Abstract 270P
Background
Poly ADP-ribose polymerase (PARP) is an enzyme that is central to the repair of DNA replication errors and are currently approved for ovary, breast, pancreas and prostate cancers. VASTUS study (NCT04174716) is a basket trial investigating the safety and efficacy of venadaparib in 6 cohorts of different tumors, including breast cancer.
Methods
VASTUS is a phase 1b/2a seamless trial. Objectives of 1b part of the trial is to assess the safety and tolerability of venadaparib and determine recommended phase 2a dose, and to assess the anticancer activity of venadaparib based on the objective response rate (ORR) and the disease control rate (DCR). Metastatic breast cancer (mBC) patients with pathogenic germline BRCA 1/2 (gBRCA1/2) mutation, somatic BRCA 1/2 (sBRCA 1/2), ATM, PALB2, or RAD51C were enrolled. 10 patients’ response evaluation is reviewed by data safety monitoring board (DSMB) to determine go/no-go decision into phase 2a.
Results
Between Feb 2020 to Apr 2021, 14 patients were enrolled into HER2 negative mBC cohort, of which 10 patients were evaluated for DSMB review. Patients were administered with venadaparib doses ranging from 120mg to 240mg, based on emerging data from ongoing phase 1a dose finding study. Frequently observed all grade treatment related adverse event (TRAE) were as follows – anemia 8/14 (57%), nausea 7/14 (50%), neutropenia 7/14 (50%) and thrombocytopenia 4/14 (29%). Based on these results, phase 2a part of the breast cancer cohort has been opened with RP2D of 160mg. Of the 10 evaluable patients (8 gBRCAmt and 2 sBRCAmt), 1 patient had complete response (CR), 7 patients had partial responses (PR) and 2 patients had stable disease (SD), leading to 80% ORR and 100% DCR. Remaining 4 patients are under evaluation.
Conclusions
Venadaparib showed efficacy in gBRCAmt or sBRCAmt mBC patients. Preliminary efficacy findings suggest strong potency of venadaparib in g/sBRCAmt mBC, while preliminary safety findings are comparable to commercially available PARP inhibitors. These findings warrant further investigation of venadaparib in breast cancer beyond gBRCAmt.
Clinical trial identification
NCT04174716.
Editorial acknowledgement
Legal entity responsible for the study
Idience Co., Ltd.
Funding
Idience Co., Ltd.
Disclosure
K.S. Lee: Financial Interests, Personal, Advisory Board: Roche; Financial Interests, Personal, Advisory Board: Pfizer; Financial Interests, Personal, Advisory Board: Lilly; Financial Interests, Personal, Advisory Board: Novartis; Financial Interests, Institutional, Research Grant: Dong-A ST. H.K. Ahn: Financial Interests, Personal, Advisory Board: Takeda; Financial Interests, Personal, Advisory Board: BMS; Financial Interests, Personal, Advisory Board: Roche; Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Personal, Speaker’s Bureau: Boehringer Ingelheim; Financial Interests, Personal, Speaker’s Bureau: MSD; Financial Interests, Institutional, Research Grant: AstraZeneca; Financial Interests, Institutional, Research Grant: Roche; Financial Interests, Institutional, Research Grant: Boehringer Ingelheim; Financial Interests, Institutional, Research Grant: MSD; Financial Interests, Institutional, Research Grant: Pfizer; Financial Interests, Institutional, Research Grant: Lilly. C. Ock: Financial Interests, Personal, Advisory Board: Idience; Financial Interests, Personal, Full or part-time Employment: Lunit. E. Roh: Financial Interests, Personal, Full or part-time Employment: Idience; Financial Interests, Personal, Full or part-time Employment: Selecxine. M. Lee, M.J. Hong, S. Song, W.S. Lee: Financial Interests, Personal, Full or part-time Employment: Idience. All other authors have declared no conflicts of interest.