Belantamab Mafodotin for Multiple Myeloma

(DREAMM12 Trial)

Recruiting in Palo Alto (17 mi)

+25 other locations

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 1

Recruiting

Sponsor: GlaxoSmithKline

No Placebo Group

Approved in 2 Jurisdictions

Trial Summary

What is the purpose of this trial?

Belantamab mafodotin is an antibody-drug conjugate (ADC) containing humanized anti- B-cell maturation antigen (BCMA) monoclonal antibody (mAb). Renal impairment is a major complication of multiple myeloma (MM) and the majority of MM participants is either at risk or already has renal dysfunction at initial diagnosis. The purpose of this study is to assess the pharmacokinetics (PK), safety, and tolerability of belantamab mafodotin monotherapy in participants with RRMM, who have had at least 3 lines of prior treatment (or at least 2 lines of prior treatment if ineligible for autologous stem cell transplantation ) and have either normal or impaired renal functions. The study will consist of two parts: part 1 will include participants with normal/mildly impaired renal function and severe renal impairment and part 2 will include participants with end-stage renal disease (ESRD), where participants are either not undergoing or require hemodialysis. Participants will be administered belantamab mafodotin at a dose of 2.5 milligram per kilogram (mg/kg) intravenously once in three weeks (Q3W) dosing in Part 1. Based on the Part 1 Safety/Pharmacokinetic (PK) data, Part 2 participants will be administered the dose of either 2.5 mg/kg or 1.9 mg/kg (or other adjusted dose). Participants will be treated with belantamab mafodotin monotherapy until confirmed disease progression, death, unacceptable toxicity, withdrawal of consent, or end of study, whichever occurs first. This study will include a screening phase, treatment phase, follow-up phase and a post analysis continued treatment (PACT) phase . The total duration of the study is approximately up to 48 months.

Do I need to stop my current medications to join the trial?

The trial protocol does not specify if you need to stop taking your current medications. However, you cannot have received an investigational drug or a strong Organic-anion transporting polypeptide inhibitor within 14 days or 5 half-lives before the first dose of the study drug. It's best to discuss your current medications with the trial team.

What data supports the idea that Belantamab Mafodotin for Multiple Myeloma is an effective drug?

The available research shows that Belantamab Mafodotin is effective for treating multiple myeloma, especially in patients who have already tried several other treatments. In the DREAMM-2 study, about 32% of patients who had been heavily pretreated showed a positive response to the drug. This means that nearly one-third of the patients experienced a reduction in their cancer after using Belantamab Mafodotin. Additionally, the drug has been approved in the USA and EU for patients who have tried at least four other therapies, indicating its effectiveness in difficult cases. ^{1 2 3 4 5}

What safety data is available for Belantamab Mafodotin in treating multiple myeloma?

Belantamab Mafodotin has been evaluated in several studies, including the DREAMM-1 and DREAMM-2 trials, and has shown manageable safety in patients with relapsed/refractory multiple myeloma. Common adverse effects include ocular toxicity, such as keratopathy, blurred vision, and changes in visual acuity, with keratopathy being the most frequent. Thrombocytopenia and infections are also noted adverse effects. The FDA has approved it with a boxed warning for ocular toxicity, and it is available under a Risk Evaluation and Mitigation Strategy. Real-world studies confirm these findings, showing a tolerable toxicity profile similar to clinical trials. ^{3 6 7 8 9}

Is the drug Belantamab Mafodotin a promising treatment for Multiple Myeloma?

Yes, Belantamab Mafodotin is a promising drug for treating Multiple Myeloma. It has shown strong anti-cancer effects in patients who have already tried several other treatments. It works by targeting and killing cancer cells, and it has been approved for use in the USA and EU for patients with relapsed or refractory Multiple Myeloma. ^{1 2 3 4 6}

Eligibility Criteria

This trial is for adults with multiple myeloma who've had at least 3 prior treatments (or 2 if they couldn't have a stem cell transplant) and have varying degrees of kidney function, including severe impairment or end-stage renal disease. Participants must be able to consent, follow study rules, and use contraception.

Inclusion Criteria

I am using birth control as required by local laws for clinical study participants.

I am at least 18 years old, or 19 if I am from the Republic of Korea.

Main additional inclusion criteria in Group 1 (matched control participants)

Exclusion Criteria

I haven't taken any experimental drugs within the last 14 days or 5 half-lives, whichever is shorter.

I have had a stem cell transplant from a donor.

I have not undergone plasmapheresis within the last week.

Treatment Details

Interventions

• Belantamab mafodotin (Monoclonal Antibodies)

Trial Overview The trial tests belantamab mafodotin monotherapy in multiple myeloma patients with different levels of kidney health. It's given intravenously every three weeks. The study has two parts based on the severity of renal dysfunction and includes screening, treatment, follow-up, and continued treatment phases.

Participant Groups

Group I: Part 2: Participants with ESRD (on hemodialysis) Experimental Treatment 1 Intervention

Participants with ESRD (iGFR: \<15 mL/min) on hemodialysis will be administered with belantamab mafodotin either 2.5 mg/kg or 1.9 mg/kg (or other adjusted dose) as an intravenous infusion over 30 minutes Q3W on Day 1 of every 21-day cycle until confirmed disease progression, death, unacceptable toxicity, withdrawal of consent, or end of study, whichever occurs first. In Part 2, the dose will be decided after evaluation of pharmacokinetic and safety data of Part 1.

Group II: Part 2: Participants with ESRD (not on dialysis) Experimental Treatment 1 Intervention

Participants with ESRD (iGFR: \<15 mL/min) not on dialysis will be administered with belantamab mafodotin either 2.5 mg/kg or 1.9 mg/kg (or other adjusted dose) as an intravenous infusion over 30 minutes Q3W on Day 1 of every 21- day cycle until confirmed disease progression, death, unacceptable toxicity, withdrawal of consent, or end of study, whichever occurs first. In Part 2, the dose will be decided after evaluation of pharmacokinetic and safety data of Part 1.

Group III: Part 1: Participants with severe renal impairment Experimental Treatment 1 Intervention

Participants with severely impaired renal function (iGFR: 15-29 mL/min) will be administered with belantamab mafodotin 2.5 mg/kg as an intravenous infusion over 30 minutes Q3W on Day 1 of every 21- day cycle until confirmed disease progression, death, unacceptable toxicity, withdrawal of consent, or end of study, whichever occurs first.

Group IV: Part 1: Participants with normal/mild impaired renal function Experimental Treatment 1 Intervention

Participants with normal or mildly impaired renal function (Normal: individual glomerular filtration rate \[iGFR\]: \>=90 milliliter per minute; Mild impairment: iGFR: 60-89 mL/min will be administered with belantamab mafodotin 2.5 mg/kg as an intravenous infusion over 30 minutes Q3W on Day 1 of every 21- day cycle until confirmed disease progression, death, unacceptable toxicity, withdrawal of consent, or end of study, whichever occurs first.

Belantamab mafodotin is already approved in United States, European Union for the following indications:

🇺🇸 Approved in United States as Blenrep for:

• Relapsed or refractory multiple myeloma (approval withdrawn)

🇪🇺 Approved in European Union as Blenrep for:

• Relapsed or refractory multiple myeloma

Find a Clinic Near You

Research Locations Nearby Select from list below to view details:

GSK Investigational Site Detroit, MI

GSK Investigational Site Monroeville, PA

GSK Investigational Site Milwaukee, WI

GSK Investigational Site Manhasset, NY

More Trial Locations

Who Is Running the Clinical Trial?

GlaxoSmithKline Lead Sponsor

References

1. England pubmed.ncbi.nlm.nih.gov

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).

2. England pubmed.ncbi.nlm.nih.gov

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.

3. United States pubmed.ncbi.nlm.nih.gov

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).

4. New Zealand pubmed.ncbi.nlm.nih.gov

Belantamab Mafodotin: First Approval. [2021] Belantamab mafodotin (BLENREP&#8482;; 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.

5. England pubmed.ncbi.nlm.nih.gov

Belantamab mafodotin for relapsed or refractory multiple myeloma (DREAMM-2): a two-arm, randomised, open-label, phase 2 study. [2020] Belantamab mafodotin (GSK2857916), an immunoconjugate targeting B-cell maturation antigen, showed single-agent activity in the phase 1 DREAMM-1 study in heavily pre-treated patients with relapsed or refractory multiple myeloma. We further investigated the safety and activity of belantamab mafodotin in the DREAMM-2 study.

6. United States pubmed.ncbi.nlm.nih.gov

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, &#223;2 -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&#160;mg/kg every 3&#160;weeks in patients with RRMM who have received four or more prior therapies.

7. England pubmed.ncbi.nlm.nih.gov

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.

8. United States pubmed.ncbi.nlm.nih.gov

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).

9. Italy pubmed.ncbi.nlm.nih.gov

Real-world study of the efficacy and safety of belantamab mafodotin (GSK2857916) in relapsed or refractory multiple myeloma based on data from the nominative ATU in France: the IFM 2020-04 study. [2023] Belantamab mafodotin (BM) is an anti-BCMA antibody-drug conjugate (GSK2857916) that represents an alternative option in multiple myeloma. We sought to assess the efficacy and safety of BM in a real-world setting in patients who benefited from an early access program. We conducted an observational, retrospective, multicenter study. Eligibility criteria were treatment of relapsed or refractory multiple myeloma (RRMM) in monotherapy in adult patients who have received at least three lines of therapy previously, including at least one immunomodulatory agent (IMiD), a proteasome inhibitor (PI) and an anti-CD38 monoclonal antibody, and whose disease progressed during the last treatment period. The primary endpoint of the study is to assess the overall survival (OS). Between November 2019 and December 2020, 106 patients were treated with BM; 97 were eligible for the efficacy evaluation and 104 for safety. The median age was 66 (range, 37-82) years. High-risk cytogenetics were identified in 40.9% of patients. Fifty-five (56.7%) patients were triple-class refractory and 11 (11.3%) were penta-class refractory. The median number of prior lines of treatment was five (range, 3-12). The median number of BM cycles administered was three (range, 1-22). The overall response rate at best response was 38.1% (37/97). The median OS was 9.3 months (95% confidence interval [CI]: 5.9-15.3), and median progression-free survival was 3.5 months (95% CI: 1.9-4.7). The median duration of response was 9 months (range, 4.65-10.4). Treatment was delayed for 55 (52.9%) patients including 36.5% for treatment-related toxicity. Ophthalmic adverse events, mainly grade ≤2, were the most common toxicity (48%). The occurrence of keratopathy was 37.5%. Overall, our data are concordant with the results from DREAMM-2 in terms of efficacy and safety on a non-biased population.