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DNA Damage Response Inhibitor

M1774 + Niraparib for Solid Tumors

Phase 1

Waitlist Available

Research Sponsored by EMD Serono Research & Development Institute, Inc.

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Presence of loss of function mutations in the genes for ARID1A, ATRX and /or DAXX and ATM

Female participants not pregnant or breastfeeding

Must not have

Calculated QTc average > 450 msec for males and > 470 msec for females that does not resolve with correction of electrolyte abnormalities

Participants diagnosed with hereditary diseases characterized by genetic defects of DNA repair mechanisms

Timeline

Screening 3 weeks

Treatment Varies

Follow Up baseline up to 30 days after the last dose of study treatment, assessed up to approximately 2.2 years

Awards & highlights

No Placebo-Only Group

Summary

This trial is testing a new drug, M1774, to see if it is safe and effective when used alone or with another drug, niraparib.

Who is the study for?

This trial is for adults with advanced solid tumors that haven't responded to standard treatments or have no suitable standard options. They should be relatively healthy (ECOG <=1), possibly with treated, symptom-free brain metastases. Specific genetic mutations are required for some parts of the study, and participants must not be pregnant or breastfeeding.

What is being tested?

The trial tests M1774 alone and combined with Niraparib, a PARP inhibitor, in people with certain solid tumors. It's an early-phase study to determine safety, tolerability, how the body processes the drugs (with/without food), and any preliminary signs of effectiveness.

What are the potential side effects?

While specific side effects aren't listed here, typical ones from similar drugs include nausea, fatigue, blood cell count changes leading to increased infection risk or bleeding problems; organ function issues; allergic reactions; and potential drug interactions.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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My cancer has specific genetic mutations in ARID1A, ATRX, DAXX, or ATM.

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I am not pregnant or breastfeeding.

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I weigh less than 77 kg or my platelet count is below 150,000/mm^3.

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I do not have cancer cells in the lining of my brain and spinal cord.

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I weigh at least 77 kg and my platelet count is 150,000 or higher.

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I am fully active and can carry on all pre-disease activities without restriction.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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My heart's electrical cycle is longer than normal and not due to electrolyte issues.

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I have a genetic condition that affects how my body repairs DNA.

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I have not received a live vaccine in the last 30 days.

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I have previously used ATR or CHK1 inhibitors.

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I have a history of AML, MDS, or prostate cancer.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ baseline up to 30 days after the last dose of study treatment, assessed up to approximately 2.2 years

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~baseline up to 30 days after the last dose of study treatment, assessed up to approximately 2.2 years

This trial's timeline: 3 weeks for screening, Varies for treatment, and baseline up to 30 days after the last dose of study treatment, assessed up to approximately 2.2 years for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Secondary study objectives

Part A3: Number of Participants With Clinical Benefit According to Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

6Treatment groups

Experimental Treatment

Group I: Part B1: Combination Therapy Dose FindingExperimental Treatment2 Interventions

B1a: Participants with baseline body weight less than (\<) 77 kilogram (kg) or platelets \<150,000 cubic per millimeter (mm\^3) will receive Niraparib once daily combined with different doses of Tuvusertib (M1774). B1b: Participants with baseline body weight greater than or equal to (\>=) 77 kg and or platelets \>= 150,000 mm\^3 will receive Niraparib once daily combined with different doses of Tuvusertib (M1774) and schedule determined as recommended dose for expansion (RDE) in Part B1a.

Group II: Part A5: China Dose Confirmation MonotherapyExperimental Treatment1 Intervention

Starting at global RDE from Part A1, in China. Participants will initially receive Tuvusertib (M1774) once daily under fasting conditions. Additional schedules may be evaluated if needed.

Group III: Part A4: Japan Dose Confirmation MonotherapyExperimental Treatment1 Intervention

Starting at global RDE from Part A1, in Japan. Participants will initially receive Tuvusertib (M1774) once daily under fasting conditions. Additional schedules may be evaluated if needed.

Group IV: Part A3 - Monotherapy ExpansionExperimental Treatment1 Intervention

Part A3 is an expansion of Part A1 where Tuvusertib (M1774) will be administered as a single agent at the RDE established in Part A1. Participants with defined loss-of-function mutation in ARID1A, ATRX and/or DAXX, and ATM will be enrolled.

Group V: Part A2 - Preliminary Food Effect AssessmentExperimental Treatment1 Intervention

Participants in the food effect assessment will receive Tuvusertib (M1774) at the dose and schedule determined as recommended dose for expansion (RDE) in Part A1. A single dose of Tuvusertib (M1774) will be administered on Day -7 under a fed (low-fat meal) or fasted condition, followed by a 1-week washout period. After completion of the scheduled food effect assessments, participants will follow the same schedule as participants in Part A1.

Group VI: Part A1: Monotherapy Dose EscalationExperimental Treatment1 Intervention

Participants will initially receive Tuvusertib (M1774) once daily under fasting conditions. Additional schedules may be evaluated if needed.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Niraparib

2018

Completed Phase 4

~2400

0 / 11Eligibility criteria met