FDA Grants Fast Track Designation to BGB-16673 for Patients With R/R CLL/SLL

The indication is for adults with relapsed or refractory chronic lymphocytic leukemia or small lymphocytic lymphoma who were treated with at least 2 prior lines of therapy.

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About the Trial

Trial Name: A Dose-Escalation and Expansion Study of BGB-16673 in Participants With B-Cell Malignancies

ClinicalTrials.gov ID: NCT05006716

Sponsor: BeiGene

Completion Date (Estimated): March 31, 2028

The FDA has granted a fast track designation to BGB-16673 (BeiGene, Ltd.) for the treatment of adult patients who have relapsed or refractory (R/R) chronic lymphocytic leukemia or small lymphocytic lymphoma (CLL/SLL) who were previously treated with at least 2 prior lines of therapy, including a Bruton tyrosine kinase inhibitor (BTKi) and B-cell lymphoma 2 (BCLC2) inhibitor. The designation was requested based on the potential for BGB-16673 to address an unmet medical need for patients whose CLL/SLL has progressed.¹

BGB-16673 is an orally available investigational BTK-targeted chimeric degradation activation compound (CDAC). It is designed to induce degradation of wild type and multiple mutant forms of BTK, including those that commonly confer resistance to BTKis in patients who have progressive disease.¹

“When disease progression for patients on BTK inhibitors occurs, there is a need for BTK-targeting agents with a different mode of action given the centrality of this pathway in CLL/SLL. BTK-protein degradation with our BTK CDAC (BGB-16673) may address this unmet need,” Mehrdad Mobasher, MD, MPH, chief medical officer of hematology at BeiGene, said in a news release.¹

Currently, more than 300 patients have been treated with BGB-16673. The BTK degrader is currently undergoing evaluation in a first-in-human phase 1/2 clinical trial (NCT05006716) for patients whose CLL/SLL has either returned or continued to progress despite previous treatments. Investigators are determining the highest dose of BGB-16673 that can be safely administered in patients with lymphoma and other B-cell cancers. The phase 1 portion of the trial will explore the recommended dosing for BGB-16673 monotherapy using dose escalation and determine the safety of doses, and the phase 2 portion will consist of expansion cohorts.^1-3

The investigational therapy will be administered orally alone as a monotherapy dose escalation (part 1a) to inform investigators of the BGB-16673’s safety, tolerability, and maximum tolerated dose (MTD). Additionally, participants with selected R/R B-cell malignancies will be enrolled at selected doses to help inform of the recommended phase 2 dose (RP2D, part 1b). Further, an additional monotherapy safety expansion will be held once4 RP2D is determined, and additional safety data will be collected to confirm the RP2D for patients who will not be evaluated in part 2 of the trial. Additionally, once the totality of data from parts 1a, 1b, and 1c are collected, the information will be used to further evaluate the safety and efficacy of BGB-16673 at the recommended dose—or doses, if more than 1—for the phase 2 expansion in specific histologies.^1,2

The primary outcome measures include treatment-emergent adverse events and serious adverse events, RP2D and MTD of BGB-16673 (phase 1), as well as overall response rate (phase 2), all of which will be assessed at approximately 3 years. Secondary outcome measures include single maximum observed plasma concentration (Cmax), single dose time to reach Cmax, single dose minimum observed concentration, single dose apparent total clearance of drug from plasma after oral administration, among others. According to the investigators, data on the BTK degrader's promising efficacy and tolerable safety were presented at the European Hematology Association 2024 Congress, which was held from June 13 to June 16.^1-2

“The FDA’s fast track designation supports our goal of efficiently developing BGB-16673 for these patients, the first investigational drug from our CDAC platform. We believe BGB-16673 strengthens our hematology leadership and complements zanubrutinib (Brukinsa; BeiGene, Ltd.), the backbone for our investigational hematology pipeline,” said Mobasher in the news release. “BGB-16673 is the most advanced BTK degrader in the clinic and is well-suited to become an important therapy for patients progressing after BTKi who have limited options.”¹

REFERENCES

1. Businesswire. BeiGene’s BGB-16673 Receives U.S. FDA Fast Track Designation for CLL/SLL. News release. August 26, 2024. Accessed August 26, 2024. https://www.businesswire.com/news/home/20240826216734/en/BeiGene%E2%80%99s-BGB-16673-Receives-U.S.-FDA-Fast-Track-Designation-for-CLLSLL

2. A Dose-Escalation and Expansion Study of BGB-16673 in Participants With B-Cell Malignancies. ClinicalTrials.gov identifier: NCT05006716. Updated August 19, 2024. Accessed August 26, 2024. https://clinicaltrials.gov/study/NCT05006716

3. UCSD. UCSD B-cell malignancy trial: Expansion study of BGB-16673 in participants with B-cell malignancies. UCSD Clinical Trials. August 16, 2021. Accessed August 26, 2024. https://clinicaltrials.ucsd.edu/trial/NCT05006716