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

Stratum C of the INSIGHT platform trial evaluates eftilagimod alpha (efti) combined with standard of care (SOC) 1st 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. Pts with 1st 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. 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. 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.