152P - TACTI-003 Cohort B: Eftilagimod alpha (Soluble LAG-3) and pembrolizumab in first-line recurrent or metastatic head & neck squamous cell carcinoma with PD-L1 negative

Background

Eftilagimod alpha (E) is a soluble LAG-3 protein that binds to a subset of MHC class II molecules to mediate antigen presenting cell activation & T-cell (CD4/CD8) recruitment/activation. Prior results from a phase II study of E plus pembrolizumab (P) as a second-line therapy in recurrent or metastatic (R/M) head and neck squamous cell carcinoma (HNSCC) led to promising response rates across all PD-L1 strata (TACTI-002; NCT03625323). We report updated results from the PD-L1 negative (CPS <1) Cohort B of the TACTI-003 study in 1^st line HNSCC (NCT04811027).

Methods

Patients (pts) with first-line R/M HNSCC, measurable disease and PD-L1 CPS <1 were recruited. PD-L1 was prospectively assessed (Dako assay; 22C3). The primary endpoint (EP) was objective response rate (ORR) by RECIST 1.1 in evaluable pts (≥1 post-baseline CT scan) by investigator assessment. Secondary EPs were ORR by iRECIST, progression free survival (PFS), duration of response (DoR), overall survival (OS), safety & biomarkers. Pts received 30 mg E s.c. q2w for 24 weeks then q3w up to 2 yrs with P 400 mg i.v. q6w up to 2 yrs. Imaging was performed q9w and assessed locally.

Results

From Apr 2022–Oct 2023, 33 pts were enrolled and thereof 31 were evaluable. Median age was 64 yrs (range: 23–83) & 74% were male. Primary tumour sites were hypopharynx (3%), larynx (32%), oral cavity (29%) & oropharynx (36%). Of the pts with primary oropharyngeal tumours, 36% were HPV positive and 64% were negative. ECOG PS was 0 in 32% & 1 in 68% of pts. Safety results were presented at the July 2024 ESMO Virtual Plenary with no new safety signals. By updated data cutoff (Aug 31, 2024), ORR per RECIST 1.1 was 36% & DCR was 58% and 39 % and 65 % acc to iRECIST, respectively. Table: 152P

*10/11 responses confirmed by RECIST 1.1 and 11/12 by iRECIST.

Conclusions

E + P leads to high ORR and DCR in a CPS negative pt population, which is typically unresponsive to P alone. Further late-stage clinical investigation is warranted for E+P in this disease setting.

Clinical trial identification

IMP321-P022 (Sponsorcode), Keynote-PNC-34 (MSDcode), 2021-000055-39 (EudraCT) and NCT04811027.

Legal entity responsible for the study

Immutep S.A.S.

Funding

Immutep S.A.S.

Disclosure

M.D. Forster: Financial Interests, Personal, Advisory Board: Bayer, Merck, MSD, Roche, Takeda, ultrahuman, Transgene, Immunotep, Amgen, BMS, EQRx, GSK, Janssen, Oxford Vacmedix, PharmaMar, Regeneron, Syncorp; Financial Interests, Institutional, Research Grant: AstraZeneca, Boehringer Ingelheim, MSD, Merck; Financial Interests, Institutional, Local PI: Roche, Apollomics, Takeda, Ellipsis, Moderna, Exsciencia, ALXOncology, GenMab; Financial Interests, Personal and Institutional, Coordinating PI, Presented data at ESMO-IO 2022: Achilles; Financial Interests, Institutional, Coordinating PI: Oxford VaxMedix, Janssen; Financial Interests, Institutional, Coordinating PI, Presented Data at SITC 2023: Immutep; Non-Financial Interests, Personal, Advisory Role, Chair of Scientific Advisory Group: Ruth Strauss Foundation. S. Laban: Financial Interests, Personal, Advisory Board: Merck Sharp & Dohme, Bristol Myers Squibb; Financial Interests, Personal, Invited Speaker: Merck Sharp & Dohme, Bristol Myers Squibb; Financial Interests, Personal, Principal Investigator: Immutep, Merck Sharp & Dohme, Bristol Myers Squibb, ISA-Pharmaceuticals. R. Metcalf: Financial Interests, Personal, Advisory Board: Ayala, Bayer, Aptus clinical, PCI Biotech, Oxsonics, Roche, Achilles Therapeutics; Financial Interests, Personal, Other: BMS, MSD, Sanofi. T. Ciuleanu: Financial Interests, Institutional, Other, Principal Investigator: Jounce Therapeutics; Financial Interests, Personal, Other, speaker, consultancy, advisory board, principal investigator: Roche, Merck Sharp & Dohme, AstraZeneca, Pfizer, Bristol Myers Squibb, Eli Lilly, Amgen, Astellas, Novartis, Takeda; Financial Interests, Personal, Other, speaker, consultancy, advisory board: Janssen, Sandoz, Sanofi, Accord, Magna Pharm; Financial Interests, Personal, Other, Principal Investigator: Tesaro, Mirati, AbbVie, Celltrion; Financial Interests, Personal, Other, Principal Investigator: BeiGene. C.A. Kristensen: Financial Interests, Personal, Advisory Board: MSD EMEAC HNSCC; Financial Interests, Personal, Other, Travel Grant: MSD Denmark, Merck A/S; Financial Interests, Personal, Other, Teaching honoraria: MSD Denmark, Merck A/S. 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, Personal, Principal Investigator, Basket of baskets: Cancer Core Europe; Non-Financial Interests, Personal, Member, Head and Neck Group: EORTC; Non-Financial Interests, Personal, Member: SEOM, ASCO. A. Soria Rivas: Financial Interests, Personal, Advisory Board: Novartis Pharma, Bristol Myers Squibb, Merck Sharp & Dohme, Sanofi Aventis, Pierre Fabre, Merck Serono; Financial Interests, Personal, Invited Speaker: Bristol Myers Squibb, Novartis Pharma, Merck Sharp & Dohme, Merck Serono, Sanofi Aventis, Pierre Fabre. All other authors have declared no conflicts of interest.