Active — Not RecruitingPhase 1

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

United States120 participantsStarted 2022-06-07

Plain-language 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).

Who can participate

Age range18 Years

SexALL

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AI-rewrites the medical criteria so a patient or caregiver can understand them. Always confirm with the trial site.

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 accordi…

What they're measuring

Part A1: Number of Participants With Dose-Limiting Toxicities (DLTs) During the DLT Evaluation Period

Timeframe: Day 1 up to Day 28

Part A1: Number of Participants With Adverse Events (AEs) and Treatment-Related AEs

Timeframe: Baseline up to 18 months

Part B1: Number of Participants with Dose-Limiting Toxicities (DLTs) During the DLT Evaluation Period

Timeframe: Day 1 up to Day 28

Part B1: Number of Participants with AEs and Treatment-Related AEs

Timeframe: Baseline up to 18 months

Part A1: Change From Baseline in Pharmacodynamic (PD) Biomarker

Timeframe: Pre-dose up to approximately 1 month

Part B1: Change From Baseline in PD Biomarker

Timeframe: Pre-dose up to approximately 1 month

Part A1.1: PK Plasma Concentration of Lartesertib Under Fed and Fasted Conditions

Timeframe: Day -1 up to Period 1 Day 1

Trial details

NCT IDNCT05396833

SponsorEMD Serono Research & Development Institute, Inc.

Sponsor typeINDUSTRY

Study typeINTERVENTIONAL

Primary completion2026-04-10

View on ClinicalTrials.gov More Metastatic or Locally Advanced Unresectable Solid Tumors trials

Plain-language summary

Who can participate

Age range18 Years

SexALL

See this in plain English?

AI-rewrites the medical criteria so a patient or caregiver can understand them. Always confirm with the trial site.

What they're measuring

Part A1: Number of Participants With Dose-Limiting Toxicities (DLTs) During the DLT Evaluation Period

Timeframe: Day 1 up to Day 28

Part A1: Number of Participants With Adverse Events (AEs) and Treatment-Related AEs

Timeframe: Baseline up to 18 months

Part B1: Number of Participants with Dose-Limiting Toxicities (DLTs) During the DLT Evaluation Period

Timeframe: Day 1 up to Day 28

Part B1: Number of Participants with AEs and Treatment-Related AEs

Timeframe: Baseline up to 18 months

Part A1: Change From Baseline in Pharmacodynamic (PD) Biomarker

Timeframe: Pre-dose up to approximately 1 month

Part B1: Change From Baseline in PD Biomarker

Timeframe: Pre-dose up to approximately 1 month

Part A1.1: PK Plasma Concentration of Lartesertib Under Fed and Fasted Conditions

Timeframe: Day -1 up to Period 1 Day 1