806MO - Phase Ib study of NT-I7 (efineptakin alfa), a long-acting IL-7, post-CD19-directed CAR T cell therapy in diffuse large B-cell lymphoma (DLBCL)

Background

Chimeric antigen receptor T (CAR T) cell efficacy depends on expansion and persistence. NT-I7 (efineptakin alfa), a long-acting interleukin 7 (IL-7), expands T cells in peripheral blood and tumors. We investigate whether NT-I7 can safely induce CAR T expansion, to improve clinical outcomes.

Methods

Phase 1b dose escalation of NT-I7 administered on day (d)21 post CAR T infusion, at 7 dose levels (DL1-7) from 60-720 μg/kg. DL1-2 enrolled 1 patient (pt) each; DL3-7 follow a 3+3 design. Primary objectives are to assess safety and find maximum tolerated dose and/or recommended phase 2 dose for NT-I7 with this regimen. Secondary objectives include exploring antitumor activity and NT-I7 effects on CAR T expansion. Fresh blood CAR T percentages were quantified in a flow cytometry validated analysis; absolute numbers calculated based on complete blood count. CAR T stemness (CD45RA+CCR7+CD95+) was determined in cryopreserved samples by flow cytometry.

Results

As of 11Jan2024, DL1-5 were closed. In 11 pts, mean age was 67 years. At diagnosis, lymphoma stage was III-IV in 9/11 pts. 6/11 (54.5%) pts had 10 Grade 1-2 NT-I7-related adverse events, most commonly injection site erythema and injection site swelling (2 subjects each, 18.2%). No cytokine release syndrome (CRS) or immune effector associated neurotoxicity (ICANS) were reported after NT-I7 administration. Median overall survival was 363 d; median progression free survival was 92 d. 9/11 pts (81.1%) had objective response, and 7/11 (63.6%) had complete response. NT-I7 increased lymphocyte counts, boosting immune reconstitution. While NT-I7 was dosed at d21 (CAR T contraction phase), a single dose of NT-I7 at each DL re-expanded the CAR T population. While CD4 and CD8 CAR T cell distribution remained unchanged, NT-I7 significantly increased CAR T stemness.

Conclusions

Interim data from this ongoing dose escalation indicates that NT-I7 treatment post CAR T is safe and well tolerated in pts with advanced DLBCL up to 480 μg/kg (DL5). NT-I7 enhances all CAR T factors associated with efficacy - expansion, persistence and stemness - when dosed at day 21 after CAR T infusion. NT-I7 administration earlier than d21 post-CAR T infusion may prove even more clinically relevant.

Clinical trial identification

NCT05075603, 13-Oct-2021 (first posted).

Editorial acknowledgement

Allison Bierly, PhD, an employee of NeoImmuneTech, Inc., provided editorial support.

Legal entity responsible for the study

NeoImmuneTech, Inc.

Funding

NeoImmuneTech, Inc.

Disclosure

A. Ghobadi: Financial Interests, Personal, Advisory Board: Celgene/Bristol Myers Squibb, Wugen Inc., Atara, Amgen, Kite, a Gilead Company, CARGO Therapeutics, Novartis; Financial Interests, Institutional, Research Funding: Wugen Inc., Atara, Amgen, Kite, a Gilead Company, Secura Bio, Genentech, CARGO Therapeutics. L.E. Budde: Financial Interests, Personal, Advisory Board: ADC Therapeutics, Roche, Genentech, Kite, Gilead; Financial Interests, Institutional, Research Funding: Merck, Amgen, AstraZeneca, Mustang Therapeutics. K. Stermer: Financial Interests, Personal, Full or part-time Employment: NeoImmuneTech, Inc.; Financial Interests, Personal, Stocks/Shares: NeoImmuneTech, Inc. S. Ferrando-Martinez: Financial Interests, Personal, Full or part-time Employment: NeoImmuneTech, Inc. B.H. Lee: Financial Interests, Personal, Officer, FTE: NeoImmuneTech, Inc.; Financial Interests, Personal, Stocks/Shares: NeoImmuneTech, Inc. J. DiPersio: Financial Interests, Institutional, Research Funding: NeoImmuneTech, Inc., Macrogenics, BioLineRx, Ltd., Wugen, Incyte; Financial Interests, Personal, Licencing Fees or royalty for IP: CAR-T Product with Washington University and Wugen, VLA-4 Inhibitor with Washington University and Magenta Therapeutics; Financial Interests, Personal, Member of Board of Directors: Hc Bioscience, Inc., RiverVest Venture Partners, Magenta Therapeutics; Financial Interests, Personal, Speaker, Consultant, Advisor: RiverVest Venture Partners, Incyte; Financial Interests, Personal, Stocks/Shares: Wugen, Magenta Therapeutics.