50P - Phase I trial of P-MUC1C-ALLO1 allogeneic CAR-T cells in advanced epithelial malignancies

Background

Epithelial cells express MUC1, with its oncogenic subunit, MUC1-C, enriched on malignant cells. P-MUC1C-ALLO1 is an allogeneic MUC1-C targeting CAR-T produced from healthy donor T-cells via non-viral transposon-based integration to express a human scFv anti-MUC1-C CAR to produce a T stem cell memory-rich product. The Cas CLOVER™ gene editing system is used to ablate the TCR beta chain and partially knock out the beta-2 microglobulin gene to prevent graft vs host disease and attenuate host vs graft respectively. P-MUC1C-ALLO1 is available “off-the-shelf” and is being evaluated in a phase 1 clinical trial (NCT05239143) in advanced epithelial malignancy patients (pts).

Methods

The trial utilizes 3+3 dose escalation to test P-MUC1C-ALLO1 doses from 0.75 to 15 × 10⁶ cells/kg and several lymphodepletion (LD) regimens that explore increasing doses of cyclophosphamide (cy) combined with fludarabine (flu). Objectives include defining Maximal Tolerated Dose, safety and efficacy.

Results

To date, 41 pts (median age 56 (29-73) years), median of 5 (1-20) prior therapies, received P-MUC1C-ALLO1 (0.75 × 10⁶ – 6.0 × 10⁶ cells/kg); two pts were retreated. No pt required bridging therapy; median time from enrollment to the start of protocol therapy was just 9 (2-20) days. Patients with the following malignancies have enrolled: breast (n=8), pancreatic (n=7), colorectal (n=12), uterine (n=2), ovarian (n=2), appendiceal (n=4), and other (n=6). Most adverse events (AEs) were LD or cancer related. The most common Grade ≥3 treatment emergent AEs were neutropenia (88%), leukopenia (47%), lymphopenia (33%), anemia (19%), thrombocytopenia (16%), and febrile neutropenia (12%). All grade treatment related AEs included CRS (16%), increased AST (12%), increased alkaline phosphatase (12%), and pyrexia (12%). No ICANS or GvHD were reported. Two patients who received 2 × 10⁶ P-MUC1C-ALLO1 cells/kg following LD with cy 1000 mg/m2 and flu 30 mg/m² × 3 days developed G3 CRS (DLT). No DLTs were reported in any other study arms.

Conclusions

P-MUC1C-ALLO1 is an “off-the-shelf” allogeneic CAR-T with a manageable toxicity profile in heavily pre-treated solid tumor patients. Updated safety and efficacy data will be presented at the conference.

Clinical trial identification

NCT05239143.

Legal entity responsible for the study

Poseida Therapeutics Inc.

Funding

Poseida Therapeutics.

Disclosure

D. Oh: Financial Interests, Personal, Advisory Board, Licensing fees relating to a patent on the use of T cell receptor sequencing as a predictive marker of immune-related adverse events with immunotherapy: Regents of the University of California; Financial Interests, Personal and Institutional, Local PI, Research support: Merck Sharp & Dohme, Nutcracker Therapeutics; Financial Interests, Institutional, Local PI, Research support: PACT Pharma, Poseida Therapeutics, TCR2 Therapeutics, Allogene Therapeutics; Financial Interests, Personal and Institutional, Local PI, Research support, travel & accommodations for Roche-sponsored research meeting: Roche/Genentech; Financial Interests, Personal, Other, Consulting: Revelation Partners; Non-Financial Interests, Institutional, Proprietary Information, Proprietary materials for laboratory experimentation: Nutcracker Therapeutics, 3T Biosciences. P. Vu, J.C. Baranda, J. Henry: Financial Interests, Institutional, Local PI: Poseida Therapeutics. I.I. Rodriguez Rivera: Financial Interests, Institutional, Local PI: Poseida Therapeutics. J.D. Eskew: Financial Interests, Personal, Full or part-time Employment: Poseida Therapeutics; Financial Interests, Personal, Stocks/Shares: Poseida Therapeutics. R. Belani, M. Martinez-Prieto, J. McCaigue, H. Namini, S. Haag, D. Bauer, C. Martin, C. Gregovics, A. Murphy, J. Coronella: Financial Interests, Personal, Full or part-time Employment: Poseida Therapeutics; Financial Interests, Personal, Stocks/Shares: Poseida Therapeutics . D.J. Shedlock: Financial Interests, Personal, Full or part-time Employment: Poseida Therapeutics ; Financial Interests, Personal, Stocks/Shares: Poseida Therapeutics; Financial Interests, Personal, Leadership Role: Poseida Therapeutics. E.E. Dumbrava: Financial Interests, Institutional, Other, Research/grant funding: Bayer HealthCare Pharmaceuticals, Immunocore Ltd, Amgen, Aileron Therapeutics, Compugen Ltd, Gilead, Bolt Therapeutics, Aprea Therapeutics, Bellicum, PMV Pharma, Triumvira, Seagen Inc., Mereo BioPharma 5 Inc., Sanofi, Rain Oncology, Astex Therapeutics, Sotio, Mersana Therapeutics, Poseida, Boehringer Ingelheim; Financial Interests, Personal, Invited Speaker: PMV Pharma; Financial Interests, Personal, Advisory Board: Bolt Therapeutics, Mersana Therapeutics, Orum Therapeutics, Summit Therapeutics.