A Phase 1, Open-Label, Dose-Escalation and -Expansion Study of the Bruton Tyrosine Kinase-Targeted Protein-Degrader BGB-16673 in Patients With B-Cell Malignancies (BGB-16673)

Research summary

This is a multicenter, Phase 1/2, open-label, FIH study of BGB-16673 in patients with B-cell malignancies. The study is divided into 2 main phases: Phase 1 “Monotherapy Dose Finding” - composed of Part 1a (Monotherapy Dose Escalation in patients with selected R/R B-cell malignancies), Part 1b (Monotherapy Safety Expansion of selected doses evaluated in Part 1a in patients with selected R/R B-cell malignancies), Part 1c (Additional Monotherapy Safety Expansion of selected doses evaluated in Part 1a in patients with selected R/R B-cell malignancies) and Phase 2 “Monotherapy” enrolling patients with R/R CLL/SLL and R/R MCL who have previously been treated with a BTK inhibitor and will be treated with BGB-16673 at the RP2D as determined by the totality of the data in Parts 1a and 1b (or in Part 1c, as applicable). Six dose levels of BGB-16673 were planned in the dose-escalation part of the study. Following enrollment of 96 patients in Parts 1a and 1b, up to 466 patients will be enrolled in the study. Part 1a will evaluate the relevant safety data to determine a MTD or maximum assessed dose (MAD) (see Section 10.2.3 ). The number of patients who are enrolled at each dose level during the dose-escalation part will be guided by a Bayesian optimal interval (BOIN) decision rule (see Section 10.2). After the completion of Part 1a and Part 1b and the determination of an RP2D based on the totality of the available clinical safety, clinical efficacy, PK, and pharmacodynamic data, Phase 2 of the study will be initiated with BGB-16673 administered at the RP2D for R/R CLL/SLL patients (Cohort 1) and R/R MCL patients (Cohort 2). Part 1b will then be closed to further enrollment and Part 1c will open to patients with selected R/R B-cell malignancies (ie, WM, MZL, FL, RT, and DLBCL) that are less represented in Part 1b at selected doses to explore and confirm RP2D that may be potentially different from those elicited after completion of Part 1b. Should sufficient data be collected to confirm RP2D for WM, MZl, FL, RT, and/or DLBCL, Phase 2 cohorts will additionally be opened for the particular histology with concurrence of the sponsor and SMC.

Principal Investigator

Dr Toby Eyre

Contact us

Email: orh-tr.earlyphasenurses@nhs.net

IRAS number

1007339