according to preliminary results from a phase 1b-2 trial.
Polatuzumab vedotin has already shown single-agent activity in relapsed/refractory diffuse large B-cell lymphoma, Hervé Tilly, MD, PhD, of the University of Rouen (France), and colleagues wrote in. “We explored the combination of polatuzumab vedotin with either rituximab, cyclophosphamide, doxorubicin, and prednisone [R-CHP] or obinutuzumab, cyclophosphamide, doxorubicin, and prednisone [G-CHP].”
With respect to polatuzumab vedotin dosing, the maximum investigated dose was 1.8 mg/kg. The novel agent was infused on day 2 of cycles 1 and 2 and subsequently on day 1 of each cycle thereafter for a total of 6-8 cycles, with each cycle lasting of 21 days.
The primary outcomes of this ongoing study were treatment safety and tolerability, as well as the establishment of recommended phase 2 dosing. Secondary endpoints included overall response rate, complete response=, among others.
A total of 82 patients were included in final analysis, 25 in the phase 1b dose escalation phase and 57 in the expansion phase.
After analysis, Dr. Tilly and his colleagues reported two dose-limiting toxicities: One patient experienced a grade 4 pulmonary embolism (1.8 mg/kg plus R-CHP) and another had grade 4 febrile neutropenia and grade 3 thrombocytopenia (1.4 mg/kg plus G-CHP).
At a median follow-up of 21.5 months, the overall response rate was 89% in study participants, including 77% of patients who achieved a complete response and 12% who had a partial response.
The recommended phase 2 dose of polatuzumab vedotin was 1.8 mg/kg. At this dose, the most common grade 3 or higher toxicities were neutropenia (30%), febrile neutropenia (18%), and thrombocytopenia (9%).
The researchers acknowledged a key limitation of the study was the nonrandomized design. As a result, dose and regimen comparisons could not be made.
The study was funded by F. Hoffmann-La Roche and Genentech. The authors reported financial affiliations with AstraZeneca, Bristol-Myers Squibb, Celgene, Gilead, Janssen, Merck, Pfizer, and others.
SOURCE: Tilly H et al. Lancet Oncol. 2019 May 14. .