GSK has initiated the process for withdrawal of belantamab mafodotin-blmf (Blenrep®) from the US market. The withdrawal of the US marketing authorization follows the request of the US Food and Drug Administration (FDA).
Belantamab mafodotin, an antibody-drug conjugate comprising a humanized BCMA monoclonal antibody conjugated to the cytotoxic agent auristatin F via a non-cleavable linker, is part of a monotherapy treatment for adult patients with relapsed or refractory multiple myeloma (RRMM) who have received at least four prior therapies including an anti-CD38 monoclonal antibody, a proteasome inhibitor, and an immunomodulatory agent.
This request to withdraw the agent was based on the outcome of the DREAMM-3 phase III confirmatory trial of belantamab mafodotin monotherapy versus pomalidomide in combination with low dose dexamethasone (PomDex) in patients with relapsed or refractory multiple myeloma (RRMM).
In the study, a total of 325 participants were randomized in a 2:1 ratio to receive either single-agent belantamab mafodotin administered as a 2.5 mg/kg dose every three weeks or PomDex. Pomalidomide was administered daily on days 1 to 21 of each 28-day cycle, with dexamethasone administered once weekly (days 1, 8, 15, and 22 of each cycle).
The results of the clinical trial showed that this study did not meet its primary endpoint of progression-free survival (PFS).
The primary endpoint of PFS demonstrated a hazard ratio (HR) of 1.03 (95% CI: 0.72 1.47). The observed median progression-free survival was longer for belantamab mafodotin vs PomDex (11.2 months vs 7 months). Secondary endpoints include overall response rate (ORR), duration of response (DOR) and overall survival (OS). The ORR was 41% for belantamab mafodotin and 36% for PomDex.
Belantamab mafodotin demonstrated a deeper response rate when compared with PomDex (25% VGPR or better with belantamab mafodotin compared to 8% with PomDex). The median follow-up was 11.5 months for belantamab mafodotin and 10.8 months for PomDex; the median DOR was not reached for belantamab mafodotin (95% CI: 17.9, –) vs 8.5 months (95% CI: 7.6, –) for PomDex; DOR rates at 12 months were 76.8% and 48.4% for belantamab mafodotin and PomDex respectively. The safety and tolerability profile of belantamab mafodotin was consistent with the known safety profile, and no new safety signals were identified.
Overall rates of grade 3 keratopathy are consistent with prior reported data.
At the time of the primary analysis, the OS data had only achieved 37.5% overall maturity. The median OS was 21.2 and 21.1 months for belantamab mafodotin and PomDex, respectively, with an HR of 1.14 (95% CI: 0.77, 1.68).
As part of the GSK’s efforts to ensure physicians and patients are supported during this important time, patients already enrolled in the belantamab mafodotin Risk Evaluation and Mitigation Strategy (REMS) program will have the option to enroll in a compassionate use program to continue to access treatment.
Based on the totality of data available from the DREAMM (DRiving Excellence in Approaches to Multiple Myeloma) clinical development program, researchers at GSK continue to believe that the benefit-risk profile of belantamab mafodotin remains favorable in this hard-to-treat RRMM patient population. Patients responding to belantamab mafodotin experienced durable clinical benefit, and safety remains consistent with the known safety profile.
“We respect the Agency’s approach to the accelerated approval regulations and associated process,” said Sabine Luik, MD, MBA, Chief Medical Officer at GSK
Multiple myeloma is the second most common blood cancer in the US and is generally considered treatable but not curable.
In the US, more than 32,000 people are estimated to be diagnosed with multiple myeloma this year, and nearly 13,000 people will die from the disease. Research into new therapies is needed as multiple myeloma commonly becomes refractory to available treatments.
The normal function of BCMA is to promote plasma cell survival by transduction of signals from two known ligands, BAFF (B-cell activating factor) and APRIL (a proliferation-inducing ligand). This pathway is important for myeloma cell growth and survival. BCMA expression is limited to B cells at later stages of development. BCMA is expressed at varying levels in myeloma patients, and BCMA membrane expression is universally detected in myeloma cell lines.
“Multiple myeloma is a challenging disease, with poor outcomes for patients whose disease has become resistant to standard-of-care treatments. We will continue the DREAMM clinical trial program and work with the US FDA on a path forward for this important treatment option for patients with multiple myeloma,” Luik explained.
More clinical studies
Additional trials within the DREAMM clinical trial program are designed to determine the benefit of belantamab mafodotin in combination treatment with novel therapies and standard-of-care treatments in earlier lines of therapy and dosing optimization to maintain efficacy while reducing corneal events. Data from the DREAMM-7 and DREAMM-8 phase III trials are event-driven, and results are anticipated in the first half of 2023. Results of these trials will be shared with health authorities and inform future regulatory pathways.
- DREAMM-3 (NCT04162210) – The DREAMM-3 phase III trial is an open-label, randomized head-to-head superiority trial evaluating the efficacy and safety of single-agent belantamab mafodotin compared to pomalidomide in combination with low-dose dexamethasone (PomDex) in patients with RRMM. A total of 325 participants were randomised in a 2:1 ratio to receive either single-agent belantamab mafodotin administered as a 2.5 mg/kg dose every three weeks or PomDex. Pomalidomide was administered daily on days 1 to 21 of each 28-day cycle, with dexamethasone administered once weekly (days 1, 8, 15, and 22 of each cycle). The primary endpoint was PFS. Secondary endpoints include overall survival, safety, ORR, duration of response and assessment of minimal residual disease.
- DREAMM-7 (NCT04246047) This clinical study evaluate the safety and efficacy of belantamab mafodotin in combination with bortezomib and dexamethasone versus daratumumab in combination with bortezomib and dexamethasone.
- DREAMM-8 (NCT04484623) – A study designed to assess the efficacy and safety of belantamab mafodotin in combination with pomalidomide and dexamethasone compared with that of a combination of pomalidomide, bortezomib and dexamethasone in participants with relapsed/refractory multiple myeloma.
Maintenance Belantamab Mafodotin (Blenrep®) After B-cell Maturation Antigen-Directed Chimeric Antigen Receptor T-cell Therapy in Patients With Relapsed and/or Refractory Multiple Myeloma (EMBRACE) – NCT05117008
Retrospective Study of the Use of Belantamab Mafodotin (Blenrep®) in Patients With Relapsed and/or Refractory Multiple Myeloma (RRMM) in Spain. – NCT05297240
Blmf, Lenalidomide and Dexamethasone in Transplant-ineligible Patients With Newly Diagnosed Multiple Myeloma (BelaRd) – NCT04808037
Belantamab Mafodotin In Plasmablastic Lymphoma & ALK+ Large B-Cell Lymphoma – NCT04676360
Pembrolizumab, Belantamab and Dexamethasone in Refractory Multiple Myeloma – NCT05493618
Belantamab Mafodotin in Newly Diagnosed Transplant Eligible Multiple Myeloma Patients – NCT04802356
Isatuximab in Combination With Novel Agents in RRMM – Master Protocol – NCT04643002
Belantamab Mafadotin Maintenance Therapy After Salvage Autologous Hematopoietic Cell Transplantation in Patients With Relapse Refractory Multiple Myeloma – NCT05065047
Belantamab Mafodotin and Lenalidomide for the Treatment of Multiple Myeloma in Patients With Minimal Residual Disease Positive After Stem Cell Transplant – NCT04876248
Belantamab Mafodotin, Pomalidomide and Dexamethasone for the Treatment of High-Risk Myeloma – NCT05208307
Selinexor and Backbone Treatments of Multiple Myeloma Patients (STOMP) – NCT02343042
Myeloma-Developing Regimens Using Genomics (MyDRUG) – NCT03732703
Study to Investigate Alternative Dosing Regimens of Belantamab Mafodotin in Participants With Relapsed or Refractory Multiple Myeloma (DREAMM 14) – NCT05064358
Belantamab Mafodotin, Lenalidomide, and Daratumumab for the Treatment of Relapsed, Refractory, or Previously Untreated Multiple Myeloma – NCT04892264
Study of Single Agent Belantamab Mafodotin Versus Pomalidomide Plus Low-dose Dexamethasone (Pom/Dex) in Participants With Relapsed/Refractory Multiple Myeloma (RRMM) (DREAMM-3) – NCT04162210
Evaluation of Efficacy and Safety of Belantamab Mafodotin, Bortezomib and Dexamethasone Versus Daratumumab, Bortezomib and Dexamethasone in Participants With Relapsed/Refractory Multiple Myeloma (DREAMM 7) – NCT04246047
Belantamab Mafodotin Plus Pomalidomide and Dexamethasone (Pd) Versus Bortezomib Plus Pd in Relapsed/Refractory Multiple Myeloma (DREAMM 8) – NCT04484623
Highlight of Prescribing Information
Belantamab mafodotin-blmf (Blenrep®; GSK) [Prescribing Information]
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