On June 19, 2019 Portola Pharmaceuticals, Inc. (Nasdaq: PTLA) reported new interim results from the Company’s ongoing Phase 2a study of cerdulatinib, an investigational, oral SYK/JAK inhibitor, in patients with relapsed/refractory follicular lymphoma (FL) receiving cerdulatinib alone or in combination with rituximab (Press release, Portola Pharmaceuticals, JUN 19, 2019, Portola Presents New Interim Data on its Oral SYK/JAK Inhibitor Cerdulatinib in Heavily Pre-Treated Patients with Relapsed/Refractory Follicular Lymphoma
[SID1234537180]). Data were presented this month in a poster session at the 24th Congress of the European Hematology Association (EHA) (Free EHA Whitepaper) in Amsterdam (June 13-16) and during an oral session today at the 15th International Conference on Malignant Lymphoma (ICML) in Lugano, Switzerland (June 18-22).
Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:
Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing
Schedule Your 30 min Free Demo!
Data included safety and efficacy findings for 40 patients who received single agent cerdulatinib at 30 mg twice daily (with the exception of two patients who initiated treatment at 35 mg) and 17 patients who received cerdulatinib at 30 mg twice daily in combination with a standard dosing regimen of rituximab. The number of prior treatment regimens including anti-CD20 antibody, bendamustine and anthracyclines ranged from one to nine, with a median of three.
Among the 40 patients in the cerdulatinib-only cohort, the objective response rate (ORR) was 45%; five patients (13%) achieved a complete response (CR), 13 patients (33%) achieved a partial response (PR) and 10 patients (25%) achieved stable disease (SD). Of the 27 patients with a PR or SD at first evaluation in the single agent cerdulatinib cohort, 17 (63%) had a further reduction in tumor volume at a subsequent efficacy evaluation. To date, 15 of the 40 patients (38%) in the cerdulatinib-only cohort have been on study drug for at least 10 months.
Among the 13 patients evaluated for efficacy in the cerdulatinib and rituximab combination cohort, the ORR was 62%; one patient (8%) achieved a CR, seven patients (54%) achieved a PR and five patients (39%) achieved SD. To date, 10 of the 13 patients have been on study drug from three to 10 months.
Cerdulatinib was generally well-tolerated and the safety profile appeared similar in both cohorts. The most common adverse events (AEs) occurring in ≥10% of patients were lipase increase (25%), neutropenia (15%), amylase increase (13%) and diarrhea (10%). The most common AEs in the combination cohort included lipase increase (35%), neutropenia (23%) and diarrhea (12%). The lipase and amylase increases were generally asymptomatic and not associated with pancreatitis. Additionally, there was no emergence of late-stage colitis, cardiac or liver abnormalities, or other evidence of cumulative toxicity among patients in the single-agent cerdulatinib arm.
"Despite recent advances, relapsed or refractory follicular lymphoma remains a challenging and heterogeneous disease. Oral therapies that can address multiple signaling pathways and overcome chemoresistance without cumulative side effects are urgently needed," said Paul Hamlin, M.D., medical director for the David H. Koch Center for Cancer Care at Memorial Sloan Kettering Cancer Center. "Cerdulatinib continues to show promise across a range of B- and T-cell malignancies, and I am encouraged by these interim results, indicating sustained clinical activity and good tolerability of cerdulatinib in these follicular lymphoma patients."
"We are very encouraged by these early findings and look forward to continuing to gather additional data that will further characterize the safety and efficacy profile of cerdulatinib in patients with relapsed/refractory follicular lymphoma," said Jeff Myers, Portola’s interim chief medical officer. "Simultaneously, we are continuing to move forward with the development of cerdulatinib in relapsed/refractory peripheral T-cell lymphoma and plans to initiate a registrational trial by the end of the year."
ICML Oral Presentation Details
Wednesday, June 19, 2019 from 17:15 p.m. CEST/ 8:15 a.m. PDT
Rapid and Durable Responses with the SYK/JAK Inhibitor Cerdulatinib in a Phase 2 Study in Relapsed/Refractory Follicular Lymphoma—Alone or in Combination With Rituximab (Abstract #30)
Presenter: Stephen Smith, M.D., of the University of Washington/Fred Hutchinson Cancer Research Center.
Cerdulatinib has demonstrated broad clinical activity in both B- and T-cell malignancies. At the American Society of Hematology (ASH) (Free ASH Whitepaper) meeting in December 2018, the Company presented an update on cerdulatinib’s activity in relapsed/refractory peripheral T-cell lymphoma (PTCL); angioimmunoblastic T-cell lymphoma (AITL), a subset of PTCL; and cutaneous T-cell lymphoma (CTCL). As of the November 1, 2018 cut-off date, the ORR in the PTCL cohort was 34% with 27% achieving a CR. Among the subset of patients in the PTCL cohort with AITL, the ORR was 57% with a CR of 50%. The ORR in the CTCL cohort was 26% with 7% of patients achieving a CR. Importantly, rapid improvements in pruritus, or severe itching – a common and often serious condition associated with CTCL – were observed. Follow-up analysis of these cohorts is ongoing with plans to start a registrational study in PTCL by the end of the year.
About the Phase 2a Study
The Phase 2a, open-label study was designed to assess the safety and efficacy of cerdulatinib in patients with relapsed/refractory FL (alone or in combination with rituximab), small lymphocytic lymphoma (SLL) and specific subtypes of T-cell Non-Hodgkin Lymphoma, including PTCL, AITL and CTCL.
Tumor response in the two cohorts evaluating patients with relapsed/refractory FL was assessed by Lugano classification, with treatment continued until disease progression or unacceptable toxicity. Tumor response assessments were performed at the end of cycle two and every three cycles thereafter.
About Cerdulatinib
Cerdulatinib is an investigational oral, dual spleen tyrosine kinase (SYK) and janus kinase (JAK) inhibitor that uniquely inhibits two key cell signaling pathways implicated in certain hematologic malignancies and autoimmune diseases. There is a strong rationale for inhibiting both SYK (B-cell receptor pathway) and JAK (cytokine receptors) in B-cell malignancies where both targets have been shown to promote cancer cell growth and survival.
The U.S. Food and Drug Administration granted cerdulatinib Orphan Drug Designation for the treatment of PTCL in September 2018.