1042P - INSIGHT 003 evaluating feasibility of eftilagimod alpha (soluble LAG-3) combined with first-line chemo-immunotherapy in metastatic non-small cell lung cancer (NSCLC) adenocarcinomas

Background

Stratum C of the INSIGHT platform trial evaluates eftilagimod alpha (efti) combined with standard of care (SOC) 1^st line chemo-immunotherapy (IC) in metastatic NSCLC patients (pts). Efti is an MHC class II agonist (soluble LAG-3 protein) activating antigen-presenting cells followed by T-cell (CD4/CD8) activation. Efti aims to enhance efficacy of IC.

Methods

Pts with 1^st line advanced or metastatic NSCLC adenocarcinomas (non-squamous) receive carboplatin AUC5 / pemetrexed 500 mg/m² q3w 4 cycles followed by optional pemetrexed 500 mg/m² q3w maintenance plus pembrolizumab 200 mg q3w combined with s.c. efti (30 mg) (q2w for 24 weeks; thereafter q3w till week 52). Imaging: q8w. Primary endpoint: feasibility (safety / tolerability). Secondary endpoints include ORR (RECIST 1.1.), PFS, OS.

Results

From 02Aug2021 till data cut off 18Apr2023 21 pts were enrolled and received treatment (median age: 65 years; 66.7% male). No occurrence of unacceptable toxicities. 10 SAE (grade 1-2: 3; grade 3: 4; grade 4: 0; grade 5: 3) were reported. 1 pancreatitis was possibly related to efti (or immunotherapy in general) and unexpected. So far, 4 pts completed max. treatment with efti for 52 weeks. The most frequent AEs were anemia in 18 pts (52.4%, grade 1-2 and 33.3%, grade 3), neutropenia in 18 pts (19.0%, grade 2 and 66.7%, grade 3-4), leukopenia in 16 pts (28.6%, grade 1-2 and 47.6%, grade 3-4) and thrombocytopenia in 14 pts (42.9%, grade 1-2 and 23.8%, grade 3-4). 5 AEs with grade 3 and no AE with grade 4 and 5 were considered related to efti. Out of 21 pts, 14 pts (67%) showed partial response, 5 (24%) stable disease, 2 (9%) progressive disease as BOR. Even pts with negative or low PD-L1 status (TPS) showed promising efficacy signals. Median follow up: 8.3 months, median OS: not reached.

Conclusions

To date, 30 mg efti combined with SOC appears to be feasible and safe with promising signals of efficacy, so that the trial was amended for inclusion of further 30 pts.

Clinical trial identification

EudraCT 2016-002309-20, NCT03252938.

Editorial acknowledgement

Legal entity responsible for the study

Institut für Klinische Krebsforschung IKF am Krankenhaus Nordwest, Steinbacher Hohl 2-26, D-60488 Frankfurt, Germany.

Funding

Immutep GmbH.

Disclosure

S. Al-Batran: Financial Interests, Personal, Advisory Board: Lilly, Bristol Myers Squibb, MacroGenics, Immutep, MSD Sharp & Dohme; Financial Interests, Personal, Invited Speaker: Bristol Myers Squibb, Lilly, AIO Studien gGmbH, MCI Deutschland GmbH; Financial Interests, Personal, Other, CEO/founder: Institute of Clinical Cancer Research IKF at Northwest Hospital; Financial Interests, Institutional, Research Grant: Sanofi, Roche, Celgene, Vifor, Medac, Hospira, Lilly, Eurozyto, Immutep, Ipsen, Bristol Myers Squibb, MSD Sharp & Dohme, AstraZeneca, German Cancer Aid (Krebshilfe), German Research Foundation, Federal Ministry of Education and Research. T.O. Goetze: Financial Interests, Personal, Advisory Role: Lilly, MSD Oncology, Bayer, SERVIER, Roche, Novartis, Incyte, Foundation Medicine, Bristol Myers Squibb; Financial Interests, Personal, Speaker’s Bureau: Lilly; Financial Interests, Personal, Research Funding: Deutsche Forschungsgemeinschaft, Gemeinsamer Bundesausschuss; Financial Interests, Institutional, Research Funding: Deutsche Krebshilfe, Lilly, AstraZeneca, Incyte. All other authors have declared no conflicts of interest.