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

NCT07340658 | Not Yet Recruiting Phase 3 DMC FDA Drug

• 2 other identifiers: ROV-SIE-2025-022025-524846-85-00
• Study Type: interventional
• Target: 300
• Locations: 0 countries
• Sites: N/A

Brief 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.

Conditions

Advanced, Metastatic Breast Cancer

Keywords

Letrozole SIE; Advanced breast cancer; Metastatic breast cancer; Endocrine therapy; Efficacy; Safety; Injectable; Ribociclib

Outcome Measures

Primary Outcomes (1)

• Progression Free Survival (PFS)

  PFS per Investigator assessment, defined as the time from the date of randomization to the date of the first documented progression or death due to any cause. PFS will be assessed via a local radiology assessment according to RECIST v1.1. PFS as assessed through a blinded independent central review will be used for supportive evidence of the primary efficacy endpoint.

  From the date of randomization to the date of the first documented progression or death due to any cause, assessed according to RECIST version 1.1 (up to approximately 30 months).

Secondary Outcomes (26)

• Overall Survival (OS): Primary analysis

  From the date of randomization to date of death from any cause (up to approximately 30 months).

• Overall Survival (OS): Final analysis

  From the date of randomization to date of death from any cause (up to approximately 88 months).

• Objective Response Rate (ORR)

  From the date of randomization to the date of the first documented progression or death due to any cause, assessed according to RECIST version 1.1 (up to approximately 30 months).

• Incidence of arthralgias/arthritis and/or myalgias

  From the date of the first dose of study intervention to the post-discontinuation visit (up to approximately 30 months).

• Time to Response (TTR)

  From the date of randomization to the date of the first documented evidence of complete response or partial response (up to approximately 30 months).

Study Arms (2)

Letrozole SIE

EXPERIMENTAL

Drug: Letrozole SIE + Ribociclib + Oral placebo

Femara® 2.5 mg

ACTIVE COMPARATOR

Drug: Oral Femara® + Ribociclib + Injectable placebo

Interventions

Letrozole SIE + Ribociclib + Oral placebo DRUG

Letrozole SIE quarterly (injectable) + Ribociclib once daily (oral) + placebo once daily (oral)

Letrozole SIE

Oral Femara® + Ribociclib + Injectable placebo DRUG

Femara® 2.5 mg/day (oral) + Ribociclib once daily (oral) + placebo quarterly (injectable)

Femara® 2.5 mg

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Female participants with inoperable locally advanced or metastatic breast cancer.
• Confirmed diagnosis of HR-positive/HER2-negative breast cancer.
• Postmenopausal woman.
• Previously untreated with any systemic anticancer therapy for their locoregionally recurrent or metastatic HR-positive disease. Participants may have received cytotoxic chemotherapy within (neo) adjuvant previous treatment of breast cancer but must show progressive disease prior to enrollment.
• Have either measurable disease or non-measurable bone-only disease.
• ECOG performance status 0-2.
• Adequate organ and marrow function.
• Resolution of all acute toxic effects of prior anticancer therapy or surgical procedures to NCI Common Terminology Criteria for Adverse Events (CTCAE) version 6.0 Grade ≤ 1 (except alopecia or other toxicities not considered a safety risk for the participant at the investigator's discretion).
• BMI ≥ 19 and ≤ 39 kg/m2.

You may not qualify if:

• Participants with advanced, symptomatic, visceral spread who are at risk of life-threatening complications in the short term.
• Participants with inflammatory breast cancer.
• Known uncontrolled or symptomatic central nervous system (CNS) metastases.
• Concurrent malignancy or malignancy within 3 years of randomization, with the exception of adequately treated basal or squamous cell carcinoma, non-melanomatous skin cancer, or curatively resected cervical cancer.
• Active cardiac disease or documented history of cardiac dysfunction.
• Uncontrolled hypertension.
• History of symptomatic vertebral fragility fracture or any fragility fracture of the hip, pelvis, wrist, or other location (defined as any fracture without a history of trauma or because of a fall from standing height or less, excluding fingers, toes, face and skull).
• Presence of medical conditions associated with low bone mass.
• History of ILD/pneumonitis.
• Other severe acute or chronic medical or psychiatric condition, including recent or active suicidal ideation/behavior, or laboratory or ECG abnormalities that may increase the risk associated with study participation or study intervention administration or may interfere with the interpretation of study results and, in the judgment of the Investigator, would make the patient inappropriate for entry into this study.
• Presence of detectable viral infection, including HBV, HCV, and HIV. Screening is not required for enrollment. Note: Participants who have been effectively treated and have a sustained virologic response are eligible for enrollment.
• Major surgery, chemotherapy, radiotherapy, any investigational agents, or other anticancer therapy within 14 days (2 weeks) before randomization. Participants who received prior radiotherapy to \> 25% of bone marrow are not eligible independent of when it was received.
• Bisphosphonates or receptor activator of nuclear factor kappa-β ligand (RANKL) inhibitors initiated or have their dose changed within 14 days prior to randomization, i.e., participants should be on stable dose treatment for at least 14 days prior to randomization.
• Hormonal medications or medications or products known to affect serum LH, FSH (except spironolactone which is allowed if medically indicated), or estrogen/E2 levels within 3 months prior to randomization. This includes, but is not limited to, estrogen or progesterone hormone replacement therapy, oral contraceptives, androgens, LHRH analogs, prolactin inhibitors, or antiandrogens and other medications, herbal remedies, and/or supplements for the treatment of vasomotor hot flush symptoms administered via any route, including topical or intravaginal administration.
• Use of the following medications within the 3 previous days or a period of 5 half-lives, (whichever is longer) prior to randomization:

Sponsors & Collaborators

• Rovi Pharmaceuticals Laboratories: lead

MeSH Terms

Conditions

Breast Neoplasms

Interventions

ribociclib; Letrozole

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Nitriles; Organic Chemicals; Triazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Central Study Contacts

Clinical Operations. Laboratorios Farmacéuticos ROVI

CONTACT

+34 913756230; departamento.medico@rovi.es

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 9, 2026
• First Posted: January 14, 2026
• Study Start (Estimated): August 1, 2026
• Primary Completion (Estimated): February 1, 2029
• Study Completion (Estimated): December 1, 2033
• Last Updated: April 2, 2026

Record last verified: 2026-03