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Combination treatment for advanced solid tumors using Tuvusertib and other therapies

An Open-label, Multicenter Phase Ib Study of the Safety, Tolerability, and Pharmacokinetic/Pharmacodynamic Profile of the ATR Inhibitor Tuvusertib (M1774) in Combination With DNA Damage Response Inhibitors or Immune Checkpoint Inhibitors in Patients With Metastatic or Locally Advanced Unresectable Solid Tumors (DDRiver Solid Tumors 320)

Phase 1 Interventional EMD Serono · NCT05396833

This study is testing a new treatment combining Tuvusertib with other therapies to see if it can help people with advanced solid tumors like prostate and endometrial cancers.

Quick facts

PhasePhase 1
Study typeInterventional
Enrollment123 (estimated)
Ages18 Years and up
SexAll
SponsorEMD Serono Industry-sponsored
Drugs / interventionsavelumab
Locations20 sites (Santa Rosa, California and 19 other locations)
Trial IDNCT05396833 on ClinicalTrials.gov

What this trial studies

This clinical trial investigates the safety and effectiveness of Tuvusertib (M1774) in combination with DNA damage response inhibitors and immune checkpoint inhibitors for patients with metastatic or locally advanced unresectable solid tumors. The study is open-label and multicenter, focusing on establishing the maximum tolerated dose and recommended dose for expansion of Tuvusertib in various combinations. Participants will be evaluated for pharmacokinetics and pharmacodynamics, as well as early signs of clinical activity, particularly in specific cancer types such as prostate and endometrial cancers. The trial includes multiple parts to assess different aspects of treatment and patient response.

Who should consider this trial

Good fit: Ideal candidates include individuals with metastatic or locally advanced unresectable solid tumors that have not responded to standard treatments or for whom no standard therapy is appropriate.

Not a fit: Patients with tumors that are amenable to standard therapies or those who have not exhausted prior treatment options may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could provide a new therapeutic option for patients with advanced solid tumors that are resistant to standard therapies.

How similar studies have performed: Other studies have shown promising results with similar combinations of DNA damage response inhibitors and immunotherapies, indicating potential for success in this approach.

Eligibility criteria

Show full inclusion / exclusion criteria 
Inclusion Criteria:

* Parts A1, A1.1, A1.2, A2, A3, and A2/3: Participants with metastatic or locally advanced unresectable solid tumors refractory to standard therapy or for which no standard therapy is judged appropriate by the Investigator, which may convey clinical benefit, or who cannot tolerate standard of care treatment
* Parts A1.1 and A1.2: Triple negative breast cancer, epithelial ovarian cancer, castrate resistant prostate cancer, urothelial cancer, endometrial cancer, and colorectal cancer independent of mutation status.
* Part A2: Participants with advanced prostate cancer whose tumor carries a genetic loss of function (LoF) mutation(s) in the gene ataxia telangiectasia mutated (ATM). No more than 3 prior lines of therapy for castrate resistant disease. Prior therapy must have included a taxane and a novel antiandrogen (example \[e.g.\] enzalutamide).
* Part A3: Participants with advanced endometrial cancer whose tumor carries a genetic LoF mutation(s) in the gene AT-rich interaction domain 1A (ARID1A). Prior therapy must have included a platinum agent. Prior therapy must also have included a checkpoint inhibitor if the participant has mismatch repair (MMR)-deficient endometrial cancer. Note for Parts A2/A3: Participants with ATM LoF mutated prostate cancer and ARID1A LoF mutated endometrial cancer should be prioritized to the respective expansion arms instead of being enrolled in Part A1.1. The presence of ATM and ARID1A LoF mutations will be determined according to historic data collected prior to prescreening, generated by an assay with appropriate regulatory status, in either tumor or liquid biopsy. The Sponsor will confirm that mutations certified by historic data fulfil this definition.
* Participants with eastern Cooperative Oncology Group (ECOG) performance status 0 or 1, with estimated life expectancy of at least 3 months
* Adequate hematological, hepatic, and renal function as defined in the protocol
* Other protocol defined inclusion criteria could apply

Exclusion Criteria:

* Participants with any condition, including any uncontrolled disease state other than with metastatic or locally advanced unresectable solid tumors, that in the Investigator's opinion constitutes an inappropriate risk or a contraindication for participation in the study or that could interfere with the study objectives, conduct, or evaluation
* Participants with a known additional malignancy that is progressing and/or requires active treatment
* Participants with carcinomatous meningitis are excluded regardless of clinical stability
* Participants with serious gastrointestinal bleeding within 3 months, refractory nausea and vomiting, uncontrolled diarrhea, known malabsorption, significant small bowel resection or gastric bypass surgery, use of feeding tubes, other chronic gastrointestinal disease, and/or other situations that may preclude adequate absorption of oral medications
* Participants with organ transplantation, including allogeneic stem cell transplant
* Other protocol defined exclusion criteria could apply

Where this trial is running

Santa Rosa, California and 19 other locations

Study contacts

How to participate

  1. Review the eligibility criteria above with your treating physician.
  2. Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
  3. Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.
View on ClinicalTrials.gov → Find more trials like this →
Conditions Metastatic or Locally Advanced Unresectable Solid TumorsATR inhibitorATM inhibitorImmunotherapyTuvusertibLartesertibAvelumabDNA Damage Response Inhibitor
Last reviewed 2026-06-09 by the Find a Trial editorial team. Information on this page is for educational purposes and is not medical advice. Always consult qualified healthcare professionals about clinical trial participation.