Chk2 Inhibitor for Recurrent EpitheliAl periToneal, fallopIan or oVarian cancEr (CREATIVE Phase IA Trial)
Status:
Recruiting
Trial end date:
2022-12-31
Target enrollment:
Participant gender:
Summary
This study aims to assess the safety and tolerability of PHI-101 in patients with
platinum-resistance/refractory ovarian, fallopian tubal, and primary peritoneal cancer. This
study also evaluates the pharmacokinetics of PHI-101 and efficacy of PHI-101 during treating
platinum-resistance/refractory ovarian, fallopian tubal, and primary peritoneal cancer.
PHI-101 is a CHK2 inhibitor that is a checkpoint kinase binding specifically to CHK2, rather
than CHK1, and it inhibits the DDR system by inhibiting the ATM-CHK2 pathway, which is
activated in response to DSBs. When a high-grade serous ovarian (HGSO) cancer cell line and
various ovarian cancer cell lines (CAOV3, OVCAR3, SK-OV-03, and SW626) were treated with
PHI-101 in a non-clinical study, the therapeutic effect of PHI-101 against ovarian cancer was
demonstrated by a decrease in viability of ovarian cancer cells. In addition, a stronger
growth inhibition effect was observed compared to that of treatment with olaparib or
rucaparib alone, and a much stronger inhibition effect was observed when concomitantly used
with paclitaxel, cisplatin, and topotecan. Based on the aforementioned results of the
non-clinical studies, the potential of PHI-101 as a new treatment or concomitant cytotoxic
chemotherapeutics for patients with ovarian cancer who are resistant to existing
antineoplastic drugs was confirmed.