LBA35 - Primary results from TACTI-003: A randomized phase IIb trial comparing eftilagimod alpha (soluble LAG-3) plus pembrolizumab versus pembrolizumab alone in first-line recurrent or metastatic head and neck squamous cell carcinoma with CPS ≥1

Background

Eftilagimod alpha (E) is a soluble LAG-3 protein binding to a subset of MHC class II molecules to mediate antigen-presenting cell (APC) activation & T-cell (CD4/CD8) recruitment/activation. Previous results from a phase II study (NCT03625323) of E plus pembrolizumab (P) showed a promising objective response rate (ORR) in second line head and neck squamous cell carcinoma (HNSCC). An encouraging ORR of 35.5% was recently reported in first line (1L) recurrent or metastatic (R/M) HNSCC patients (pts) with CPS <1 treated with E+P (Cohort B; NCT04811027). We report primary results from the randomized Cohort A of TACTI-003 in 1L R/M HNSCC expressing PD-L1 (CPS ≥1).

Methods

Pts with measurable disease and CPS ≥1 were randomized to receive either E + P or P alone (E: 30 mg SC q2w for 24 weeks then q3w up to 2 yrs. P: 400 mg IV q6w up to 2 yrs). Primary endpoint (EP) was ORR by RECIST 1.1 in evaluable pts (≥1 post-baseline scan). Secondary EPs are ORR by iRECIST, duration of response, progression free survival, overall survival, safety & biomarkers. Imaging was done q9w & PD-L1 was prospectively assessed (22C3).

Results

138 pts enrolled between Oct 2021–Oct 2023, resulting in 118 evaluable, 58 in E+P and 60 in P. Median age was 65 yrs (range: 38–87) & 74.6% were male. Primary tumor sites were hypopharynx (16.1%), larynx (17.8%), oral cavity (28.8%) & oropharynx (37.3%). ECOG PS was 0 in 43.2% & 1 in 56.8% of pts. 52.5% had CPS 1–19 and 47.5% had CPS ≥20. By data cutoff (Mar 11, 2024), 7 (E+P) vs 8 pts (P) experienced Grade ≥3 treatment emergent adverse reactions (TEARs). 3 pts per arm discontinued study treatment due to TEARs. E+P resulted in numerically higher ORR & DCR compared to P only in CPS ≥1 pts, with the largest differential in CPS ≥20. Table: LBA35

Conclusions

E+P is well tolerated with positive efficacy data and should be investigated further in HNSCC.

Clinical trial identification

IMP321-P022 (Sponsorcode); Keynote-PNC-34 (MSDcode); 2021-000055-39 (EudraCT); NCT04811027 (ClinicalTrials.gov).

Editorial acknowledgement

Legal entity responsible for the study

Immutep S.A.S.

Funding

Immutep S.A.S.

Disclosure

R. Metcalf: Financial Interests, Personal, Advisory Board: Ayala, Bayer, Aptus Clinical, PCI Biotech, Oxsonics, Roche, Achilles Therapeutics; Financial Interests, Personal, Other, Honoraria: BMS, MSD, Sanofi. I. Braña: Financial Interests, Personal, Advisory Board: Achilles Therapeutics, Bristol Myers Squibb, Cancer Expert Now, eTheRNA Immunotherapies, Merck Serono, Merck Sharp & Dohme (MSD), Rakuten Pharma, Boehringer Ingelheim, PCI Biotech, Guidepoint; Financial Interests, Personal, Invited Speaker: Bristol Myers Squibb, Merck Serono, Merck Sharp & Dohme (MSD), Roche; Financial Interests, Institutional, Local PI: AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, GSK, Gliknik, Incyte, ISA pharmaceuticals, Janssen Oncology, Kura, Merck Serono, Debiopharm, Merck Sharp & Dohme (MSD), Nanobiotix, Novartis, Northern Biologics, Regeneron, Pfizer, Seattle Genetics, Shattuck Labs, VCN Biosciences, Roche, Immutep, MacroGenics, Sanofi, PharmaMar, Odonate Therapeutics, Bicycle Therapeutics, Dragonfly therapeutics, Gilead; Non-Financial Interests, Principal Investigator, Basket of baskets: Cancer Core Europe; Non-Financial Interests, Member, Head and Neck Group: EORTC; Non-Financial Interests, Member: SEOM, ASCO. S. Laban: Financial Interests, Institutional, Advisory Board: Merck Sharp & Dohme, Bristol Myers Squibb, Sanofi Genzyme; Financial Interests, Institutional, Invited Speaker: Merck Sharp & Dohme, Bristol Myers Squibb; Financial Interests, Personal, Advisory Board: Merck Sharp & Dohme; Financial Interests, Institutional, Other, patent for an oropharyngeal cancer multi-peptide vaccine (pending): filed patent (patent pending); Non-Financial Interests, Principal Investigator: Immutep, Merck Sharp & Dohme, Bristol Myers Squibb, ISA-Pharmaceuticals. A. Soria Rivas: Financial Interests, Personal, Advisory Board: Novartis Pharma, Bristol Myers Squibb, Merck Sharp & Dhome, Sanofi Aventis, Pierre Fabre, Merck Serono; Financial Interests, Personal, Invited Speaker: Bristol Myers Squibb, Novartis Pharma, Merck Sharp & Dhome, Merck Serono, Sanofi Aventis, Pierre Fabre. J. Rubio Casadevall: Other, Personal, Advisory Board: Lilly, Merck, Novartis, Sanofi. S. Kasper-Virchow: Financial Interests, Personal, Invited Speaker: BMS, MSD, Lilly, Merck, Amgen, Servier, Daiichi Sankyo, Pierre-Fabre; Financial Interests, Personal, Advisory Board: GSK, Novartis, AstraZeneca; Financial Interests, Personal, Research Grant, IMAGINE Trial: BMS; Financial Interests, Personal, Coordinating PI, PIONEER and ANTONIO: Roche; Financial Interests, Personal, Coordinating PI, RAMTAS: Lilly; Non-Financial Interests, Advisory Role: BMS, MSD, Amgen, Merck, Lilly, Servier, AstraZeneca; Non-Financial Interests, Member: ASCO, DGHO. F.D. Vogl: Other, Consultancy honoraria: Cellestia Biotech; Other, Employee; officer: Immutep; Cellestia Biotech; Other, Stocks or ownership: Amgen, Cellestia Biotech. C. Mueller: Other, Employment: Immutep; Other, Stocks and other ownership: Immutep Ltd. F. Triebel: Other, Employment: Immutep; Other, Stock and Other Ownership Interests: Immutep ; Other, Patents, Royalties, Other Intellectual Property: Being an inventor on patents on LAG-3 owned by Immutep SAS. All other authors have declared no conflicts of interest.