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The FDA granted breakthrough therapy designation to sonrotoclax for relapsed/refractory mantle cell lymphoma.
The FDA has granted breakthrough therapy designation to the investigational BCL2 inhibitor sonrotoclax (BGB-11417) as a potential therapeutic option for patients with relapsed/refractory mantle cell lymphoma (MCL).1
In an announcement from BeOne Medicines, the company also stated that the FDA accepted a request to include sonrotoclax as a part of Project Orbis, which is intended to help facilitate collaboration between global regulatory bodies when reviewing oncology medicines.
“Breakthrough therapy designation is reserved for medicines with the potential to transform outcomes for patients with serious diseases. This recognition affirms the strength of the emerging data for sonrotoclax and its potential to become a new standard of care for people with relapsed or refractory MCL,” Julie Lepin, senior vice president and chief regulatory affairs officer at BeOne Medicines, stated in a news release. “Additionally, by participating in Project Orbis, we may be able to accelerate access to sonrotoclax, potentially helping patients faster than previously imagined.”
The breakthrough therapy designation and acceptance into Project Orbis were supported by data from the phase 1/2 BGB-11417-201 trial (NCT05471843). In August 2025, BeOne Medicines announced that the study met its primary end point of overall response rate (ORR) in patients with relapsed/refractory MCL who had received prior treatment with a BTK inhibitor and an anti-CD20 agent.2 Encouraging topline data were also reported for secondary end points such as complete response rate, duration of response, and progression-free survival.
Sonrotoclax was well tolerated with manageable toxicities. Full data will be presented at an upcoming medical meeting.
Additionally, the ongoing phase 3 CELESTIAL-RRMCL trial (NCT06742996) is evaluating sonrotoclax plus zanubrutinib (Brukinsa) compared with placebo plus zanubrutinib in patients with relapsed/refractory MCL.1
The single-arm, open-label, multicenter phase 1/2 trial enrolled patients at least 18 years of age with histologically confirmed relapsed/refractory MCL who received prior treatment with at least 1 anti-CD20 agent and at least 1 covalent or noncovalent BTK inhibitor.3 Patients were required to have measurable disease, an ECOG performance status of 0 or 1, and adequate organ function.
Investigators excluded patients with known central nervous system involvement; those with a prior malignancy other than MCL within 3 years of enrollment, other than curatively treated basal or squamous cell skin cancer, superficial bladder cancer, cervix or breast carcinoma in situ, or localized prostate cancer with a Gleason score of 6; patients who received prior treatment with a BCL2 inhibitor; those with clinically significant cardiovascular disease; patients who underwent major surgery or had a significant injury less than 4 weeks prior to enrollment; and patients with active fungal, bacterial, or viral infections requiring systemic therapy.
During the first part of the study, patients (n = 22) received sonrotoclax monotherapy at 160 mg or 320 mg per day, with the intention of establishing the recommended dose.1 In Part 2, patients (n = 103) were administered the recommended dose of sonrotoclax at 320 mg per day after a ramp-up period.
In part 1, the incidence of dose-limiting toxicities, treatment-emergent adverse effects (TEAEs), and tumor lysis syndrome served as the primary end points.3 ORR was the primary end point in part 2. Other secondary end points included pharmacokinetics (part 1), time to response, overall survival, the incidence of TEAEs (part 2), and patient-reported outcomes (part 2).
Previously, the FDA granted fast track designations to sonrotoclax for the treatment of patients with MCL and Waldenström macroglobulinemia.1 The agent has also received FDA orphan drug designations for the treatment of patients with MCL, Waldenström macroglobulinemia, multiple myeloma, and acute myeloid leukemia.
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