Portola Pharmaceuticals, Inc., a biopharmaceutical company focused on thrombosis and other hematologic diseases, recently announced positive safety and efficacy data on its product cerdulatinib in patients with hematologic cancers who have failed several therapies. The data is the result of a Phase 1 study part of an ongoing Phase 1/2a proof-of-concept trial, and has been presented on May 31 during the 2015 American Society of Clinical Oncology (ASCO) Annual Meeting held in Chicago.
Cerdulatinib is an oral drug able to inhibit two key signaling pathways that induce cancer cell growth in certain hematologic diseases – the spleen tyrosine kinase (Syk) and the janus kinase (JAK). Cerdulatinib is currently being tested in a multicenter Phase 1/2a proof-of-concept study in patients with lymphomas (B-cell leukemias) with a particular interest in genetically-defined subtypes [chronic lymphocytic leukemia (CLL), small lymphocytic leukemia (SLL), follicular lymphoma (FL) and B-cell non-Hodgkin lymphoma]. The drug is also being evaluated in patients who have failed previous therapy due to cancer relapse or acquired mutations.
Researchers found that cerdulatinib has anti-tumor activity in patients with relapsed/refractory B-cell malignancies. They observed partial responses and tumor reduction, including in patients who had failed prior therapy. Cerdulatinib was found to be well tolerated in these heavily pre-treated patients. Dose-escalation is ongoing to determine the maximum tolerated dose.
The team reported that cerdulatinib selectively inhibited the Syk/JAK signaling pathways with a maximal inhibition greater than 80%, and significantly reduced the levels of several proteins known to be markers of inflammation in the blood, which had a direct effect in tumor response.
“The clinical activity that we have seen with cerdulatinib in this hematologic cancer study is particularly notable given that these patients have advanced disease and have failed previous therapies,” noted Dr. Manish Patel, who was involved in the Phase 1/2a study, in a news release. “New treatment options are urgently needed for these patients, and we are looking forward to continuing to study cerdulatinib, a unique dual pathway anti-cancer agent.”
“These preliminary results from the ongoing dose-escalation Phase 1 part of the study, including partial responses, provide additional evidence that cerdulatinib is active and well tolerated in patients with hematologic cancers who have failed multiple therapies,” said the executive vice president, research and development for Portola Dr. John T. Curnutte. “We recently opened enrollment in larger expansion cohorts in the Phase 2a part of the study, which will include patients with CLL/small lymphocytic leukemia (SLL) or FL whose cancer has progressed or relapsed following treatment with multiple agents. We hope to identify a genetically-defined patient population for whom the inhibition of both Syk and JAK by cerdulatinib may provide clinical benefit beyond current treatment options. If we are successful, we plan to work closely with the FDA to seek an accelerated development path for this agent.”