Study of Tuvusertib (M1774) in Combination With DNA Damage Response Inhibitor or Immune Checkpoint Inhibitor (DDRiver Solid Tumors 320)

Running, not enrolling · Phase 1

Conditions studied: Metastatic or Locally Advanced Unresectable Solid Tumors

In brief

This is an open-label, multicenter, clinical study conducted in multiple parts to establish the safety, tolerability, Pharmacokinetic/Pharmacodynamic (PK/PD) profile, maximum tolerated dose (MTD) combinations (if observed) and recommended dose for expansion (RDE) combination for tuvusertib in combination with lartesertib (in Part A1), food effect on the PK of lartesertib as monotherapy followed by treatment with tuvusertib in combination with lartesertib in participants with specific tumor types (in Part A1.1), relative bioavailability of a tuvusertib tablet formulation vs capsule formulation followed by treatment with tuvusertib (capsule) in combination with lartesertib in participants with specific tumor types (in Part A1.2), safety/tolerability and early signs of clinical activity of tuvusertib (capsule)and lartesertib in combination in participants with prostate cancer harboring loss of function (LoS) mutation in the gene ATM based on historic data collected prior to prescreening in circulating tumor (ct) DNA (liquid biopsies) or tumor biopsies (in Part A2), safety/tolerability and early signs of clinical activity of tuvusertib and lartesertib in combination in participants with endometrial cancer harboring LoS mutation(s) in the gene ARID1A based on historic data collected prior to prescreening in ctDNA (liquid biopsies) or tumor biopsies (in Part A3), the relative bioavailability of a tuvusertib tablet formulation (TF1, test) compared to a capsule formulation (reference) will also be investigated (in Part A2/A3), and identify a potential set of MTD combinations, and establish the RDE for the combination of tuvusertib and avelumab in participants with metastatic or locally advanced unresectable solid tumors (in Part B1).

Key facts

Study ID

NCT05396833

Run by

EMD Serono Research & Development Institute, Inc.

People needed

120

Starts

2022-06-07

Expected to finish

2027-01-14

Last updated by the study team

2026-05-28

Who can join

Age: 18 and older. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

• 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

You may not qualify if…

• 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 it is running

• Providence Medical Foundation — Santa Rosa, California, United States
• University of Miami School of Medicine — Miami, Florida, United States
• Augusta University - formerly Georgia Regents University — Augusta, Georgia, United States
• The University of Kansas Medical Center Research Institute, Inc. — Kansas City, Kansas, United States
• Carolina Urologic Research Center — Myrtle Beach, South Carolina, United States
• Mary Crowley Cancer Research Centers — Dallas, Texas, United States
• University of Texas M. D. Anderson Cancer Center - Partner — Houston, Texas, United States
• NEXT Oncology — San Antonio, Texas, United States
• Royal North Shore Hospital — St Leonards, Australia
• Calvary Mater Newcastle - PARENT — Waratah, Australia
• Princess Margaret Cancer Centre — Toronto, Canada
• Seoul National University Bundang Hospital — Seongnam-si, South Korea
• Severance Hospital, Yonsei University Health System - Division of Infectious Diseases — Seoul, South Korea
• Asan Medical Center — Seoul, South Korea
• Samsung Medical Center — Seoul, South Korea
• The Catholic University of Korea, Seoul St. Mary's Hospital — Seoul, South Korea
• Korea University Guro Hospital — Seoul, South Korea
• Hospital QuironSalud Barcelona - Next Oncology — Barcelona, Spain
• Hospital Clinic de Barcelona - Servicio de Oncologia — Barcelona, Spain
• Centro Integral Oncologico Clara Campal - Unidad de Fase I-Oncologica — Madrid, Spain
• Hospital Universitario Quironsalud Madrid - NEXT Oncology — Madrid, Spain
• Hospital Universitario Fundacion Jimenez Diaz - START Madrid FJD - Oncology Phase I — Madrid, Spain

Full record on ClinicalTrials.gov

Trial information comes from ClinicalTrials.gov and is refreshed daily. TrialsForMe does not provide medical care and does not run the studies it lists.