Belumosudil for Multiple Myeloma

Overseen By Robert Orlowski, M D

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: M.D. Anderson Cancer Center

Must not be taking: Antiretrovirals

Disqualifiers: Active hepatitis, Active CNS involvement, others

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

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

36 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores the use of belumosudil mesylate for individuals with multiple myeloma, a type of blood cancer that has recurred or is resistant to treatment. In Phase 1, researchers determine the safest dose to administer. In Phase 2, they assess whether this dose can help control the disease. Individuals with multiple myeloma who have tried at least three other treatments without success might be suitable candidates for this trial. As a Phase 1 and Phase 2 trial, the research aims to understand how the treatment works in people and measure its effectiveness in controlling the disease, offering participants a chance to contribute to potentially groundbreaking advancements in multiple myeloma treatment.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you must have completed any radiation therapy or corticosteroids for myeloma at least 2 weeks before starting the trial. You can continue using corticosteroids for other conditions if the dose is low.

Is there any evidence suggesting that belumosudil mesylate is likely to be safe for humans?

A previous study found that belumosudil, also known as Rezurock, was well tolerated by patients with chronic graft-versus-host disease (cGVHD). These patients often take other immune-suppressing medications, yet belumosudil demonstrated a good safety profile. Long-term research has also supported its safety and effectiveness without serious issues.

While primarily used for cGVHD, this treatment is now being tested for multiple myeloma, a type of blood cancer. Since testing for this condition is in the early stages, researchers are still collecting safety information specific to multiple myeloma. However, its existing approval for cGVHD suggests it could be safe for many people, though individual experiences may vary.

It is important to discuss potential risks and benefits with a healthcare provider before joining a clinical trial. ^{1 2 3 4 5}

Why are researchers excited about this possible treatment for multiple myeloma?

Belumosudil mesylate is unique because it targets ROCK2, a protein involved in inflammation and immune response, which is a different mechanism of action compared to most standard treatments for multiple myeloma that typically involve chemotherapy, immunomodulatory drugs, or proteasome inhibitors. This novel approach could potentially offer a new pathway for controlling the disease, especially for patients who have exhausted other options. Researchers are excited about belumosudil mesylate because its targeted mechanism may provide a more effective and potentially less toxic treatment alternative, improving outcomes and quality of life for patients with multiple myeloma.

What evidence suggests that belumosudil mesylate might be an effective treatment for multiple myeloma?

Studies have shown that Belumosudil mesylate can reduce the growth of various multiple myeloma cancer cells, suggesting it might help prevent the cancer from spreading. Research indicates that Belumosudil is safe and effective, with no new safety concerns identified. Clinical experts find the treatment results promising, suggesting it could be a viable option for managing multiple myeloma. These findings support the potential of Belumosudil in controlling this type of cancer. Participants in this trial will receive Belumosudil mesylate, with the dose determined by the study phase they join. ^{5 6 7 8 9}

Who Is on the Research Team?

Robert Z. Orlowski, M.D., Ph.D.

Principal Investigator

M.D. Anderson Cancer Center

Are You a Good Fit for This Trial?

This trial is for adults over 18 with relapsed/refractory multiple myeloma who've tried at least three treatments and still have measurable disease. They must be in fair to good health (ECOG PS of 0-3 if due to the disease), agree to use contraception, and not be on certain anti-HIV drugs or have other serious illnesses or second cancers.

Inclusion Criteria

I was diagnosed with multiple myeloma based on a tissue or cell test.

I have multiple myeloma that didn't respond to 3+ treatments, including 3 types of drugs.

My blood, liver, heart, and kidney functions are all good, and if I have HIV, my CD4+ count is over 1,000 without anti-retroviral therapy.

Exclusion Criteria

I do not have severe health issues or other cancers, and I am not HIV positive on antiretroviral therapy.

I am not on any experimental treatments for myeloma and my side effects from previous treatments have mostly gone away.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Phase 1: Dose Escalation

Define the toxicities and recommended Phase II dose (RP2D) of belumosudil mesylate in patients with relapsed/refractory multiple myeloma.

8-12 weeks

Phase 2: Dose Expansion

Obtain preliminary evidence of efficacy of belumosudil mesylate and further expand the safety experience in this patient population.

16-24 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Belumosudil Mesylate

Trial Overview The study is testing Belumosudil mesylate's effectiveness alone and combined with Dexamethasone in two phases. Phase I determines the safest dose, while Phase II checks if that dose can control multiple myeloma symptoms.

How Is the Trial Designed?

Group I: Phase 2 (dose expansion) Experimental Treatment 1 Intervention

Phase 2, participants will receive belumosudil mesylate at the recommended dose that was found in Phase 1.

Group II: Phase 1 (dose escalation) Experimental Treatment 1 Intervention

Phase 1, the dose of belumosudil mesylate participants receive will depend on when participants join this study. The first group of participants will receive the lowest dose level of belumosudil mesylate.

Belumosudil Mesylate is already approved in United States, Canada for the following indications:

Approved in United States as Rezurock for:

• Chronic graft-versus-host disease (cGvHD)

Approved in Canada as Rholistiq for:

• Chronic graft-versus-host disease (cGvHD)

Who Is Running the Clinical Trial?

M.D. Anderson Cancer Center

Lead Sponsor

Trials

3,107

Recruited

1,813,000+

Sanofi US Services, Inc

Collaborator

Trials

1

Recruited

40+

Published Research Related to This Trial

Belumosudil, an oral medication targeting ROCK2, showed a high overall response rate of 74% for the 200 mg daily dose and 77% for the 200 mg twice daily dose in patients with chronic graft-versus-host disease (cGVHD) after multiple prior treatments, indicating its efficacy in this challenging condition.

The treatment was well tolerated, with a median duration of response of 54 weeks and significant symptom reduction in 59% to 62% of subjects, while adverse events were consistent with those expected in cGVHD patients, suggesting a favorable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Belumosudil for chronic graft-versus-host disease after 2 or more prior lines of therapy: the ROCKstar Study. Cutler, C., Lee, SJ., Arai, S., et al.[2022]

Idecabtagene vicleucel (ide-cel) significantly improves progression-free survival (PFS) and overall survival (OS) in patients with relapsed and refractory multiple myeloma compared to the approved therapies selinexor plus dexamethasone and belantamab mafodotin, based on data from the phase 2 KarMMa trial.

The hazard ratios indicate that ide-cel offers substantial clinical benefits, with a PFS hazard ratio of 0.46 versus selinexor and 0.45 versus belantamab, and an OS hazard ratio of 0.23 versus selinexor and 0.35 versus belantamab, suggesting it is a promising treatment option for heavily pretreated patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Matching adjusted indirect comparisons of efficacy outcomes for idecabtagene vicleucel (ide-cel, bb2121) versus selinexor + dexamethasone and belantamab mafodotin in relapsed and refractory multiple myeloma. Rodriguez-Otero, P., Ayers, D., Cope, S., et al.[2021]

Belumosudil (REZUROCK™) is a newly approved ROCK inhibitor specifically designed for treating chronic graft-versus-host disease (cGVHD) in patients aged 12 and older who have not responded to at least two prior treatments.

The drug has received regulatory approval in the USA and is currently under review in several other countries, with ongoing clinical development for systemic sclerosis, highlighting its potential as a significant therapeutic option for these conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Belumosudil: First Approval. Blair, HA.[2022]

Belumosudil, a selective Rho-associated protein kinase 2 inhibitor, shows promise in treating chronic graft-versus-host disease by restoring immune balance and reducing fibrosis, with no significant adverse events reported during the study.

The pharmacokinetics of belumosudil are significantly affected by other medications, such as itraconazole and rifampicin, indicating that dosage adjustments may be necessary when coadministered with proton pump inhibitors like rabeprazole and omeprazole.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Phase 1 Pharmacokinetic Drug Interaction Study of Belumosudil Coadministered With CYP3A4 Inhibitors and Inducers and Proton Pump Inhibitors. Schueller, O., Willson, A., Singh, N., et al.[2022]

Patients with paroxysmal nocturnal hemoglobinuria (PNH) treated with either ravulizumab or eculizumab for 26 weeks reported better quality of life and functioning compared to the general population, indicating the efficacy of these treatments.

Ravulizumab showed larger effect sizes than eculizumab, and both treatments facilitated adaptive changes in patients' responses over time, suggesting they not only manage symptoms but also improve overall well-being.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Norm-based comparison of the quality-of-life impact of ravulizumab and eculizumab in paroxysmal nocturnal hemoglobinuria. Schwartz, CE., Stark, RB., Borowiec, K., et al.[2021]

In a subgroup analysis of the phase 3 CANDOR study involving 66 Asian patients with relapsed/refractory multiple myeloma, the KdD treatment reduced the risk of disease progression or death by 25% compared to Kd, indicating improved efficacy.

While KdD showed a trend towards better efficacy, it also had a higher incidence of serious adverse events (58.7% vs. 40.0% in Kd), highlighting the need for careful consideration of the benefit-risk profile in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Carfilzomib, dexamethasone, and daratumumab in Asian patients with relapsed or refractory multiple myeloma: post hoc subgroup analysis of the phase 3 CANDOR trial. Suzuki, K., Min, CK., Kim, K., et al.[2022]

Belumosudil (BLM) is a ROCK inhibitor approved by the FDA for treating chronic graft-versus-host disease (cGVHD) in patients aged 12 and older who have not responded to at least two prior therapies, highlighting its efficacy in a challenging patient population.

BLM received breakthrough therapy designation and orphan drug status, indicating its potential significance in treating rare diseases like cGVHD and systemic sclerosis, and it is currently undergoing further regulatory assessments and clinical trials for additional indications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Belumosudil with ROCK-2 inhibition: chemical and therapeutic development to FDA approval for the treatment of chronic graft-versus-host disease. Ali, F., Ilyas, A.[2022]

In a phase I trial involving 28 patients with relapsed/refractory multiple myeloma, ruxolitinib combined with lenalidomide and methylprednisolone showed a clinical benefit rate of 46% and an overall response rate of 38%, indicating its potential effectiveness in overcoming resistance to lenalidomide.

The trial reported no dose-limiting toxicities, suggesting that ruxolitinib is safe to use in this combination therapy, although some patients experienced grade 3 or 4 adverse events like anemia and thrombocytopenia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Phase I Study of Ruxolitinib, Lenalidomide, and Steroids for Patients with Relapsed/Refractory Multiple Myeloma. Berenson, JR., To, J., Spektor, TM., et al.[2021]

The introduction of novel agents for treating relapsed and/or refractory multiple myeloma (RRMM) has significantly improved response rates, rising from about 30% with single agents to up to 90% with combination therapies.

Newer treatments, including pomalidomide, panobinostat, carfilzomib, ixazomib, and monoclonal antibodies like daratumumab and elotuzumab, have enhanced overall response rates, even in heavily pretreated patients, while also improving the tolerability of treatment regimens and health-related quality of life.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

How have evolutions in strategies for the treatment of relapsed/refractory multiple myeloma translated into improved outcomes for patients? Sonneveld, P., De Wit, E., Moreau, P.[2022]

In a phase 2 study of 38 patients with relapsed/refractory multiple myeloma and varying degrees of renal impairment, the recommended dose adjustments for lenalidomide resulted in appropriate plasma exposure and a high overall response rate of 76%.

The safety profiles were consistent across different levels of renal function, indicating that the dosing adjustments based on creatinine clearance were effective and did not lead to increased toxicity or reduced efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacokinetics, safety, and efficacy of lenalidomide plus dexamethasone in patients with multiple myeloma and renal impairment. Bridoux, F., Chen, N., Moreau, S., et al.[2018]

Citations

1. ncbi.nlm.nih.gov ncbi.nlm.nih.gov/books/NBK604459/

Clinical Review - Belumosudil (Rezurock) - NCBI Bookshelf The treatment effect point estimates for response and survival outcomes were considered potentially clinically meaningful by the clinical experts. Although ...

2. pro.campus.sanofi pro.campus.sanofi/ae/payor/articles/rezurock-efficacy

Rezurock Efficacy Belumosudil showcased promising efficacy and safety results with no new safety signals identified. This was consistently demonstrated across ...

3. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0006497123112900

Poster Abstracts 651.Multiple Myeloma and Plasma Cell ... Belumosudil mesylate as a single agent reduced the viability of a panel of myeloma cell lines representing different molecular subtypes in a time- and ...

4. ashpublications.org ashpublications.org/blood/article/142/Supplement%201/4689/499354/Inhibition-of-Rho-Associated-Coiled-Coil

Inhibition of Rho-Associated Coiled-Coil Containing Protein ... Belumosudil mesylate as a single agent reduced the viability of a panel of myeloma cell lines representing different molecular subtypes in a ...

5. news.sanofi.us news.sanofi.us/2025-11-04-ASH-new-data-reinforce-Sanofis-leadership-in-rare-diseases-and-blood-cancers

new data reinforce Sanofi's leadership in rare diseases ... The medicines bortezomib, lenalidomide and dexamethasone, to treat adults with newly diagnosed multiple myeloma who cannot receive a type of ...

6. pro.campus.sanofi pro.campus.sanofi/ae/payor/articles/rezurock-safety

Rezurock Safety Long term data on Rezurock demonstrates efficacy without compromising safety ... Multiple Myeloma · Immune Thrombocytopenic (ITP). Other topics.

7. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/nda/2021/214783Orig1s000MultidisciplineR.pdf

214783Orig1s000 - accessdata.fda.gov There were 65 patients with active cGVHD treated on the belumosudil 200 mg once daily arm in Study KD025-213. The patients has a median age of 53 years ...

8. rezurockhcp.com rezurockhcp.com/rezurock-safety-data

Safety Data - REZUROCK® (belumosudil) REZUROCK was well tolerated in patients with cGVHD · Consider the safety profile of REZUROCK in patients with cGVHD who often receive immunosuppressive therapy.

9. medchemexpress.com medchemexpress.com/SLx-2119.html?srsltid=AfmBOopax5_E5uq4Kj6hi5nXl70s2Wq9H0NSZAmaWo4o_wP05rGMcKjD

Belumosudil (KD025) | ROCK2 Inhibitor Belumosudil (KD025) is a selective inhibitor of ROCK2 with IC50s of 105 nM and 24 μM for ROCK2 and ROCK1, respectively. Anti-fibrotic properties.