NCT05601440

Liquid-biopsy Informed Platform Trial to Evaluate CDK4/6-inhibitor Resistant ER+/HER2- Metastatic Breast Cancer

A Liquid-biopsy Informed Platform Trial to Evaluate Treatment in CDK4/6-inhibitor Resistant ER+/HER2- Metastatic Breast Cancer

• Status: Recruiting
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 484 (estimated)
• Sponsor: Canadian Cancer Trials Group · Network
• Sex: All
• Age: —
• Healthy volunteers: Not accepted

Summary

This study is being done to answer the following question: Can testing breast cancer for DNA abnormalities or "biomarkers" help predict which patients are most likely to be helped by certain treatments? The pre-study screening is being done to test a sample of blood (or tumour tissue) for biomarkers to see if patients can participate in the study

Detailed description

This is a 2-stage master protocol with multiple substudies testing investigational drugs/drug combinations in patients with CDK4/6-inhibitor resistant ER+/HER2- metastatic breast cancer. First line endocrine therapy (1LET, aromatase inhibitors; AI) improve clinical outcomes, but are not curative, and acquired resistance develops (median \~2 years). CDK4/6i-resistant MBC is a clinical unmet need, and is marked by numerous potential resistance alterations / mechanisms. Currently, most patients receive second line (2L) ET (e.g., fulvestrant) which has a median progression-free survival (PFS) of \~2 months in this setting. Circulating tumour DNA (ctDNA) is detectable in peripheral blood in \>90% of patients with MBC. Patients who wish to participate but progression has not yet occurred may be enrolled in the monitoring substudy and followed until progression. This monitoring component of IND.241 aims to characterize the molecular and clinical features of CDK4/6i resistance as it occurs after first line CDK4/6i + AI. Besides addressing the principal objectives described above (ctDNA genotyping and evaluation of dynamic changes in ctDNA levels), banked samples will create a biorepository for interrogation of emerging assays (e.g., DNA methylation, or single cell analyses) that may have prognostic or predictive application. These data will inform future efforts that may consider intervention prior to clinical treatment failure.

Conditions

• Breast Cancer

Interventions

Type	Name	Description
DRUG	RP-6306	Dose and schedule will be assigned at enrolment
DRUG	Gemcitabine	Dose and schedule will be assigned at enrolment
OTHER	Observation	Monitoring arm
DRUG	Niraparib	Dose and schedule will be assigned at enrolment
DRUG	Fulvestrant	Dose and schedule will be assigned at enrolment
DRUG	RP-3500	Dose and schedule will be assigned at enrolment
DRUG	CFI-402257	Dose and schedule will be assigned at enrolment
DRUG	CFI-400945	Dose and schedule will be assigned at enrolment
DRUG	Sacituzumab govitecan	Dose and schedule will be assigned at enrolment

Timeline

• Start date: 2023-06-13
• Primary completion: 2027-12-31
• Completion: 2028-06-30
• First posted: 2022-11-01
• Last updated: 2026-03-27

Locations

10 sites across 1 country: Canada