Investigational Drug
Tuvusertib
TrialFetch AI Analysis
Show TrialFetch AI Analysis
Overview
Tuvusertib (M1774) is an investigational oral cancer drug studied alone and in combinations. Human results are available, but they are from small, early-stage studies and a phase II conference abstract; its clinical benefit remains uncertain. In 2025, its developer stopped investigating combinations with other DNA-damage-response inhibitors after an underwhelming efficacy signal in a phase II ovarian-cancer study. (aacrjournals.org)
Mechanism of action
Tuvusertib inhibits ATR, a protein kinase that helps cells respond to DNA damage and stress during DNA replication. Blocking ATR is intended to make cancer cells less able to survive that stress. (aacrjournals.org)
Efficacy
- Alone: In a phase I study of 55 people with advanced solid tumors, one patient had an unconfirmed partial response, and 15 (27%) had stable disease. (aacrjournals.org)
- With niraparib: A phase I conference abstract reported responses in 5 of 32 evaluable patients (15.6%); 3 were confirmed. These preliminary results do not establish how much either drug contributed. (ascopubs.org)
- With avelumab: In a phase II study of Merkel cell carcinoma that had progressed after immunotherapy, 5 of 24 eligible patients receiving the combination responded (20.8%), including one complete response. None of the 10 patients initially assigned tuvusertib alone responded, and that arm closed early for futility. These findings were reported in a conference abstract. (ascopubs.org)
Safety
In the 55-person monotherapy study, the most common adverse events were anemia (71%), nausea (62%), and fatigue (40%); grade 3 or higher anemia occurred in 36%. In the tuvusertib–niraparib study, grade 3 or higher anemia occurred in 41.9% and decreased platelet count in 14.0%. In the Merkel cell study, grade 3 or higher adverse events occurred in 80% of those assigned tuvusertib alone and 58% of those assigned the avelumab combination; the groups were small. (aacrjournals.org)
Further reading
- First-in-human monotherapy study (aacrjournals.org)
- Phase I tuvusertib–niraparib abstract (ascopubs.org)
- Phase II Merkel cell carcinoma abstract (ascopubs.org)
Last updated: Sep 2026
Active trials using Tuvusertib
Found 3 active trials using this drug:
TrialFetch AI summary: For adults with measurable, ARID1A loss-of-function–mutated recurrent endometrial cancer previously treated with chemotherapy and PD-1/PD-L1 therapy, this single-arm study combines avelumab, a PD-L1–blocking antibody, with oral tuvusertib (M1774), an ATR inhibitor.
ClinicalTrials.gov ID: NCT06518564
TrialFetch AI summary: Adults with recurrent clear cell or endometrioid ovarian cancer or clear cell or grade 1 endometrioid endometrial cancer after 1–3 prior cytotoxic regimens receive oral tuvusertib, an ATR inhibitor, plus oral ZEN-3694, a BET inhibitor. Dose escalation also permits platinum-resistant high-grade serous ovarian cancer; expansion enrolls separate ARID1A-altered and wild-type cohorts.
ClinicalTrials.gov ID: NCT05950464
TrialFetch AI summary: Adults with selected advanced or metastatic solid tumors receive oral temozolomide plus tuvusertib (M1774), an investigational ATR inhibitor that disrupts the DNA-damage response. The expansion cohort is limited to previously treated, MGMT promoter-hypermethylated, mismatch repair-proficient/microsatellite-stable metastatic colorectal cancer; prior temozolomide or ATR inhibitor therapy is excluded.
ClinicalTrials.gov ID: NCT05691491
