Phase 2a Study of the Dual SYK/JAK Inhibitor Cerdulatinib (ALXN2075) As Monotherapy or in Combination with Rituximab in Patients with Relapsed/Refractory Follicular Lymphoma

• Published in: Blood 2021-11, Vol.138 (Supplement 1), p.2423-2423
• Main Authors: Hamlin, Paul A., Patel, Manish R., Stevens, Don, Hess, Brian T., Munoz, Javier, Feldman, Tatyana A., Smith, Sonali M., Coffey, Greg P., Osman, Muhtarjan, Holland, Jaymes S, Guzman, Cristina B, Smith, Stephen D.
• Format: Article
• Language: English
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood-2021-148313

Background Relapsed/refractory follicular lymphoma (FL) is a challenging disease; novel therapeutics with different mechanisms of action are needed. Spleen tyrosine kinase (SYK) and Janus kinase (JAK) signaling pathways are activated in FL and appear to play important roles in tumor survival. Cerdulatinib (ALXN2075) is an orally active, small molecule, reversible ATP-competitive dual inhibitor of SYK/JAK (JAK1, JAK2, TYK2) family members. The clinical activity and safety of cerdulatinib monotherapy were investigated in a multicenter, single-arm Phase 2a dose-expansion study (NCT01994382) of patients (pts) with T- or B-cell malignancies (N=220), including relapsed/refractory FL. Methods Eligible pts were aged ≥18 years with histologically confirmed FL (grade 1-3A) and relapsed/refractory disease after ≥1 systemic therapy (≥2 cycles including an anti-CD20 agent [e.g. rituximab] + chemotherapy, unless contraindicated). Pts with relapsed/refractory FL were initially enrolled in the monotherapy cohort (N=42) to verify single-agent activity. Additional pts were enrolled to combination therapy with rituximab (N=26). Most pts received oral cerdulatinib at a starting dose of 30 mg twice daily (BID) every 28-day cycle (both cohorts). Pts received IV rituximab 375 mg/m 2 on Days 1, 8, 15, and 22 of Cycle 1, and Day 1 of Cycles 4, 6, 8, and 10. Dosing continued until disease progression or unacceptable toxicity. The primary endpoint was investigator-assessed overall response rate (ORR; Lugano criteria). Secondary endpoints, including time to response (TTR), duration of response (DoR), and progression-free survival (PFS), were estimated. Final efficacy and safety data are presented for pts in the two FL cohorts who received ≥1 dose of cerdulatinib. Results The monotherapy cohort included 42 pts: 61.9% male; median (range) age 65 (42-81) years; median (range) prior regimens 2 (1-7); 31.0% refractory to their last treatment; ≥4 prior regimens in 26.2%. The combination cohort comprised 26 pts: 65.4% male; median (range) age 65 (42-85) years; median (range) prior regimens 2.5 (1-13); 11.5% refractory to their last treatment; ≥4 prior regimens in 38.5%. ORR (95% CI) for monotherapy was 52.9% (35.1-70.2%) for 34 efficacy-evaluable pts (8 complete responses [CRs]; 10 partial responses [PRs]; 9 stable disease [SD]). ORR (95% CI) for the safety population (N=42) was 42.9% (27.7-59.0%). ORR (95% CI) for the combination was 76.9% (56.4-91.0%) for 26 evaluable pts (6 CRs; 14 PRs;