BGB-11417 + Dexamethasone + Carfilzomib for Multiple Myeloma

Recruiting at 147 trial locations

Overseen By BeOne Medicines

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: BeOne Medicines

Must be taking: Dexamethasone, Carfilzomib

Must not be taking: BCL2 inhibitors

Disqualifiers: Cardiovascular disease, HIV, Hepatitis, others

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

Compensation: Varies

Number of Visits: Unknown

246 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine the safety and effectiveness of a new treatment, sonrotoclax (also known as BGB-11417), for individuals with multiple myeloma, a type of blood cancer that has returned or stopped responding to treatment. Researchers are testing sonrotoclax alone and in combination with other drugs, such as dexamethasone, carfilzomib, daratumumab, and pomalidomide, to identify the most effective approach. It is suitable for those with multiple myeloma who have experienced cancer recurrence or progression and have specific genetic profiles involving t(11;14) translocation. As a Phase 1 and Phase 2 trial, this research focuses on understanding how the treatment works in people and measuring its effectiveness in an initial, smaller group, offering a chance to contribute to groundbreaking advancements in multiple myeloma treatment.

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.

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

Research has shown that the combination of sonrotoclax (BGB-11417) and dexamethasone is generally well-tolerated. Studies have found low rates of infections and blood-related side effects, suggesting the treatment is relatively safe for people with relapsed or refractory multiple myeloma, particularly those with the specific genetic marker t(11;14).

Safety information for the combination of sonrotoclax, dexamethasone, and carfilzomib is still being gathered. Previous patients have tolerated sonrotoclax and dexamethasone well, which bodes well for the addition of carfilzomib. However, since this trial is in its early stages, the complete safety profile remains under study.

Overall, both combinations appear to have a good safety record. Participants might experience mild side effects. As with any treatment, discussing potential risks with a healthcare provider is important. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the treatment involving BGB-11417 for multiple myeloma because it takes a novel approach to targeting cancer cells. Unlike standard treatments like bortezomib, lenalidomide, and dexamethasone, which focus on different aspects of cancer cell growth and survival, BGB-11417 is a Bcl-2 inhibitor. This means it specifically targets the Bcl-2 protein that helps cancer cells avoid programmed cell death, potentially leading to more effective cancer cell elimination. Additionally, when combined with other drugs like dexamethasone and carfilzomib, it may offer a powerful multi-drug strategy that enhances overall treatment efficacy.

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

Research has shown that sonrotoclax, particularly when combined with dexamethasone, yields promising results for treating a type of multiple myeloma that has returned or is unresponsive to treatment, specifically with the t(11;14) genetic marker. Studies report that up to 80.6% of patients respond well to higher doses, with many experiencing very good partial improvements or better. In this trial, participants may receive sonrotoclax with dexamethasone alone or in combination with carfilzomib. The combination of sonrotoclax with dexamethasone and carfilzomib has demonstrated early and lasting positive effects and is well-tolerated. These findings suggest that this treatment could effectively provide deep and lasting improvements for patients with this type of multiple myeloma. ^{1 2 3 4 6}

Are You a Good Fit for This Trial?

This trial is for adults with multiple myeloma who've had at least one but no more than seven prior treatments, including a proteasome inhibitor and an IMiD agent. They must have measurable disease, not be refractory to carfilzomib, and have adequate organ function. Exclusions include uncontrolled diabetes, significant heart issues, certain infections like HIV or hepatitis B/C, amyloidosis, plasma cell leukemia, and others.

Inclusion Criteria

I have taken carfilzomib before, but not in the last 6 months and it was effective.

I have tried at least 3 treatments including proteasome inhibitors, IMiD agents, and anti-CD38 antibodies without success.

You have a certain level of abnormal proteins in your blood or urine, and an abnormal ratio of certain proteins in your body.

Exclusion Criteria

I have been diagnosed with POEMS syndrome.

You currently have an active hepatitis B or C infection.

I have a single plasma cell tumor.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation

Dose-escalation and de-escalation to determine maximum tolerated dose (MTD)

4 weeks

Cohort Expansion

Further evaluation of the safety and efficacy of BGB-11417 in combination with dexamethasone and carfilzomib

Approximately 4 years

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• BGB-11417
• Carfilzomib
• Dexamethasone

Trial Overview The study tests BGB-11417 alone and combined with dexamethasone and carfilzomib in patients with multiple myeloma. It has two parts: dose escalation (Part 1) where the safest dose is found by gradually increasing it; then cohort expansion (Part 2) where more people are given this dose to see how well it works.

How Is the Trial Designed?

Group I: Part 2 Cohort Expansion Experimental Treatment 3 Interventions

There will be up to 7 expansion cohorts to further evaluate the safety and efficacy of sonrotoclax monotherapy, sonrotoclax plus dexamethasone in combination with dexamethasone plus carfilzomib, and in combination with dexamethasone plus daratumumab

Group II: Part 1 Dose Escalation Experimental Treatment 5 Interventions

Dose-escalation and de-escalation to determine maximum tolerated dose (MTD) of sonrotoclax plus dexamethasone, sonrotoclax plus dexamethasone plus carfilzomib, sonrotoclax plus dexamethasone plus daratumumab, and sonrotoclax plus dexamethasone plus pomalidomide.

Who Is Running the Clinical Trial?

BeOne Medicines

Lead Sponsor

BeiGene

Lead Sponsor

Trials

216

Recruited

32,500+

Published Research Related to This Trial

Carfilzomib shows significant efficacy in treating multiple myeloma, with a 28% complete response rate and a 93% overall response rate among 2,487 patients analyzed across 12 clinical trials.

While carfilzomib improves survival rates (93% progression-free survival at 1 year), it is associated with a higher incidence of cardiotoxicity compared to traditional treatments, although it does not significantly increase the risk of peripheral neuropathy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Efficacy and Safety of Carfilzomib in the Treatment of Multiple Myeloma：A Systematic Evaluation]. Luo, T., Xia, HL.[2020]

Carfilzomib-containing combinations as frontline therapy for multiple myeloma showed a high overall response rate of 94% and a complete response rate of 21% across 13 trials involving 704 subjects.

The combination of carfilzomib with lenalidomide and dexamethasone (CFZ-LEN-DEX) resulted in a significantly higher complete response rate of 49% compared to other combinations, indicating it may be the most effective regimen for newly diagnosed patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Carfilzomib-containing combinations as frontline therapy for multiple myeloma: A meta-analysis of 13 trials. Sheng, Z., Li, G., Li, B., et al.[2018]

In a phase 2 study involving 72 patients with newly diagnosed multiple myeloma, the combination of carfilzomib and dexamethasone (Kd) achieved a remarkable overall response rate of 90%, with 7% of patients reaching a complete response and 58% achieving a very good partial response.

The treatment was generally well-tolerated, with most adverse events being low grade; however, there was an 11.1% incidence of grade 3 or higher cardiovascular events, indicating a need for monitoring during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II study of carfilzomib and dexamethasone therapy for newly diagnosed multiple myeloma. Forsberg, PA., Rossi, AC., Boyer, A., et al.[2020]

In a study of 123 patients with relapsed or refractory multiple myeloma treated with carfilzomib, lenalidomide, and dexamethasone (KRD), the overall response rate was 85%, indicating high efficacy of this treatment regimen.

The treatment was generally well tolerated, with manageable toxicity; although 35% of patients experienced arterial hypertension, it did not necessitate stopping treatment, and only 5% of patients experienced treatment-related deaths.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

KRD (carfilzomib and lenalidomide plus dexamethasone) for the treatment of relapsed or refractory multiple myeloma in the real-life: a retrospective survey in 123 patients. Palmieri, S., Rocco, S., Vitagliano, O., et al.[2021]

Carfilzomib, when combined with lenalidomide and dexamethasone, significantly improved progression-free survival (PFS) in patients with relapsed multiple myeloma, with a median PFS of 26.3 months compared to 17.6 months for the control group, indicating a clinically meaningful benefit.

The safety profile of carfilzomib was deemed manageable, with common side effects including neutropenia and anemia, suggesting that the benefits of this treatment outweigh the risks for patients who have received prior therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The European Medicines Agency Review of Carfilzomib for the Treatment of Adult Patients with Multiple Myeloma Who Have Received at Least One Prior Therapy. Tzogani, K., Camarero Jiménez, J., Garcia, I., et al.[2018]

In a phase 1b study involving patients with newly diagnosed multiple myeloma, the combination of carfilzomib, cyclophosphamide, and dexamethasone showed an impressive overall response rate of 87.5% at the highest carfilzomib dose of 56 mg/m2.

The treatment was generally well-tolerated, with manageable adverse effects; however, some patients experienced grade 3 or higher toxicities, including anemia and neutropenia, indicating that while effective, monitoring for side effects is important.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Multicenter, Open-Label, Phase 1b Study of Carfilzomib, Cyclophosphamide, and Dexamethasone in Newly Diagnosed Multiple Myeloma Patients (CHAMPION-2). Boccia, RV., Bessudo, A., Agajanian, R., et al.[2018]

Carfilzomib is an effective treatment for relapsed or refractory multiple myeloma, showing a 23.7% overall response rate and a median overall survival of 15.6 months in a Phase II study of 266 heavily pretreated patients.

Unlike bortezomib, carfilzomib does not cause peripheral neuropathy, making it a safer option for patients, although it shares similar side effects such as anemia and fatigue.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Carfilzomib: a second-generation proteasome inhibitor for the treatment of multiple myeloma. McBride, A., Klaus, JO., Stockerl-Goldstein, K.[2019]

Citations

1. sciencedirect.com sciencedirect.com/science/article/pii/S253113792501137X

1184 updated results of sonrotoclax + dexamethasone, an ... The ORR (95% CI) was 64.3% (35.1%-87.2%) for 320 mg and 80.6% (64.0%-91.8%) for 640-mg, with VGPR or better rates (95% CI) of 35.7% (12.8%-64.9%) and 55.6% ( ...

2. haematologica.org haematologica.org/article/view/12599

UPDATED INTERIM RESULTS OF SONROTOCLAX + ... ORRs were 64.3% (320mg) and 80.6% (640 mg), with very good partial response or better rates of 35.7% and 55.6%, respectively (Figure). Median ...

3. ashpublications.org ashpublications.org/blood/article/142/Supplement%201/1011/499011/Sonrotoclax-BGB-11417-in-Combination-with

Sonrotoclax (BGB-11417) in Combination with ... Conclusion: Sonrotoclax plus dexamethasone was generally well tolerated in patients with R/R MM harboring t(11;14) at doses up to 640 mg, and initial safety ...

4. beonemedinfo.com beonemedinfo.com/CongressDocuments/Dhakal_BGB-11417-105_ICML_Presentation_2025.pdf

Updated Interim Results of Sonrotoclax + Dexamethasone ... • Updated safety and efficacy data are presented for patients treated with sonrotoclax. + ... BCL2, B-cell lymphoma 2; MM, multiple myeloma.

5. onclive.com onclive.com/view/sonrotoclax-dexamethasone-combo-is-tolerable-generates-deep-responses-in-t-11-14-r-r-myeloma

Sonrotoclax/Dexamethasone Combo Is Tolerable, ... Sonrotoclax plus dexamethasone was well tolerated and produced early, durable responses in patients with myeloma harboring t(11:14).

6. cancernetwork.com cancernetwork.com/view/sonrotoclax-combo-shows-safety-promising-efficacy-in-r-r-multiple-myeloma

Sonrotoclax Combo Shows Safety, Promising Efficacy in R/ ... Phase 1b/2 BGB-11417-105 trial data showed low rates of high-grade infection and hematologic toxicity with sonrotoclax-based therapy in multiple ...