ACTIVE_NOT_RECRUITING

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

Conditions

Metastatic or Locally Advanced Unresectable Solid Tumors ATR inhibitor ATM inhibitor Immunotherapy Tuvusertib (M1774)Lartesertib (M4076)Avelumab DNA Damage Response Inhibitor Immune Checkpoint Inhibitor

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Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

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).

Official Title

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)

Quick Facts

Study Start:2022-06-07

Study Completion:2026-04-03

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:ACTIVE_NOT_RECRUITING

Study ID

NCT05396833

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:18 Years

Sexes Eligible for Study:ALL

Accepts Healthy Volunteers:No

Standard Ages:ADULT, OLDER_ADULT

Inclusion Criteria	Exclusion 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	* 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

Inclusion Criteria

Exclusion 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

* 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

Contacts and Locations

Principal Investigator

Medical Responsible

STUDY_DIRECTOR

Merck Healthcare KGaA, Darmstadt, Germany, an affiliate of Merck KGaA, Darmstadt, Germany

Study Locations (Sites)

Providence Medical Foundation

Santa Rosa, California, 95403

United States

University of Miami School of Medicine

Miami, Florida, 33136

United States

Augusta University - formerly Georgia Regents University

Augusta, Georgia, 30912

United States

The University of Kansas Medical Center Research Institute, Inc.

Kansas City, Kansas, 66205

United States

Carolina Urologic Research Center

Myrtle Beach, South Carolina, 29572

United States

Mary Crowley Cancer Research Centers

Dallas, Texas, 75230

United States

University of Texas M. D. Anderson Cancer Center - Partner

Houston, Texas, 77030

United States

NEXT Oncology

San Antonio, Texas, 78229

United States

Collaborators and Investigators

Sponsor: EMD Serono Research & Development Institute, Inc.

Medical Responsible, STUDY_DIRECTOR, Merck Healthcare KGaA, Darmstadt, Germany, an affiliate of Merck KGaA, Darmstadt, Germany

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2022-06-07

Study Completion Date2026-04-03

Study Record Updates

Study Start Date2022-06-07

Study Completion Date2026-04-03

Terms related to this study

Keywords Provided by Researchers

ATR inhibitor
ATM inhibitor
Immunotherapy
Tuvusertib (M1774)
Lartesertib (M4076)
Avelumab
Metastatic or Locally Advanced Unresectable Solid Tumors
DNA Damage Response Inhibitor
Immune Checkpoint Inhibitor

Additional Relevant MeSH Terms

Metastatic or Locally Advanced Unresectable Solid Tumors