BGB-16673 for Chronic Lymphocytic Leukemia

(CaDAnCe-302 Trial)

Recruiting at 186 trial locations

Overseen By Study Director

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: BeiGene

Disqualifiers: Richter's transformation, CNS involvement, others

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

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

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

Compensation: Varies

Number of Visits: Unknown

Duration: Approximately 36 months

250 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial examines the effectiveness of a new treatment, BGB-16673, for individuals with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) who have previously tried other treatments. It compares BGB-16673, an experimental treatment, with standard treatment options selected by doctors. The study targets individuals diagnosed with CLL or SLL who have been treated with both BTK inhibitors and BCL2 inhibitors. Participants should have measurable disease via scans and meet specific health criteria. As a Phase 3 trial, this study represents the final step before potential FDA approval, offering participants the opportunity to contribute to the development of a promising new treatment.

Will I have to stop taking my current medications?

The trial information does not specify whether 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 new treatment, BGB-16673, appears safe. Earlier studies found that BGB-16673 has a tolerable safety profile, with most patients not experiencing severe side effects. The reported side effects were manageable and similar to those of other treatments targeting BTK, a protein involved in cell growth.

So far, no major safety concerns have arisen. Patients have tolerated the treatment well, even those who have tried several other medications. This suggests that BGB-16673 could be a safe option for individuals with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) who have not had success with other treatments. ^{1 2 3 4}

Why do researchers think this study treatment might be promising?

Most treatments for chronic lymphocytic leukemia (CLL) involve combinations of drugs like idelalisib or venetoclax, often paired with rituximab. However, BGB-16673 stands out because it is a monotherapy that patients take once daily, potentially simplifying treatment regimens. Researchers are excited about BGB-16673 because it targets CLL in a unique way, offering an alternative that may reduce the need for combining multiple drugs. By focusing on BGB-16673's singular approach, there is hope for improved outcomes with fewer side effects compared to traditional combination therapies.

What evidence suggests that BGB-16673 might be an effective treatment for chronic lymphocytic leukemia?

Studies have shown that BGB-16673, a new medication, effectively treats chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL). In this trial, one group of participants will receive BGB-16673 monotherapy. Previous research indicates that BGB-16673 helped 84.8% of patients with recurrent or treatment-resistant CLL/SLL see improvements. Additionally, 77.4% of these patients experienced a period where their disease did not worsen. These findings suggest that BGB-16673 holds strong potential as a treatment for those who have not succeeded with other therapies. ^{1 2 4 5}

Who Is on the Research Team?

Study Director

Principal Investigator

BeOne Medicines

Are You a Good Fit for This Trial?

This trial is for people with chronic lymphocytic leukemia (CLL) who have already been treated with BTK and BCL2 inhibitors. Participants should be in need of treatment due to disease progression after previous therapies.

Inclusion Criteria

Measurable disease by computer tomography/magnetic resonance imaging

I can take care of myself but may not be able to do heavy physical work.

My liver is working well.

Exclusion Criteria

I have or am suspected to have had a specific type of leukemia or its transformation.

I have had a stem cell transplant or CAR-T therapy in the last 3 months.

I have not been treated with BTK protein degraders before.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive BGB-16673 or investigator's choice of treatment until treatment discontinuation criteria are met

Approximately 36 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

Approximately 36 months

What Are the Treatments Tested in This Trial?

Interventions

• BGB-16673

Trial Overview

The study compares the effectiveness and safety of a new drug, BGB-16673, against other chosen treatments combined with rituximab (either idelalisib, bendamustine, or venetoclax). Patients will randomly receive either the new drug or one of the standard options.

How Is the Trial Designed?

Group I: Arm A: BGB-16673 monotherapy Experimental Treatment 1 Intervention

Participants will receive BGB-16673 once daily until any of the treatment discontinuation criteria are met

Group II: Arm B: Investigator's Choice Active Control 4 Interventions

Participants will receive investigator's choice of idelalisib plus rituximab for CLL only or bendamustine plus rituximab, or venetoclax plus rituximab retreatment.

Who Is Running the Clinical Trial?

BeiGene

Lead Sponsor

Trials

216

Recruited

32,500+

BeOne Medicines

Lead Sponsor

Published Research Related to This Trial

BTK inhibitors (BTKis) have significantly improved treatment for chronic lymphocytic leukemia (CLL) by targeting Bruton's tyrosine kinase, which is crucial for B-cell receptor signaling, leading to reduced cell proliferation and activation of harmful pathways.

While BTKis like ibrutinib and acalabrutinib are effective, they come with notable long-term adverse effects, including cardiac issues and infections, highlighting the need for careful management of these side effects during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Managing toxicities of Bruton tyrosine kinase inhibitors. Lipsky, A., Lamanna, N.[2023]

Acalabrutinib, a next-generation BTK inhibitor, has shown improved safety and efficacy in treating chronic lymphocytic leukemia (CLL) compared to the first-in-class drug ibrutinib, with completed phase 3 trials demonstrating better outcomes for both relapsed/refractory and treatment-naive patients.

The drug selectively inhibits BTK with fewer off-target effects, and early studies suggest that combining acalabrutinib with other therapies, like a CD20 antibody and venetoclax, can lead to high rates of undetectable minimal residual disease in patients, indicating a potential for fixed-duration treatment options.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Assessing the pharmacokinetics of acalabrutinib in the treatment of chronic lymphocytic leukemia. Miao, Y., Xu, W., Li, J.[2022]

Ibrutinib is a first-in-class selective inhibitor of Bruton tyrosine kinase that shows promise in inhibiting the survival and proliferation of chronic lymphocytic leukemia (CLL) cells, based on preclinical studies.

Early clinical data indicate that ibrutinib may significantly impact CLL treatment, suggesting it could become a key part of therapy targeting the B-cell receptor signaling pathway.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ibrutinib (PCI-32765) in chronic lymphocytic leukemia. Jain, N., O'Brien, S.[2021]

Bruton's tyrosine kinase inhibitor (ibrutinib) and phosphatidylinositol 3-kinase inhibitor (idelalisib) are effective and well-tolerated treatment options for chronic lymphocytic leukemia, especially in older patients who may struggle with traditional chemotherapy side effects.

While these B cell receptor inhibitors are promising, they come with specific side effects: ibrutinib can increase the risk of bleeding and atrial fibrillation, while idelalisib may cause transaminitis, diarrhea, and pneumonitis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

B cell receptor inhibition as a target for CLL therapy. Jeyakumar, D., O'Brien, S.[2021]

Citations

1.

ashpublications.org

ashpublications.org/blood/article/144/Supplement%201/885/530857/Preliminary-Efficacy-and-Safety-of-the-Bruton

Preliminary Efficacy and Safety of the Bruton Tyrosine Kinase ...

Conclusions: Emerging data from this ongoing, first-in-human study demonstrate that the novel BTK degrader BGB-16673 has a tolerable safety ...

2.

haematologica.org

haematologica.org/article/view/12820

C056 | UPDATED EFFICACY/SAFETY OF THE BRUTON ...

CONCLUSIONS: Novel BTK degrader BGB-16673 is tolerable, with robust and deepening responses in pts with heavily pretreated R/R CLL/SLL, ...

3.

clinicaltrials.gov

clinicaltrials.gov/study/NCT06973187

A Study to Evaluate the Safety and Efficacy of BGB-16673 ...

The purpose of this study is to evaluate the efficacy and safety of BGB-16673 alone compared with pirtobrutinib in patients with relapsed or refractory (R/R) ...

4.

onclive.com

onclive.com/view/bgb-16673-is-safe-elicits-nearly-85-orr-in-relapsed-refractory-cll-sll

BGB-16673 Is Safe, Elicits Nearly 85% ORR in Relapsed/ ...

BGB-16673 showed safety and efficacy in relapsed/refractory CLL/SLL, with an 84.8% overall response rate and 77.4% progression-free survival at ...

5.

onclive.com

onclive.com/view/dr-scarf-on-early-safety-data-with-bgb-16673-in-r-r-cll-sll

Dr Scarfò on Early Safety Data With BGB-16673 in R/R ...

“The safety profile appears [to be] tolerable and manageable according to what we know about previous [BTK-targeted] agents.”.