990O - Final results from phase I, first-in-human, dose escalation study of a first-in-class anti-ILT2 antibody, SAR444881, alone and with pembrolizumab or cetuximab, in patients with advanced solid tumors

Background

SAR444881 (SAR), a first-in-class humanized IgG4 mAb, selectively binds to ILT2 on NK/T cells/macrophages, blocking its interaction with MHC I. Here, we report final results from a Phase 1 dose escalation study of SAR monotherapy in combination with pembrolizumab or cetuximab in patients (pts) with advanced solid tumors (NCT04717375).

Methods

Dose escalation phase of this study had 3 parts testing 6 SAR dose levels (0.1–20 mg/kg). Part 1A explored SAR monotherapy (intravenous [IV], every two weeks [Q2W]), Part 1B SAR+pembrolizumab (200 mg IV, Q3W), and Part 1C SAR+cetuximab (500 mg/m² IV, Q2W). Primary objectives were safety and tolerability. Key secondary objectives were antitumor activity and biomarker assessment.

Results

A total of 76 pts (Part 1A: n=31, Part 1B: n=23, Part 1C: n=22) received ≥1 dose of SAR. No treatment related dose limiting toxicities were observed. Most common (≥10%) treatment related Aes were: Part 1A, fatigue (19%); Part 1B, nausea (17%); Part 1C, rash (50%). Median PFS in months was Part 1A: 1.8 (1.6–3.4); Part 1B: 1.6 (1.5–2.1); Part 1C: 3.9 (1.8–NC). Partial responses were observed in Part 1A (1/31), Part 1B (1/23) and Part 1C (2/22) pts (Table). The 3 mg/kg and 10 mg/kg doses were safe and showed antitumor activity with high target receptor occupancy (>93%). All responders at 3–10 mg/kg had tumors predicted to be insensitive or progressing after anti-PD1 and/or cetuximab. SAR treatment at doses of ≥3 mg/kg led to upregulation of activation markers in monocytes and ILT2-expressing T and NK cell subsets. Increase in intratumoral necrosis and CD8 T cell subsets infiltration was observed. Based on these data, SAR 10 mg/kg has been defined as the initial dose for dose optimization. Table: 990O

Treatment-related SAEs:^aOne SAE (elevated liver enzymes);^bOne SAE (back pain).^cTwo grade 2 infusion-related reactions.Tumor types:^dGastroesophageal junction carcinoma;^eColorectal cancer.∗Per RECIST v1.1.AE, adverse event; SAE, serious AE, TEAE, treatment emergent AE.

Conclusions

These data provide initial clinical evidence for targeting ILT2 and warrant further exploration in dose optimization and expansion cohorts.

Clinical trial identification

NCT04717375.

Editorial acknowledgement

Medical writing support for this abstract was provided by Ujara Shaikh of Sanofi.

Legal entity responsible for the study

Sanofi.

Funding

Sanofi.

Disclosure

R. Perets: Financial Interests, Personal, Other, consulting fees: Karyopharm Therapeutics and Janssen; Financial Interests, Personal, Other, Honoraria: MSD. S.M. Stemmer: Other, Personal and Institutional, Research Grant: CAN-FITE, AstraZeneca, BiolineRx, BMS, Halozyme, Clovis Oncology, CTG Pharma, Exelixis, Geicam, Incyte, Lilly, Moderna, Teva Pharmaceuticals and Roche; Financial Interests, Personal, Stocks/Shares: CTG Pharma, DocBoxMD, TyrNovo, VYPE, Cytora and CAN-FITE. R. Geva: Financial Interests, Personal, Other, Honoraria: Roche, MSD, Merck, Medison, Janssen, Pfizer, BMS; Financial Interests, Personal, Advisory Board, 07/2022: AstraZeneca; Financial Interests, Personal, Advisory Board, Ended 3/2022: BOL Pharma; Financial Interests, Personal, Advisory Board: Roche, Ranium, JNJ, Bayer, Oncotest; Financial Interests, Personal, Advisory Board, 06/2022: MSD; Financial Interests, Personal, Other, Travel/Accommodations/Expenses 01/2022: Takeda; Financial Interests, Personal, Other, Travel/Accommodations/Expenses – 06/2022: Medison; Financial Interests, Personal, Other, Options: Pyxis; Financial Interests, Personal, Other, Medical lead: Pyxis. T. Golan: Financial Interests, Personal, Advisory Board: AstraZeneca, AbbVie, Teva, Merck MSD; Financial Interests, Personal, Invited Speaker: Roche; Financial Interests, Institutional, Other, Grant: AstraZeneca; Financial Interests, Institutional, Other, grant: Merck MSD; Financial Interests, Personal, Stocks/Shares: Curesponse. M. Fakih: Financial Interests, Personal, Advisory Board, Consultant: AbbVie, Inc., AstraZeneca, Bayer Corporation; Financial Interests, Personal, Advisory Board, Consultant/One Meeting: Bristol Myers Squibb; Financial Interests, Personal, Advisory Board, One meeting: Eisai Oncology; Financial Interests, Personal, Advisory Board, One meeting: Entos, Seattle Genetics, Xenthera; Financial Interests, Personal, Advisory Board, One Meeting: Janssen; Financial Interests, Personal, Advisory Board: Merck, Nouscom, Roche / Genentech; Financial Interests, Personal, Advisory Board, Also Editorial Boards & Consulting: Mirati Therapeutics; Financial Interests, Personal, Advisory Board, Consulting/One Meeting: Pfizer; Financial Interests, Personal, Advisory Board, Consulting: Taiho Oncology; Financial Interests, Institutional, Research Grant: AgenusBio, Genentech/imCORE, Verastem. J.E. Cohen: Non-Financial Interests, Personal, Other, Honoraria: AstraZeneca, Roche, Medison Pharma ; Financial Interests, Personal, Other, Travel and accommodation expenses: Medison Pharma. C. Lieu: Financial Interests, Institutional, Local PI, Research Funding: Genentech. Z. Jin: Non-Financial Interests, Personal, Advisory Role: Novartis, QED Therapeutics, Lilly, GSK, Daiichi Sankyo/AstraZeneca. P. Lorusso: Non-Financial Interests, Personal, Advisory Role: AbbVie, Roche, Takeda, Pfizer, GSK, AstraZeneca, Seagen; Financial Interests, Personal, Other, Honoraria: Five Prime Therapeutics; Financial Interests, Institutional, Research Funding: Gegentech. I. Friedman: Financial Interests, Personal, Full or part-time Employment, Previously employed: Biond Biologics Ltd. M. Hakim, D. Haves Ziv, S. Hashmueli, I. Mandel, T. Ben Moshe: Financial Interests, Personal, Full or part-time Employment: Biond Biologics Ltd; Financial Interests, Personal, Stocks/Shares: Biond Biologics Ltd. N. Crawford: Financial Interests, Personal, Full or part-time Employment: Sanofi; Financial Interests, Personal, Stocks/Shares: Sanofi. G. Abbadessa: Financial Interests, Personal, Full or part-time Employment: Sanofi; Financial Interests, Personal, Stocks/Shares: Sanofi; Non-Financial Interests, Advisory Role, member of Scientific Advisory Board: HiFi Bio, BIOND Biologics; Non-Financial Interests, Member: ASCO, ASH, AACR, SITC. R. Perez: Financial Interests, Personal, Full or part-time Employment: Sanofi; Financial Interests, Personal, Stocks/Shares: Sanofi. M. Wu: Financial Interests, Personal, Full or part-time Employment: Sanofi; Financial Interests, Personal, Stocks/Shares: Sanofi. M. Borad: Financial Interests, Institutional, Research Grant: Senhwa Pharmaceuticals, Adaptimmune, Agios Pharmaceuticals, Halozyme Pharmaceuticals, Five Prime Pharmaceuticals, Celgene Pharmaceuticals, EMD Merck Serono, Toray, Dicerna, Taiho Pharmaceuticals, Sun Biopharma, Isis Pharmaceuticals, Redhill Pharmaceutical; Financial Interests, Personal, Other, Travel Support: AstraZeneca.