1312MO - Combining the antigen-presenting cell activator eftilagimod alpha (soluble LAG-3) and pembrolizumab: Overall survival data from the first line non-small cell lung carcinoma (NSCLC) cohort of TACTI-002 (phase II)

Background

Eftilagimod alpha (E), a soluble LAG-3 protein, acts as an MHC class II agonist triggering activation of antigen-presenting cells (APC). Subsequently downstream T-cells (e.g. CD4/CD8) are recruited, possibly leading to stronger anti-tumor responses than with pembrolizumab (P) alone, especially in tumors non-overexpressing PD-L1. We hereby report initial overall survival (OS) results of the 1st line non-small cell lung carcinoma (NSCLC) cohort in TACTI-002.

Methods

Patients (pts) with measurable 1st line metastatic NSCLC unselected for PD-L1 were recruited. Primary endpoint (EP) was objective response rate (ORR) by iRECIST. Secondary EPs included OS, ORR by RECIST 1.1, duration of response (DoR), progression free survival (PFS), safety & biomarkers. Pts received 30 mg E SC q2w for 8 cycles (1 cycle= 3 weeks) & then q3w up to 1 yr with P 200 mg IV q3w up to 2 yrs. Imaging was done q9w & assessed by investigator. PD-L1 was centrally assessed (22C3). The study was powered (80%) with a 1-sided alpha of 2.5% to detect an ORR increase from 23% (historical results for P) to 35%.

Results

From Mar 2019-Nov 2021, 114 pts enrolled using modified Simon’s two-stage design. Median follow up of 20.4 mo (cut-off Mar 31, 2023). Median age was 67 (44–85) & 74% were male. ECOG PS was 0 & 1 in 37% & 63% of pts. Pts had squamous (35%) or non-squamous (63%) carcinoma. All PD-L1 subgroups were represented; 77.8% had TPS <50%. Pts received median 9 (1–35) P & 13 (1–22) E doses. Median (m) OS unselected for PD-L1 was 22.6 mo (52.6% events) & mDoR was 21.6 mo. Onset of responses was quick (median: 2.1 mo). Comparable results by RECIST 1.1. Efficacy by PD-L1 shown in the table. Safety was presented prior at SITC 2022.

Table: 1312MO

Conclusions

E + P shows encouraging OS results in line with excellent ORR, PFS and DOR in 1st line NSCLC overall and in all PD-L1 subgroups. This combination warrants further late-stage clinical investigation.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

Immutep S.A.

Funding

Immutep S.A.

Disclosure

E. Carcereny: Other, Consultant or Advisory Role: AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, MSD, Novartis, Roche, Takeda; Other, Speaking: AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, MSD, Novartis, Pfizer, Roche, Takeda; Other, Grant: Merk; Other, N/A: :Bristol Myers Squibb, Pfizer, Roche, Takeda. E. Felip: Financial Interests, Personal, Advisory Board: AbbVie, Amgen, AstraZeneca, Bayer, BeiGene, Boehringer Ingelheim, Bristol Myers Squibb, Eli Lilly, F. Hoffmann-La Roche, Gilead, GSK, Janssen, Merck Serono, Merck Sharp & Dohme, Novartis, Peptomyc, Regeneron, Sanofi, Takeda, Turning Point, Pfizer; Financial Interests, Personal, Invited Speaker: Amgen, Daiichi Sankyo, Genentech, Janssen, Medical Trends, Medscape, Merck Serono, PeerVoice, Pfizer, Sanofi, Takeda, Touch Oncology, AstraZeneca, Bristol Myers Squibb, Eli Lilly, F. Hoffmann-La Roche, Merck Sharp & Dohme; Financial Interests, Personal, Member of Board of Directors, Independent member: Grifols; Financial Interests, Institutional, Local PI, Clinical Trial: AstraZeneca AB, AbbVie, Amgen, Bayer Consumer Care AG, BeiGene, Boehringer Ingelheim GmbH, Bristol Myers Squibb International Corporation, Daiichi Sankyo Inc., Exelixis Inc., F. Hoffmann-La Roche Ltd., Genentech Inc., GSK Research and Development Limited, Janssen Cilag International NV, Merck Sharp & Dohme Corp, Merck KGAA, Mirati Therapeutics Inc, Novartis Pharmaceutica SA, Pfizer, Takeda Pharmaceuticals International; Non-Financial Interests, Leadership Role, President (2021-2023): SEOM (Sociedad Espanola de Oncologia Medica); Non-Financial Interests, Member, Member of Scientific Committee: ETOP (European Thoracic Oncology Platform); Non-Financial Interests, Member, Member of the Scientific Advisory Committee: CAC Hospital Universitari Parc Taulí. M. Majem: Financial Interests, Personal, Advisory Board: Amgen, Roche, AstraZeneca, Takeda, Janssen, Cassen Recordati, BMS; Financial Interests, Personal, Invited Speaker: Amgen, Roche, AstraZeneca, Pfizer, Takeda, Helsinn; Financial Interests, Institutional, Funding: BMS, AstraZeneca, Roche. T.D. Clay: Other, Honoraria: Specialised Therapeutics, Wiley, Lilly, Roche; Other, Stock and Other Ownership Interests: ClinicIQ; Other, Consulting or Advisory Role: AstraZeneca/MedImmune, Cipla, Foundation Medicine, Takeda, Merck KGaA, Merck/Pfizer, Ipsen; Other, Speakers' Bureau: AstraZeneca/MedImmune, MSD; Other, Travel, Accommodations, Expenses: AstraZeneca; Other, Research Funding: Exelixis, Immutep, Clovis Oncology, MSD Oncology, Pfizer, Amgen, Daiichi Sankyo/AstraZeneca, AbbVie, Janssen Oncology, BeiGene, Bayer, BridgeBio Pharma, BMS GmbH & Co. KG. J. Peguero: Other, Employment: Oncology Consultants; Other, Leadership: Director, Research Department. M.D. Forster: Other, Consulting or Advisory Role: Achilles Therapeutics; AstraZeneca; Bayer; Bristol Myers Squibb; Celgene; Guardant Health; Lilly; Merck Sharp & Dohme; Nanobiotix; Novartis; Oxford VacMedix; Pfizer; PharmaMar; Roche; Takeda; Other, Research Funding: AstraZeneca (Inst); Boehringer Ingelheim (Inst); Merck Serono (Inst); MSD Oncology (Inst); Other, Travel, Accommodations, Expenses: AstraZeneca; Bristol Myers Squibb; Celgene; Guardant Health; MSD Oncology; Roche. E. Kalinka: Financial Interests, Personal, Advisory Board, advisory board member, clinical trial and lectures honoraria: Bristol Myers Squibb; Financial Interests, Personal, Invited Speaker, lectures and clinical trial honoraria: Merck Sharp and Dohme; Financial Interests, Personal, Invited Speaker, lectures honoraria: GSK, Roche; Financial Interests, Personal, Invited Speaker, lectures honoraria and writing engagement: Sanofi, Regeneron; Financial Interests, Personal, Advisory Board, advisory role, clinical trials honoraria: AstraZeneca; Financial Interests, Personal, Invited Speaker: Gilead, Amgen; Financial Interests, Personal, Ownership Interest: Instytut MSF Sp zoo; Financial Interests, Personal and Institutional, Local PI: AstraZeneca, Roche, Bristol Myers Squibb, Gilead; Financial Interests, Personal, Local PI: Merck Sharp Dohme. G.M. Garcia Ledo: Other, Employment: Roche Farma; Other, Stock or Ownership: AbbVie; Other, Honoraria: BMS, MSD; Other, Consulting or Advisory Role: Natera. L. Vila Martinez: Other, Consulting or Advisory Role: Boehringer Ingelheim; Other, Honoraria: Roche, Bristol Myers Squibb/Pfizer, Pfizer, AstraZeneca Spain. W. Iams: Financial Interests, Personal, Advisory Board: Tempus, EMD Serono, Amgen, Sanofi, NovoCure, Genentech, AstraZeneca, Catalyst, Jazz Pharma, Elevation Oncology, Bristol Myers Squibb, Janssen, Takeda, Mirati, G1 Therapeutics. M.G. Krebs: Financial Interests, Personal, Advisory Board: Bayer, Roche, Janssen, Guardant Health; Financial Interests, Personal, Invited Speaker: Roche, Janssen; Financial Interests, Institutional, Advisory Board: AstraZeneca, Seattle Genetics; Financial Interests, Institutional, Coordinating PI: AstraZeneca, Carrick, Janssen, Pyramid Biosciences; Financial Interests, Institutional, Local PI: Blueprint, Astex, Bayer, BerGenBio, Immutep, Novartis, Nurix, Nuvalent, Roche, Seattle Genetics, Turning Point Therapeutics; Financial Interests, Institutional, Research Grant: Roche, Novartis; Other, Travel expenses for congress: Immutep, Janssen; Other, Travel expenses: Roche. K. Efthymiadis: Other, Honoraria: Amgen Hellas, MSD Greece, Pfizer Hellas, Roche Hellas; Other, Advisory Boards: Faran SA; Other, Travel & Educational Grants: Amgen Hellas, DEMO SA, Innovis Pharma SA, Merck Greece, MSD Greece, Novartis Greeve, Pfizer Hellas, Roche Hellas, Sanofi Greece, Specifar SA. C. Mueller: Other, Employment: Immutep; Other, Stock and Other Ownership Interests: Immutep. F. Triebel: Other, Employment: Immutep SAS; Other, Stock and Other Ownership Interests: Immutep Ltd; 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.