Belantamab Mafodotin for Multiple Myeloma
(DREAMM 13 Trial)
Recruiting in Palo Alto (17 mi)
+17 other locations
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 1
Recruiting
Sponsor: GlaxoSmithKline
Must not be taking: Antivirals, Antiretrovirals
Disqualifiers: Active infections, Cardiovascular risk, others
No Placebo Group
Approved in 2 Jurisdictions
Trial Summary
What is the purpose of this trial?The purpose of this study is to assess the pharmacokinetics (PK), safety, and tolerability of belantamab mafodotin monotherapy in Relapsed/Refractory Multiple Myeloma (RRMM) participants with impaired hepatic function and in matched RRMM participants with normal hepatic function.
Will I have to stop taking my current medications?
The trial information does not specify if you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.
What data supports the effectiveness of the drug Belantamab Mafodotin for treating multiple myeloma?
Research shows that Belantamab Mafodotin has been effective in treating patients with multiple myeloma who have tried several other treatments. In one study, about 32% of patients had a positive response, and in another, 41.8% showed improvement, indicating its potential as a treatment option for this condition.
12345Is Belantamab Mafodotin safe for humans?
Belantamab Mafodotin has been studied for safety in patients with multiple myeloma, showing common side effects like eye problems (keratopathy, blurred vision) and low blood platelet counts (thrombocytopenia). It is available only through a special program due to these risks, indicating that while it can be effective, it requires careful monitoring for safety.
23678What makes the drug Belantamab Mafodotin unique for treating multiple myeloma?
Belantamab Mafodotin is unique because it is a first-in-class antibody-drug conjugate that targets BCMA (B-cell maturation antigen) on myeloma cells, delivering a powerful cancer-killing agent directly to the cells. This drug is specifically used for patients with multiple myeloma who have already tried several other treatments, making it a novel option for those with relapsed or refractory disease.
345910Eligibility Criteria
Adults with Multiple Myeloma who've had at least one prior treatment can join this trial. They must have a certain level of organ function and be able to consent. Women and men must use contraception, and those with previous stem cell transplants or specific viral exposures may qualify under conditions.Inclusion Criteria
My organs are functioning well.
You can join the study if you have had a certain type of stem cell transplant in the past.
I am using approved methods of contraception.
+8 more
Exclusion Criteria
I have specific blood, nerve, or skin conditions related to my cancer.
You have HIV under certain conditions.
I have not received belantamab mafodotin therapy in the last 90 days.
+12 more
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2-4 weeks
Treatment
Participants receive Belantamab mafodotin monotherapy to assess pharmacokinetics, safety, and tolerability
8 weeks
Follow-up
Participants are monitored for safety and effectiveness after treatment
4 weeks
Participant Groups
The study is testing Belantamab Mafodotin's effects on patients with different liver functions. It aims to understand how the drug moves in the body, its safety, and tolerability in those with normal liver function versus those with impairments.
3Treatment groups
Experimental Treatment
Group I: Part 2,Group 3: Participants with severe hepatic impairmentExperimental Treatment1 Intervention
Participants with severe hepatic impairment (Serum bilirubin \>3 times ULN and any AST) will be administered with Belantamab mafodotin
Group II: Part 1, Group 2: Participants with moderate hepatic impairmentExperimental Treatment1 Intervention
Participants with moderate hepatic impairment (Serum bilirubin greater than \>1.5 - 3 times ULN and any AST) will be administered with Belantamab mafodotin
Group III: Part 1, Group 1: Participants with normal hepatic functionExperimental Treatment1 Intervention
Participants with normal hepatic function (Serum bilirubin and Aspartate aminotransferase \[AST\] less than or equal to \[\<=\] Upper limit of normal \[ULN\]) will be administered with Belantamab mafodotin
Belantamab Mafodotin is already approved in European Union, United States for the following indications:
🇪🇺 Approved in European Union as Blenrep for:
- Relapsed or refractory multiple myeloma
🇺🇸 Approved in United States as Blenrep for:
- Relapsed or refractory multiple myeloma
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
GSK Investigational SiteBaltimore, MD
GSK Investigational SiteMonroeville, PA
GSK Investigational SiteBeverly Hills, CA
GSK Investigational SiteHackensack, NJ
More Trial Locations
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Who Is Running the Clinical Trial?
GlaxoSmithKlineLead Sponsor
References
Budget Impact of Belantamab Mafodotin (Belamaf) Adoption in the Treatment of Patients with Relapsed or Refractory Multiple Myeloma in the United States. [2022]Estimate the budget impact of belantamab mafodotin (belamaf) for patients with relapsed/refractory multiple myeloma (RRMM) who have received ≥4 prior therapies, including an anti-CD38 monoclonal antibody, a proteasome inhibitor, and an immunomodulatory agent.
Belantamab Mafodotin in Patients with Relapsed/Refractory Multiple Myeloma: Results of the Compassionate Use or the Expanded Access Program in Spain. [2023]Belantamab-mafodotin (belamaf) is a novel antibody-drug conjugate targeting B-cell maturation antigen that showed anti-myeloma activity in patients with relapsed and refractory multiple myeloma (RRMM). We performed an observational, retrospective, and multicenter study aimed to assess the efficacy and safety of single-agent belamaf in 156 Spanish patients with RRMM. The median number of prior therapy lines was 5 (range, 1-10), and 88% of patients were triple-class refractory. Median follow-up was 10.9 months (range, 1-28.6). The overall response rate was 41.8% (≥CR 13.5%, VGPR 9%, PR 17.3%, MR 2%). The median progression-free survival was 3.61 months (95% CI, 2.1-5.1) and 14.47 months (95% CI, 7.91-21.04) in patients achieving at least MR (p < 0.001). Median overall survival in the entire cohort and in patients with MR or better was 11.05 months (95% CI, 8.7-13.3) and 23.35 (NA-NA) months, respectively (p < 0.001). Corneal events (87.9%; grade ≥ 3, 33.7%) were the most commonly adverse events, while thrombocytopenia and infections occurred in 15.4% and 15% of patients, respectively. Two (1.3%) patients discontinued treatment permanently due to ocular toxicity. Belamaf showed a noticeably anti-myeloma activity in this real-life series of patients, particularly among those achieving MR or better. The safety profile was manageable and consistent with prior studies.
DREAMM-2: Indirect Comparisons of Belantamab Mafodotin vs. Selinexor + Dexamethasone and Standard of Care Treatments in Relapsed/Refractory Multiple Myeloma. [2022]Single-agent belantamab mafodotin (belamaf; BLENREP) demonstrated deep and durable responses in patients with relapsed/refractory multiple myeloma and ≥ 3 prior lines of therapy, including an immunomodulatory agent, proteasome inhibitor, and anti-CD38 antibody (DREAMM-2; NCT03525678).
Corneal Epithelial Findings in Patients with Multiple Myeloma Treated with Antibody-Drug Conjugate Belantamab Mafodotin in the Pivotal, Randomized, DREAMM-2 Study. [2020]Patients with relapsed or refractory multiple myeloma (RRMM) represent an unmet clinical need. Belantamab mafodotin (belamaf; GSK2857916) is a first-in-class antibody-drug conjugate (ADC; or immunoconjugate) that delivers a cytotoxic payload, monomethyl auristatin F (MMAF), to myeloma cells. In the phase II DREAMM-2 study (NCT03525678), single-agent belamaf (2.5 mg/kg) demonstrated clinically meaningful anti-myeloma activity (overall response rate 32%) in patients with heavily pretreated disease. Microcyst-like epithelial changes (MECs) were common, consistent with reports from other MMAF-containing ADCs.
Belantamab Mafodotin: First Approval. [2021]Belantamab mafodotin (BLENREP™; belantamab mafodotin-blmf) is a first-in-class monoclonal antibody-drug conjugate (ADC) that has been developed for the treatment of multiple myeloma by GlaxoSmithKline. The ADC comprises an antibody targeting B-cell maturation antigen (BCMA) conjugated to the microtubule inhibitor monomethyl auristatin F (MMAF). The antibody moiety binds to BCMA on the tumour cell surface, delivering the cytotoxic microtubule inhibitor MMAF to the therapeutic target. Based on preliminary results from the multinational DREAMM-2 trial, belantamab mafodotin was approved in early August 2020 in the USA for the treatment of relapsed or refractory multiple myeloma in adult patients who have received at least four prior therapies, including an anti CD38 monoclonal antibody, a proteasome inhibitor, and an immunomodulatory agent. The ADC was also approved in the EU for this indication in late August 2020. This article summarizes the milestones in the development of belantamab mafodotin leading to this first approval.
Real-world experience with belantamab mafodotin therapy for relapsed/refractory multiple myeloma: A multicentre retrospective study. [2023]Belantamab mafodotin, an immuno-conjugate targeting B-cell maturation antigen, showed single-agent activity in phase 1 and 2 studies, and was recently approved for heavily pretreated relapsed/refractory multiple myeloma (RRMM) patients. Real-world data and long-term follow-up are scarce. We conducted a multisite retrospective study aimed to assess safety and efficacy of belantamab mafodotin monotherapy administered via the GSK expanded access compassionate care programme. One-hundred and six RRMM patients were treated with belantamab mafodotin between July 2019 and March 2021. The median age was 69.4 years. Patients were heavily pretreated with a median of six (range 2-11) prior therapy lines. Major adverse effects included ocular toxicity (keratopathy 68.4%, grade ≥3: 40.5%; blurred vision 36.8%, grade ≥3: 6.3%), thrombocytopenia (27.4%, grade ≥3: 17.9%) and infections (11.3%, grade ≥3: 7.5%). Median follow-up time was 11.9 [95% confidence interval (CI) 10.0-13.8] months. Overall response rate was 45.5%. Median progression-free survival was 4.7 (95% CI 3.5-5.9) months in the entire cohort and 8.8 (95% CI 6.6-10.9) months among responders. Median overall survival was 14.5 (95% CI 9.5-19.6) months, and not reached for responders. To conclude, in a real-world setting, belantamab mafodotin monotherapy showed efficacy comparable with the prospective clinical trials, with a tolerable toxicity profile.
FDA Approval Summary: Belantamab Mafodotin for Patients with Relapsed or Refractory Multiple Myeloma. [2023]On August 5, 2020, the FDA granted accelerated approval to belantamab mafodotin-blmf (BLENREP; GlaxoSmithKline) for the treatment of adult patients with relapsed or refractory multiple myeloma who have received at least four prior therapies including an anti-CD38 monoclonal antibody, a proteasome inhibitor, and an immunomodulatory agent. Substantial evidence of effectiveness was obtained from the phase II, multicenter DREAMM-2 trial. Patients received belantamab mafodotin 2.5 or 3.4 mg/kg intravenously once every 3 weeks until disease progression or unacceptable toxicity. The trial demonstrated an overall response rate of 31% in the 2.5 mg/kg cohort and 34% in the 3.4 mg/kg cohort. Keratopathy was the most frequent adverse event, occurring in 71% and 77% of patients, respectively. Other ocular toxicities included changes in visual acuity, blurred vision, and dry eye. The U.S. prescribing information for belantamab mafodotin includes a boxed warning for ocular toxicity, and belantamab mafodotin is available only through a restricted program under a Risk Evaluation and Mitigation Strategy. This article summarizes the data and the FDA review process supporting accelerated approval of belantamab mafodotin 2.5 mg/kg intravenously once every 3 weeks. This approval may be contingent upon verification and description of clinical benefit in confirmatory trial(s).
Exposure-Response Analyses for Therapeutic Dose Selection of Belantamab Mafodotin in Patients With Relapsed/Refractory Multiple Myeloma. [2022]Belantamab mafodotin is an antibody-drug conjugate comprising a humanized anti-B-cell maturation antigen (BCMA) monoclonal antibody conjugated to monomethyl auristatin F (MMAF) via a protease-resistant maleimidocaproyl linker. Single-agent belantamab mafodotin showed clinically meaningful activity and manageable safety in patients with heavily pretreated relapsed/refractory multiple myeloma (RRMM) in the phase I DREAMM-1 and phase II DREAMM-2 studies and is approved by the US Food and Drug Administration and European Medicines Agency for RRMM treatment. To support monotherapy dose selection, the relationship between Cycle 1 exposure (derived using a population pharmacokinetic model) and clinical response (for multiple efficacy and safety end points) was explored. In DREAMM-2, efficacy end points (probability of response (PoR) and progression-free survival (PFS)) were associated with exposure in univariate evaluation; however, once disease burden factors were included in the model (e.g., baseline soluble BCMA, ß2 -microglobulin), exposure was no longer significant. Patients with higher disease burden had lower exposure. In DREAMM-1, belantamab mafodotin exposure was the only variable to correlate with PoR and PFS. Probability of corneal events (keratopathy), but not dry eye or blurred vision, was strongly associated with belantamab mafodotin exposure (DREAMM-2). Higher cys-mcMMAF maximum plasma drug concentration (Cmax ) and lower baseline platelet count were associated with increased probability of thrombocytopenia (DREAMM-1 and DREAMM -2). In general, safety end points were more strongly associated with belantamab mafodotin exposure than efficacy end points, particularly after disease factors and patient characteristics were taken into account. Overall, these findings supported the monotherapy dose recommendation of belantamab mafodotin as 2.5 mg/kg every 3 weeks in patients with RRMM who have received four or more prior therapies.
Belantamab mafodotin in combination with novel agents in relapsed/refractory multiple myeloma: DREAMM-5 study design. [2021]Belantamab mafodotin (belamaf) is a BCMA-targeted antibody-drug conjugate recently approved as monotherapy for adults with relapsed/refractory multiple myeloma who have received ≥4 prior therapies. Belamaf binds to BCMA and eliminates myeloma cells by multimodal mechanisms of action. The cytotoxic and potential immunomodulatory properties of belamaf have led to novel combination studies with other anticancer therapies. Here, we describe the rationale and design of DREAMM-5, an ongoing Phase I/II platform study evaluating the safety and efficacy of belamaf combined with novel agents, including GSK3174998 (OX40 agonist), feladilimab (an ICOS; GSK3359609), nirogacestat (a gamma-secretase inhibitor; PF-03084014) and dostarlimab (a PD-1 blocker) versus belamaf monotherapy for patients with relapsed/refractory multiple myeloma. Clinical trial registration: NCT04126200 (ClinicalTrials.gov).
Longer term outcomes with single-agent belantamab mafodotin in patients with relapsed or refractory multiple myeloma: 13-month follow-up from the pivotal DREAMM-2 study. [2022]On the basis of the DREAMM-2 study (ClinicalTrials.gov identifier NCT03525678), single-agent belantamab mafodotin (belamaf) was approved for patients with relapsed or refractory multiple myeloma (RRMM) who received ≥4 prior therapies, including anti-CD38 therapy. The authors investigated longer term efficacy and safety outcomes in DREAMM-2 after 13 months of follow-up among patients who received belamaf 2.5 mg/kg.