Purpose: 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 then 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 than observed with pembrolizumab alone. Combining an APC activator with an immune checkpoint inhibitor aims to increase efficacy without additional toxicity. We hereby report initial results of a phase II trial (NCT03625323). Methods: A predefined number of patients (pts) are recruited into this umbrella trial irrespective of PD-L1 expression. In part A: 1st line, PD-X naïve NSCLC; in part B: 2nd line, PD-X refractory NSCLC and in part C: 2nd line PD-X naive HNSCC. The study has a Simon's 2-stage design, with objective response rate (ORR) as primary endpoint. Secondary endpoints include progression free and overall survival, PK, PD and immunogenicity. Additional pts (N2) will be recruited for each part if the pre-specified threshold for ORR is met. Up to 109 pts will be enrolled. Efti is administered as 30 mg subcutaneous injection every 2 weeks for 8 cycles and then every 3 weeks for 9 cycles. Pembrolizumab is administered at a standard dose (200 mg intravenous infusion every 3 weeks for up to 2 years). The study was approved by ethic committees and institutional review boards. Results: Between 04 Mar 19 and 17 Jan 2020, 46 pts were enrolled and evaluated for safety. The median age was 66 years (range 48-84) and 74 % were male. The ECOG was 0 in 52 % and 1 in 48 % of the pts, respectively. Pts received a median of 5 (7) pembrolizumab (efti) administrations until data cut-off in Jan 2020. The most common (≥ 10%) adverse events (AEs) being cough (28 %), asthenia (24 %), dyspnea (17 %), decreased appetite (17 %), fatigue (15 %), diarrhea (15 %), non-cardiac chest pain (11 %), neck pain (11 %) and hypothyroidism (11 %). Two pts discontinued any study treatment due to AEs. All pts part A (1st line NSCLC) stage 1 (n=17) are evaluable for efficacy. Eight pts (47 %) had a partial response (iPR) and six (35 %) had stable disease according to iRECIST leading to an ORR of 47 %. Ten (10; 59 %) pts are still under therapy (7+ months). In part C (2nd line HNSCC) stage 1 13/18 pts are evaluable and five (39 %) had an iPR so far. Conclusions: Efti s.c. administered every 2 weeks in combination with pembrolizumab is safe and shows encouraging antitumor activity in all comer PD-L1 1st line NSCLC and 2nd line HNSCC. Stage 2 for both parts has been opened and stage 1 for part B is still recruiting.

Citation Format: Martin Forster, Enriqueta Felip, Bernhard Doger, Margarita Majem, Enric Carcereny, Julio Peguero, Pawan Bajaj, Tim Clay, Matthew Krebs, Patricia Roxburgh, Leora Horn, Frederic Triebel. Initial results from a phase II study (TACTI-002) in metastatic non-small cell lung or head and neck carcinoma patients receiving eftilagimod alpha (soluble lag-3 protein) and pembrolizumab [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr CT202.