Corvus Pharmaceuticals Reports Promising Phase 1/1b Results for Soquelitinib in T Cell Lymphoma at ASH 2025
核心洞察
Corvus Pharmaceuticals presented final Phase 1/1b data for soquelitinib at ASH 2025, showing median progression-free survival of 6.2 months and overall survival of 28.1 months in the 200 mg twice-daily cohort.
The ITK (搜索) inhibitor demonstrated objective responses in 9 of 24 patients with 1-3 prior therapies, including 6 complete responses and 3 partial responses, with no dose-limiting toxicities observed.
The results support the ongoing registration Phase 3 trial in relapsed/refractory peripheral T cell lymphoma (搜索), addressing a significant unmet medical need where current treatments yield poor outcomes.
Corvus Pharmaceuticals presented compelling final data from its Phase 1/1b trial of soquelitinib in T cell lymphoma (搜索) patients at the 67th American Society of Hematology Annual Meeting & Exposition in Orlando, demonstrating significant survival benefits that compare favorably to existing therapies in this challenging disease setting.
Strong Survival Outcomes in Heavily Pretreated Patients
The Phase 1/1b trial enrolled 75 patients with various T cell lymphomas, including peripheral T cell lymphoma (搜索) (PTCL), T follicular helper cell lymphoma, natural killer cell T cell lymphoma (搜索), cutaneous T cell lymphoma (搜索), anaplastic large cell lymphoma (搜索), and adult T cell lymphoma/leukemia. Patients had received a median of 3 prior therapies (range 1-18), with only 31% achieving an objective response to their most recent prior therapy.
In the 200 mg twice-daily cohort, patients with 1-3 prior therapies and adequate peripheral blood lymphocyte counts (N=24) showed particularly promising results. This population achieved objective responses in 9 of 24 patients, including 6 complete responses and 3 partial responses. The median progression-free survival reached 6.2 months with an 18-month PFS of 30%, while median overall survival extended to 28.1 months with a 24-month OS of 67%.
"For most relapsed/refractory PTCL patients, an overall survival less than 6 months is anticipated. In the phase 1 study, median progression free survival was 6.2 months and median overall survival exceeded 2 years," said Ryan Wilcox, M.D., Ph.D., Associate Professor of Internal Medicine at University of Michigan Medical School.
Favorable Safety Profile Across All Dose Levels
The trial evaluated four dose levels in the escalation portion: 100 mg, 200 mg, 400 mg, and 600 mg twice-daily. Notably, no dose-limiting toxicities or significant adverse events were observed across all dose cohorts up to 600 mg twice-daily, including no myelosuppression or immunosuppression. The 200 mg twice-daily dose was selected for expansion based on biomarker studies indicating complete ITK (搜索) target occupancy at doses of 200 mg or higher.
Novel ITK Inhibition Mechanism Shows Immunological Effects
Soquelitinib selectively inhibits ITK (搜索) (interleukin-2-inducible T cell kinase (搜索)), affecting T cell differentiation and inducing Th1 helper cell generation while blocking Th2 and Th17 cell development. In vitro studies demonstrated that soquelitinib produces Th1 skewing through blockade of Th2 differentiation. Biomarker studies of blood samples and tumor biopsies showed increased Th1 cells in blood and tumor samples, along with reduced serum IL-5 levels, consistent with Th2 and Th17 inhibition.
Paired tumor biopsies from 6 patients compared at baseline and day 8 revealed increased intratumor Th1 cells with treatment, analyzed using RNA sequencing.
"The mechanism operates upstream in T cell signaling pathways, which may indicate that resistance pathways are unlikely to evolve," explained Richard A. Miller, M.D., co-founder, president and chief executive officer of Corvus Pharmaceuticals.
Addressing Critical Unmet Need in T Cell Lymphomas
Peripheral T cell lymphoma (搜索) represents a heterogeneous group of malignancies accounting for approximately 10% of non-Hodgkin's lymphomas in Western populations, reaching 20-25% in some parts of Asia and South America. Approximately 75% of patients either do not respond to first-line combination chemotherapy or relapse within two years. In the relapsed/refractory setting, patients face poor outcomes with median progression-free survival of 3-4 months and overall median survival of 6-12 months. Currently, no FDA-approved agents exist for relapsed/refractory PTCL based on randomized trials.
"The T-cell lymphomas are devastating diseases, associated with dismal outcomes, and are thus an area of high unmet need," Wilcox noted. "In the relapsed/refractory setting, complete and durable responses are rarely achieved with currently available agents."
Registration Phase 3 Trial and Regulatory Support
Based on these Phase 1/1b results, Corvus is currently enrolling patients in a registration Phase 3 clinical trial of soquelitinib in relapsed/refractory PTCL. The randomized controlled trial will enroll 150 patients and evaluate soquelitinib versus physicians' choice of either belinostat or pralatrexate, with progression-free survival as the primary endpoint.
The FDA has granted soquelitinib Orphan Drug Designation for T cell lymphoma (搜索) treatment and Fast Track designation for adult patients with relapsed or refractory PTCL after at least 2 lines of systemic therapy. Corvus anticipates reporting interim Phase 3 data in late 2026 and completing the trial in 2027.
Expansion Beyond Oncology
Beyond its oncology applications, soquelitinib is being investigated in atopic dermatitis (搜索), a chronic inflammatory skin condition affecting up to 20% of children and 10% of adults. The company plans to present additional data from extension cohort 4 of its Phase 1 atopic dermatitis trial in January and initiate a Phase 2 trial in early Q1 2026.
"Outside of oncology, we are focused on the development of soquelitinib in atopic dermatitis (搜索) and evaluating its potential in a broad range of immune and inflammatory diseases," Miller added.