BMS-986393 for Multiple Myeloma

Recruiting at 119 trial locations

Overseen By BMS Clinical Trials Contact Center www.BMSClinicalTrials.com

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 3

Recruiting

Sponsor: Juno Therapeutics, Inc., a Bristol-Myers Squibb Company

Disqualifiers: CNS involvement, Solitary plasmacytomas, others

No Placebo Group

Pivotal Trial (Near Approval)

Prior Safety Data

Breakthrough Therapy

Trial Summary

What is the purpose of this trial?

The purpose of this study is to compare the efficacy and safety of BMS-986393 versus standard regimens in adult participants with Relapsed or Refractory and Lanalidomide-refractory Multiple Myeloma.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

What data supports the effectiveness of the drug BMS-986393 for Multiple Myeloma?

Research shows that combinations including carfilzomib, pomalidomide, and dexamethasone, with or without daratumumab, have been effective in treating relapsed multiple myeloma, with high overall response rates and prolonged survival times. These findings suggest that similar combinations could be promising for patients with multiple myeloma. ^{1 2 3 4 5}

What safety data exists for Carfilzomib in treating multiple myeloma?

Carfilzomib has been studied for its safety in treating multiple myeloma, with research covering its pharmacology, clinical trials, and potential side effects. ^{6 7 8 9 10}

What makes the drug BMS-986393 unique for treating multiple myeloma?

BMS-986393 combines several drugs, including daratumumab, which is a monoclonal antibody targeting CD38, and pomalidomide, an immunomodulatory drug, both of which have shown effectiveness in multiple myeloma. This combination aims to enhance treatment efficacy by targeting the cancer cells directly and modulating the immune system, offering a potentially more comprehensive approach compared to standard therapies. ^{1 11 12 13 14}

Research Team

Bristol-Myers Squibb

Principal Investigator

Bristol-Myers Squibb

Eligibility Criteria

Adults with relapsed or refractory multiple myeloma, specifically those who have not responded to lenalidomide treatment. They should have tried no more than three prior treatments including a proteasome inhibitor, an immunomodulatory drug, and an anti-CD38 monoclonal antibody. Participants need good organ function and measurable disease but cannot have central nervous system involvement by the myeloma.

Inclusion Criteria

My multiple myeloma has returned or is not responding to treatment.

My organs are functioning well.

Participants must have measurable disease during screening

Exclusion Criteria

Other protocol-defined Inclusion/Exclusion criteria apply

I have never had my multiple myeloma spread to my brain or spinal cord.

My multiple myeloma is not worsening quickly.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive BMS-986393 or standard regimens for relapsed or refractory multiple myeloma

Variable, based on treatment protocol

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 5 years

Treatment Details

Interventions

• Carfilzomib (Other)
• Cyclophosphamide (Other)
• Daratumumab (Monoclonal Antibodies)
• Dexamethasone (Other)
• Fludarabine (Other)
• Pomalidomide (Other)

Trial Overview The trial is testing BMS-986393's effectiveness and safety against standard therapies for multiple myeloma that has come back or hasn't responded to treatment. It includes adults who've had previous treatments fail them, especially after using lenalidomide.

Participant Groups

Group I: Arm A Experimental Treatment 7 Interventions

Group II: Arm B Active Control 4 Interventions

Carfilzomib is already approved in Canada, Japan for the following indications:

Approved in Canada as Kyprolis for:

• Multiple myeloma

Approved in Japan as Kyprolis for:

• Multiple myeloma

Who Is Running the Clinical Trial?

Juno Therapeutics, Inc., a Bristol-Myers Squibb Company

Lead Sponsor

Trials

19

Recruited

3,100+

Celgene Corporation

Industry Sponsor

Trials

446

Recruited

58,500+

Mark Alles

Celgene Corporation

Chief Executive Officer since 2016

Bachelor's degree from Lock Haven University of Pennsylvania

Sol J. Barer

Celgene Corporation

Chief Medical Officer since 2006

PhD in Organic and Physical Chemistry from Rutgers University

Findings from Research

The introduction of carfilzomib, a new proteasome inhibitor, and pomalidomide, an immunomodulatory drug, has significantly improved the effectiveness of multiple myeloma treatment.

Updated NCCN Clinical Practice Guidelines now recommend the use of these drugs, indicating a positive shift in treatment options as new therapies, including monoclonal antibodies, continue to emerge.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Multiple myeloma: new uses for available agents, excitement for the future. Anderson, KC.[2019]

The combination of carfilzomib, pomalidomide, and dexamethasone (KPd) showed a high overall response rate of 79% in patients with relapsed/refractory multiple myeloma, indicating its efficacy as a treatment option.

Adding daratumumab to the KPd regimen (Dara-KPd) resulted in even better outcomes, with an overall response rate of 89% and a significant rate of measurable residual disease negativity, suggesting that Dara-KPd may provide deeper and more durable responses without compromising safety.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase 1/2 study of carfilzomib, pomalidomide, and dexamethasone with and without daratumumab in relapsed multiple myeloma. Derman, BA., Zonder, J., Reece, D., et al.[2023]

Pomalidomide, when combined with low-dose dexamethasone, significantly improves progression-free survival and overall survival in adults with relapsed and refractory multiple myeloma, based on results from multinational phase II and III studies involving patients who had undergone at least two prior treatments.

The treatment has a manageable safety profile, with the most common serious side effects being neutropenia, infections, anemia, and thrombocytopenia, making it a viable option for patients with limited treatment alternatives.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pomalidomide: A Review in Relapsed and Refractory Multiple Myeloma. Hoy, SM.[2018]

In a study of 315 patients with relapsed and refractory multiple myeloma, carfilzomib monotherapy showed a similar overall survival (OS) rate compared to a control regimen of low-dose corticosteroids and optional cyclophosphamide, with median OS of 10.2 months for carfilzomib versus 10.0 months for control.

Carfilzomib demonstrated a higher overall response rate (19.1%) compared to the control group (11.4%), although both groups experienced similar progression-free survival and comparable rates of severe adverse events.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A randomized phase III study of carfilzomib vs low-dose corticosteroids with optional cyclophosphamide in relapsed and refractory multiple myeloma (FOCUS). Hájek, R., Masszi, T., Petrucci, MT., et al.[2022]

Four new agents have been approved for treating relapsed/refractory multiple myeloma, including bortezomib, lenalidomide, thalidomide, and liposomal doxorubicin, but there is no standard treatment, making personalized therapy essential.

New agents like carfilzomib and pomalidomide are being studied for their effectiveness and side effects, highlighting the importance of understanding treatment-related adverse events in choosing the best therapy for individual patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment-related adverse events in patients with relapsed/refractory multiple myeloma. Vij, R.[2017]

Acyclic nucleoside phosphonates like cidofovir, adefovir, and tenofovir are effective against various DNA viruses and retroviruses, with cidofovir approved for treating CMV retinitis in AIDS patients, adefovir for chronic hepatitis B, and tenofovir for HIV infections.

While cidofovir can cause nephrotoxicity at higher doses, adefovir and tenofovir have shown no significant toxic side effects at their approved dosages, making them safer options for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical potential of the acyclic nucleoside phosphonates cidofovir, adefovir, and tenofovir in treatment of DNA virus and retrovirus infections. De Clercq, E.[2021]

In a study of 46 AIDS patients receiving intravitreal injections of cidofovir (HPMPC), 26% experienced mild to moderate anterior nongranulomatous uveitis after their first injection, but no permanent vision impairment occurred.

Probenecid prophylaxis significantly reduced the incidence of uveitis from 71% to 18% compared to those who did not receive it, while topical corticosteroids and cycloplegics did not effectively prevent the condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Anterior nongranulomatous uveitis after intravitreal HPMPC (cidofovir) for the treatment of cytomegalovirus retinitis. Analysis and prevention. Chavez-de la Paz, E., Arevalo, JF., Kirsch, LS., et al.[2019]

In a study involving 16 eyes from 16 patients, intravitreal cidofovir was found to be safe and effective for treating cytomegalovirus retinitis, with a median time to retinitis progression of 64 to 78 days depending on the treatment group.

While most doses of cidofovir were well-tolerated, higher doses (100 micrograms) caused hypotony in some cases, suggesting that careful dosing is important for safety.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I/II study of intravitreal cidofovir for the treatment of cytomegalovirus retinitis in patients with the acquired immunodeficiency syndrome. Kirsch, LS., Arevalo, JF., De Clercq, E., et al.[2019]

Carfilzomib is an effective treatment for patients with relapsed or refractory multiple myeloma, as shown in the PX-171-003-A1 phase II trial, which involved patients who had already undergone at least two prior therapies.

Common side effects of carfilzomib include fatigue, anemia, nausea, and thrombocytopenia, and it is recommended to use dexamethasone as premedication to reduce the risk of infusion reactions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Carfilzomib: A new proteasome inhibitor for relapsed or refractory multiple myeloma. Steele, JM.[2014]

HDP-cyclic-CDV is safely converted to HDP-CDV in the eye, with no observed toxicity from intravitreal injections up to 28 μg/eye, indicating its potential for safe use in treating CMV retinitis.

The pharmacokinetics of HDP-CDV show a two-phase elimination process with half-lives of approximately 8.4 days in the retina, allowing for sustained antiviral activity that can prevent viral retinitis for up to 68 days after a single dose.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intraocular safety and pharmacokinetics of hexadecyloxypropyl-cidofovir (HDP-CDV) as a long-lasting intravitreal antiviral drug. Wang, H., Chhablani, J., Freeman, WR., et al.[2021]

Immunomodulatory drugs like thalidomide and lenalidomide have shown significant effectiveness in treating multiple myeloma and related blood disorders, demonstrating high response rates across various treatment phases.

These drugs not only target cancer cells directly but also enhance the immune response within the bone marrow, and have been successfully combined with other treatments, leading to FDA approval for their use in multiple myeloma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Therapeutic use of immunomodulatory drugs in the treatment of multiple myeloma. Raje, N., Hideshima, T., Anderson, KC.[2018]

Intravenous daratumumab, when combined with bortezomib, thalidomide, and dexamethasone, significantly improves treatment outcomes for adults with newly diagnosed multiple myeloma, leading to higher rates of stringent complete response and prolonged progression-free survival, as shown in the phase III CASSIOPEIA trial.

The addition of daratumumab has a minimal impact on overall toxicity, with the most common serious side effects being blood-related issues, indicating it is a relatively safe option for patients undergoing treatment for multiple myeloma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Daratumumab: A Review in Combination Therapy for Transplant-Eligible Newly Diagnosed Multiple Myeloma. Lamb, YN.[2021]

In a subgroup analysis of the CASTOR trial involving 498 patients, daratumumab combined with bortezomib and dexamethasone (D-Vd) significantly prolonged progression-free survival (PFS) in patients with high cytogenetic risk (12.6 months) compared to bortezomib and dexamethasone alone (6.2 months).

D-Vd also demonstrated a higher rate of minimal residual disease (MRD) negativity, indicating deeper responses in treatment effectiveness, while maintaining a safety profile consistent with the overall study population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Daratumumab, bortezomib, and dexamethasone in relapsed or refractory multiple myeloma: subgroup analysis of CASTOR based on cytogenetic risk. Weisel, K., Spencer, A., Lentzsch, S., et al.[2021]

References

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

Multiple myeloma: new uses for available agents, excitement for the future. [2019]

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

Phase 1/2 study of carfilzomib, pomalidomide, and dexamethasone with and without daratumumab in relapsed multiple myeloma. [2023]

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

Pomalidomide: A Review in Relapsed and Refractory Multiple Myeloma. [2018]

4. England pubmed.ncbi.nlm.nih.gov

A randomized phase III study of carfilzomib vs low-dose corticosteroids with optional cyclophosphamide in relapsed and refractory multiple myeloma (FOCUS). [2022]

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

Treatment-related adverse events in patients with relapsed/refractory multiple myeloma. [2017]

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

Clinical potential of the acyclic nucleoside phosphonates cidofovir, adefovir, and tenofovir in treatment of DNA virus and retrovirus infections. [2021]

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

Anterior nongranulomatous uveitis after intravitreal HPMPC (cidofovir) for the treatment of cytomegalovirus retinitis. Analysis and prevention. [2019]

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

Phase I/II study of intravitreal cidofovir for the treatment of cytomegalovirus retinitis in patients with the acquired immunodeficiency syndrome. [2019]

9. England pubmed.ncbi.nlm.nih.gov

Carfilzomib: A new proteasome inhibitor for relapsed or refractory multiple myeloma. [2014]

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

Intraocular safety and pharmacokinetics of hexadecyloxypropyl-cidofovir (HDP-CDV) as a long-lasting intravitreal antiviral drug. [2021]

11. England pubmed.ncbi.nlm.nih.gov

Therapeutic use of immunomodulatory drugs in the treatment of multiple myeloma. [2018]

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

Daratumumab: A Review in Combination Therapy for Transplant-Eligible Newly Diagnosed Multiple Myeloma. [2021]

13. England pubmed.ncbi.nlm.nih.gov

The MUK five protocol: a phase II randomised, controlled, parallel group, multi-centre trial of carfilzomib, cyclophosphamide and dexamethasone (CCD) vs. cyclophosphamide, bortezomib (Velcade) and dexamethasone (CVD) for first relapse and primary refractory multiple myeloma. [2022]

14. England pubmed.ncbi.nlm.nih.gov

Daratumumab, bortezomib, and dexamethasone in relapsed or refractory multiple myeloma: subgroup analysis of CASTOR based on cytogenetic risk. [2021]