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idetrexed + olaparib
- Development stage
- Unknown
- Lead developer
- Algok Bio
- Modality
- Small Molecules
- Administration
- Intravenous, Oral
01
Overview
Idetrexed + olaparib is a combination therapy being evaluated in the Phase I/Ib IDOL study for the treatment of platinum-resistant high-grade serous ovarian cancer (HGSOC) that overexpresses the alpha-folate receptor (FRα). Idetrexed is a small-molecule thymidylate synthase inhibitor designed to selectively target cancer cells via the FRα, which is frequently overexpressed in ovarian tumors. Olaparib is a potent PARP inhibitor that blocks DNA repair mechanisms. By combining these agents, the therapy aims to induce DNA damage through thymidylate synthase inhibition while simultaneously preventing the repair of such damage, leading to enhanced cancer cell death. The combination has shown significant preclinical synergy, particularly in FRα-high models. At Dose Level 1 of the IDOL study, idetrexed is administered intravenously at 9 mg/m² on days 1 and 8, while olaparib is administered orally at 200 mg twice daily on days 1-7 and 15-21 of a 28-day cycle.
- Other names
- Idetrexed and Olaparib combinationIDOL study combination
02
Targets
FOLR1 (FRα)PARP1 (Poly (adp-ribose) polymerase 1)PARP2 (Poly (adp-ribose) polymerase 2)RFC1 (Reduced folate carrier type 1)TNKS (Poly(ADP-ribose) Polymerase 5a)TS (Thymidylate synthase)
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