BGB-11417 + Dexamethasone + Carfilzomib for Multiple Myeloma

Recruiting at 124 trial locations

Overseen By BeiGene

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: BeiGene

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

167 Participants Needed

Trial Summary

What is the purpose of this trial?

Study consists of two parts, a part 1 dose escalation and a part 2 cohort expansion in combination with dexamethasone and carfilzomib intravenously across two cohorts with a monotherapy component as well.

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 combination BGB-11417, Dexamethasone, and Carfilzomib for treating multiple myeloma?

Research shows that combinations including Carfilzomib and Dexamethasone are effective for multiple myeloma, with studies reporting high response rates and manageable side effects. For example, a study found that Carfilzomib and Dexamethasone together achieved a 90% overall response rate in newly diagnosed patients. ^{1 2 3 4 5}

Is the combination of BGB-11417, Dexamethasone, and Carfilzomib safe for humans?

Carfilzomib, when used with dexamethasone, has been studied for safety in multiple myeloma patients. Common side effects include low blood cell counts, fatigue, high blood pressure, and infections, but these are generally considered manageable. ^{1 2 3 6 7}

What makes the drug BGB-11417 combined with dexamethasone and carfilzomib unique for treating multiple myeloma?

The drug BGB-11417 (Sonrotoclax) combined with dexamethasone and carfilzomib is unique because it introduces a novel component, BGB-11417, which may offer a new mechanism of action compared to existing treatments that typically use carfilzomib with other drugs like lenalidomide. This combination could potentially enhance treatment effectiveness or provide an alternative for patients who have not responded well to standard therapies. ^{1 2 4 5 6}

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

Group I: Part 2 Cohort Expansion Experimental Treatment 3 Interventions

There will be 5 expansion cohorts to further evaluate the safety and efficacy of BGB-11417

Group II: Part 1 Dose Escalation Experimental Treatment 5 Interventions

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

Who Is Running the Clinical Trial?

BeiGene

Lead Sponsor

Trials

216

Recruited

32,500+

Findings from Research

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 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 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]

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]

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]

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]

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]

References

1. England pubmed.ncbi.nlm.nih.gov

Carfilzomib-containing combinations as frontline therapy for multiple myeloma: A meta-analysis of 13 trials. [2018]

2. United States 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). [2018]

3. China pubmed.ncbi.nlm.nih.gov

[Efficacy and Safety of Carfilzomib in the Treatment of Multiple Myeloma：A Systematic Evaluation]. [2020]

4. Germany 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. [2021]

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

Phase II study of carfilzomib and dexamethasone therapy for newly diagnosed multiple myeloma. [2020]

6. England 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. [2018]

7. England pubmed.ncbi.nlm.nih.gov

Carfilzomib: a second-generation proteasome inhibitor for the treatment of multiple myeloma. [2019]