FDA grants accelerated approval to mosunetuzumab-axgb for relapsed or refractory follicular lymphoma

5 Jan 2023
FDA grants accelerated approval to mosunetuzumab-axgb for relapsed or refractory follicular lymphoma

On December 22, 2022, the Food and Drug Administration (FDA) granted accelerated approval to mosunetuzumab-axgb (Lunsumio, Genentech, Inc.), a bispecific CD20-directed CD3 T-cell engager for adult patients with relapsed or refractory follicular lymphoma (FL) after two or more lines of systemic therapy.

Mosunetuzumab-axgb was evaluated in GO29781 (NCT02500407), an open-label, multicenter, multi-cohort study.

The efficacy population consisted of 90 patients with relapsed or refractory FL who had received at least two prior lines of systemic therapy, including an anti-CD20 monoclonal antibody and an alkylating agent.

The main efficacy outcome measure was the objective response rate (ORR) assessed by an independent review facility according to standard criteria for non-Hodgkin’s lymphoma (Cheson 2007).

The ORR was 80% (95% CI: 70, 88), with 60% achieving complete responses.

With a median follow-up of 14.9 months among responders, the estimated median duration of response (DOR) was 22.8 months (95% CI: 10, not reached) and the estimated DOR rate at 12 months and 18 months was 62% and 57%, respectively.

The prescribing information has a Boxed Warning for serious or life-threatening cytokine release syndrome (CRS). Warnings and precautions include neurologic toxicity, infections, cytopenias, and tumour flare.

Among 218 patients with hematologic malignancies who received mosunetuzumab-axgb at the recommended dose, CRS occurred in 39% of patients, neurologic toxicity in 39% (including ICANS in 1%), serious infections in 17%, and tumour flare in 4%. For CRS, Grade 2 occurred in 15%, Grade 3 in 2%, and Grade 4 in 0.5%.

In the pooled safety population of 218 patients, the most common adverse reactions (≥20%) were cytokine release syndrome, fatigue, rash, pyrexia, and headache.

The most common Grade 3 to 4 laboratory abnormalities (≥10%) were decreased lymphocyte count, decreased phosphate, increased glucose, decreased neutrophil count, increased uric acid, decreased white blood cell count, decreased hemoglobin, and decreased platelets.

The recommended mosunetuzumab-axgb dose is 1 mg on Cycle 1 Day 1, 2 mg on Cycle 1 Day 8, 60 mg on Cycle 1 Day 15, 60 mg on Cycle 2 Day 1, and 30 mg on Day 1 in subsequent cycles.

A treatment cycle is 21 days. 

Mosunetuzumab-axgb should be administered for 8 cycles unless patients experience unacceptable toxicity or disease progression.

After 8 cycles, patients with a complete response should discontinue therapy.

Patients with a partial response or stable disease should continue treatment up to 17 cycles unless they experience progressive disease or unacceptable toxicity.

Source: US Food and Drug Administration