On December 4, 2018 Portola Pharmaceuticals, Inc. (Nasdaq: PTLA) reported updated interim results from the Company’s ongoing Phase 2a study of cerdulatinib, an investigational, oral Syk/JAK inhibitor, in patients with specific subtypes of T-cell Non-Hodgkin Lymphoma, including relapsed/refractory peripheral T-cell lymphoma (PTCL); angioimmunoblastic T-cell lymphoma (AITL), a subset of PTCL; and cutaneous T-cell lymphoma (CTCL) (Press release, Portola Pharmaceuticals, DEC 4, 2018, View Source;p=RssLanding&cat=news&id=2379193 [SID1234531875]). The data will be presented today during an oral session at the 60th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting in San Diego (December 1-4).

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As of the November 1, 2018 cut-off date, 41 PTCL patients and 27 CTCL patients were evaluable for response. The objective response rate (ORR) was 34 percent in the PTCL cohort and 26 percent in the CTCL cohort. Among the subset of patients in the PTCL cohort with AITL, the ORR was 57 percent.

PTCL Cohort Data

Eleven of 41 patients (27 percent) achieved a complete response (CR), and three patients (7 percent) achieved a partial response (PR).
In the subgroup of 14 patients with AITL, seven patients (50 percent) achieved a CR and one patient (7 percent) achieved a PR.
One patient who achieved a CR went on to transplant.
Eight responding patients have remained on drug for three to more than 12 months and five patients have had a duration of response of six months or greater. Follow-up is ongoing.
CTCL Cohort Data

In the CTCL cohort, two patients (7 percent) achieved a CR and five patients (19 percent) achieved a PR. Responses have been seen in patients with Mycosis Fungoides and Sezary Syndrome.
Eleven of 23 patients (48 percent) achieved a ≥ 50 percent reduction in skin lesions, based on the Modified Severity Weighted Assessment Tool (mSWAT).
Rapid improvements in pruritus, or severe itching – a common and often serious condition associated with CTCL – have been observed, as measured by the Likert scale.
The CTCL cohort continues to enroll and data analysis is ongoing.
Cerdulatinib has demonstrated tolerability in both PTCL and CTCL. The most common grade 3 or greater adverse events across the PTCL and CTCL cohorts with a frequency > 5 percent were lipase increase (23 percent), amylase increase (18 percent), sepsis/bacteremia (8 percent), and neutropenia, pneumonia/lung infection and diarrhea (7 percent each). These events are manageable and further accrual is ongoing.

"The ongoing Phase 2a cerdulatinib data continue to demonstrate meaningful clinical activity, with particularly compelling complete response rates among AITL patients and the potential for durable response among patients with PTCL and CTCL," said Steven M. Horwitz, M.D., Memorial Sloan Kettering Center, and study investigator. "Like many others with T-cell malignancies, the patients in this study have failed prior therapies and are in need of additional treatment options. It is encouraging to see such a strong early signal in both disease response and quality-of-life measures, such as itching."

"While still early, the continuing and durable response rates in PTCL and the encouraging responses in CTCL underscore the potential of cerdulatinib to control relapsed/refractory T-cell malignancies," said John Curnutte, M.D., Ph.D., executive vice president and head of research and development at Portola. "We will apply our learnings from this study to inform the design of a pivotal trial, and look forward to continuing discussions with the U.S. Food and Drug Administration about the potential for an accelerated approval pathway for cerdulatinib in PTCL."

ASH Oral Session Details – Monday, December 3, 2018 at 7:15 p.m. PST

Title: 1001. The Novel Syk/JAK Inhibitor Cerdulatinib Demonstrates Good Tolerability
and Clinical Response in a Phase 2a Study in Relapsed/Refractory Peripheral
T-Cell Lymphoma and Cutaneous T-Cell Lymphoma

Session: 624 (Hodgkin Lymphoma and T/NK Cell Lymphoma—Clinical Studies: T Cell
Lymphoma: Chemotherapy and Targeted Approaches)

Presenter: Steven M. Horwitz, M.D., Memorial Sloan-Kettering Cancer Center

Session Time: 6:15 – 7:45 p.m. PST; Room 6F

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. In addition, pre-clinical data suggest an important role for Syk and JAK in PTCL tumor survival.

The U.S. Food and Drug Administration granted cerdulatinib Orphan Drug Designation for the treatment of PTCL in September 2018.