Abstract 779TiP
Background
Adoptive T-cell therapy is an emerging strategy for solid tumors. Cancer cells frequently harbor driver-mutations in KRAS, TP53, and EGFR genes that can be targeted by T-cell receptors (TCRs). These neoepitopes are presented on the tumor cell surface by human leukocyte antigen (HLA) molecules to TCRs. We have developed, using non-viral Sleeping Beauty transposition, a library of TCRs able to target KRAS, TP53 and EGFR mutations for the treatment of solid tumors.
Trial design
This is a first in human phase 1/2 study of TCR-T cell therapy for patients with non-small cell lung, colorectal, endometrial, pancreatic, ovarian and bile duct cancer. Eligible patients have received and failed standard of care therapy for their tumor and have a mutation and HLA type match for a TCR in the library. After enrollment, patients will undergo leukapheresis, optional bridging therapy during manufacturing and lymphodepletion. The patient’s TCR-T cells will be administered to the patient intravenously following lymphodepletion. The starting dose will be 5 x 109 TCR-T cells (Dose Level 1 (DL1)), in the absence of a Dose Limiting Toxicity (DLT) escalating to 4 x 1010 (DL2) and 1 x 1011 (DL3) TCR-T cells, as safety allows. After completion of DL2, an analysis of TCR-T cell persistence will be performed, and, if deemed necessary, interleukin-2 (IL-2) will be administered after the TCR-T cell infusion. The primary objective of the phase I portion is to define the incidence of DLTs and the maximum tolerated dose (MTD) or recommended phase II dose (RP2D) of TCR-T cells administered without IL-2 (Arm A) or with IL-2 (Arm B). Clinical and radiologic responses will be assessed by RECIST (v1.1) at six and 12 weeks after TCR-T cell infusion and every 12 weeks thereafter for up to two years or until study discontinuation, whichever occurs first. All patients will continue to be monitored in a long-term follow-up protocol for up to 15 years post-TCR-T cell infusion. The study has been initiated and enrollment is ongoing.
Clinical trial identification
NCT05194735, 18 January 2022.
Editorial acknowledgement
Legal entity responsible for the study
Alaunos Therapeutics, Inc.
Funding
Alaunos Therapeutics, Inc.
Disclosure
M.V. Negrao: Financial Interests, Institutional, Funding: Mirati, Novartis, Checkmate, Alaunos Therapeutics, Inc., AstraZeneca, Pfizer, Genentech; Financial Interests, Personal, Advisory Board: Mirati, Merck/MSD, Genentech. A. Jazaeri: Financial Interests, Institutional, Funding: Bristol Myers Squibb, Iovance, AstraZeneca, Aravive, Merck, Eli Lilly, Pfizer; Financial Interests, Personal, Advisory Role: Gerson Lehrman Group, Guidepoint, Macrogenics, Bristol Myers Squibb, Agenus, Alkermes, Nurpobe, Avenge Bio, Blueprint, Green Fire Bio, Immune-Onc, TwoXAR; Financial Interests, Personal, Stocks/Shares: Avenge Bio. B. Johnson: Financial Interests, Personal, Advisory Role: Gritstone Bio, Incyte, Taiho Oncology, Insmed Oncology; Financial Interests, Institutional, Funding: Bristol Myers Squibb, Syntrix, Gateway for Cancer Research. D. Deniger: Financial Interests, Personal, Full or part-time Employment: Alaunos Therapeutics, Inc.; Financial Interests, Personal, Stocks/Shares: Alaunos Therapeutics, Inc.. M. Collinson-Pautz: Financial Interests, Personal, Full or part-time Employment: Alaunos Therapeutics, Inc.; Financial Interests, Personal, Stocks/Shares: Alaunos Therapeutics, Inc.. N. Demars: Financial Interests, Personal, Full or part-time Employment: Alaunos Therapeutics, Inc.; Financial Interests, Personal, Stocks/Shares: Alaunos Therapeutics, Inc., Abb AbbVie vie, Verastem Oncology. J. Heymach: Financial Interests, Personal, Advisory Role: AstraZeneca, EMD Serono, Boehringer-Ingelheim, Catalyst, Genentech, GlaxoSmithKline, Hengrui Therapeutics, Eli Lilly, Spectrum, Sanofi, Takeda, Mirati Therapeutics, Bristol Myers Squibb, BrightPath Biotherapeutics, Jannsen Global Services, Nexus Health Systems, Pneuma Respiratory, Kairos Venture Investments, Roche, Leads Biolabs, RefleXion, Chugai Pharmaceuticals; Financial Interests, Institutional, Funding: AstraZeneca, Bristol Myers Squibb, Spectrum, Takeda; Financial Interests, Institutional, Licensing Fees: Spectrum; Financial Interests, Institutional, Royalties: Spectrum. S. Kopetz: Financial Interests, Personal, Advisory Board: Roche, EMD Serono, Merck, Novartis, Lilly, Boehringer Ingelheim, Boston Biomedical, AstraZeneca, Bayer, Pierre Fabre, Redx Pharma, Ipsen, Daiichi, Natera, HalioDx, Jacobio, Pfizer, Repare Therapeutics, GlaxoSmithKline, Jazz, Xilis, AbbVie, Gilead, Mirati, Flame, Servier, Carina, Bicara, Endeavor BioMedicines, Numab Pharma, Janssen; Financial Interests, Personal, Research: Inivata; Financial Interests, Personal, Stocks/Shares: Lutris, Iylon, Navire, Xilis. All other authors have declared no conflicts of interest.