NCT07340658

A Study to Investigate the Efficacy and Safety of Letrozole SIE Compared With Femara® (Both Combined With the CDK4/6 Inhibitor Ribociclib) in Postmenopausal Women With HR-Positive, HER2-Negative, Inoperable Locally Advanced or Metastatic Breast Cancer

A Multicenter, Randomized, Double-Blind, Double-Dummy, Phase III Study to Evaluate the Efficacy and Safety of Letrozole SIE Compared to Femara® (Both in Combination With the CDK4/6 Inhibitor Ribociclib) in Postmenopausal Women With HR-Positive, HER2-Negative, Inoperable Locally Advanced or Metastatic Breast Cancer (SIE-3)

• Status: Not Yet Recruiting
• Phase: Phase 3
• Study type: Interventional
• Enrollment: 300 (estimated)
• Sponsor: Rovi Pharmaceuticals Laboratories · Industry
• Sex: Female
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

The purpose of this study is to evaluate the efficacy and safety of Letrozole SIE (injectable) compared to Femara® (oral tablet), both given together with ribociclib, for the first-line treatment of postmenopausal women with HR-positive, HER2-negative, inoperable locally advanced or metastatic breast cancer.

Detailed description

This is a multicenter, randomized, double-blind, double-dummy, active-controlled Phase III study comparing Letrozole SIE with Femara® (both in combination with the CDK4/6 inhibitor ribociclib) in postmenopausal women with HR-positive, HER2-negative, inoperable locally advanced or metastatic breast cancer. The study employs double-blinding with matching placebos (double-dummy technique) to minimize bias on the part of participants, investigators, and analysts. Participants will be randomized in a 1:1 ratio to receive either Letrozole SIE (experimental use) or Femara® (active comparator), both in combination with the CDK4/6 inhibitor ribociclib. Randomization occurs after Screening and confirmation of eligibility and will be stratified by visceral metastasis (Yes/No) and prior adjuvant endocrine therapy (Yes/No). The Treatment Period will last from Cycle 1 Day 1 (C1D1) until study intervention discontinuation due to disease progression, symptomatic deterioration, unacceptable toxicity, withdrawal of consent, loss to follow-up, participant's death, or end of study, whichever occurs first. After study intervention discontinuation, a post-discontinuation visit will be performed. Then, participants will be followed until withdrawal of consent, loss to follow-up, the participant's death, or end of study, whichever occurs first.

Conditions

• Advanced, Metastatic Breast Cancer

Interventions

Type	Name	Description
DRUG	Letrozole SIE + Ribociclib + Oral placebo	Letrozole SIE quarterly (injectable) + Ribociclib once daily (oral) + placebo once daily (oral)
DRUG	Oral Femara® + Ribociclib + Injectable placebo	Femara® 2.5 mg/day (oral) + Ribociclib once daily (oral) + placebo quarterly (injectable)

Timeline

• Start date: 2026-08-01
• Primary completion: 2029-02-01
• Completion: 2033-12-01
• First posted: 2026-01-14
• Last updated: 2026-04-02

Regulatory

• FDA-regulated drug study