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Abstract
VP5-2024: Eftilagimod alpha (soluble LAG-3) and pembrolizumab in first-line recurrent or metastatic head and neck squamous cell carcinoma: Primary results from Cohort B (CPS less-than 1) of the TACTI-003 study
1 Oncology Dept., The Christie NHS Foundation Trust, Manchester, UK
2 Department of Otorhinolaryngology and Head & Neck Surgery, Ulm University Medical Center, Ulm, Germany
3 Oncology Dept., Copenhagen University Hospital, Copenhagen, Denmark
4 Medical Oncology Department, Arensia Exploratory Medicine – Institutul Oncologic, Cluj-Napoca, Romania
5 Oncology Dept., Vall d'Hebron University Hospital, Barcelona, Spain
6 Medical Oncology Department, Hospital Universitario Ramon y Cajal, Madrid, Spain
7 Medical Oncology, Nationales Centrum für Tumorerkrankungen Heidelberg, Heidelberg, Germany
8 Oncology Dept., AZ Sint-Jan Brugge-Oostende AV, Brugge, Belgium
9 Oncology Dept., UCL - University College London - The Development Education Research Centre (DERC), London, UK
10 Oncology Dept., Hospital Universitario Lucus Augusti (HULA), Lugo, Spain
11 Oncology Dept., Nottingham University Hospital NHS Trust, Nottingham, UK
12 Clinical Development, Immutep GmbH - Berlin, Berlin, Germany
13 Clinical Research, Immutep GmbH, Paris, France
Published: July 11, 2024
DOI: https://doi.org/10.1016/j.annonc.2024.06.012 Download PDF
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. Previous 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) resulted in promising response rates across all PD-L1 strata (TACTI-002; NCT03625323). We report results from the primary analysis of the first-line (1L) R/M HNSCC PD-L1 CPS negative Cohort B of the TACTI-003 study.
Methods
Patients (pts) with 1L[SC1] R/M HNSCC[FV2] , measurable disease and PD-L1 CPS <1 were recruited. PD-L1 was prospectively assessed (Dako assay; 22C3). Primary endpoint (EP) is objective response rate (ORR) by RECIST 1.1 in evaluable pts (≥1 post-baseline CT scan) by investigator assessment. Secondary EPs are duration of response, progression free survival, overall survival, safety & biomarkers. Pts received 30 mg E SC q2w for 24 weeks then q3w up to 2 yrs with P 400 mg IV q6w up to 2 yrs. Imaging was performed q9w.
Results
From Apr 2022-Oct 2023, 33 pts enrolled, including 31 evaluable pts. Median age was 64 yrs (range: 23–83) & 74% were male. Primary sites were hypopharynx (3%), larynx (32%), oral cavity (29%) &[SC1] oropharynx (36%). ECOG PS was 0 in 32% & 1 in 68% of pts. By data cutoff (Mar 13, 2024), pts received median[SC2] 4 (1–12) P & 12 (1–27) E doses. 7% of pts had Grade ≥3 adverse reactions (immune thrombocytopenia; G4 & [SC3] immune-induced hepatitis; G3). ORR (unconfirmed) per RECIST 1.1 was 36% & DCR was 58% (Table), including 10% complete responses.
Best overall response by RECIST 1.1, |
N=31; n (%) |
CR* |
3 (9.7) |
PR* |
8 (22.6) |
SD |
7 (25.8) |
PD |
13 (41.9) |
| |
ORR* (95% CI) |
35.5 (9.2–54.6) |
DCR (95% CI) |
58.1 (39.1–75.5) |
*unconfirmed; 9/11 responses have been confirmed by data cut-off | |
Conclusions
E + P is very well tolerated & shows encouraging ORR in CPS negative pts who typically do not respond to P alone. Further late-stage clinical investigation is warranted for E+P in this disease setting.
Clinical trial identification
IMP321-P022 (Sponsor code), Keynote-PNC-34 (MSD code), 2021-000055-39 (EudraCT) and NCT04811027 (ClinicalTrials.gov).
Legal entity responsible for the study
Immutep S.A.S.
Funding
Immutep S.A.S.
Disclosure
R. Metcalf: Financial Interests, Personal and Institutional, Advisory Board: Ayala, Bayer, Aptus Clinical, PCI Biotech, Oxsonics, Roche, Achilles Therapeutics; Other, Personal and Institutional, Other: BMS, MSD, Sanofi.
S. Laban: Financial Interests, Personal and Institutional, Advisory Board: Merck Sharp & Dohme, Bristol Myers Squibb; Other, Personal and Institutional, Invited Speaker: Merck Sharp & Dohme, Bristol Myers Squibb; Other, Personal and Institutional, Principal Investigator: Merck Sharp & Dohme, Bristol Myers Squibb, Immutep, ISA-Pharmaceuticals.
C.A. Kristensen: Financial Interests, Personal and Institutional, Advisory Board: MSD EMEAC HNSCC; Other, Personal and Institutional, Other, Teaching honoraria & travel grant: MSD MSD Denmark, Merck A/S.
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, MagnaPharm; Financial Interests, Personal, Other, Principal Investigator: Tesaro, Mirati, AbbVie, Celltrion; Financial Interests, Personal, Other, Principal Investigator: BeiGene.
I. Braña: Financial Interests, Personal, Advisory Board: Achilles Therapeutics, Bristol Myers Squibb, eTheRNA Immunotherapies, Merck Sharp & Dohme (MSD), Rakuten Pharma, PCI Biotech, Guidepoint; Financial Interests, Personal, Invited Speaker: Bristol Myers Squibb, Merck Serono, Merck Sharp & Dohme (MSD), Roche; Financial Interests, Personal, Expert Testimony: Cancer Expert Now, Merck Serono, Boehringer Ingelheim; Financial Interests, Institutional, Invited Speaker: 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.
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, Invited Speaker: Roche, Oxford VaxMedix, Apollomics, Takeda, Ellipsis, Moderna, Exsciencia, ALX Oncology, GenMab, Janssen; Financial Interests, Personal and Institutional, Invited Speaker, Presented data at ESMO-IO 2022: Achilles; Financial Interests, Institutional, Invited Speaker, Presented Data at SITC 2023: Immutep; Non-Financial Interests, Personal, Advisory Role, Chair of Scientific Advisory Group: Ruth Strauss Foundation.
All other authors have declared no conflicts of interest.