Orlando, Florida—Results from an interim analysis of a phase 2 study show that cerdulatinib yielded response in patients with relapsed/refractory peripheral T-cell lymphoma (PTCL) and cutaneous T-cell lymphoma (CTCL), according to data that will be presented by Steven Horwitz, MD, Memorial Sloan Kettering Cancer Center, New York, at the 2019 ASH Annual Meeting.

Citing pre-clinical data that suggests SYK expression in PTCL and CTCL may act as an oncogenic driver by mediating chronic T-cell antigen receptor-independent signaling, Dr Horwitz and colleagues conducted this phase 2a dose expansion study to analyze response.

“Overall, the data suggest that dual inhibition of SYK and JAK may perturb multiple and independent survival mechanisms implicated in PTCL and CTCL…Cerdulatinib is a small-molecule reversible ATP competitive inhibitor of SYK and JAK family members,” explained Dr Horwitz et al.

Patients in the study with relapsed/refractory PTCL or CTCL who received at least 1 prior systemic therapy were eligible for treatment with cerdulatinib 30 mg twice daily. An analysis of 61 patients with PTCL and 37 with CTCL who were treated with single-agent cerdulatinib was conducted in July 2019.

Enrolled patients with PTCL had a median age of 65 years, median of 2 prior systemic therapies, and 48% were refractory to their last therapy. Patients with CTCL had a median age of 62 years, median of 5 prior system therapies, and 62% were refractory to their last therapy.

The primary end point was response, according to the Lugano criteria for patients with relapsed/refractory PTCL and the Global Assessment for patients with CTCL. 

All treated patients received antimicrobial prophylaxis and were treated until disease progression, intolerance, or an adequate response was achieved to allow stem cell transplantation.

The overall response rate (ORR) of the PTCL arm was 35%, with responses primarily seen in patients with the AITL/TFH subtype (ORR, 55% [12 of 22); 41% of these patients achieved complete responses (CR). Among the CTCL arm, ORR was 35%, with responses primarily observed in patients with mycosis fungoides (ORR, 45%; 9% of whom had CRs) or Sezary Syndrome (ORR, 17%; no CR).

Overall, 29% of patients experienced grade 3 or higher infections.

"The most common grade 3 or higher adverse events was an asymptomatic lipase or amylase increase, and we saw that both in patients with peripheral and cutaneous T-cell lymphoma," stated Dr Horwitz during the ASH 2019 presentation, noting that the most common toxicities were low-grade nausea and diarrhea. 

“Cerdulatinib has shown good tolerability and clinical activity in PTCL and CTCL. Complete and durable responses across a spectrum of PTCL and CTCL subtypes were observed,” concluded Dr Horwitz and colleagues, who added that these results will inform design of a pivotal new trial.—Kaitlyn Manasterski

Horwitz SM, Feldman TA, Khodadoust MS, et al. A Phase 2 Study of the Dual SYK/JAK Inhibitor Cerdulatinib Demonstrates Good Tolerability and Clinical Response in Relapsed/Refractory Peripheral T-Cell Lymphoma and Cutaneous T-Cell Lymphoma. Presented at: the 2019 ASH Annual Meeting & Exposition; December 7-10, 2019; Orlando, FL. Abstract 466.