Spectrum Pharmaceuticals, a biotechnology company with fully integrated commercial and drug development operations and a primary focus in Hematology and Oncology, and Onxeo S.A., an innovative company specializing in the development of orphan oncology drugs, have jointly announced the results from their Phase 1 combination trial of belinostat (Beleodaq®) with the CHOP (Cyclophosphamide, Hydroxyl-doxorubicin; Vincristine, and Prednisone) chemotherapy regimen as first-line treatment for newly diagnosed peripheral T-cell lymphoma (PTCL). Beleodaq® is a histone deacetylase (HDAC) inhibitor that received accelerated approval by the U.S. Food and Drug Administration (FDA) for the treatment of relapsed or refractory PTCL in July 2014.
The results were presented in an oral presentation at the 57th American Society of Hematology (ASH) Annual Meeting & Exposition by Dr. Patrick Johnston, MD, PhD, Assistant Professor of Medicine at the Mayo Clinic, Rochester, MN, USA.
Abstract #253: Safe and Effective Treatment of Patients with Peripheral T-cell Lymphoma (PTCL) with the Novel HDAC Inhibitor, Belinostat, in Combination with CHOP: Results of the Bel-CHOP Phase 1 Trial
This open-label, two-part trial enrolled a total of 23 patients. Eleven were enrolled in Part A, the dose-escalation phase, to determine the study's primary endpoint, the maximum tolerated dose (MTD). Part B of the study, the Expansion Phase, enrolled 12 additional patients at this dose level. The MTD of belinostat was established at 1,000 mg/m2 IV infusion on Days 1-5 (the recommended single agent dose) when combined with the CHOP regimen, with each component given at its full recommended dose. Secondary endpoints included safety, tolerability, Objective Response Rate (ORR: Complete Response + Partial Response), and pharmacokinetics.
Results outlined in the oral presentation showed an ORR of 86% with the belinostat and CHOP combination, based on 21 evaluable patients (18/21), with the vast majority, 67%, achieving a Complete Response (14/21), and 19% achieving a Partial Response (4/21). In addition, the belinostat and CHOP combination was shown to have an acceptable safety profile with no new or unexpected toxicities. The most common (>10%) Grade 3-4 hematologic adverse events (AEs) reported with Bel-CHOP were as expected: neutrophil count decreased (30%), anemia (22%), neutropenia (22%), white blood cell (WBC) count decreased (22%), febrile neutropenia (17%) and lymphocyte count decreased (17%). No Grade 3-4 non-hematologic AEs >10% were reported. No patient discontinued therapy due to AEs. One patient died as a result of disease progression during the study.
Dr. Patrick Johnston, MD, PhD, Assistant Professor of Medicine at the Mayo Clinic and investigator on the trial, commented, "PTCL is a very difficult lymphoma to treat due to its heterogeneous nature, and its association with multiple recurrence and poor prognosis; only approximately 37% of patients achieve 5-year overall survival. New combination treatment strategies are undeniably needed to improve efficacy without compromising tolerability, and we are encouraged by these Phase 1 study results indicating that the combination of belinostat and CHOP is a potentially viable treatment option. A good safety profile combined with an Objective Response Rate of 86%, and 67% of patients achieving complete response, are unusual in an early trial of this cancer type. We look forward to further evaluating the combination in a planned Phase 3 trial."
"We are proud to have had several presentations on our products at the ASH meeting, and are optimistic about the new combination data with belinostat," said Rajesh C. Shrotriya, MD, Chairman and Chief Executive Officer of Spectrum Pharmaceuticals. "Beleodaq was approved for the treatment of patients with relapsed or refractory PTCL based on an Objective Response Rate in the pivotal Phase 2 BELIEF study of 25.8%. The results of this Phase 1 study indicate encouraging safety and efficacy for the combination of belinostat and CHOP in newly diagnosed patients. The clinical activity suggests that earlier treatment with belinostat could be beneficial for the treatment of this devastating disease. Spectrum has a unique PTCL franchise with two FDA approved drugs; we are very proud to be able to offer patients and clinicians additional treatment options for a disease which had no FDA-approved treatments until a few years ago."
Graham Dixon, PhD, Chief Scientific Officer of Onxeo, added, "We are very excited to have these results discussed in an oral presentation at the ASH Annual Meeting. Collectively, the efficacy and safety findings demonstrate the potential value of belinostat plus CHOP, and Onxeo is thrilled to continue the development of belinostat to more broadly assess this promising therapy in PTCL and beyond."