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Table 2 Clinical trials of navitoclax in hematological malignancies

From: Clinical experiences with venetoclax and other pro-apoptotic agents in lymphoid malignancies: lessons from monotherapy and chemotherapy combination

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%

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