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Two cases of cytokine release syndrome occurred during the first cycle of step-up dosing; however, both were considered non-severe and were treated without the need of tocilizumab, admission to the ICU or use of vasopressors.
The use of mosunetuzumab with polatuzumab vedotin (Polivy) in patients with relapsed/refractory B-cell non-Hodgkin lymphoma (B-NHL) conferred increased efficacy, according to findings from a phase 1b cohort.
The results, which were presented at the 2021 ASCO Annual Meeting, also demonstrated that the combination had an acceptable safety profile among the patient population.
Prior research has shown that treatment with mosunetuzumab — which is a full-length, humanized, IgG1 bispecific antibody — alone was safe and effective in treating relapsed/refractory B-NHL.
Additionally, recent results from a xenograft mouse model indicated that the combination induced increased efficacy compared to either agent administered as a monotherapy.
“These data supported a phase 1b/2, open-label, multicenter trial of [mosunetuzumab with polatuzumab vedotin] for relapsed-refractory B-NHL,” lead study author Elizabeth Budde, MD, PhD, of City of Hope, said during a presentation of the study results.
Here, Budde presented early clinical data from the dose-finding phase 1b cohort comprised of 22 patients (median age, 70 years; male, 50%) with either relapsed/refractory follicular lymphoma (FL) or aggressive NHL, including diffuse large B-cell lymphoma (n = 12), transformed FL (n = 4) and FL grade 3b (n = 3).
Patients were excluded from enrollment onto trial if they had received CD20-directed bispecific antibodies, as well as immunochemotherapy within 4 weeks of the first dose of study drug or radiotherapy within 2 weeks of first dose of study drug.
The study participants received a step-up dose of mosunetuzumab at 1 mg on day 1 of treatment and 2 mg on day 8 and then continued the target dose of 2 mg. That dose was given every 21 days for 8 cycles, or 17 cycles if patients achieved stable disease or a partial response after the eighth treatment cycle. Polatuzumab vedotin was administered at a dose of 1.8 mg/kg with mosunetuzumab on the first day of each treatment cycle for 6 cycles.
Determining a recommended phase 2 dose of study drug served as this cohort’s primary endpoint.
Patients had received a median 3 prior lines of therapy (range, 1-10), and 7 patients had previously received treatment with a CAR T-cell therapy.
At a median follow-up of 9.6 months (range, 0.7-23.7 months), all patients experienced at least 1 adverse event (AE). Neutropenia and nausea (40.9%, respectively), as well as fatigue and diarrhea (36.4%, respectively) were the most common treatment-related AEs (TRAEs). Two patients experienced a fatal grade 5 AE — one because of sudden cardiac death and another because of respiratory failure. Those deaths were not considered related to treatment, the study authors noted. Of note, AEs led to dose modification among 8 patients and treatment discontinuation in 3 patients.
Two cases of cytokine release syndrome occurred during the first cycle of step-up dosing; however, both were considered non-severe and were treated without the need of the immunosuppressive drug tocilizumab (Actemra), admission to the ICU or use of vasopressors.
Importantly, Budde noted, no neurotoxicity syndrome-like events occurred.
Of the study population, 15 patients achieved a best overall response (OR), of which 12 achieved a complete response (CR).
“[Mosunetuzumab with polatuzumab vedotin] showed promising efficacy in patients with relapsed/refractory NHL with predominantly aggressive histology,” Budde concluded. “Complete response rate was seen in 54.5% (of patients) and were also seen in patients who failed prior CAR Ts and patients with high-grade lymphoma.”
The phase 2 expansion cohort in patients with relapsed/refractory DLBCL is currently ongoing.
Budde E, Ghosh N, Chavez JC, et al. Promising tolerability and efficacy results from dose-escalation in an ongoing phase Ib/II study of mosunetuzumab (M) with polatuzumab vedotin (Pola) in patients (pts) with relapsed/refractory (R/R) B-cell non-Hodgkin’s lymphoma (B-NHL). J Clin Oncol. 2021;39(suppl 15):Abstract 7520.