Phase 1/2 study of acalabrutinib and the PI3K delta inhibitor ACP-319 in relapsed/refractory B-cell Non-Hodgkin lymphoma

Figures & data

Table 1. Patients with adverse events from part 1 (patients with R/R B-cell NHL receiving acalabrutinib 100 mg BID and 25, 50, or 100 mg ACP-319 BID) and part 2 (patients with GCB DLBCL or non-GCB DLBCL receiving acalabrutinib 100 mg BID and 50 mg ACP-319 BID).

Adverse Event, n (%)	Part 1 N = 18		Part 2 N = 25
	Grade 1/2	Grade ≥3	Grade 1/2	Grade ≥3
Any TEAE	5 (27.8)	13 (72.2)	7 (28.0)	18 (72.0)
TEAEs occurring in ≥ 5 patients
Diarrhea	9 (50.0)	4 (22.2)	11 (44.0)	3 (12.0)
Upper respiratory tract infection	9 (50.0)	0	2 (8.0)	0
Nausea	8 (44.4)	0	4 (16.0)	2 (8.0)
ALT increased	1 (5.6)	6 (33.3)	6 (24.0)	7 (28.0)
AST increased	2 (11.1)	5 (27.8)	7 (28.0)	5 (20.0)
Dizziness	7 (38.9)	0	4 (16.0)	0
Headache	6 (33.3)	1 (5.6)	5 (20.0)	1 (4.0)
Contusion	6 (33.3)	0	2 (8.0)	0
Cough	6 (33.3)	0	2 (8.0)	0
Abdominal pain	5 (27.8)	0	1 (4.0)	2 (8.0)
Fatigue	5 (27.8)	0	9 (36.0)	0
Edema peripheral	5 (27.8)	0	2 (8.0)	0
Rash	5 (27.8)	0	7 (28.0)	3 (12.0)
Hypotension	2 (11.1)	0	5 (20.0)	2 (8.0)
Thrombocytopenia	1 (5.6)	0	4 (16.0)	3 (12.0)
Decreased appetite	4 (22.2)	0	4 (16.0)	1 (4.0)
Any serious TEAE	2 (11.1)	9 (50.0)	3 (12.0)	10 (40.0)
Serious TEAEs in ≥2 patients
ALT increased	0	2 (11.1)	0	0
AST increased	0	2 (11.1)	0	1 (4.0)
Immune-mediated hepatitis^a	0	0	0	2 (8.0)
Any TEAE leading to treatment discontinuation	3 (16.7)^b	4 (22.2)^b	4 (16.0)^c	5 (20.0)^c
TEAE leading to treatment discontinuation
Myelodysplastic syndrome	1 (5.6)	0	0	0
Transaminases increased	1 (5.6)	0	0	0
ALT increased	1 (5.6)^d	2 (11.1)	0	1 (4.0)^e
AST increased	1 (5.6)^d	–	0	0
Maculopapular rash	0	1 (5.6)	0	0
Febrile neutropenia	0	1 (5.6)	0	0
Thrombocytopenia	0	0	0	1 (4.0)
Nausea	0	0	1 (4.0)^e	0
Immune-mediated hepatitis^a	0	0	0	1 (4.0)
Rash	0	0	1 (4.0)	0
Diarrhea	0	0	0	2 (8.0)
Pyrexia	0	0	1 (4.0)	0
Pneumonitis	0	0	1 (4.0)	0

^aImmune-mediated hepatitis is defined as elevated liver function tests requiring corticosteroids for treatment with no alternate etiology [13].

^bIn total, 7 patients in part 1 discontinued treatment due to TEAEs.

^cIn total, 8 patients in part 2 discontinued treatment due to TEAEs.

^dPatient experienced both grade 1 ALT increased and grade 1 AST increased.

^ePatient experienced both grade 3 ALT increased and grade 2 nausea.

Abbreviations: ALT: alanine aminotransferase; AST: aspartate aminotransferase; BID: twice daily; DLBCL: diffuse large B-cell lymphoma; GCB: germinal center B-cell; NHL: non-Hodgkin lymphoma; R/R: relapsed/refractory; TEAE: treatment-emergent adverse events.

Figure 1. Efficacy outcomes in patients with non-GCB or GCB subtype DLBCL (part 2). (A) Responses and percentage change in tumor burden in individual patients (n = 20). Data are not shown for 3 patients with GCB subtype DLBCL and 2 patients with non-GCB DLBCL, who were not on study long enough to complete response assessment and were thus not evaluable. These patients were treated for ≤42 days. (B) Progression-free survival. Abbreviations: CR: complete response; DLBCL: diffuse large B-cell lymphoma; GCB: germinal center B-cell; PD: progressive disease; PFS: progression-free survival; PR: partial response; SD: stable disease; SPD: sum of product diameters.

Hsu C, Marshall JL, He AR. Workup and management of immune-mediated hepatobiliary pancreatic toxicities that develop during immune checkpoint inhibitor treatment. Oncologist. 2020;25(2):105–111.

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Data-sharing statement

Data underlying the findings described in this manuscript may be obtained in accordance with AstraZeneca’s data sharing policy described at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.