Abstract 1051: Combination of senaparib with temozolomide for the treatment of cancer

Poly (ADP-ribose) polymerase (PARP) is a critical enzyme for DNA repair and PARP inhibitors have been found to be efficacious against cancers with defects in DNA repair pathways such as with BRCA mutations. In addition, in vitro and in vivo studies have found that for PARP inhibitors with good trapping activity, combination with temozolomide (TMZ) produced the best synergetic effects among different types of chemotherapies. Several clinical combination studies of PARP inhibitors with TMZ have been reported, such as the combination of olaparib with TMZ in small cell lung cancer (SCLC). In this presentation, we will report in vitro and in vivo studies of PARP inhibitor senaparib (IMP4297) in combination with TMZ. Synergetic effects were observed when senaparib was combined with TMZ in vitro against human SCLC NCI-H209 cells. In vivo studies of high-dose senaparib in combination with low-dose TMZ once a day continuously in human SCLC NCI-H209 xenograft model was found to be highly synergetic and well tolerated. A clinical study of senaparib in combination with TMZ in patients with advanced solid tumors and SCLC is ongoing (ClinicalTrials.gov Identifier: NCT04434482). Citation Format: Sui Xiong Cai, Ning Ma, Xiaozhu Wang, Jie Ma, Mingchuan Guo, Ruiyu Zhou, Lan Liu, Chih-Yi Hsieh, Ye Edward Tian. Combination of senaparib with temozolomide for the treatment of cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 1051.