TABLE 1.
Ongoing or completed clinical trials of ATR/CHK1/WEE1 pathway inhibitors combination with PARPi.
| Clinicaltrials. Gov registration/Study name | Phase | Condition or disease | Patients (n) | Combination | Results | |
|---|---|---|---|---|---|---|
| Ongoing | NCT04267939 | Ib | Advanced solid tumors, including PARP inhibitor resistant OC | 56 | BAY1895344 (ATRi) + Niraparib | MTD and/or RP2D Incidence of TEAEs Severity of TEAEs-DLT |
| CAPRI/NCT03462342 | II | ROC (platinum-sensitive or platinum-resistant) | 86 | AZD6738 (ATRi) + Olaparib | Incidence of TEAEs RRPFS | |
| NCT04149145 | I | PARP inhibitor resistant recurrent OC | 40 | M4344 (ATRi) + Niraparib | Percentage of patients with TEAEs MTD ORR PFS | |
| NCT04065269 | II | Gynaecological Cancers with ARID1A Loss or no Loss | 40 | AZD6738 (ATRi) + Olaparib or AZD6738 alone | ORR (complete or partial response) | |
| NCT03579316 | II | PARP inhibitor resistant recurrent OC | 104 | AZD1775(WEE1i) + Olaparib or AZD1775 alone | ORR DCR | |
| Completed | NCT02723864 | I | Refractory solid tumors | 53 | M6620 (ATRi) + Veliparib + Cisplatin | Incidence of adverse events PR:13.6% |
| NCT03057145 Do et al. (2021) PMID: 34131002 | I | Advanced solid tumors, including HGSOC with BRCA1/2 mutation | 29 | Prexasertib (CHKi) +Olaparib | MTD: prexasertib 70 mg/m2 iv and olaparib 100 mg, bid BRCA1mut, PARPi resistant, HGSOC (N = 18): PR 22.22% |
DCR-disease control rate; DLT-dose limiting toxicities; MTD-maximum tolerated dose; ORR-overall response rate; OS- overall survival; PFS- progression free survival; RFS- relapse-free survival; RR-response rate; TEAEs- treatment emergent adverse events.