BGB-3111-11417-101: This phase I trial is trying to determine the best dosing level of a targeted therapy drug (BGB-11417), and assess its effectiveness both by itself and in combination with another targeted therapy (Zanubrutinib)A Phase 1a/1b Open-Label Dose Escalation and Expansion Study of Bcl-2 Inhibitor BGB-11417 in Patients With Mature B-Cell Malignancies

Summary

This is a non-randomised trial with two treatment arms, both with a dose finding and dose escalation phase. In the Experimental BGB-11417 Monotherapy Dose Finding (Part 1) Arm, participants with relapsed/refractory (R/R) non-Hodgkin lymphoma (NHL) including follicular lymphoma (FL), diffuse large B-cell lymphoma (DLBCL), marginal zone lymphoma (MZL) or transformed NHL; chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL) with low tumor burden or low creatine clearance; CLL/SLL with without high tumor burden or low creatine clearance will receive oral BGB-11417 until the maximum tolerated dose (MTD) (or maximum ascending dose (MAD)) and recommended phase 2 dose can be determined. In the Experimental BGB-11417 Monotherapy Expansion Arm (Part 2), Participants with R/R indolent NHL including FL, MZL; aggressive NHL including DLBCL, transformed NHL; CLL/SLL with low tumor burden or low creatine clearance; CLL/SLL with without high tumor burden or low creatine clearance will receive oral BGB-11417 at the RP2D dose to further define the safety profile. In the Experimental BGB-11417 + Zanubrutinib combination therapy dose finding (Part 3) Arm, Participants with R/R indolent NHL including FL, MZL; aggressive NHL including DLBCL, transformed NHL; CLL/SLL with low tumor burden or low creatine clearance; CLL/SLL with without high tumor burden or low creatine clearance will receive oral BGB-11417 until RP2D can be determined in combination with zanubrutinib. In the Experimental BGB-11417 + Zanubrutinib Combination Therapy Dose Expansion (Part 4) Arm, Participants with R/R indolent NHL including FL, MZL; aggressive NHL including DLBCL, transformed NHL; CLL/SLL with low tumor burden or low creatine clearance; CLL/SLL with without high tumor burden or low creatine clearance will receive oral BGB-11417 at the RP2D dose to further define the safety profile in combination with zanubrutinib. BGB-11417 will be administered via film-coated tablets once daily at a dose as specified in the treatment arm. Zanubrutinib will be administered 320mg twice-daily as two 80mg capsules (160mg twice a day) or once-daily zanubrutinib should be administered as four 80mg capsules once a day (320mg once a day).