A phase IA dose-escalation study of PHI-101, a new checkpoint kinase 2 inhibitor, for platinum-resistant recurrent ovarian cancer

Soo Jin Park, Suk-Joon Chang, Dong Hoon Suh, Tae Wook Kong, Heekyoung Song, Tae Hun Kim, Jae-Weon Kim, Hee Seung Kim, Sung-Jong Lee, Soo Jin Park, Suk-Joon Chang, Dong Hoon Suh, Tae Wook Kong, Heekyoung Song, Tae Hun Kim, Jae-Weon Kim, Hee Seung Kim, Sung-Jong Lee

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 prospective, 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 carcinoma, or primary peritoneal cancer. Also, patients who showed disease progression during platinum-based chemotherapy 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 new combination regimen for the treatment of ovarian cancer.

Trial registration: ClinicalTrials.gov Identifier: NCT04678102 .

Keywords: Chk2 inhibitor; PARP inhibitor; Phase IA; Platinum-resistance; ovarian cancer.

© 2021. The Author(s).

Figures

Fig. 1
Fig. 1
Study design schema. (Abbreviations: DLT, dose-limiting toxicity; EOT, end of treatment; PK, pharmacokinetic sampling)
Fig. 2
Fig. 2
Accelerated dose escalation and switching to standard 3+3 dose escalation scheme.

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Source: PubMed

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