128P - A phase I dose escalation and expansion trial of LYT-200, a Galectin-9 antibody +/- tislelizumab

Background

Galectin-9 (gal9) is a promising novel target for the treatment of both solid tumors and hematologic malignancies. When overexpressed, gal9 has broad immunosuppressor effects disabling immune-mediated cancer attack via T cell modulation, macrophages and other immune functions. LYT-200 is a fully human, anti-gal9, IgG4 monoclonal antibody that blocks gal9 mediated immunosuppression and protumor function.

Methods

Safety, pharmacokinetics (PK), pharmacodynamics (PD) and efficacy of LYT-200 are being assessed in this Phase 1/2 trial (NCT04666688) in advanced solid tumors as monotherapy and in combination with a PD-1 inhibitor, tislelizumab (TIS) in patients (pts) with relapsed, refractory head and neck squamous cell carcinoma (HNSCC) or urothelial cancer (UC) where gal9’s role is thought to be prominent.

Results

In monotherapy, 20 pts received IV LYT-200 in 7 escalation dose cohorts of 0.2 mg/kg to 16 mg/kg Q2W or 10 mg/kg QW. Median prior regimens (MPR) were 4 (1-7). No DLTs or LYT-200 related SAEs or G≥3 AEs were seen. LYT-200 related AEs of G≤2 were seen in 5 pts. 2 infusion related reactions (IRR) occurred in pts with IRRs on prior treatment. Single-agent cohorts have completed with 10 mg/kg QW selected as clinically relevant dose. Of 19 RECIST evaluable pts, 3 had stable disease (SD): 2 pancreatic cancer pts at 2 mg/kg QW and 6.3 mg Q2W with SD for 18 and 4 months (mo), and a colorectal cancer pt for 13 mo at 10 mg/kg QW. In the initial LYT-200/TIS combination cohort (LYT-200 6.3 mg/kg QW + TIS 300 mg Q4W) 6 pts have started treatment with 4 RECIST evaluable to date. MPR was 3 (1-5). No DLTs, irAEs or treatment related SAEs or G≥3 AEs. Of the 3 evaluable HNSCC pts, there have been 2 responses: 1 CR on treatment 9+mo and 1 PR on treatment 8+ mo. The 1 evaluable UC pt has had SD for 4+ mo, with near resolution of pleural effusion and ascites. LYT-200 has linear, dose-proportional PK. Geometric mean LYT-200 half-life is 6.6 days, supporting QW dosing.

Conclusions

LYT-200 has an acceptable safety profile in monotherapy and TIS combination, with observed antitumor activity in R/R pts who historically have very low response rates to an anti-PD1 agent alone. Enrollment into LYT-200 + TIS arms continues. The presentation will include additional safety, PK, PD and efficacy data.

Clinical trial identification

NCT04666688.

Editorial acknowledgement

The authors.

Legal entity responsible for the study

PureTech Health.

Funding

PureTech Health.

Disclosure

C. Korth: Financial Interests, Institutional, Advisory Board, works for Sponsor: Puretech health. A. Filipovic: Other, Institutional, Other, Head of Oncology at PureTech Health who is the Sponsor of the study: PureTech health. All other authors have declared no conflicts of interest.