 225Ac-J591, exhibited enhanced therapeutic efficacy in treating patients with CRPC. Furthermore, promising treatment approaches for CRPC included dual anti-cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) and anti-programmed death-1 (PD-1) blockade in rare tumors (DART)-Lorigerlimab, prostate stem cell antigen (PSCA)-directed chimeric antigen receptor (CAR)-T cell immunotherapy-BPX-601, and protein kinase inhibitor (AKTi)-CAPltello-280. We have summarized the latest CRPC treatment strategies presented at the 2023 ASCO-GU Cancers Symposium, along with recent advances in CRPC clinical trials.

BPX-601, a PSCA-directed GoCAR-T cell product, has preliminary evidence of biologic activity with toxicity characteristic of previously reported CAR-T studies. Markers of rimiducid-induced GoCAR-T cell activation and proliferation were observed. Exploration of escalating weekly rimiducid doses > 0.4 mg/kg and BPX-601 cell doses is planned.

Our previously published results demonstrated that iMC costimulation, activated by the small molecule dimerizer, rimiducid (Rim), enhanced CAR-T proliferation and anti-tumor efficacy. These results predict that GoCAR-T activation with Rim will convert TAMs within a solid tumor microenvironment from T cell inhibitors to tumor-caustic agents.

Previously, we described a GoCAR platform that uses a rimiducid (Rim)-inducible cytoplasmic costimulatory switch, inducible MyD88/CD40 (iMC), to drive the proliferation, survival, cytokine release and anti-tumor efficacy of T cells expressing a 1st generation CAR. iMC activation via Rim infusion provides on-demand control of CAR-T cell signaling to resist CAR-T cell exhaustion, enhance persistence, produce cytokines, and induce antitumor toxicity against solid tumors.

BPX-601 is an autologous GOCAR-T cell therapy engineered to express a PSCA-CD3ζ CAR and the MyD88/CD40 (iMC) costimulatory domain activated by rimiducid (Rim), designed to boost CAR-T performance in solid tumors. BPX-601 GOCAR-T cells expand and persist in patients with PSCA+ metastatic pancreatic cancer and infiltrate metastatic lesions. A peripheral cytokine signature was observed following BPX-601 infusion. Select cytokines were enhanced after GOCAR-T cell activation and may correlate with clinical response.