NCT06408168

Phase II Study of REPotrectinib With or Without Fulvestrant in Patients With Hormone Receptor-positive Human Epidermal Growth Factor 2-negative Metastatic Invasive LObular Carcinoma Who Received a Prior Endocrine Therapy in Combination With Cyclin-dependent Kinase 4 and 6 Inhibitor (REPLOT Trial)

• Status: Terminated
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 6 (actual)
• Sponsor: M.D. Anderson Cancer Center · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

To find out if the combination of repotrectinib and fulvestrant can control the disease in participants with metastatic invasive lobular carcinoma.

Detailed description

Primary Objectives • To evaluate the 6-month progression free survival (PFS) of repotrectinib with or without fulvestrant in HR+ HER2- mILC patients who received a prior ET in combination with CDK4/6i Secondary Objectives * To evaluate the 12-month PFS and median PFS (mPFS) of repotrectinib with or without fulvestrant in HR+ HER2- mILC patients who received a prior ET in combination with CDK4/6i * To evaluate the overall response rate (ORR) of reporectinib with or without fulvestrant in HR+ HER2- mILC patients who received a prior ET in combination with CDK4/6i * To assess the clinical benefit rate (CBR), median duration of response (mDOR), and median overall survival (mOS). * To evaluate the safety and tolerability of repotrectinib alone and in combination with fulvestrant, as assessed by the National Cancer Institute Common Terminology Criteria for Adverse Events v5.0 Exploratory/Correlative Objectives * To explore response to repotrectinib based on ROS1 and P120 expression by IHC * To explore if changes in serum thymidine kinase 1 activity (TKa) between baseline and C1D15 correlates with response * To explore whether changes in circulating tumor DNA (ctDNA) levels between baseline and C1D15 predict response to repotrectinib * To correlate whole exome sequencing (WES) and RNA sequencing (RNAseq) findings with response (or lack of) to repotrectinib * To explore changes in the tumor microenvironment (TME) composition using mIF in response to repotrectinib

Conditions

• Hormone Receptor-positive Human Epidermal Growth Factor 2-negative
• Metastatic Invasive LObular Carcinoma

Interventions

Type	Name	Description
DRUG	Fulvestrant	Given by PO
DRUG	Repotrectinib	Given by IV

Timeline

• Start date: 2024-08-08
• Primary completion: 2025-12-08
• Completion: 2025-12-08
• First posted: 2024-05-10
• Last updated: 2026-01-05

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study