Cerdulatinib Alone or with Rituxan Effective in Previously Treated Follicular Lymphoma, Data Show

Treatment with the oral therapy cerdulatinib alone or in combination with Rituxan (rituximab) shows durable efficacy, including some complete responses, in patients with follicular lymphoma who failed prior medications, according to early results of a Phase 2a trial.

The study, “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,” was presented at the 15^th International Conference on Malignant Lymphoma, held in Lugano, Switzerland, and the 24^th Congress of the European Hematology Association, in Amsterdam.

Cerdulatinib, developed by Portola Pharmaceuticals, works by inhibiting two enzymes — spleen tyrosine kinase and janus kinase — that promote tumor growth and survival in certain blood malignancies and autoimmune diseases.

The open-label Phase 1/2a study (NCT01994382) was designed to assess the safety and efficacy of cerdulatinib in patients with relapsed/refractory follicular lymphoma, small lymphocytic lymphoma and subtypes of T-cell non-Hodgkin’s lymphoma, including peripheral T-cell lymphoma (PTCL) and cutaneous T-cell lymphoma (CTCL).

Patient recruitment is ongoing across the United States; find more information on study locations and contacts here.

The analysis included 40 follicular lymphoma patients who took cerdulatinib alone at 30 mg twice daily (two of whom started at 35 mg) and 17 who received cerdulatinib in combination with a standard regimen of Rituxan (by Genentech and Biogen).

The number of prior treatments ranged from one to nine, with a median of three. Efficacy was analyzed after cycle two and every three cycles thereafter, with treatment continued until cancer progression or unacceptable toxicity. The median age of current participants is 64.

The objective response rate (the proportion of patients with a significant reduction in tumor size) in the group on cerdulatinib alone was 45%, with five patients (13%) achieving a complete response  (disappearance of all cancer signs); 13 (33%) a partial response, and 10 (25%) achieving stable disease.

Among 27 patients with a partial response or stable disease at first evaluation, 17 (63%) experienced further tumor shrinkage upon a subsequent visit. As of the latest analysis, 15 of the 40 participants (38%) have been on cerdulatinib for at least 10 months, with 10 for more than one year.

For the 13 patients who have been evaluated for the combination with Rituxan, the response rate was 62%, with one patient (8%) showing complete response, seven (54%) partial response and five (39%) stable disease. Ten of these 13 patients have been treated from three to 10 months.

Treatment was generally well-tolerated, with a similar safety profile comparing the two groups. The most common adverse events were increased levels of the pancreatic enzymes lipase (25%) and amylase (13%), reduced levels of pf neutrophils (15%), and diarrhea (10%).

The higher levels of lipase were generally asymptomatic and were not associated with pancreatitis. No patient on cerdulatinib alone had late-stage colitis, nor cardiac or liver abnormalities.

“The cerdulatinib rituximab combination appears to be well-tolerated, with tumor reductions in all evaluable [patients],” the scientists stated.

In 2018, cerdulatinib was granted orphan drug status by the U.S. Food and Drug Administration for the treatment of PTCL, after nearly one-third (27%) of relapsed or refractory patients achieved a complete response.

“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,” Paul Hamlin, MD, medical director at the David H. Koch Center for Cancer Care at Memorial Sloan Kettering Cancer Center, said in a press release.

Jeff Myers, Portola’s interim chief medical officer, said: “We are very encouraged by these early findings and look forward to continuing to gather additional data.”

Data shown at the American Society of Hematology meeting in December 2018 revealed that treatment with cerdulatinib was particularly effective in patients with relapsed/refractory angioimmunoblastic T-cell lymphoma, a subset of PTCL, with 50% of the patients experiencing a complete response.

The efficacy in overall PTCL and CTCL was lower, although a subset of these patients also had complete response.

“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,” Myers said. Registrational trials are expected to be the basis for regulatory approval.

The first part of the trial, completed in 2016, showed that cerdulatinib was well-tolerated and had anti-tumor activity in several blood cancer types.

Of note, seven of the study authors received honoraria/funding or had a consultant advisory role with Portola and/or Genentech. Five hold employment leadership positions or own stocks at Portola.