Belantamab Mafodotin + Nirogacestat + Pomalidomide for Multiple Myeloma

Not currently recruiting at 6 trial locations

Overseen By Sham Mailankody, MD

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Memorial Sloan Kettering Cancer Center

Must not be taking: CYP3A4 inhibitors, CYP1A2 inhibitors

Disqualifiers: AL amyloidosis, Active infection, HIV, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

Duration: 9 weeks (3 cycles of 3 weeks each)

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a combination of three drugs—belantamab mafodotin (an antibody-drug conjugate), nirogacestat (a gamma-secretase inhibitor), and pomalidomide—to determine their safety and effectiveness for people with multiple myeloma that has returned or is unresponsive to treatment. Researchers aim to find safe ways to combine these drugs and assess their ability to slow or stop the growth of this bone marrow cancer. Individuals who have undergone multiple treatments for multiple myeloma and have experienced relapses or no response to prior treatments might be suitable candidates for this trial. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the chance to be among the first to receive this new combination therapy.

Will I have to stop taking my current medications?

The trial protocol does not specify if you must stop taking your current medications, but it does mention that you cannot take certain drugs like strong CYP3A4 inhibitors or inducers within 14 days before starting the study. It's best to discuss your current medications with the study team to see if any adjustments are needed.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that the combination of belantamab mafodotin and nirogacestat generally has a manageable safety profile. One study found that a low dose of belantamab mafodotin (0.95 mg/kg) with nirogacestat (100 mg twice daily) was mostly well tolerated, with most participants not experiencing severe side effects.

Belantamab mafodotin has also been tested alone at higher doses, such as 3.4 mg/kg, and was deemed safe enough for further studies. However, side effects can still occur. For instance, some patients might experience vision issues or low blood cell counts. Regular check-ups and treatment adjustments usually manage these side effects.

In summary, while side effects are possible, current evidence suggests that the combination of belantamab mafodotin and nirogacestat is generally safe for people with multiple myeloma. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Unlike the standard treatments for multiple myeloma, which often focus on chemotherapy and immunomodulatory drugs, the combination of Belantamab Mafodotin, Nirogacestat, and Pomalidomide offers a novel approach. Belantamab Mafodotin is an antibody-drug conjugate that specifically targets and eliminates cancer cells by delivering a potent anti-cancer agent directly to them. Nirogacestat is a gamma-secretase inhibitor that may enhance the effectiveness of Belantamab Mafodotin by increasing the expression of its target on cancer cells. This combination promises a more focused attack on the cancer cells, potentially improving outcomes with fewer side effects. Researchers are particularly excited about the possibility of a more effective treatment that can be precisely directed at the cancer cells while sparing healthy cells.

What evidence suggests that this trial's treatments could be effective for multiple myeloma?

Research has shown that belantamab mafodotin, when used alone, yields promising results for patients with relapsed or refractory multiple myeloma, with nearly half of the patients experiencing a response to the treatment. In this trial, participants will receive a combination of belantamab mafodotin and nirogacestat. Early findings suggest this combination can be both effective and safe. Specifically, a study using a low dose of belantamab mafodotin with nirogacestat showed positive results, with the cancer's growth slowing or stopping in some cases. Overall, these treatments appear effective in managing the disease, offering hope to those battling this type of bone marrow cancer. ^{3 4 6 7 8}

Who Is on the Research Team?

Malin Hultcrantz

Principal Investigator

Memorial Sloan Kettering Cancer Center

Are You a Good Fit for This Trial?

This trial is for adults with multiple myeloma that hasn't improved or has returned after treatment. Participants must have measurable disease, may have had a stem cell transplant or be ineligible for one, and should not have major health issues that could affect safety. They need to agree to contraception use and follow specific drug safety programs.

Inclusion Criteria

Participants must enroll in and comply with the REMS program for pomalidomide

I have had a stem cell transplant using my own cells or am not eligible for one.

My cancer can be measured by blood tests, urine tests, imaging, or biopsy.

Exclusion Criteria

I have not had major surgery in the last 4 weeks.

I have an active liver or biliary disease.

I have a cancer type other than multiple myeloma.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Run-in

Participants receive nirogacestat 100 mg BID or 100 mg QD during the 4-day run-in period prior to starting belantamab mafodotin

4 days

Treatment

Participants receive belantamab mafodotin via IV infusion and nirogacestat 100 mg BID continuously during each cycle. Pomalidomide is added to certain dose cohorts.

9 weeks (3 cycles of 3 weeks each)

Follow-up

Participants are monitored for safety and effectiveness after treatment

2 years

What Are the Treatments Tested in This Trial?

Interventions

• Belantamab Mafodotin
• Nirogacestat

Trial Overview Researchers are testing the combination of belantamab mafodotin, nirogacestat, and pomalidomide on patients with relapsed or refractory multiple myeloma. They aim to determine the safest doses and effectiveness in slowing down or stopping cancer growth.

How Is the Trial Designed?

Group I: Belantamab Mafodotin and Nirogacestat Experimental Treatment 3 Interventions

There will be a 1:1 randomization betweennirogacestat 100 mg BID or 100 mg QD during the 4day run-in period prior to starting belantamab mafodotin on Cycle 1 Day 1 (days -4 to -1). The cycle length for Cycles 1-3 is 21 days (3 weeks). Treatment with nirogacestat will be 100 mg BID continuously during each cycle for all subjects. Belantamab mafodotin will be administered via IV infusion in an outpatient setting on Day 1 of Cycles 1-3 and nirogacestat 100mg BID will be administered continuously on Days 1-21 of each cycle. Treatment with belantamab mafodotin will be given at an initial dose of 1.0 mg/kg. The study will have a 3+3 dose escalation design for belantamab mafodotin. Belantamab mafodotin dose levels are 1.0 mg/kg, 1.4 mg/kg, and 1.9 mg/kg. Pomalidomide was added, 2 mg to the 1.4 mg/kg and 1.9 mg/kg dose cohorts.

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

Who Is Running the Clinical Trial?

Memorial Sloan Kettering Cancer Center

Lead Sponsor

Trials

1,998

Recruited

602,000+

Published Research Related to This Trial

Belantamab mafodotin is a first-in-class monoclonal antibody-drug conjugate designed to treat relapsed or refractory multiple myeloma by targeting B-cell maturation antigen (BCMA) and delivering a cytotoxic agent directly to cancer cells.

It received regulatory approval in the USA and EU in August 2020 based on promising results from the DREAMM-2 trial, specifically for patients who have undergone at least four prior therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Belantamab Mafodotin: First Approval. Markham, A.[2021]

In a study of 36 patients with multiple myeloma who had received a median of eight prior therapies, belantamab mafodotin demonstrated an overall response rate of 33%, which aligns with results from the DREAMM-2 trial.

Keratopathy was a notable side effect, affecting 43% of patients, with 8% discontinuing treatment due to this issue, highlighting the need for monitoring eye health during therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

"Real-life" data of the efficacy and safety of belantamab mafodotin in relapsed multiple myeloma-the Mayo Clinic experience. Vaxman, I., Abeykoon, J., Dispenzieri, A., et al.[2022]

In a study of 156 patients with relapsed and refractory multiple myeloma, belantamab-mafodotin (belamaf) demonstrated an overall response rate of 41.8%, with significant improvements in progression-free survival for those achieving at least minimal response (MR).

The safety profile of belamaf was manageable, with corneal events being the most common adverse effects, affecting 87.9% of patients, though only 1.3% discontinued treatment due to ocular toxicity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Belantamab Mafodotin in Patients with Relapsed/Refractory Multiple Myeloma: Results of the Compassionate Use or the Expanded Access Program in Spain. de la Rubia, J., Alonso, R., Clavero, ME., et al.[2023]

Belantamab mafodotin (belamaf) significantly improves overall survival (OS) and duration of response (DoR) in patients with relapsed/refractory multiple myeloma compared to selinexor plus low-dose dexamethasone, with a hazard ratio of 0.53 for OS and 0.41 for DoR, indicating its efficacy as a treatment option.

Belamaf also shows a favorable safety profile, with fewer severe adverse events compared to selinexor plus dexamethasone, making it a promising single-agent therapy for patients who have already undergone multiple lines of treatment.

NCBI (Pubmed)

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. Prawitz, T., Popat, R., Suvannasankha, A., et al.[2022]

Belantamab mafodotin (BLENREP™) is a promising new treatment for relapsed/refractory multiple myeloma, showing at least a partial response in heavily pre-treated patients, indicating its potential efficacy in difficult cases.

The treatment was well tolerated by the patients, suggesting a favorable safety profile, which is important for those who have already undergone multiple therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Belantamab Mafodotin and Relapsed/Refractory Multiple Myeloma: This Is Not Game Over. Condorelli, A., Garibaldi, B., Gagliano, C., et al.[2021]

Belantamab mafodotin, an antibody-drug conjugate, has shown significant efficacy and manageable safety in treating heavily pretreated relapsed/refractory multiple myeloma, as demonstrated in the phase I DREAMM-1 and phase II DREAMM-2 studies.

The recommended dose of belantamab mafodotin is 2.5 mg/kg every 3 weeks, with safety outcomes like corneal events and thrombocytopenia being closely linked to drug exposure, highlighting the importance of monitoring patient characteristics and disease burden in treatment planning.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Exposure-Response Analyses for Therapeutic Dose Selection of Belantamab Mafodotin in Patients With Relapsed/Refractory Multiple Myeloma. Ferron-Brady, G., Rathi, C., Collins, J., et al.[2022]

Belantamab mafodotin (belamaf) is an effective treatment for relapsed or refractory multiple myeloma, showing a 32% overall response rate in the phase II DREAMM-2 study with 95 patients.

While most patients experienced microcyst-like epithelial changes (MECs) as a side effect, these were generally manageable, with a high resolution rate and no permanent vision loss reported, indicating a need for careful monitoring and collaboration between eye care and oncology professionals.

NCBI (Pubmed)

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. Farooq, AV., Degli Esposti, S., Popat, R., et al.[2020]

Belantamab mafodotin (BLENREP) received accelerated FDA approval for treating relapsed or refractory multiple myeloma in adults who have undergone at least four prior therapies, showing an overall response rate of 31% to 34% in the DREAMM-2 trial with 2.5 or 3.4 mg/kg doses.

The most common side effect was keratopathy, affecting 71% to 77% of patients, leading to a boxed warning for ocular toxicity, indicating the need for careful monitoring and a restricted distribution program.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Belantamab Mafodotin for Patients with Relapsed or Refractory Multiple Myeloma. Baines, AC., Ershler, R., Kanapuru, B., et al.[2023]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT04126200

NCT04126200 | Platform Study of Belantamab Mafodotin ... This is a phase I/II, randomized, open-label, platform study designed to evaluate the effects of belantamab mafodotin in combination with other anti-cancer ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10251850/

Belantamab Mafodotin: From Clinical Trials Data to Real-Life ... This paper deals with Belantamab mafodotin, a novel anti-BCMA antibody-drug conjugate licensed by regulatory agencies for the treatment of anti-CD38-refractory ...

3. ashpublications.org ashpublications.org/bloodneoplasia/article/2/3/100103/536762/Belantamab-mafodotin-in-patients-with-relapsed

Belantamab mafodotin in patients with relapsed/refractory ... Key PointsBelantamab mafodotin showed ORR 45%, PFS 3.8 months, and OS 17.2 months in relapsed/refractory multiple myeloma in a real-world ...

4. onclive.com onclive.com/view/low-dose-belantamab-mafodotin-nirogacestat-demonstrates-encouraging-clinical-activity-in-r-r-myeloma

Low-Dose Belantamab Mafodotin/Nirogacestat ... These data including findings from a substudy of 10 patients assigned to 0.95 mg/kg of belamaf every 3 weeks plus continuous nirogacestat.

5. ascopubs.org ascopubs.org/doi/10.1200/JCO.2022.40.16_suppl.8019

DREAMM-5 study. | Journal of Clinical Oncology Encouraging clinical activity and a manageable safety profile is observed with low dose belamaf (0.95 mg/kg Q3W) + nirogacestat (100 mg BID continuously) in ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT07084896

NCT07084896 | Sub-study of Belantamab Mafodotin ... The primary purpose is to determine the safety and tolerability of belantamab mafodotin in combination with nirogacestat and to establish the recommended ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7924384/

Belantamab Mafodotin to Treat Multiple Myeloma A dosage of 3.4 mg/kg was designated as the recommended phase II dose (RP2D) based on data suggesting an acceptable efficacy and safety profile. Dose ...

8. sciencedirect.com sciencedirect.com/science/article/pii/S295032802500038X

Belantamab mafodotin in patients with relapsed/refractory ... Results. Ninety-four patients with relapsed/refractory multiple myeloma were treated with at least 1 dose of commercial belantamab mafodotin were identified and ...