Phase 2, multicenter, open‑label study of extended‑dosing belantamab mafodotin in combination therapy for relapsed/refractory multiple myeloma

The primary objective is to assess the response rate in participants with relapsed or refractory multiple myeloma receiving belantamab mafodotin combined with bortezomib‑dex, bortezomib‑pomalidomide, or carfilzomib‑dexamethasone using an extended dosing schedule, providing a direct measure of therapeutic efficacy. Secondary objectives include further evaluation of the efficacy of these combination regimens, assessment of the safety and tolerability of the treatments, and determination of the concordance between reported ocular symptoms and findings on ophthalmic examination, addressing additional clinical outcomes relevant to patient management.

The trial enrolled 155 participants diagnosed with Relapsed or Refractory Multiple Myeloma, all of whom were 18 years of age or older and included both male and female patients. Eligible individuals had received one to two prior lines of therapy, demonstrated measurable disease by serum or urine M‑protein criteria, and possessed an Eastern Cooperative Oncology Group performance status of 0–2 with adequate organ function. Enrollment required the ability to provide informed consent and adherence to contraceptive guidelines for men and women of reproductive potential. Patients with prior autologous stem‑cell transplantation were permitted if the transplant occurred more than 100 days before study entry and no active infections were present. Prior treatment‑related toxicities had to be grade ≤ 1 (except alopecia). No specific dietary, physical‑activity, or other lifestyle restrictions were stipulated in the inclusion criteria.

The study is a multicenter, open‑label, non‑randomized Phase 2 trial evaluating extended‑dose belantamab mafodotin in combination with standard‑of‑care regimens (bortezomib‑dexamethasone, pomalidomide‑dexamethasone, or carfilzomib‑dexamethasone) in participants with relapsed or refractory multiple myeloma. Eligible adults (≥18 years) with documented disease progression after one to two prior lines of therapy undergo a screening visit to confirm eligibility, followed by a baseline visit on Day 1 prior to the first dose. Treatment cycles are administered according to the respective combination schedules, with study visits scheduled every 3 weeks to monitor response, safety, laboratory parameters, and ocular examinations; additional visits occur at the end of each treatment course and at the end‑of‑study visit, which is performed after treatment discontinuation or study completion. Participants remain in the trial for the duration of therapy and a follow‑up period until disease progression, unacceptable toxicity, withdrawal of consent, or a protocol‑specified early termination event, whichever occurs first. The overall recruitment period is planned from 22 April 2026 to 12 July 2030, with each participant’s involvement lasting up to the point of discontinuation or study end. Early termination criteria include grade ≥ 3 treatment‑related adverse events, failure to meet compliance requirements, or investigator decision based on clinical judgment.

The investigational agent, belantamab mafodotin, is supplied as a powder for solution for injection and administered intravenously. The prescribed dose is 0 mg/kg, delivered according to the study dosing schedule.

Pomalidomide is provided for oral use at a dose of 4 mg per administration. It is incorporated as part of the standard‑of‑care regimen in the combination arms.

Dexamethasone is administered orally at a dose of 40 mg per dose and is used concomitantly with the other agents in each combination therapy.

Bortezomib is given subcutaneously at a dose of 1.3 mg/m² per administration and serves as the proteasome‑inhibitor component of the BVd combination.

Carfilzomib is administered intravenously at a dose of 70 mg/m² per administration and comprises the proteasome‑inhibitor component of the BKd combination.

All oral medications are dispensed in blister packs, and compliance is assessed through pill count reconciliation at each visit. Intravenous and subcutaneous infusions are documented in infusion logs, with adherence monitored by review of administration records and scheduled dosing intervals.

Efficacy will be evaluated primarily by the overall response rate (ORR), defined as the proportion of participants who achieve a confirmed partial response or better, including very good partial response, complete response, or stringent complete response. Assessments will be conducted in accordance with International Myeloma Working Group criteria.

Key secondary efficacy parameters include the complete response rate (CRR), defined as the proportion of participants with a confirmed complete response or better; the MRD negativity rate, defined as the proportion of participants who attain measurable residual disease–negative status at least once during a confirmed complete response or better; and the duration of response (DoR), measured from the first documentation of a partial response or better until disease progression or death from any cause.