Isatuximab + Belantamab for Multiple Myeloma

(ISABELA Trial)

Recruiting at 1 trial location

Overseen By Andrew Yee, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Massachusetts General Hospital

Must be taking: Acetylsalicylic acid

Must not be taking: Anti-CD38, Anti-BCMA

Disqualifiers: Corneal disease, HIV, Hepatitis B, others

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

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 1

Duration: Until progression, adverse events, or withdrawal of consent

50 Participants Needed

Trial Summary

What is the purpose of this trial?

The main goal of this phase II study is to evaluate the overall response rate of isatuximab, belantamab mafodotin, pomalidomide, and dexamethasone in relapsed and refractory multiple myeloma. The study drugs provided for research purposes are isatuximab and belantamab mafodotin.

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

The trial does not specify if you need to stop taking your current medications. However, you cannot have had myeloma therapy or investigational drugs within 2 weeks before starting the trial, and certain therapies like anti-CD38 monoclonal antibodies and high-dose corticosteroids are restricted. It's best to discuss your specific medications with the trial team.

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

Research shows that Belantamab mafodotin, when used alone, has shown promising results in treating patients with multiple myeloma who have tried several other treatments before. In a study, it achieved a response rate of about 31-34% in patients, meaning that a significant number of patients experienced a reduction in their cancer. ^{1 2 3 4 5}

What makes the drug combination of Isatuximab and Belantamab mafodotin unique for treating multiple myeloma?

This drug combination is unique because Belantamab mafodotin is a first-in-class antibody-drug conjugate that targets BCMA on myeloma cells, delivering a toxic payload to kill them, and has shown promising results in patients who have already undergone multiple treatments. The combination with Isatuximab, an anti-CD38 antibody, may enhance the treatment's effectiveness by using different mechanisms to attack the cancer cells. ^{1 2 4 5 6}

Research Team

Andrew Yee, MD

Principal Investigator

Massachusetts General Hospital

Eligibility Criteria

Adults with relapsed/refractory multiple myeloma who have adequate liver function, can take aspirin daily, and are not pregnant or breastfeeding. Participants must agree to contraception methods and join the Pomalyst REMS program. They should be able to swallow capsules whole, have an ECOG status ≤ 2, certain levels of hemoglobin and measurable disease indicators.

Inclusion Criteria

I am 18 years old or older.

My liver is functioning well.

My hemoglobin level is at least 8 g/dL, possibly after a blood transfusion.

Exclusion Criteria

I had a stem cell transplant using my own cells less than 6 months ago.

I had a stem cell transplant from a donor less than a year ago.

Side effects from my past cancer treatment have mostly gone away.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive isatuximab, belantamab mafodotin, pomalidomide, and dexamethasone. Isatuximab is given intravenously on specific days of each cycle, belantamab mafodotin every 8 weeks, pomalidomide orally on days 1-21, and dexamethasone orally on specified days of each cycle.

Until progression, adverse events, or withdrawal of consent

Cycle 1: 4 visits (in-person), Cycle 2 and onwards: 2 visits (in-person) every 28 days

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Long-term follow-up

Participants are monitored for progression-free survival and overall survival

Up to 10 years

Treatment Details

Interventions

• Belantamab mafodotin
• Dexamethasone
• Isatuximab
• Pomalidomide

Trial Overview The trial is testing a combination of drugs: Isatuximab, Belantamab Mafodotin (Bela Maf), Pomalidomide (Pom), and Dexamethasone (Dex) for their effectiveness in treating multiple myeloma that has come back or hasn't responded to treatment.

Participant Groups

Group I: Isatuximab + Belantamab mafodotin + Pomalidomide + Dexamethasone Experimental Treatment 4 Interventions

Isatuximab will be given once daily into your vein (by intravenous infusion) over about 30-60 minutes. This will occur during cycle 1 (cycle equals 28 days) on days 1, 8, 15, and 22 and cycle 2 and onwards days 1 and 15. Belantamab mafodotin will be given once every 8 weeks into your vein (by intravenous infusion) over about 60 minutes after completion of isatuximab infusion. Pomalidomide will be taken orally once daily during days 1-21 of each cycle. Dexamethasone will be taken orally once daily during days 1, 2, 8, 9, 15, 16, 22, and 23 of each cycle. Drug diaries will be provided to participants to document information about taking pomalidomide and dexamethasone.

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

Who Is Running the Clinical Trial?

Massachusetts General Hospital

Lead Sponsor

Trials

3,066

Recruited

13,430,000+

Sanofi

Industry Sponsor

Trials

2,246

Recruited

4,085,000+

Paul Hudson

Sanofi

Chief Executive Officer since 2019

Degree in Economics from Manchester Metropolitan University

Christopher Corsico

Sanofi

Chief Medical Officer

MD from Cornell University, MPH in Chronic Disease Epidemiology from Yale University

GlaxoSmithKline

Industry Sponsor

Trials

4,834

Recruited

8,389,000+

Headquarters

London, UK

Known For

Vaccines & Medicines

Top Products

**Advair (salmeterol, fluticasone propionate)**, **Shingrix (shingles vaccine)**, **Augmentin (amoxicillin/clavulanate potassium)**, **Ventolin (salbutamol sulfate)

Dame Emma Walmsley

GlaxoSmithKline

Chief Executive Officer since 2017

MA in Classics and Modern Languages from Oxford University

Dr. Hal Barron

GlaxoSmithKline

Chief Medical Officer since 2018

MD from Harvard Medical School

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]

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]

Belantamab mafodotin (belamaf) is an approved treatment for adults with relapsed/refractory multiple myeloma, showing effectiveness by targeting BCMA and eliminating myeloma cells through multiple mechanisms.

The ongoing DREAMM-5 study is exploring the safety and efficacy of belamaf in combination with other novel therapies, which may enhance its anticancer effects compared to belamaf alone.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Belantamab mafodotin in combination with novel agents in relapsed/refractory multiple myeloma: DREAMM-5 study design. Nooka, AK., Weisel, K., van de Donk, NW., et al.[2021]

In the DREAMM-2 study, after 13 months of follow-up, 32% of patients with relapsed or refractory multiple myeloma achieved an overall response to belantamab mafodotin (belamaf) at a dose of 2.5 mg/kg, indicating its efficacy in a heavily pretreated population.

The study found that belamaf maintained clinical activity without new safety concerns, even in patients experiencing prolonged dose delays due to corneal events, suggesting it is a safe treatment option for this patient group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.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. Lonial, S., Lee, HC., Badros, 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. 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]

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

Belantamab mafodotin in combination with novel agents in relapsed/refractory multiple myeloma: DREAMM-5 study design. [2021]

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