1046P - Phase I/II open-label study on an anti-GPC3 T cell engager, SAR444200, in patients with advanced solid tumors: Preliminary dose escalation results

Background

SAR444200 is a novel NANOBODY® T cell engager that simultaneously binds TCRαβ and glypican-3 (GPC3) to co-engage T cells with GPC3-expressing tumor cells, resulting in T cell-dependent cellular cytotoxicity. Here, we present the preliminary safety, pharmacokinetics (PK) and biomarker data for the first two dose levels (DLs) of SAR444200 in patients with advanced solid tumors in dose escalation cohort (Part 1A) from the study (EudraCT 2021-006623-17/ NCT05450562).

Methods

This ongoing phase 1/2 open-label trial, evaluated intravenously administered SAR444200 in adult patients with GPC3+ solid tumors. Treatment was administered weekly following a lead- in dose administration at two DLs (DL1 and DL1A). Whole blood samples were collected to assess biomarkers and plasma concentrations of SAR444200. PK analysis was performed with ECL-based total PK assay using Meso Scale Discovery platform. A validated multiplex ELISA based assay was used for cytokine analysis.

Results

Tumor tissues from 115 patients were prescreened to identify GPC3-positive tumor cells by immunohistochemistry in a central lab. The positivity rate for hepatocellular carcinoma (HCC) was 18/21 patients (86%), and for non-small cell lung cancer was 3/6 patients (50%). As of 17th January 2023, a total of 8 patients received SAR444200 (DL1: n=4; DL1A: n=4). Most patients (87%) presented with HCC. No dose-limiting toxicities were observed. Six of 8 patients (75%) reported treatment-related adverse events (TRAEs) of any grade (Gr), including one patient with a serious TRAE (prolonged hospitalization due to Gr 2 CRS [cytokine release syndrome]). Gr 1 or 2 CRS was observed in 5 (62%) patients. Infusion-related reaction occurred in 1 (25%) patient. Following lead-in dosing up to Day 15, the maximum observed concentration (C_max) of SAR444200 at first two DLs occurred at the end or shortly after the end of infusion. Biomarker analysis showed an increase of cytokines (interleukin-6 and interferon gamma) during Cycle 1. Cytokines declined after Cycle 1.

Conclusions

These preliminary results from the first two DLs suggest that SAR444200 is tolerable at the tested DLs in patients with advanced solid tumors. Dose escalation continues at this time.

Clinical trial identification

EudraCT 2021-006623-17, NCT05450562.

Editorial acknowledgement

Ajay Francis Christopher, Sanofi Global Hub.

Legal entity responsible for the study

Sanofi.

Funding

Sanofi.

Disclosure

J. Yong Hong: Financial Interests, Personal, Advisory Role: AstraZeneca, Eisai; Financial Interests, Personal, Other, Honoraria: Dong-A Socio. M. Chenard-Poirier: Financial Interests, Personal, Other, Honoraria: Pfizer, Eisai, Incyte; Financial Interests, Personal, Advisory Role: Bristol Myers Squibb, Merck; Financial Interests, Personal and Institutional, Research Funding: Fusion Pharmaceuticals, AstraZeneca Co., VelosBio, Merck. K. Almhanna: Financial Interests, Personal, Advisory Role: Daiichi Sankyo; Financial Interests, Personal, Speaker’s Bureau: Eisai, AstraZeneca. D.W. Lim: Financial Interests, Personal, Other, Honoraria: Roche, Pfizer, Taiho Pharmaceutical, Merck; Financial Interests, Personal and Institutional, Research Funding: Bristol Myers Squibb. J. Samol: Financial Interests, Personal, Advisory Board: AstraZeneca, BeiGene, Bristol Myers Squibb, Eisai, Ipsen, Merck Sharp & Dohme, Roche, Taiho; Financial Interests, Personal and Institutional, Research Funding: AstraZeneca; Financial Interests, Personal, Other, Travel: AstraZeneca, MSD. G. Abbadessa, R. Meng, S. Masciari,A. Kefsi,Y. Zhang, H. Guillemin-Paveau, B. Pasquier, L. Lepine: Financial Interests, Personal, Full or part-time Employment, Employment: Sanofi. E.E. Dumbrava: Financial Interests, Personal, Advisory Board: Bolt Biotherapeutics; Financial Interests, Personal and Institutional, Research Funding: Bayer, Immunocore, Amgen, Aileron Therapeutics, Compugen, TRACON Pharma, Unum Therapeutics, Bolt Biotherapeutics, Aprea Therapeutics, Bellicum Pharmaceuticals, PMV Pharma, Triumvira Immunologics, Inc, Seagen, Mereo BioPharma 5, Sanofi, Astex Pharmaceuticals, Immunomedics/Gilead, Rain Therapeutics, Gateway Foundation. All other authors have declared no conflicts of interest.