Follicular lymphoma indication granted for zanubrutinib in the EU

24th November 2023

Zanubrutinib (brand name Brukinsa) has been granted marketing authorisation by the European Commission (EC) for use in combination with obinutuzumab for eligible patients with follicular lymphoma, its manufacturer BeiGene has announced.

This highly selective, oral Bruton’s tyrosine kinase (BTK) inhibitor is now approved for the treatment of adult patients with relapsed or refractory (R/R) follicular lymphoma who have received at least two prior lines of systemic therapy.

The EC approval is based on positive results from the phase 2 ROSEWOOD study which looked at zanubrutinib plus obinutuzumab compared with the anti-CD20 monoclonal antibody obinutuzumab alone.

Some 217 patients with R/R follicular lymphoma who had received at least two prior lines of systemic therapy were included in the global, randomised, open-label study.

The primary endpoint was overall response rate (ORR) by independent central review. Secondary endpoints included duration of response (DOR), progression-free survival (PFS), overall survival, and safety.

The researchers found the ORR to be 69.0% in the zanubrutinib plus obinutuzumab arm versus 45.8% in the obinutuzumab arm (P = 0.0012), with a median follow-up of approximately 20 months.

Responses were durable with 18-month landmark DOR of 69.3% in the zanubrutinib combination arm. Additionally, the median PFS for patients treated in the combination arm was 28.0 months, compared to 10.4 months for patients treated with only obinutuzumab (HR: 0.50 [95% CI: 0.33, 0.75]; P = 0.0007).

Zanubrutinib plus obinutuzumab was generally well-tolerated, with safety results consistent with previous studies of both medicines.

Zanubrutinib a ‘practice-changing option’

Dr Pier Luigi Zinzani, full professor of haematology at the Institute of Haematology ‘Seràgnoli’, University of Bologna, Italy, said: ‘People living with follicular lymphoma often experience relapse and have poor responses to subsequent lines of therapy, making it imperative to improve outcomes.

‘The results from the ROSEWOOD trial demonstrated a significant clinical benefit of Brukinsa plus obinutuzumab for patients with relapsed or refractory follicular lymphoma. Brukinsa is a chemotherapy-free, oral treatment option that can be a practice-changing option for eligible patients with relapsed or refractory follicular lymphoma.’

This is the fourth approved indication for this drug in the EU, which gives it ‘the broadest label of any medicine in its class globally’, according to Mehrdad Mobasher, chief medical officer, hematology at BeiGene.

In addition to R/R follicular lymphoma, zanubrutinib is approved in the EU as monotherapy for the treatment of adult patients with: chronic lymphocytic leukaemia, marginal zone lymphoma who have received at least one prior anti-CD20-based therapy, and Waldenström’s macroglobulinemia who have received at least one prior therapy, or in firstline treatment for patients unsuitable for chemo-immunotherapy.

The use of zanubrutinib in R/R follicular lymphoma is currently under review by regulatory authorities in Switzerland and the United Kingdom as part of the Access Consortium New Active Substance Work-sharing Initiative.

Mosunetuzumab induces high and durable remission in patients with follicular lymphoma

13th December 2021

Mosunetuzumab mono-therapy has been shown to induce both a high and durable response in patients with refractory follicular lymphoma

The use of mosunetuzumab mono-therapy in patients who have refractory follicular lymphoma (FL) gave rise to a high response rate and durable remission. This was the finding from a Phase II trial by a team from the BC Cancer Centre for Lymphoid Cancer and University of British Columbia, Vancouver, Canada, presented at ASH 2021.

FL is a type of non-Hodgkin lymphoma and associated with frequent relapses and decreasing progression-free intervals with successive lines of conventional therapy. Mosunetuzumab (Mosun) is a CD20xCD3 bi-specific antibody that re-directs T cells to eliminate malignant B cells and in the dose-escalation phase of an ongoing Phase I/II study (NCT02500407), Mosun was highly active and well tolerated in relapse-refractory follicular lymphoma (R/R FL) patients who had received 2 or more prior therapies. The Canadian team have now presented pivotal data from the same study from a large expansion cohort of R/R FL patients who received Mosun mono-therapy at the recommended Phase II dose (1/2/60/30mg).

All patients had FL (Grade 1–3a) and had at least 2 prior lines of therapy and the primary endpoint was complete response (CR) rate based on PET/CT scanning and assessed by an independent review facility (IRF) using standard response criteria.

Findings

A total of 90 patients with a median age of 60 years (61.1% male) were enrolled in the study and at entry, 76.7% had stage III or IV disease and the median number of prior lines of therapy was 3 (range: 2–10). In addition to Mosun, alkylators were given to all patients. Overall, 68.9% of patients were refractory to their last therapy, 78.9% to any prior aCD20 Ab, and 53.3% to any prior aCD20 Ab and an alkylator (double refractory).

The median time on mosunetuzumab was 12.9 months and CR rates by IRF was 57.8% and the overall response rate (ORR) was 78.9% with the median time to first response being 1.4 months and the median progression free survival time was 17.9 months. Among patients with at least two prior treatment failures the CR was 48% and the ORR 69%.

Cytokine release syndrome was the most common adverse event, occurring in 44.4% of all patients although this was mostly confined to grade 1 severity. Other common adverse events were fatigue (36.7%), headache (31.1%), neutropenia and pyrexia (28.9% each), hypophosphataemia (22.2%), and pruritus (21.1%).

The authors concluded that Mosun induces deep and durable remissions and with a high response rates that was maintained for ≥12 months in the majority of patients and that it represents an active new therapy for relapse-refractory patients with follicular lymphoma.

Citation

Budde E et al. Mosunetuzumab Monotherapy Is an Effective and Well-Tolerated Treatment Option for Patients with Relapsed/Refractory (R/R) Follicular Lymphoma (FL) Who Have Received ≥2 Prior Lines of Therapy: Pivotal Results from a Phase I/II Study. ASH Conference 2021