Reference Detail

Ref Type

PMID

Authors

J. Lickliter, L. Mileshkin, M. Voskoboynik, M. Millward, A. Freimund, T. Meniawy, T. Tang, R. Wei, M. Li, V. Paton

Title

Dose escalation/expansion study to investigate the safety, pharmacokinetics, food effect, and antitumor activity of BGB-290 in patients with advanced solid tumors

Journal	Vol	Issue	Date	Pages	Journal Short Title
Ann Oncol

URL

https://www.annalsofoncology.org/article/S0923-7534(20)37789-9/fulltext

Abstract Text

Background: Poly (ADP-ribose) polymerase inhibitors (PARPis) represent a class of antitumor agents that exert their cytotoxic effects by inhibiting PARP activity. Some PARPis are capable of trapping PARP proteins on DNA further augmenting cell death. BGB-290 is a potent and selective PARP1/2 inhibitor with strong PARP-trapping and antitumor activity in both in vitro and in vivo preclinical tumor models harboring BRCA gene mutations or other homologous recombination defects. Methods: This two-staged study (NCT02361723) consists of a Phase 1A dose-escalation/dose-finding component to establish the maximum tolerated dose (MTD) and/or recommended Phase 2 dose (RP2D) of BGB-290 in patients with solid tumors and a two-part Phase 2 component that includes expansion in targeted indications (Part A) and the effect of food on the BGB-290 pharmacokinetic (PK) profile (Part B). Results: As of 1 May 2017, Phase 1A had completed enrollment (n = 45); 3 patients remain on treatment. Objective responses were observed across the dose range (2.5–120 mg BID). Of the 23 evaluable patients with gynecological cancer, 10 (43%) achieved an objective response per RECIST 1.1 (n = 3 complete; n = 7 partial). More patients with germline BRCA 1/2 mutated ovarian cancer achieved an objective response (n = 7/12, 58%) than patients not carrying the mutation (n = 2/8, 25%). Drug-related adverse events (AEs) reported in ≥ 10% of patients were nausea, fatigue, anemia, vomiting, diarrhea, anorexia and neutropenia. Anemia and neutropenia were the most common drug-related Grade 3 AEs; no Grade 4 drug-related AEs were reported. Three BGB-290-related serious AEs were reported (anemia, n = 2; nausea, n = 1). Four deaths were associated with an AE; however, none were considered drug-related. The BGB-290 RP2D was determined as 60 mg BID and is being evaluated in Phase 2 to determine antitumor activity and food effects. Dose escalation to determine MTD with QD dosing is ongoing. Conclusions: BGB-290 has demonstrated a favorable safety profile and promising preliminary antitumor activity in phase 1A; phase 2 is ongoing evaluating in patients with ovarian, breast, prostate, gastric and small cell lung cancer.

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Molecular Profile	Treatment Approach

Gene Name	Source	Synonyms	Protein Domains	Gene Description	Gene Role

Therapy Name	Drugs	Efficacy Evidence	Clinical Trials

Drug Name	Trade Name	Synonyms	Drug Classes	Drug Description

Gene	Variant	Impact	Protein Effect	Variant Description	Associated with drug Resistance

Molecular Profile	Indication/Tumor Type	Response Type	Therapy Name	Approval Status	Evidence Type	Efficacy Evidence	References