Immunotherapy, Hormone Therapy, and AKT Inhibitor for Premenopausal ER Positive MBC

Phase 2

Recruiting

• Conditions: Metastatic Breast Cancer; Premenopausal Breast Cancer; ER Positive Breast Cancer
• Interventions: Drug: Goserelin; Drug: Fulvestrant; Drug: Durvalumab; Drug: Capivasertib

• Registration Number: NCT05720260
• Lead Sponsor: National Taiwan University Hospital

Brief Summary

This is an open-label randomized phase II study in estrogen receptor positive locally advanced or metastatic breast cancer patients. The main inclusion population are either luminal subtype B by PAM50 analysis or failed less than 2 lines of hormonal therapy for locally advanced or metastatic breast cancer. The subjects have to be premenopausal or perimenopausal and are not allowed to receive any systemic chemotherapy for their locally advanced or metastatic breast cancer. Eligible subjects will be randomized into goserelin/ fulvestrant/ durvalumab (Arm A), goserelin/ fulvestrant/ capivasertib/ durvalumab (Arm B), or goserelin/ fulvestrant/ capivasertib (Arm C) at a 1:1:1 ratio. The primary endpoint is objective response rate (ORR) of the whole other three arm compared to historical goserelin/ fulvestrantcontrol arm. The major secondary endpoint will be progression-free survival or ORR compared among different treatment arms.

Detailed Description

This is an open-label randomized phase II study in estrogen receptor positive locally advanced or metastatic breast cancer patients. The main inclusion population are either luminal subtype B by PAM50 analysis or failed less than 2 lines of hormonal therapy for locally advanced or metastatic breast cancer. The subjects have to be premenopausal or perimenopausal and are not allowed to receive any systemic chemotherapy for their locally advanced or metastatic breast cancer. Eligible subjects will be randomized into goserelin/ fulvestrant/ durvalumab (Arm A), goserelin/ fulvestrant/ capivasertib/ durvalumab (Arm B), or goserelin/ fulvestrant/ capivasertib (Arm C) at a 1:1:1 ratio. The primary endpoint is objective response rate (ORR) of the whole other three arm compared to historical goserelin/ fulvestrant control arm. The major secondary endpoint will be progression-free survival or ORR compared among different treatment arms. Secondary endpoints include PFS and ORR comparison between arms. Exploratory endpoints include biomarkers, such as TILs, PD-L1 correlation with treatment response.

Study Timeline

• Study Start: 2023-01-17
• Study First Submitted: 2023-01-26
• Study First Submitted QC: 2023-02-07
• Study First Posted: 2023-02-09
• Status Verified: 2024-04
• Last Update Submitted: 2024-06-07
• Last Update Posted: 2024-06-10
• Primary Completion: 2024-12-31
• Study Completion: 2027-01-31

Recruitment & Eligibility

• Status: RECRUITING
• Sex: Female
• Target Recruitment: 42

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Arm A: goserelin/ fulvestrant/ durvalumab	Goserelin	Historical control arm (goserelin, fulvestrant) plus immunotherapy
Arm A: goserelin/ fulvestrant/ durvalumab	Fulvestrant	Historical control arm (goserelin, fulvestrant) plus immunotherapy
Arm A: goserelin/ fulvestrant/ durvalumab	Durvalumab	Historical control arm (goserelin, fulvestrant) plus immunotherapy
Arm B: goserelin/ fulvestrant/ capivasertib/ durvalumab	Fulvestrant	Historical control arm (goserelin, fulvestrant) plus AKT inhibitor and immunotherapy
Arm B: goserelin/ fulvestrant/ capivasertib/ durvalumab	Goserelin	Historical control arm (goserelin, fulvestrant) plus AKT inhibitor and immunotherapy
Arm B: goserelin/ fulvestrant/ capivasertib/ durvalumab	Durvalumab	Historical control arm (goserelin, fulvestrant) plus AKT inhibitor and immunotherapy
Arm B: goserelin/ fulvestrant/ capivasertib/ durvalumab	Capivasertib	Historical control arm (goserelin, fulvestrant) plus AKT inhibitor and immunotherapy
Arm C: goserelin/ fulvestrant/ capivasertib	Goserelin	Historical control arm (goserelin, fulvestrant) plus AKT inhibitor and immunotherapy
Arm C: goserelin/ fulvestrant/ capivasertib	Fulvestrant	Historical control arm (goserelin, fulvestrant) plus AKT inhibitor and immunotherapy
Arm C: goserelin/ fulvestrant/ capivasertib	Capivasertib	Historical control arm (goserelin, fulvestrant) plus AKT inhibitor and immunotherapy

Primary Outcome Measures

Name	Time	Method
Progression-free survival	From time of randomization to death or tumor progression whichever comes first in 200 months	PFS comparison between historical control (fulvestrant and goserelin) and Arm A/B/C

Trial Locations

Locations (1)

Department of Oncology, National Taiwan University Hospital; 🇨🇳 Taipei City, Taiwan