Ligand-inducible, prostate stem cell antigen (PSCA)-directed GoCAR-T™ cells in advanced solid tumors: Preliminary results from a dose escalation study

Background: PSCA, a cell surface protein, is upregulated in many solid tumors & correlates with disease stage. BPX601 is an autologous, T-cell product engineered to contain a PSCA-CD3ξ CAR plus the small molecule rimiducid (Rim)-inducible MyD88/CD40 costimulatory domain. BPX601 is optimized for antigen-directed & independent T cell activation, proliferation & persistence, potentially enhancing efficacy in solid tumors versus traditional CARs. This first-in-human study assesses the safety, biological & clinical activity of BPX601 plus Rim in select PSCA-positive cancers. Methods: NCT02744287 is a 2-part, open-label trial. Part 1 is an ongoing 3 + 3 cell dose escalation to identify the recommended BPX601 cell dose (Day 0) given in combination with a fixed, single Rim dose (0.4 mg/kg; Day 7). Eligibility criteria include previously treated metastatic pancreatic cancer (mPDAC) with measurable disease & positive PSCA expression. Results: Patients received only cyclophosphamide (CTX) for lymphodepletion (LD) within 3 days before BPX601 infusion. Nine adults have been treated across 3 cell dose levels (cells/kg): 1.25x106 (cells only), 1.25x106+Rim, 2.5x106+Rim. All had mPDAC with ≥2 prior therapies. Common AEs were fatigue & nausea. No DLTs, related SAEs, neurotoxicity or CRS events were reported. Rapid cell engraftment by Day 4 was observed in all patients. No evidence of LD with CTX was seen. Of 6 patients that received Rim: 2 had cell expansion 10- to 20-fold within 7 days; 2 had cell persistence >3 weeks; all had elevated serum cytokines (IP-10, TNFα) correlated with cell expansion. Best response after ≥1 scan was 4 SD ≥ 8 weeks with 2 minor responses (not confirmed; 1 patient had matched CA19-9 decrease) & 2 PD. Disease control without new therapy was 16 & >11 weeks (ongoing) in 1 & 3 patients, respectively. Conclusions: BPX601 with single-dose Rim was well-tolerated & resulted in enhanced T cell expansion & prolonged persistence in some patients despite lack of LD. Evidence of clinical benefit in this heavily pretreated mPDAC population was seen. Part 2 is planned to open soon & will include CTX/fludarabine LD to maximize engraftment as well as gastric & prostate cancers. Clinical trial identification: NCT02744287. Legal entity responsible for the study: Bellicum Pharmaceuticals. Funding: Bellicum Pharmaceuticals. Disclosure: C.R. Becerra: Hhonoraria: Taiho Pharmaceutical; Consulted: SOBI, Ipsen, Takeda, Bayer, Heron, Agenus; Speakers' bureau: Taiho Pharmaceutical, BMS, Merck Serono, Celgene. S. Paulson: Stock: Immunomedics, Juno, Alexion, Actinium; Consulted: Ipsen, Eisai, AAA, BMS, Merrimack, Taiho; Research funding: Taiho, Eli Lilly, AstraZeneca. G.A. Manji: Consultant: Ardelyx; Research funding: Plexxikon. O. Gardner: Employee of Bellicum Pharmaceuticals. A. Malankar, J. Shaw, D. Blass, B. Ballard, M. Anumula, A. Foster, J. Senesac, P. Woodard: Employee and stock owner: Bellicum Pharmaceuticals. X. Yi: Employee of Bellicum Pharmaceuticals. All other authors have declared no conflicts of interest.