Abstract 334TiP
Background
Homologous recombination repair (HRR) genes play an important role in DNA double strand damage repair. For tumors with HRR gene mutations, DNA double strand damage may not be repaired by homologous recombination, and PARP inhibitor blocks DNA single strand damage repair, which result in synergistic lethality. HRR gene mutations can be detected in many solid tumors, patients with HRR gene mutations may benefit from PARP inhibitor. Preclinical studies have shown that antiangiogenic drugs can induce hypoxia and increase the sensitivity to PARP inhibitor. The combination of PARP inhibitor and antiangiogenic drug may play a synergistic anti-tumor role and achieve better efficacy in HRR gene-mutated tumors. The phase I trial determines the dose limiting toxicity (DLT) and maximum tolerable dose (MTD) of Niraparib plus Anlotinib in HRR gene-mutated advanced solid tumors, and evaluates the safety and effectiveness of this combination therapy preliminarily.
Trial design
This is a phase I trial of dual targeted drugs Niraparib plus Anlotinib in HRR gene-mutated advanced solid tumors. In this study, 52 histological or cytological diagnosis, previous treatment failure patients of HER2 negative breast cancer, cholangiocarcinoma, gastric adenocarcinoma and pancreatic cancer are included. Patients are required to carry pathogenic or suspected pathogenic germline BRCA or somatic BRCA mutations, or HRR gene mutations defined by the inclusion criteria. The study will be divided into two stages. The first stage will include 6-12 patients on a 21-day cycle to determine the DLT and MTD based on a 3+3 design. Two dose groups will be set up. The first one is Niraparib 100mg administered orally (PO) daily (QD) plus Anlotinib 12mg PO QD D1-D14, the second one is Niraparib 200mg PO QD plus Anlotinib 12mg PO QD D1-D14. In the second stage, 40 patients will be included to treated with Niraparib plus Anlotinib every 21 days using the MTD determined by the first stage, until disease progression or intolerable toxicity or withdrawal of the trial. Currently, 1 of the planned 52 patients have been enrolled; enrollment is ongoing.
Clinical trial identification
NCT04764084.
Editorial acknowledgement
Legal entity responsible for the study
Beijing University Cancer Hospital.
Funding
Zai Lab Limited and Chiatai Qianqing.
Disclosure
All authors have declared no conflicts of interest.