Belantamab Mafodotin Continues to Show Promise in Advanced Myeloma Trials

Belantamab mafodotin, GlaxoSmithKline’s investigational antibody-drug conjugate, continues to show promise when used alone or in combination with other approved therapies to treat people with relapsed or refractory multiple myeloma, according to data from two clinical trials.

Findings from both trials — DREAMM-2 (NCT03525678) and DREAMM-6 (NCT03544281) — were presented in two posters at the recent 2020 American Society of Clinical Oncology (ASCO) Virtual Scientific Program, held online.

An antibody-drug conjugate, belantamab mafodotin is made up of an antibody targeting the B-cell maturation antigen (BCMA) — a protein found on the surface of myeloma cells — that is bound to the cancer-killing agent auristatin F. Once the antibody binds to cancer cells containing the BCMA protein on their surface, auristatin F is released into the cells, eliminating them.

Belantamab mafodotin is currently being investigated in multiple clinical trials as a potential therapy for heavily treated patients with multiple myeloma that has relapsed or did not respond to treatment (refractory).

DREAMM-2 is an open-label, Phase 2 trial that is investigating the safety and efficacy of two doses of belantamab mafodotin (2.5 mg/kg or 3.4 mg/kg) given every three weeks to people with advanced myeloma.

The study enrolled 196 patients who had received at least three prior lines of therapy, and failed to respond to treatment with an immunomodulatory agent, a proteasome inhibitor, and an anti-CD38 antibody. Participants received a median of seven prior lines of treatment, with some having been treated up to 21 times.

Previous data from DREAMM-2 showed that approximately a third of the patients receiving both doses of belantamab mafodotin responded to treatment. More than half of those responding from each group achieved very good partial responses — meaning partial cancer elimination — or better.

However, treatment adjustments and serious adverse events resulting in patients’ deaths were more frequent among those receiving the highest dose of the medication. That led GlaxoSmithKline (GSK) to submit an application requesting the approval of the lowest dose of belantamab mafodotin for the treatment of heavily treated patients with multiple myeloma in the U.S. and European Union.

Updated findings from DREAMM-2, presented at the meeting, showed that, after 13 months of treatment, those given the lowest dose of belantamab mafodotin had a median response duration of 11 months, and lived for a median of 14.9 months.

The percentage of patients responding to treatment in the lowest dose group was consistent with previous findings, with 32% responding to belantamab mafodotin. Among those participants, 58% attained very good partial responses or better. These included two patients with stringent complete responses and five with complete responses. Of note, complete responses refer to total cancer eradication, while stringent complete responses are a stronger type of a complete response.

These benefits of belantamab mafodotin were consistent across several patient subgroups, including those with mild-to-moderate kidney impairment and those with genetic abnormalities in their cancer cells that indicated a higher disease risk.

No new safety signals were identified with a longer follow-up in DREAMM-2. The most common severe, life-threatening, or fatal adverse events among those receiving the 2.5 mg/kg dose included keratopathy, or cornea damage, low platelet counts, anemia, and low white blood cell counts. In more than half (77%) of the cases, keratopathy was rapidly resolved, and none of the participants had permanent vision loss.

“The updated results from the DREAMM-2 study being presented at ASCO further demonstrate the potential of belantamab mafodotin to help address a significant unmet need for patients whose multiple myeloma continues to progress despite available treatment options,” Axel Hoos, senior vice president and head of oncology research and development at GSK, said in a press release.

“We are encouraged by these data as we work to bring belantamab mafodotin to patients suffering from this aggressive disease,” Hoos said.

Additionally, a separate analysis demonstrated that belantamab mafodotin was more effective than the combination therapy of Xpovio (selinexor) and low-dose dexamethasone, which was tested in the STORM Phase 2b trial (NCT02336815).  Belantamab mafodotin worked better to prolong the time myeloma patients lived and responded to treatment, the analysis found.

“These latest results from DREAMM-2 continue to reinforce that belantamab mafodotin has the potential to be an important treatment option for patients whose disease continues to progress despite currently available therapies,” said Sagar Lonial, chief medical officer of the Winship Cancer Institute of Emory University and principal investigator of the DREAMM-2 trial.

In addition to the latest findings from DREAMM-2, GSK presented the first data from DREAMM-6, an open-label, Phase 1/2 trial assessing the safety, tolerability, and efficacy of belantamab mafodotin in combination with other approved therapies for multiple myeloma. These include combination therapies of Velcade (bortezomib) plus dexamethasone, and Revlimid (lenalidomide) plus dexamethasone.

The study, which is still recruiting participants in Europe, Australia, and the U.S., is enrolling relapsed or refractory myeloma patients whose disease returned after at least one prior line of therapy.

Early findings from DREAMM-6 showed that 78% of patients receiving belantamab mafodotin at a dose of 2.5 mg/kg, every three weeks, together with Bortezomib and dexamethasone, responded to treatment. From these, 50% achieved very good partial responses and 28% partial responses.

At a median follow-up of 18.2 weeks (about 4.5 months), the median duration of response has not yet been reached, indicating that at least half of the patients are still responding to treatment.

The most common severe or worse adverse events reported during the trial included keratopathy and low platelet counts. No cases of life-threatening keratopathy were reported.

“We are encouraged by these initial results from the DREAMM-6 study showing the potential of combination therapy with belantamab mafodotin in patients with earlier stages of multiple myeloma and look forward to sharing the full data once it is available,” Hoos said.