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Study of Tuvusertib (M1774) in Combination With DNA Damage Response Inhibitor or Immune Checkpoint Inhibitor (DDRiver Solid Tumors 320)
Sponsor: EMD Serono Research & Development Institute, Inc.
Summary
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)
Key Details
Gender
All
Age Range
18 Years - Any
Study Type
INTERVENTIONAL
Enrollment
120
Start Date
2022-06-07
Completion Date
2026-04-10
Last Updated
2026-02-19
Healthy Volunteers
No
Interventions
Tuvusertib
Tuvusertib will be administered orally once daily over a defined period of time in Part A1, A1.1, A1.2, A2, A3, A2/A3, and Part B1 until disease progression, death, discontinuation, or end of study.
Lartesertib
Lartesertib will be administered orally once daily over a defined period of time in Part A1, A1.1, A1.2, A2, A3, A2/A3, until disease progression, death, discontinuation, or end of study.
Avelumab
Avelumab will be administered by intravenous infusion once a day over a defined period of time in Part B1 until disease progression, death, discontinuation, or end of study.
Locations (22)
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