Cerdulatinib Shows Promising Phase 2a Trial Results in Blood Cancer Patients, Including NHL

Cerdulatinib Shows Promising Phase 2a Trial Results in Blood Cancer Patients, Including NHL

Portola Pharmaceuticals‘ investigative therapy cerdulatinib is effective and well-tolerated in patients with several types of blood cancer, including non-Hodgkin’s lymphoma, who failed multiple prior therapies, according to interim results of a Phase 2a trial.

The poster, “The dual SYK/JAK inhibitor cerdulatinib demonstrates rapid tumor responses in a phase 2 study in patients with relapsed/refractory B- and T-cell non-Hodgkin lymphoma (NHL),” was presented at the 2018 American Society of Clinical Oncology (ASCO) Annual Meeting, held June 1-5 in Chicago.

Results will also be included on another poster presentation June 15 at the 23rd Congress of the European Hematology Association (EHA), June 14-17 in Stockholm, Sweden.

Cerdulatinib is an oral medication candidate that inhibits the activity of two different enzymes — the spleen tyrosine kinase (SYK) and the janus kinase (JAK) — that promote tumor cell growth and survival in certain blood malignancies and autoimmune diseases.

To investigate its potential in leukemia and lymphoma, researchers designed a Phase 1/2 trial (NCT01994382) that determined the therapy’s maximum tolerated dose and preliminary efficacy.

The trial included patients with chronic lymphocytic leukemia and B- or T-cell non-Hodgkin’s lymphoma who had received several prior lines of therapy.

In the Phase 1 part of the study, completed in 2016, researchers found that cerdulatinib was well-tolerated and had anti-tumor activity in several types of blood cancers. The therapy also inhibited more than 80% of SYK and JAK activity.

After these promising results, the second part of the trial focused on confirming the safety and effectiveness of cerdulatinib, dosed at 30 mg twice a day, by patients who had received at least three prior therapies.

Participants were included in one of five groups, including follicular lymphoma (FL), peripheral T-cell lymphoma (PTCL) and cutaneous T-cell lymphoma (CTCL), chronic lymphocytic lymphoma/small lymphocytic lymphoma (CLL/SLL), aggressive non-Hodgkin’s lymphoma (aNHL), and B-cell non-Hodgkin’s lymphoma (NHL).

Among the 101 patients evaluated through May 2018, 47% experienced a significant reduction in tumor burden. Among the 35 patients with follicular lymphoma, responses were seen in 46%, with a median duration of response of eight months.

For the 20 patients with PTCL, responses were seen in 43% of patients, including seven complete responses — five in angioimmunoblastic T-cell lymphoma and two in PTCL not otherwise specified.

Patients with CLL/SLL had the best response rates, with 61% of the 28 patients achieving a partial or complete response

Additionally, the first sign of success was also reported in CTCL, with the first patient enrolled in the trial now achieving a complete remission.

In general, cerdulatinib was well-tolerated, with the most common side effects including lipase increase, low neutrophil levels, and pneumonia.

However, five deaths caused by sepsis or septic shock (three of which were concomitant with pneumonia) were attributed to cerdulatinib. These occurred primarily in patients with CLL/SLL.

“Cerdulatinib continues to demonstrate promising results across a wide range of B- and T-cell malignancies, including early indications of the potential for durable responses,” Paul Hamlin, MD, medical director for the David H. Koch Center for Cancer Care at Memorial Sloan Kettering Cancer Center, said in a press release.

“The new signals in relapsed/refractory PTCL and CTCL are particularly compelling when you consider the limited treatment options for patients that fail front-line therapy,” he added. “I am encouraged by these data and the potential of cerdulatinib to provide a significant clinical benefit to a group of patients with limited treatment options.”

John Curnutte, MD, executive vice president of research and development at Portola, said the interim results “provide evidence for cerdulatinib’s unique mechanism of action of possibly disrupting two key cell signaling pathways, and its potential to control relapsed/refractory B-cell and T-cell malignancies in combination with standard and investigational therapies.”

With the trial now nearing its estimated completion date in July 2018, the company is preparing to advance cerdulatinib forward.

“We look forward to continuing discussions with the U.S. Food and Drug Administration regarding next steps for the development of cerdulatinib, including the potential for an accelerated approval pathway in the U.S. for certain tumor subtypes,” Curnutte added.

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