Phase 2a Study of the Dual SYK/JAK Inhibitor Cerdulatinib (ALXN2075) As Monotherapy in Patients with Relapsed/Refractory Peripheral T-Cell Lymphoma

• Published in: Blood 2021-11, Vol.138 (Supplement 1), p.622-622
• Main Authors: Horwitz, Steven M., Feldman, Tatyana A., Ye, Jing C., Khodadoust, Michael S., Munoz, Javier, Hamlin, Paul A., Kim, Youn H., Wilcox, Ryan A., Patel, Manish R., Coffey, Greg P., Osman, Muhtarjan, Holland, Jaymes S, Guzman, Cristina B, Smith, Sonali M.
• Format: Article
• Language: English
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood-2021-148352

Background Peripheral T-cell lymphoma (PTCL) comprises a heterogeneous group of T-cell non-Hodgkin's lymphomas with poor prognosis that are often refractory to treatment. Spleen tyrosine kinase (SYK) and Janus kinase (JAK) signaling pathways are important tumor survival mechanisms in PTCL. Cerdulatinib (ALXN2075) is an orally active, small molecule, reversible ATP-competitive dual inhibitor of SYK/JAK family members. The efficacy and safety of cerdulatinib monotherapy were investigated in a multicenter, single-arm Phase 2a dose-expansion study (NCT01994382) of patients with T- or B-cell malignancies; we report the final results from the PTCL cohort. Methods Eligible patients in the PTCL cohort were aged ≥18 years and had histologically confirmed PTCL with relapsed/refractory disease after ≥1 prior systemic therapy (prior brentuximab was required for CD30+ patients) and an Eastern Cooperative Oncology Group performance status ≤1. Patients received oral cerdulatinib 30 mg twice daily in 28-day cycles until disease progression or unacceptable toxicity. The primary endpoint was investigator-assessed overall response rate (ORR) based on Lugano criteria. Secondary endpoints, including time to response (TTR), duration of response (DoR), and progression-free survival (PFS), were estimated. Efficacy was evaluated in patients who had ≥1 post-baseline scan. Safety was evaluated in all patients who received ≥1 dose. Results Overall, 220 patients (with various subtypes of B- and T-cell malignancies) were enrolled across 6 study cohorts. A total of 65 patients in the PTCL cohort received ≥1 dose of cerdulatinib and were included in this analysis: 63.1% male; median (range) age 65 (21-85) years; median (range) prior regimens 2 (1-10); 49.2% refractory to last treatment; 18 patients (27.7%) had prior stem cell transplant. Histologic types were angioimmunoblastic T-cell lymphoma/T follicular helper (AITL/TFH [N=29; 44.6%]); PTCL not otherwise specified (NOS [N=11; 16.9%]); and other rare T-cell leukemias and lymphomas (N=25; 38.5%; Table 1). Of 65 patients with PTCL, 58 were evaluable for efficacy (Table 1). ORR was 36.2% (95% CI 24.0-49.9%) for the overall PTCL cohort (12 complete responses [CRs]; 9 partial responses [PRs]; 14 stable disease [SD]). For the AITL/TFH subgroup (N=27), ORR was 51.9% (95% CI 31.9-71.3%) (10 CR; 4 PR; 3 SD). ORR (95% CI) in the safety population was 32.3% (21.2-45.1%) for PTCL overall (N=65) and 48.3% (29.4-67.5%) for AITL/TFH (N=29). Median (r