Abstract CT234: VASTUS - a phase 1b/2a basket trial of a new PARP inhibitor, IDX-1197, including PARP inhibitor resistant cohort
Authors: Lee Kyung-Hun , Min Ahrum , Ahn Hee Kyung , Lee Keun Seok , Moon Yong Wha , Kim Seung Tae , Kim Jeong Eun , Sohn Joo Hyuk , Kim Il Hwan , Bae Woo Kyun , Lee Myong Jae , Roh Eun-Jihn , Ock Chan-Young , Lee Won Sik , Im Seock-Ah 
Published: July 2021

Abstract
[BACKGROUND]Poly ADP-ribose polymerase (PARP) is an enzyme that is central to the repair of DNA replication errors known as single-strand breaks (SSBs). PARP inhibitors are currently approved for breast, pancreatic and prostate cancers which harbor germline or somatic BRCA1/2 mutations (g/sBRCAmt) and/or germline or somatic homologous recombinant repair mutation (g/sHRRmt), and advanced serous ovarian cancer that are homologous recombination deficiency (HRD)-positive, g/sBRCAmt or sensitive to prior platinum treatment. However, there is limited knowledge about the efficacy of PARP inhibitors in other cancers with HRD with or without gBRCAmt, in platinum-resistant settings, and about efficacy after prior PARP inhibitor treatment. IDX-1197 is a new PARP inhibitor which is active against cell lines with acquired resistance to platinum and PARP inhibitors. VASTUS study is a basket trial composed of 9 different cohorts investigating use of IDX-1197 in various tumors known to be responsive to PARP inhibitors, as well as in tumors and settings that have not been well-investigated so far.
[METHOD]VASTUS is a multi-center, basket trial (NCT04174716) to evaluate safety and efficacy of IDX-1197 as a monotherapy in 1) cancers that are known to be responsive to PARP inhibitors (breast cancer, ovarian cancer, and pancreatic cancer), 2) cancers where PARP inhibitors' safety and efficacy have not been confirmed (small cell lung cancer, biliary tract cancer, uroepithelial cancer, and gastric cancer), 3) any solid tumors resistant to prior platinum-based therapy, excluding refractory to prior platinum based therapy, and 4) any solid tumors that have been exposed to prior PARP inhibitors. In VASTUS trial, patients are selected by pathogenic mutations in HRD-related genes. In the cohort for tumors with prior exposure to PARP inhibitors, patients are eligible regardless of gene mutations as long as they have received prior PARP inhibitor. Study is composed of two parts – phase 1b to assess safety and tolerability of IDX-1197 and to determine recommended phase 2 dose; after review by data safety monitoring committee and go/no-go decision, phase 2a will be commenced to assess the efficacy of IDX-1197 based on objective response rate (ORR). Retrospective translational researches with tumor tissue and peripheral blood are planned (circulating tumor DNA), specifically for prior PARP inhibitor exposure cohort. As of 05 Jan 2021, 32 patients have been enrolled.
Citation Format: Kyung-Hun Lee, Ahrum Min, Hee Kyung Ahn, Keun Seok Lee, Yong Wha Moon, Seung Tae Kim, Jeong Eun Kim, Joo Hyuk Sohn, Il Hwan Kim, Woo Kyun Bae, Myong Jae Lee, Eun-Jihn Roh, Chan-Young Ock, Won Sik Lee, Seock-Ah Im. VASTUS - a phase 1b/2a basket trial of a new PARP inhibitor, IDX-1197, including PARP inhibitor resistant cohort [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr CT234.