FDA Accepts BLA for Belantamab Mafodotin Combinations in R/R Multiple Myeloma

• The FDA has accepted a biologics license application (BLA) for belantamab mafodotin (Blenrep) in combination with bortezomib (Velcade) and dexamethasone (BVd), as well as with pomalidomide (Pomalyst) and dexamethasone (BPd), for the treatment of patients with multiple myeloma who have received at least 1 prior line of therapy.
• Findings from the phase 3 DREAMM-7 (NCT04246047) and DREAMM-8 (NCT04484623) trials support this FDA decision.
• A Prescription Drug User Fee Act (PDUFA) target action date has been set for July 23, 2025.

The FDA has accepted for review a BLA for belantamab mafodotin in combination with bortezomib and dexamethasone, and with pomalidomide and dexamethasone, for patients with multiple myeloma who have undergone at least 1 previous line of therapy.¹ With this, a PDUFA date of July 23, 2025, has been set.

Data from the phase 3 DREAMM-7 and DREAMM-8 trials support this regulatory decision as both studies met their primary end points. Improvements that were statistically significant and clinically meaningful in progression-free survival (PFS) were observed with belantamab mafodotin combinations vs standard triplet combinations used for the treatment of patients with relapsed/refractory multiple myeloma.

Both the DREAMM-7 and DREAMM-8 trials demonstrated clinically significant improvements in all other secondary efficacy end points, including more profound and sustained responses vs the respective standard-of-care regimens. For safety and tolerability, the profiles of the belantamab mafodotin combinations in these trials were generally consistent with the established profiles of the individual agents.

“Relapsed/refractory multiple myeloma treatment could be transformed by additional, efficacious treatment options with manageable [adverse events (AEs)] and community-based administration. The evidence from DREAMM-7 and DREAMM-8 supporting our [belantamab mafodotin]combinations submission has been further strengthened by the statistically significant overall survival [OS] results from the DREAMM-7 trial. We look forward to working with the FDA on this review,” said Hesham A. Abdullah, MD, MSc, senior vice president, global head oncology, research and development, GSK, in a press release.

A planned interim analysis of the DREAMM-7 trial also achieved the key secondary end point of OS, demonstrating a statistically significant and clinically meaningful OS benefit that favored the belantamab mafodotin combination. Detailed efficacy and safety data from this analysis will be presented at the 66th American Society of Hematology (ASH) Annual Meeting. Further, although a positive OS trend was observed in DREAMM-8, it did not reach statistical significance at the time of the interim analysis, and OS follow-up is ongoing.

About The DREAMM Clinical Development Program

Multiple myeloma multiplex: © LASZLO - stock.adobe.com

The DREAMM clinical development program is exploring the use of belantamab mafodotin in earlier treatment lines, as well as in combination with novel agents and established therapies.

DREAMM-7 is a multicenter, open-label, global trial evaluating belantamab mafodotin combined with bortezomib and dexamethasone vs daratumumab [Darzalex] plus bortezomib and dexamethasone in patients with relapsed/refractory multiple myeloma after at least 1 previous line of therapy.² A total of 494 patients were randomly assigned in a 1:1 fashion to the belantamab mafodotin or daratumumab arms. Patients in the belantamab mafodotin arm received 2.5 mg/kg of the agent administered intravenously every 3 weeks.

PFS was the primary end point of the study and secondary end points included complete response rate, overall response rate (ORR), clinical benefit rate, duration of response (DOR), time to response, time to progression, OS, PFS2, minimal residual disease, and incidence of AEs.³

In the DREAMM-7 study, patients treated with belantamab mafodotin (n = 243) had a median PFS of 36.6 months vs 13.4 months in the comparator arm (n = 251; HR, 0.41; P <.001). At 18 months, PFS rates were 69% vs 43%, respectively. The median OS was 33.9 months for the belantamab mafodotin group vs 15.2 months for the comparator (HR, 0.57), with 18-month OS rates of 84% vs 73%. The ORR was 83% vs 71%, and the median DOR was 35.6 months vs 17.8 months.

Regarding safety, both groups had high rates of AEs, with 95% of the belantamab mafodotin arm and 78% of the comparator arm experiencing grade 3 or higher AEs. Common events included blood and lymphatic disorders, infections, and ocular issues. Discontinuations due to AEs occurred in 5% in the treatment arm and 2% in the comparator, with serious AEs leading to death in 10% vs 8% of patients, respectively.

DREAMM-8 is a phase 3 study assessing the combination of belantamab mafodotin, pomalidomide, and dexamethasone in patients with relapsed or refractory multiple myeloma. A total of 302 participants were included and randomly assigned in a 1:1 ratio to receive either BPd or PVd.¹

The primary end point is PFS as per an independent review committee, and the key secondary end points are OS and MRD negativity rate as assessed by next-generation sequencing. Additional secondary end points being evaluated are ORR, DOR, safety, and patient-reported and quality-of-life outcomes.

In this study, the median PFS was not reached (NR; 95% CI, 20.6 months to NR) in the BPd arm vs 12.7 months (95% CI, 9.1-18.5) in the PVd arm (HR, 0.52; 95% CI, 0.37-0.73; P < .001).⁴ The PFS rate at 12 months was 71% and 51% in each respective arm. The ORR with BPd was 77% (95% CI, 70.0%-83.7%) vs 72% (95% CI, 64.1%-79.2%) with PVd, and complete responses (CRs) were reported in 40% (95% CI, 32.2%-48.2%) and 16% (95% CI, 10.7%-23.3%) of patients, respectively.

MRD negativity was seen in 23.9% (95% CI, 17.4%-31.4%) and 4.8% (95% CI, 1.9%-9.6%) of those with a CR or stringent CR and in 32.3% (95% CI, 25.0%-40.2%) and 5.4% (95% CI, 2.4%-10.4%) of patients with a CR, stringent CR, or very good partial response (VGPR) in the respective arms. The median DOR was NR (95% CI, 24.9 months to NR) vs 17.5 months (95% CI, 12.1-26.4), respectively.

Additional data showed the median PFS2 was NR (95% CI, 33.0 months to NR) in the BPd arm compared with 22.4 months (95% CI, 13.8-NR) in the PVd arm (HR, 0.61; 95% CI, 0.43-0.86). The median OS was NR with both the belantamab mafodotin triplet (95% CI, 33.0 months to NR) and bortezomib-based therapy (95% CI, 25.2 months to NR; HR, 0.77; 95% CI, 0.53-1.15; P = .095). According to results presented at the 2024 ASCO Annual Meeting, investigators plan to continue to follow up with patients for additional OS data for future prespecified analyses.

This BLA marks the sixth major regulatory filing acceptance this year for belantamab mafodotin combinations in the treatment of relapsed/refractory multiple myeloma, as supported by data from the DREAMM-7 and DREAMM-8 trials.¹

Belantamab mafodotin combinations were accepted for review in the European Union, Japan, United Kingdom, Canada, and Switzerland in 2024. Breakthrough therapy designation for the agent was also granted in China by the National Medical Products Administration in combination with bortezomib and dexamethasone. Here, priority review for the regulatory application was also granted based on the results of the DREAMM-7 study.

REFERENCES:

1. Blenrep combinations accepted for review by the US FDA for the treatment of relapsed/refractory multiple myeloma. News release. GSK plc. November 25, 2024. Accessed November 25, 2024. https://tinyurl.com/45hh2e38

2. Hungria V, Robak P, Hus M, et al. Belantamab mafodotin, bortezomib, and dexamethasone for multiple myeloma. N Engl J Med. 2024;391(5):393-407. doi:10.1056/NEJMoa2405090

3. 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). ClinicalTrials.gov. Updated October 24, 2024. Accessed November 25, 2024. https://clinicaltrials.gov/study/NCT04246047

4. Trudel S, Beksac M, Pour L, et al. Results from the randomized phase 3 DREAMM-8 study of belantamab mafodotin plus pomalidomide and dexamethasone (BPd) vs pomalidomide plus bortezomib and dexamethasone (PVd) in relapsed/refractory multiple myeloma (RRMM). J Clin Oncol. 2024;(suppl 17):LBA105. doi:10.1200/JCO.2024.42.17_suppl.LBA105