## Soquelitinib Shows Promising Clinical Outcomes in Advanced T Cell Lymphoma: Key Data from Phase 1/1b Trial

A clinical-stage biopharmaceutical company unveiled final data from its Phase 1/1b trial investigating soquelitinib in patients with T cell lymphoma. Presented at the 67th American Society of Hematology Annual Meeting in December 2025, the findings demonstrate significant therapeutic potential for this ITK inhibitor in one of hematology's most challenging disease spaces.

### Clinical Trial Design and Patient Population

The trial enrolled 75 patients across multiple T cell lymphoma subtypes, including peripheral T cell lymphoma (PTCL), T follicular helper cell lymphoma (TFHC), natural killer cell T cell lymphoma (NKTCL), cutaneous T cell lymphoma (CTCL), anaplastic large cell lymphoma (ALCL), and adult T cell lymphoma/leukemia (ATLL). This diverse patient cohort reflected the heterogeneous nature of T cell malignancies encountered in clinical practice.

Patients were heavily pretreated, with a median of 3 prior therapies (range 1-18), and only 31% had demonstrated objective responses to their most recent treatment regimen. This advanced, refractory disease population represents patients with limited therapeutic alternatives and historically poor prognosis.

### Breakthrough Efficacy Data

The dose escalation and expansion phases led to selection of 200 mg administered twice daily as the optimal dosing regimen, based on biomarker studies confirming complete target occupancy at this dose level and higher.

In the 200 mg BID cohort, results were notable:
- The cohort comprised 36 patients, with 24 identified as optimal responders based on having 1-3 prior therapies and adequate peripheral blood lymphocyte counts
- Among these 24 patients, objective responses were achieved in 9 (37.5%), including 6 complete responses and 3 partial responses
- **Median progression-free survival reached 6.2 months**, with 30% of patients maintaining disease control at 18 months
- **Median overall survival extended to 28.1 months**, with 67% surviving beyond 24 months

These survival metrics represent substantial improvements compared to historical controls, where relapsed/refractory PTCL patients typically experience median overall survival of 6-12 months and progression-free survival of 3-4 months.

### Safety Profile

No dose-limiting toxicities emerged across any cohort, with doses escalating up to 600 mg twice daily. Notably, the drug demonstrated absence of myelosuppression and immunosuppression—side effects commonly associated with conventional lymphoma therapies. This favorable tolerability profile suggests potential for use in patients unable to tolerate standard chemotherapeutic approaches.

### Mechanism of Action: ITK Inhibition and T Cell Differentiation

Soquelitinib functions as a selective ITK inhibitor, targeting interleukin-2-inducible T cell kinase—an enzyme predominantly expressed in T cells with critical roles in T cell receptor signaling and immune function.

The mechanistic data revealed a distinct immunobiological effect: soquelitinib drives Th1 differentiation while simultaneously blocking Th2 and Th17 development. Supporting evidence includes:
- In vitro studies demonstrated robust Th1 skewing at clinically relevant concentrations
- Biomarker analysis from blood and tumor samples showed increased intratumor Th1 cells alongside reduced serum IL-5 levels
- Paired tumor biopsies at baseline and day 8 of treatment confirmed treatment-induced elevation in intratumor Th1 infiltration by RNA sequencing

This mechanism operates upstream in T cell signaling pathways, suggesting resistance pathways may be unlikely to emerge—a theoretical advantage over therapies targeting downstream signaling components.

### Implications for Relapsed/Refractory PTCL

Peripheral T cell lymphoma represents approximately 10% of non-Hodgkin lymphomas in Western populations and up to 20-25% in parts of Asia and South America. The disease arises from mature helper T cells frequently expressing ITK and harboring T cell receptor signaling pathway mutations that drive lymphomagenesis.

The relapsed/refractory setting remains particularly urgent, as approximately 75% of patients fail frontline combination chemotherapy or relapse within two years. Few FDA-approved options exist specifically for this population, and patients experience dismal outcomes despite salvage therapy.

The clinical trial data support advancement to a registration Phase 3 trial enrolling 150 patients with relapsed/refractory PTCL, comparing soquelitinib against physicians' choice of belinostat or pralatrexate, with progression-free survival as the primary endpoint. Interim data are expected in late 2026.

### Expansion into Immune and Inflammatory Disease

Beyond oncology, soquelitinib is being evaluated in atopic dermatitis—a chronic inflammatory skin condition affecting up to 20% of children and 10% of adults. The disease pathophysiology involves Th2 lymphocytes secreting pro-inflammatory cytokines, providing a mechanistic rationale for ITK inhibition.

Preclinical studies demonstrated that soquelitinib inhibits cytokine production from Th2 cells, while recent clinical observations showed a shift toward T regulatory cell differentiation upon ITK inhibition. This dual mechanism—reducing pathogenic Th2 inflammation while promoting immunosuppressive T regulatory cells—may address both acute inflammation and underlying immune dysregulation in allergic diseases.

A Phase 1 trial in atopic dermatitis is currently ongoing, with extension cohort data anticipated in early 2026 and Phase 2 initiation planned for Q1 2026.

### Regulatory Status and Clinical Timeline

Soquelitinib has received Orphan Drug Designation for T cell lymphoma treatment and Fast Track designation for relapsed/refractory PTCL after at least 2 lines of prior systemic therapy. These designations reflect the FDA's recognition of unmet clinical need and the potential for accelerated development pathways.

The registration Phase 3 trial is actively enrolling across multiple centers, with anticipated trial completion in 2027. Success in this pivotal trial could establish soquelitinib as a meaningful therapeutic option for one of hematology's most challenging malignancies.