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Abstract
Background Eftilagimod alpha (E) is a soluble LAG-3 protein binding to a subset of MHC class II molecules to mediate antigen-presenting cell (APC) activation & T-cell (CD4/CD8) recruitment/activation. By stimulating APCs with E, T cells are recruited, possibly leading to stronger anti-tumor responses than with pembrolizumab (P) alone, especially in tumors not overexpressing PD-L1. Herein we report results of the 1st line non-small cell lung carcinoma (NSCLC) cohort in the TACTI-002 (“Two ACTive Immunotherapies”) trial.
Methods Pts with measurable, 1st line metastatic NSCLC unselected for PD-L1 were recruited. The objective response rate (ORR) by iRECIST was the primary endpoint (EP). Secondary EPs include ORR by RECIST 1.1, ORR by blinded independent central read (BICR), duration of response (DoR), progression-free survival (PFS), overall survival (OS), PD-L1 and IFN-gamma, safety & tolerability. Pts received 30mg E SC q2w for 8 cycles (1 cycle= 3 weeks) & then q3w for up to 1 year with P (200 mg IV q3w for up to 2 years). Imaging was done every 8 weeks & assessed by investigator. PD-L1 was assessed centrally (22C3 antibody). The study was powered to detect a 52% increase in ORR compared to historical results for P 80% power & 1-sided alpha of 2.5%. Planned recruitment=110 pts.
Results From Mar 2019-Nov 2021, 114 pts were enrolled. Median follow-up was 13 mo (data cut-off Jul 1st 2022). Median age was 67 yrs (44-85) & 74% were male. ECOG PS was 0 & 1 in 37% & 63% of pts. Pts presented with squamous (35%) or non-squamous (63%) carcinoma and 93% had metastatic disease. All PD-L1 subgroups were represented (table 1). Pts received median 9.0 (range 1–18) P & 13.0 (1-22) E. 11 (9.6%) pts discontinued due to related adverse events (AEs). Common (≥15%) AEs were dyspnea (35%), asthenia (33%), decreased appetite (25%), cough (25%), anemia (23%), fatigue (21%), pruritus (21%), constipation (18%), nausea (17%), hemoptysis (16%) & diarrhea (16%).
ORR by iRECIST (primary EP) was 39.5% (95% CI 30.5-49.1) & median PFS was 6.9 mo (95% CI 4.9-9.3). Responses were observed in all PD-L1 subgroups (table 1). ORR (iRECIST) for squamous & non-squamous were 37.5% & 38.9%. Median duration of response was 21.6 mo. Results acc. to RECIST 1.1 were comparable. Early & sustained increases of circulating CXCL-10 & IFN-gamma levels were observed.
Conclusions E + P is safe & shows encouraging antitumor activity in 1st line metastatic NSCLC patients unselected for PD-L1, warranting late-stage clinical investigation.
Acknowledgements We thank all the participating patients & their families.
We thank the dedicated clinical trial investigators & their team members.
Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA provided pembrolizumab for the study. Sponsored by Immutep.
Trial Registration The trial identifiers are TACTI-002 (sponsor code), IMP321-P015 (Sponsor code), Keynote-PN798 (MSD code), 2018-001994-25 (EudraCT) and NCT03625323 (ClinicalTrials.gov).
Ethics Approval This has been approved by relevant Competent Authorities, Ethics Committees, and Institutional Review Boards.