tailieunhanh - A phase IA dose-escalation study of PHI101, a new checkpoint kinase 2 inhibitor, for platinum-resistant recurrent ovarian cancer

PHI-101 is an orally available, selective checkpoint kinase 2 (Chk2) inhibitor. PHI-101 has shown antitumour activity in ovarian cancer cell lines and impaired DNA repair pathways in preclinical experiments. Furthermore, the in vivo study suggests the synergistic effect of PHI-101 through combination with PARP inhibitors for ovarian cancer treatment. | Park et al. BMC Cancer 2022 22 28 https s12885-021-09138-z STUDY PROTOCOL Open Access A phase IA dose-escalation study of PHI- 101 a new checkpoint kinase 2 inhibitor for platinum-resistant recurrent ovarian cancer Soo Jin Park1 Suk Joon Chang2 Dong Hoon Suh3 Tae Wook Kong2 Heekyoung Song4 Tae Hun Kim5 Jae Weon Kim1 Hee Seung Kim1 and Sung Jong Lee4 Abstract Background PHI-101 is an orally available selective checkpoint kinase 2 Chk2 inhibitor. PHI-101 has shown anti- tumour activity in ovarian cancer cell lines and impaired DNA repair pathways in preclinical experiments. Furthermore the in vivo study suggests the synergistic effect of PHI-101 through combination with PARP inhibitors for ovarian cancer treatment. The primary objective of this study is to evaluate the safety and tolerability of PHI-101 in platinum- resistant recurrent ovarian cancer. Methods Chk2 inhibitor for Recurrent EpitheliAl periToneal fallopIan or oVarian cancEr CREATIVE trial is a prospec tive multi-centre phase IA dose-escalation study. Six cohorts of dose levels are planned and six to 36 patients are expected to be enrolled in this trial. Major inclusion criteria include 19 years with histologically confirmed epithelial ovarian cancer fallopian tube carci noma or primary peritoneal cancer. Also patients who showed disease progression during platinum-based chemo therapy or disease progression within 24 weeks from completion of platinum-based chemotherapy will be included and prior chemotherapy lines of more than five will be excluded. The primary endpoint of this study is to determine the dose-limiting toxicity DLT and maximum tolerated dose MTD of PHI-101. Discussion PHI-101 is the first orally available Chk2 inhibitor expected to show effectiveness in treating recurrent ovarian cancer. Through this CREATIVE trial DLT and MTD of this new targeted therapy can be confirmed to find the recommended dose for the phase II clinical trial. This study may contribute to developing a