9O - Phase I/II, open-label, first-in-human study of the anti-GPC3 T cell engager SAR444200 in patients with advanced solid tumors: Updated safety and pharmacokinetic analysis

Background

SAR444200 is a novel NANOBODY® T cell engager that simultaneously binds TCRαβ and glypican-3 (GPC3) to co-engage T cells with GPC3+ tumor cells, resulting in T cell-dependent cellular cytotoxicity. Here, we present updated safety and pharmacokinetic (PK) data from the dose escalation cohort (Part 1A) of the multicenter, first in human phase 1/2 trial (NCT05450562).

Methods

Patients (Pts) with GPC3+ refractory solid tumors received SAR444200 intravenously weekly with lead-in doses at dose levels (DLs) 1 (3 mg), 1A (1 mg), 2A (2.5 mg), 3A (4.5 mg), 4A (18 mg), 5A (36 mg), 6A and 7A (different lead-in doses and a final target of 70 mg). Primary objectives for Part 1A included safety and efficacy. Key secondary objectives included PK profile characterization and evaluation of immunogenicity. Study imaging was performed every 9 weeks. SAR444200 PK parameters were computed by non-compartmental analysis of plasma concentrations determined by qualified Meso Scale Discovery-based immunoassay. Anti-drug antibodies (ADAs) were detected using PandA assay.

Results

As of October 15, 2024, 33 pts [23 pts with hepatocellular carcinoma (HCC)] were treated with SAR444200 for a median of 23 cycles (range, 1–32). TEAEs and TRAEs are summarized in the table. Two Grade 3 cytokine release syndrome events were reported as DLTs at DL6A and one at DL7A during the lead-in dosing. Most patients developed ADAs during treatment. Mean SAR444200 PK exposure increased with dose increments. Generally, from the 6^th administration, a drop in exposure associated with high ADA titer was observed at the lower DLs, while sustained exposure was observed from 36 mg with low ADA titer. Among 18 pts with HCC having baseline alpha-fetoprotein (AFP, marker of HCC) >20 ng/mL, 2 (11.1%) pts showed a ≥20% decrease in AFP post treatment. Table: 9O

AE, Adverse effect; TEAE, Treatment-emergent adverse effect; TRAE, Treatment-related adverse effect; W, Weeks.

Conclusions

SAR444200 demonstrated a manageable safety profile at the DLs investigated in pts with GPC3+ advanced solid tumors.

Clinical trial identification

NCT05450562.

Editorial acknowledgement

Writing support for this abstract was provided by Tania Ahalya Thimraj, PhD, of Sanofi.

Legal entity responsible for the study

Sanofi.

Funding

Sanofi.

Disclosure

M. Chenard-Poirier: Financial Interests, Personal, Invited Speaker: Merck, Pfizer, Incyte; Financial Interests, Personal, Advisory Board: AstraZeneca, Bristol Myers Squibb; Financial Interests, Institutional, Invited Speaker: Sanofi, Amgen, AstraZeneca, Merck. D.W. Lim: Financial Interests, Institutional, Advisory Board: MSD, Daiichi-Sankyo, Janssen, Pfizer, Amgen; Financial Interests, Institutional, Invited Speaker: Beigene, Junshi Pharma; Financial Interests, Personal, Stocks/Shares: Mesh Bio; Financial Interests, Institutional, Invited Speaker, Grant funding for investigator-sponsored study: Taiho Pharmaceuticals. A.B. El-Khoueiry: Financial Interests, Personal, Advisory Board: Exelixis, AstraZeneca, Genentech, Agenus, Tallac, ABL Bio, Senti Biosciences, Qurient; Financial Interests, Institutional, Funding: Fulgent, Astex, AstraZeneca; Financial Interests, Personal, Invited Speaker: Merck, Genentech, Genentech; Financial Interests, Institutional, Invited Speaker, trial; funding: Auransa; Non-Financial Interests, Personal, Principal Investigator: Agenus, Affimed, Bayer. J. Samol: Financial Interests, Personal, Advisory Board: AstraZeneca, BeiGene, Bristol Meyers Squib, Eisai, Ipsen, Merk Sharp & Dohme, Roche, Taiho; Financial Interests, Institutional, Research Grant: AstraZeneca; Financial Interests, Personal, Other, Travel: AstraZeneca, Merk Sharp & Dohme. A. Kefsi, R. Perez, H. Guillemin-Paveau, L. Lepine, Y. Zhang: Financial Interests, Personal, Stocks/Shares, Employee of Sanofi and may hold stock and/or stock options: Sanofi. R. Meng: Financial Interests, Personal, Invited Speaker, Former employee of Sanofi at the time of study conduct and may hold stock/stock options in the company: Sanofi. S. Masciari, G. Abbadessa: Financial Interests, Personal, Stocks/Shares, Former employee of Sanofi at the time of study conduct and may hold stock/stock options in the company: Sanofi. E.E. Dumbrava: Financial Interests, Institutional, Other, Research/grant funding: Bayer HealthCare Pharmaceuticals, Immunocore Ltd., Amgen, Aileron Therapeutics, Compugen Ltd., Gilead, BOLT Therapeutics, Aprea Therapeutics, Bellicum, PMV Pharma, Triumvira, Seagen Inc, Mereo BioPharma 5 Inc, Sanofi, Rain Oncology, Astex Therapeutics, Sotio, Mersana Therapeutics, Poseida, Boehringer Ingelheim; Financial Interests, Personal, Invited Speaker: PMV Pharma; Financial Interests, Personal, Advisory Board: BOLT Therapeutics, Mersana Therapeutics, Orum Therapeutics, Summit Therapeutics. All other authors have declared no conflicts of interest.