MedTrace Logo

I/II Phase Study Evaluating M1774 in Combination With Fulvestrant in HR+ and HER2- Advanced Breast Cancers

NCT05986071 · Status: NOT_YET_RECRUITING · Phase: PHASE1/PHASE2 · Type: INTERVENTIONAL · Enrollment: 57

Last updated 2024-03-29

No results posted yet for this study

Summary

CDK4/6 inhibitor in combination with endocrine treatment is the standard of care in advanced breast cancer (ABC) with expression of hormone receptors and without HER2 overexpression (ER+/HER2-). When patients experience disease progression under this strategy, options of second-line endocrine treatment in combination with other targeted therapies are limited and have failed to improve overall survival to date over endocrine treatment alone. A significant fraction of ER+/HER2- ABC display genetic alterations associated with homologous recombination deficiency (HRD) which may be associated with efficacy of therapeutic targeting DNA damage response (DDR) pathways. Moreover, other molecular alterations associated with replicative stress may be found in ER+/HER2- ABC patients which may also favor antitumor activity of DDR targeting therapeutics. M1774 is a novel orally administered inhibitor of ataxia telangiectasia and rad3-related (ATR), a protein kinase with key activity in DDR pathway. MATRIx is a phase I/II study aiming to determine the recommended phase II dose (RP2D, phase I) as well as efficacy and safety (phase II) of M1774 in combination with fulvestrant in ER+/HER2-ABC patients whose disease has become resistant to aromatase inhibitor plus CDK4/6 inhibitor, and whose tumor displays molecular alterations associated with HRD, oncogenic driver activation and/or replicative stress. Primary endpoints will include: maximum tolerated dose (MTD) of M1774 in combination with fulvestrant (phase I), the clinical benefit rate and toxicity of the combination at RP2D of M1774 in the molecularly selected population (phase II). Baseline, on-treatment and post-treatment blood and tumor tissue samples will be collected for pharmacokinetics and translational analyses including genomic characterization of tumor tissue and ctDNA as well as functional studies focusing on DDR pathways.

Conditions

Interventions

DRUG

M1774

• Phase I part = administration of M1774 in combination with fulvestrant in ER+/HER2- ABC resistant to CDK4/6 inhibitor and aromatase inhibitor-based endocrine therapy in order to detemine the recommended phase II dose Phase II part = administration of M1774 at RP2D in combination with fulvestrant

DRUG

Fulvestrant injection

Phase I part = administration of M1774 in combination with fulvestrant in ER+/HER2- ABC resistant to CDK4/6 inhibitor and aromatase inhibitor-based endocrine therapy in order to detemine the recommended phase II dose Phase II part = administration of M1774 at RP2D in combination with fulvestrant

Sponsors & Collaborators

  • National Cancer Institute, France

    collaborator OTHER_GOV

  • Merck KGaA, Darmstadt, Germany

    collaborator INDUSTRY

  • Institut Paoli-Calmettes

    lead OTHER

Study Design

Allocation
NA
Purpose
TREATMENT
Masking
NONE
Model
SINGLE_GROUP

Eligibility

Min Age
18 Years
Sex
FEMALE
Healthy Volunteers
No

Timeline & Regulatory

Start
2024-05-01
Primary Completion
2027-04-01
Completion
2027-10-15

Countries

  • France

Study Locations

More Related Trials

Entities

Diseases

Read the full study record

This page highlights key information. For complete eligibility criteria, study locations, investigator contacts, and the full protocol, visit the original record on ClinicalTrials.gov.

View NCT05986071 on ClinicalTrials.gov