Table 2.

Clinical trials of navitoclax in hematological malignancies

Study	Cohort	Design	ORR/CRR MRD	PFS/OS	III/IV toxicity (> 10%)	Note
Phase I
Wilson et al.[45] NCT00406809	n = 55 R/R lymphoid malignancies	Dose escalation of navitoclax given 14 or 21 days out of 21-day cycle	ORR 22%	Median PFS 16 months (among responders)	Neutropenia 31% Thrombocytopenia 53%	Continuous dosing appeared to reduce platelet nadir
Roberts et al.[15] NCT00481091	n = 29 RR CLL	Dose escalation of navitoclax given 14 or 21 days out of 21-day cycle	ORR 35% among patients receiving ≥ 110 mg daily	Median PFS 25 months	Neutropenia 28% Thrombocytopenia 28%	Navitoclax MTD: 250 mg daily
Roberts et al.[43] NCT00788684	n = 29 Previously treated B cell malignancies FL (n = 12) Aggressive lymphoma (n = 9) CLL/SLL (n = 5)	3 + 3 dose escalation of navitoclax 200-325 mg daily + rituximabx4	FL: ORR 75% CRR 42% Aggressive lymphoma: ORR 11% CRR 11% CLL: ORR 100% CRR 0%	Median PFS 11 months	Neutropenia 28% Thrombocytopenia 17%	Navitoclax MTD: 250 mg daily
Pullarkat et al.[50] NCT03181126	n = 47 Pediatric and adult R/R ALL	Dose escalation of low dose navitoclax with venetoclax 400 mg daily, plus chemotherapy	ORR 66% CRR 60% uMRD 34%	Median DOR 4.2 months Median OS 7.8 months 28% proceeded to CAR-T or alloSCT	Febrile neutropenia 47% Neutropenia 38% Thrombocytopenia 26%	RP2D of navitoclax 50 mg daily for adult, 25 mg if < 45 kg, with venetoclax 400 mg daily and chemotherapy
Phase II
Kipps et al.[42] NCT01087151	n = 118 Previously untreated CLL/SLL	Randomized 1:1:1 A: Rituximab × 8 B: Rituximab × 8 + navitoclax 12 weeks C: Rituximab × 8 + indefinite venetoclax Navitoclax 100 mg daily for 1st week, then 250 mg daily	A: ORR 35% CRR 0% B: ORR 55% CRR 0% C: ORR 75% CRR 5%	A: Median PFS 9.1 months B: Median PFS 15.6 months C: Not reached	Arm C Neutropenia 45% Thrombocytopenia 33% Liver enzyme increase 25%	Study closed prematurely due to sponsor decision to develop ABT-199 (venetoclax)
de Vos et al.[46] NCT00406809	N = 26 Previously treated B cell malignancies A: FL (n = 11) B: Other (n = 15)	Navitoclax 150 mg daily for 1st week, then 250 mg daily. Optional escalation to 325 mg daily if well tolerated. Continuous dosing	A: ORR 9% CRR 9% B: ORR 33% CRR 0%	Median PFS 4.9 months Median OS 24.8 months	Thrombocytopenia 39% Neutropenia 31%