The FDA has placed a partial clinical hold on the phase I trial of ACTR707 in combination with rituximab in patients with relapsed/refractory B-cell lymphoma from Unum Therapeutics, following the submission of a safety report from the company. The FDA notified Unum of the hold verbally on March 4. Unum Therapeutics acknowledged the partial clinical hold in filings with the Securities and Exchange commission.
The FDA has placed a partial clinical hold on the phase I trial of ACTR707 in combination with rituximab (Rituxan) in patients with relapsed/refractory B-cell lymphoma from Unum Therapeutics, following the submission of a safety report from the company. The FDA notified Unum of the hold verbally on March 4. Unum Therapeutics acknowledged the partial clinical hold in filings with the Securities and Exchange commission.1
The safety report revealed a grade 3 adverse event (AE) experienced by 1 patient. Although the trial is on hold, the patients who previously received ACTR707 are eligible to continue rituximab infusions on the study.
Preliminary results from the multicenter study were presented at the 2019 American Society of Hematology (ASH) Annual Meeting and signaled clinical activity with the combination.
The study population consisted of patients with diffuse large B-cell lymphoma (83%) and follicular lymphoma (17%). The median age of patients in the study was 61 years (range, 57-76). The majority of patients were male (83%), and 50% were treated with 3 or more prior lines of therapy. Sixty-seven percent had no response to or relapsed on treatment within 6 months from the immediate therapy.2
A total of 6 patients were enrolled and complete responses were observed in 3 patients, who received the first dose level of ACTR707 in combination with rituximab. The duration of the complete response ranged from above 47 to above 81 days. No dose-limiting toxicities (DLTs) were observed at the first dose level in the 4 patients who were evaluable for DLT, but 2 patients did experience disease progression during the DLT evaluation period. There were no cases of cytokine release syndrome or autoimmune AEs, serious AEs defined as grade 3 and above, neurotoxicity AEs, or death on treatment.
More than 1 of the participants in the study experienced an all-grade AE. The AEs observed included neutropenia, anemia, decreased appetite, febrile neutropenia, and thrombocytopenia. The two cases of neutropenia were considered serious.
Patients were treated with 3 days of cyclophosphamide 400 mg/m2and fludarabine 30 mg/m2plus rituximab 375 mg/m2and ACTR707. For patients that did not progression during the study were given 1 dose of additional every 3 weeks. The study was divided into two sequential phases, 1 was the dose escalation phase, and the other was the safety expansion phase. During dose escalation, ACTR707 was administered at increasing doses in combination with rituximab.
The co-primary end points of the study were safety as assessed by DLTs and the determination of the maximum tolerated dose proposed recommended phase II dose. The secondary end points were evaluation of antitumor activity, and assessment of ACTR707 T cell persistence, cytokine levels, and the pharmacokinetics of rituximab.
Eligible patients had a histologically-confirmed, biopsy-confirmed CD20+ expression, at least 1 measurable lesion on imaging, and ECOG performance status of 0 or 1, a life expectancy of at least 6 months, a platelet count greate than 50,000 µL, and patients must have received adequate prior theerapy for the underlying CD20+ B-cell lymphoma.
Patients were ineligible for the study if they had known active central nervous system (CNS) involvement by malignancy, clinically significant cardiac disease, clinically significant CNS disorder clinical history, prior diagnosis, or overt evidence of autoimmune disease, known bone marrow involvement due to underlying malignant disease , as well as those who received prior therapies that were against the study protocol.
Results from the study supported the continued dose escalation of ACTR707 in combination with rituximab. Outside of this study, ACTR707 is also being evaluated in HER2-positive solid tumors, in a phase I study (NCT03680560).