11MO - Final data from a phase II study (TACTI-002) of eftilagimod alpha (soluble LAG-3) and pembrolizumab in 2nd-line metastatic NSCLC pts resistant to PD-1/PD-L1 inhibitors

Background

Eftilagimod alpha (E), a soluble LAG-3 protein, acts as an MHC class II agonist triggering activation of antigen-presenting cells (APC) and CD8 T-cells. Stimulating APCs and subsequent T cell recruitment with efti may revert PD-1/PD-L1 resistance. We report updated results from Part B of the TACTI-002 trial: 2^nd-line PD-1/PD-L1-resistant non-small cell lung carcinoma (NSCLC) patients (pts) treated with efti plus pembrolizumab (P).

Methods

Pts with metastatic NSCLC unselected for PD-L1 expression and with resistance to 1^st-line PD-1/PD-L1 inhibitor-based therapy were enrolled. Primary endpoint (EP) was objective response rate (ORR) by iRECIST. Secondary EPs were disease control rate (DCR), progression-free survival (PFS), overall survival (OS) and tolerability. Post-hoc analysis included tumor growth kinetics (TGK). Pts received E (30 mg SC Q2W for eight 3-week cycles and then Q3W up to 1 yr) with P (200 mg IV Q3W up to 2 yrs). Imaging was performed every 9 wks and locally evaluated. PD-L1 TPS was assessed using IHC 22C3 kit.

Results

36 pts enrolled between Apr 2019 – Aug 2021. Median age was 67 yrs (46–84) and 61% were male. ECOG PS was 0 and 1 in 33% and 67% of pts. Pts had squamous (19%) and non-squamous (78%) histology. All PD-L1 subgroups were included: 39% with TPS <1% and 82% with TPS <50%. Pts received a PD-1/PD-L1 inhibitor alone (28%) or combined with platinum-based chemo (72%) as 1^st-line therapy. Pts received median of 5 (2–35) P and 7 (2–22) E doses. ORR and DCR (iRECIST) was 8.3% and 33%. All PRs were confirmed with pts on study 19+ m. TGK analysis was performed on pts with data available on the same lesions from prior failed therapy and post-baseline. Vast majority (83%) of pts showed deceleration (50%) in tumor growth or shrinkage (33%) of target lesions. Median PFS was 2.1 months with PFS rate at 6 m of 25%. 44% were alive at 12 m with median OS of 9.7 m. Most common (>15%) adverse events were decreased appetite (33%), dyspnea (31%), cough (28%), asthenia (22%), fatigue (19%), arthralgia (17%) and weight decreased (17%).

Conclusions

Efti + pembrolizumab is safe and shows encouraging signs of antitumor activity in NSCLC pts resistant to PD-1/PD-L1 inhibitors, warranting further investigation.

Clinical trial identification

EudraCT 2018-001994-25, NCT03625323.

Legal entity responsible for the study

Immutep S.A.

Funding

Immutep S.A.

Disclosure

M. Majem: Other, Institutional, Other, Consulting or Advisory Role: AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, Helsinn Therapeutics, Eli Lilly, Merck Sharp & Dohme, Novartis, Pfizer, Roche, Takeda, Tesaro, Sanofi, Janssen, Amgen; Other, Institutional, Funding: BMS, AstraZeneca, Roche (ALL Inst); Other, Institutional, Other, Travel, Accommodations, Expenses: AstraZeneca, Roche. M.D. Forster: Financial Interests, Personal, Advisory Board: Bayer, Merck, MSD, Novartis, Roche, Takeda, Ultrahuman, Transgene, Ixogen, Immunotep; Financial Interests, Institutional, Research Grant: AstraZeneca, Boehringer Ingelheim, MSD, Merck; Financial Interests, Institutional, Invited Speaker: StarPharma, Roche. M.G. Krebs: Financial Interests, Personal, Advisory Board: Bayer, Roche, Janssen, Guardant Health; Financial Interests, Personal, Invited Speaker: Roche, Janssen; Financial Interests, Institutional, Expert Testimony: AstraZeneca; Financial Interests, Institutional, Advisory Board: Seattle Genetics; Financial Interests, Institutional, Invited Speaker: AstraZeneca, Blueprint, Astex, Bayer, BerGenBio, Carrick, Immutep, Janssen, Novartis, Nurix, Nuvalent, Pyramid Biosciences, Roche, Seattle Genetics, Turning Point Therapeutics; Financial Interests, Institutional, Research Grant: Roche, Novartis; Other, Personal, Other, Travel expenses for congress: Immutep, Janssen. J. Peguero: Financial Interests, Personal, Full or part-time Employment: Oncology Consultants; Financial Interests, Institutional, Leadership Role: Director, Research Department. T.D. Clay: Other, Personal, Other, Honoraria: Specialised Therapeutics, Wiley, Eli Lilly, Roche; Other, Personal, Stocks/Shares: ClinicIQ; Other, Personal, Advisory Board: AstraZeneca/MedImmune, Cipla, Foundation Medicine, Takeda, Merck KGaA, Merck/Pfizer, Ipsen; Other, Personal, Speaker's Bureau: AstraZeneca/MedImmune, MSD; Other, Personal, Other, Travel, Accommodations, Expenses: AstraZeneca; Other, Institutional, Funding: Exelixis, Immutep, Clovis Oncology, MSD Oncology, Pfizer, Amgen, Daiichi Sankyo/AstraZeneca, AbbVie, Janssen Oncology, BeiGene, Bayer, BridgeBio Pharma, BMS GmbH & Co. KG. E. Felip: Other, Institutional, Other, Advisory Board and Invited Speaker: Amgen, AstraZeneca, Bristol-Myers Squibb, Eli Lilly, F. Hoffman-La Roche, Janssen, Merck Sharp & Dohme, Merck Serono, Pfizer; Other, Institutional, Advisory Board: Bayer, BeiGene, Boehringer Ingelheim, Glaxo Smith Kline, Medical Trends, Peptomyc, Puma Biotechnology, Regeneron, Sanofi, Takeda; Other, Institutional, Invited Speaker: Peervoice, Springer, Touch Medical; Other, Institutional, Funding: Grant for Oncology Onnovation, MERCK Healthcare Kgaa, Fundación Merck Salud; Other, Institutional, Other, Independent Member Of The Board: Grífols. W. Iams: Other, Personal, Advisory Role: Genentech, Jazz Pharmaceuticals, G1 Therapeutics, Mirati, Bristol Myers Squibb, Takeda, Janssen; Financial Interests, Personal, Other, Consultancy: OncLive, Clinical Care Options, Chardan, Outcomes Insights, Cello Health, Curio Science. P. Roxburgh: Other, Institutional, Funding: AstraZeneca, Tesaro/GSK, Atrios; Other, Institutional, Other, Honoraria: AstraZeneca, Tesaro/GSK; Other, Institutional, Other, Funding to institution for role as site PI: Sierra oncology, PsiOxus, AstraZeneca, Starpharma, Forma Therapeutics, Iovance, Immutep, Bayer, Athenex, Replimune, Clovis, Nucana. C. Mueller: Financial Interests, Institutional, Full or part-time Employment: Immutep; Financial Interests, Personal, Stocks/Shares: Immutep. F. Triebel: Financial Interests, Institutional, Full or part-time Employment: Immutep SAS; Financial Interests, Personal, Stocks/Shares: Immutep Ltd; Other, Personal, 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.