Safety and efficacy of navitoclax, a BCL-2 and BCL-X_L inhibitor, in patients with relapsed or refractory lymphoid malignancies: results from a phase 2a study

Figures & data

Figure 1. Dosing schematic for the phase 2a portion of the phase 1/2a study. C: cycle; D: day.

Table 1. Patient demographics and baseline characteristics.

	Arm A	Arm B	Total
	(n = 11)	(n = 15)	(N = 26)
Age, years
Median (range)	62.0 (42–77)	62.0 (44–86)	62.0 (42–86)
<65, n (%)	8 (72.7)	10 (66.7)	18 (69.2)
≥65, n (%)	3 (27.3)	5 (33.3)	8 (30.8)
Sex, n (%)
Female	3 (27.3)	5 (33.3)	8 (30.8)
Male	8 (72.7)	10 (66.7)	18 (69.2)
Race, n (%)
White	8 (72.7)	11 (73.3)	19 (73.1)
Black	1 (9.1)	3 (20.0)	4 (15.4)
Asian	2 (18.2)	0	2 (7.7)
Mixed	0	1 (6.7)	1 (3.8)
Ethnicity, n (%)
Hispanic	1 (9.1)	0	1 (3.8)
No ethnicity stated	10 (90.9)	15 (100)	25 (96.2)
Baseline ECOG performance status^a
0	8 (80.0)	10 (66.7)	18 (72.0)
1	2 (20.0)	5 (33.3)	7 (28.0)
Baseline LDH
High	1 (9.1)	3 (20.0)	4 (15.4)
Normal or low	10 (90.9)	12 (80.0)	22 (84.6)
Median no. of prior therapies (range)	5 (1–7)	2 (1–11)	3.5 (1–11)
Stage III/IV^b, n (%)	5 (50.0)	9 (69.2)	14 (60.9)
	n = 10	n = 13	n = 23
Cancer type, n (%)
Follicular lymphoma	11 (100)	/	11 (42.3)
Chronic lymphocytic leukemia	/	7 (46.7)	7 (26.9)
Small lymphocytic lymphoma	/	2 (13.3)	2 (7.7)
Lymphoplasmacytic lymphoma	/	2 (13.3)	2 (7.7)
Mantle cell lymphoma	/	2 (13.3)	2 (7.7)
Low-grade B-cell lymphoma	/	1 (6.7)	1 (3.8)
Marginal zone B-cell lymphoma	/	1 (6.7)	1 (3.8)
Cutaneous T-cell lymphoma	/	/	/
Peripheral T-cell lymphoma	/	/	/

ECOG: Eastern Cooperative Oncology Group; LDH: lactate dehydrogenase.

^aData missing for 1 patient in Arm A.

^bData not available for all patients.

Table 2. Summary of treatment-emergent adverse events related to navitoclax.

TEAEs	Total
	(N = 26)
Any AE (≥20% patients), n (%)	26 (100)
Diarrhea	23 (88.5)
Nausea	16 (61.5)
Thrombocytopenia	14 (53.8)
Fatigue	11 (42.3)
Vomiting	10 (38.5)
Neutropenia	8 (30.8)
Grade 3 or 4 AEs (≥5% patients), n (%)	17 (65.4)
Thrombocytopenia	10 (38.5)
Neutropenia	8 (30.8)
Increased alanine aminotransferase	2 (7.7)
Lymphopenia	2 (7.7)
Serious AEs	2 (7.7)
Bacterial sepsis	1 (3.8)
Increased white blood cell count	1 (3.8)
Overview of TEAE	Total	Arm A	Arm B
	(N = 26)	(n = 11)	(n = 15)
Any AE leading to navitoclax
Discontinuation	10 (38.5)	2 (18.2)	8 (53.3)
Dose reduction	9 (34.6)	3 (27.3)	6 (40.0)
Dose interruption	13 (50.0)	3 (27.3)	10 (66.7)
Dose delay	2 (7.7)	0	2 (13.3)
Any serious AE leading to navitoclax
Discontinuation	2 (7.7)	0	2 (13.3)
Dose reduction	0	0	0
Dose interruption	2 (7.7)	0	2 (13.3)
Dose delay	0	0	0

AE: adverse event; TEAE: treatment-emergent adverse event.

Table 3. Tumor response rate.

Response, n/N (%) [95% CI]^a	Arm A (FL) (n = 11)	Arm B							Total (N = 26)
		All	CLL	SLL	LPL	MCL	Low-grade B-cell lymphoma	Marginal zone B-cell lymphoma
		(n = 15)	(n = 7)^c	(n = 2)	(n = 2)	(n = 2)	(n = 1)	(n = 1)
Objective response^b
CR	1/11 (9.1)	0/15	0	0	0	0	0	0	1/26 (3.8)
nPR	0/11	0/15	0	0	0	0	0	0	0/26
PR	0/11	5/15 (33.3)	3/7 (42.9)	0	1/2 (50.0)	0	1/1 (100)	0	5/26 (19.2)
CR + nPR + PR	1/11 (9.1) [0.2, 41.3]	5/15 (33.3) [11.8, 61.6]	3/7 (42.9) [9.9, 81.6]	0	1/2 (50.0) [1.3, 98.7]	0	1/1 (100)	0	6/26 (23.1) [9.0, 43.6]

CLL: chronic lymphocytic leukemia, CR: complete response; FL: follicular lymphoma; LPL: lymphoplasmacytic lymphoma; MCL: mantle cell lymphoma; nPR: nodular partial response; PD: progressive disease; PR: partial response; SLL: small lymphocytic lymphoma.

^a95% CI determined from the exact binomial distribution.

^bComplete or partial responses needed to be confirmed >4 weeks (28 days) apart for an objective response.

^cOne patient with CLL was not evaluable.

Figure 2. (A) PFS, (B) TTP, (C) OS for patients by arm (Arm A = solid line, Arm B = dotted line). OS: overall survival; PFS: progression-free survival; TTP: time to tumor progression.

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