Eftilagimod alpha (efti) is a soluble LAG-3 protein that binds to a subset of MHC class II molecules to mediate antigen presenting cell (APC) activation and CD8 T-cell activation. The stimulation of the dendritic cell network and subsequent T cell recruitment with efti may lead to stronger anti-tumor responses in combination than observed with pembrolizumab alone. We hereby report initial results of the non-small cell lung cancer (NSCLC) part (NCT03625323).
The study has a Simon's 2-stage design, with objective response rate (ORR) as primary endpoint (EP). Secondary EPs include tolerability, disease control rate (DCR), progression free survival (PFS), PK, PD and immunogenicity. Treatment naïve PD-L1 unselected NSCLC patients (pts) are eligible for part A. Initially, 17 pts were recruited in stage 1, with an additional 19 pts enrolled into stage 2 if a pre-specified threshold is reached. Efti is administered as 30 mg SC injection every 2 wks for 8 cycles and then every 3 wks for 9 cycles with pembrolizumab (200 mg IV infusion every 3 wks for up to 2 yrs).
Between Mar 2019 and May 2020 33 pts were enrolled into stages 1 + 2. The median age was 67 yrs (range 53-84) and 70 % were male. ECOG PS 0:1 was 42 % and 58 % respectively. Pts from all PD-L1 subgroups were recruited. Pts received a median of 5 pembrolizumab and 7 efti administrations. All pts in stage 1 (n=17) were evaluable. Nine pts (53 %) had a partial response (iPR) and five (29 %) had stable disease according to iRECIST representing an ORR (DCR) of 53 % (82 %). Responses were observed among all PD-L1 subgroups with 1/3 iPRs in <1%, 3/6 iPRs in 1-49 %, 3/4 iPRs in ≥50% and 2/4 in the NE group. The most common (> 10 %) adverse events (AEs) were cough (29 %), asthenia (24 %), decreased appetite (18 %), dyspnea (18 %), fatigue (17 %), diarrhea (15 %) and nausea (12 %). Seven (7; 41 %) pts are still on therapy and median PFS is not yet reached (follow-up of 9+ months). The threshold (r>4) for opening of stage 2 was reached and initial data for stage 2 pts will be presented at the meeting.
Efti in combination with pembrolizumab is safe and shows encouraging antitumor activity in 1st line NSCLC across all PD-L1 expression levels.
Clinical trial identification
EudraCT: 2018-001994-25, NCT03625323.
Legal entity responsible for the study
M. Majem: Advisory/Consultancy: AstraZeneca; Boehringer Ingelheim; Bristol-Myers Squibb; Helsinn Therapeutics; Lilly; Merck Sharp & Dohme; Novartis; Pfizer; Roche; Takeda; Tesaro; Research grant/Funding (institution): BMS (Inst); Travel/Accommodation/Expenses: AstraZeneca; Roche. E. Felip: Advisory/Consultancy: AbbVie; AstraZeneca; BerGenBio; Blueprint Medicines; Boehringer Ingelheim; Bristol-Myers Squibb; Celgene; Guardant Health; Janssen; Lilly; Medscape; Merck KGaA; Merck Sharp & Dohme; Novartis; Pfizer; priME Oncology; Roche; Samsung; Takeda; Touchtime; Speaker Bureau/Expert testimony: AbbVie; AbbVie; AstraZeneca; BerGenBio; Blueprint Medicines; Boehringer Ingelheim; Bristol-Myers Squibb; Celgene; Guardant Health; Janssen; Lilly; medscape; Merck KGaA; Merck Sharp & Dohme; Novartis; Pfizer; Prime Oncology; Roche; Samsung; Takeda;; Research grant/Funding (institution): EMD Serono (Inst); FUNDACIÓN MERCK SALUD (Inst); Non-remunerated activity/ies, Other : GRÍFOLS. E. Carcereny: Advisory/Consultancy: AstraZeneca; Boehringer Ingelheim; Bristol-Myers Squibb; Lilly; Merck Sharp & Dohme; Novartis; Pfizer; Roche; Takeda; ; Travel/Accommodation/Expenses: Roche, Takeda. T. Clay: Honoraria (self): AstraZeneca; Novartis; Roche; Speaker Bureau/Expert testimony: AstraZeneca; Novartis; Novarti; Research grant/Funding (institution): Bayer (Inst); Bayer (Inst); BeyondSpring Pharmaceuticals (Inst); Clovis Oncology (Inst); Exelixis (Inst); Immutep (Inst); Merck Sharp & Dohme (Inst); Travel/Accommodation/Expenses: Astellas Pharma; AstraZeneca; Bristol-Myers Squibb; Foundation Medicine; Roche/Genentech. M.G. Krebs: Honoraria (self), Speaker Bureau/Expert testimony, Research grant/Funding (institution): Roche; Advisory/Consultancy: Achilles Therapeutics; Bayer; Janssen; Octimet; Roche; ; Travel/Accommodation/Expenses: AstraZeneca; BerGenBio; BerGenBio; Research grant/Funding (institution): BerGenBio (Inst). J. Peguero: Full/Part-time employment: Oncology Consultants, P.A.; Leadership role: Director, Research Department. F. Triebel: Full/Part-time employment: Immutep SAS; Shareholder/Stockholder/Stock options: Immutep Ltd; Licensing/Royalties: Being an inventor on patents on LAG-3 owned by Immutep SAS. All other authors have declared no conflicts of interest.