Belantamab Mafodotin + Nirogacestat + Pomalidomide for Multiple Myeloma

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)

9 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial is testing a combination of three drugs to treat people whose bone marrow cancer has come back or didn't respond to previous treatments. The drugs aim to kill cancer cells, help the immune system fight the cancer, and stop the cancer from growing. Researchers are looking for the safest dose and checking if this combination is effective.

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.

What data supports the effectiveness of the drug Belantamab Mafodotin for treating multiple myeloma?

Belantamab Mafodotin has shown effectiveness in treating relapsed or refractory multiple myeloma, with studies reporting an overall response rate of around 31-34% in patients who have tried multiple other treatments. It was approved by the FDA based on these results, although it can cause eye-related side effects. ^{1 2 3 4 5}

Is the combination of Belantamab Mafodotin, Nirogacestat, and Pomalidomide safe for humans?

Belantamab Mafodotin has been studied in patients with multiple myeloma and is generally considered safe, but it can cause eye problems like changes in vision and dry eyes, and is only available through a special program due to these risks. There is no specific safety data available for the combination with Nirogacestat and Pomalidomide. ^{1 3 4 6 7}

What makes the drug combination of Belantamab Mafodotin, Nirogacestat, and Pomalidomide unique for treating multiple myeloma?

This drug combination is unique because Belantamab Mafodotin is a first-in-class antibody-drug conjugate that targets a specific protein on myeloma cells, delivering a powerful cancer-killing agent directly to the tumor. It is used for patients who have already tried multiple other treatments, offering a new option for those with relapsed or refractory multiple myeloma. ^{1 2 4 5 8}

Research Team

Malin Hultcrantz

Principal Investigator

Memorial Sloan Kettering Cancer Center

Eligibility Criteria

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 am 18 years old or older.

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

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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 (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]

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 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 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, 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]

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]

References

1. 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]

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]

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

FDA Approval Summary: Belantamab Mafodotin for Patients with Relapsed or Refractory Multiple Myeloma. [2023]

4. Switzerland pubmed.ncbi.nlm.nih.gov

Belantamab Mafodotin and Relapsed/Refractory Multiple Myeloma: This Is Not Game Over. [2021]

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

Belantamab Mafodotin: First Approval. [2021]

6. Switzerland 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. [2023]

7. 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]

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

"Real-life" data of the efficacy and safety of belantamab mafodotin in relapsed multiple myeloma-the Mayo Clinic experience. [2022]