Efficacy and safety ofGiredestrant, inpatients with advanced breast cancer

Phase 3

• Conditions: Health Condition 1: C509- Malignant neoplasm of breast of unspecified site

• Registration Number: CTRI/2024/03/064777
• Lead Sponsor: F Hoffmann La Roche Ltd

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Last Update Posted: 19 August 2024

Recruitment & Eligibility

• Status: ot Yet Recruiting
• Sex: Not specified
• Target Recruitment: 0

Inclusion Criteria

1. Signed Informed Consent Form

2. Age more than or equal to 18 years.

3. Locally advanced or metastatic adenocarcinoma of the breast, not amenable to treatment with curative intent.

4. Documented ER plus tumor according to American Society of Clinical Oncology/College of American Pathologists (ASCO/CAP) or ESMO guidelines or any national guidelines with criteria conforming to ASCO/CAP or ESMO guidelines, defined as more than or equal to 1 percent of tumor cells stained positive, assessed locally based on the most recent tumor biopsy (or archived tumor sample)

5. Documented HER2 tumor according to ASCO/CAP or ESMO guidelines or any national guidelines with criteria conforming to ASCO/CAP or ESMO guidelines, assessed locally based on the most recent tumor biopsy (or archived tumor sample)

6. Confirmed ESR1 mutation status (mutation detected [ESR1m] vs. no mutation detected [ESR1nmd]) in baseline ctDNA, as assessed through central lab testing of a blood sample freshly collected at screening, using the investigational FMI F1LCDx assay. A valid central testing result using investigational F1LCDx is always required; in localities where FMI central testing is not available, samples will be submitted to an alternative, Sponsor-designated central laboratory. Participants without a valid ESR1 mutation status central result (i.e., unknown ESR1 mutation status that cannot be classified as ESR1m or ESR1nmd) are not eligible. Eligible ESR1 mutations are defined as short variants known to affect protein function occurring within amino acids 310 to 547.

7. Consent to provide and confirmed availability of the most recently collected and representative tumor tissue specimen suitable for biomarker testing with associated pathology (i.e., archived formalin-fixed paraffin-embedded tissue block [preferred] or 15 to 20 slides containing unstained, freshly cut, serial sections).

8. Participants who have relapsed with prior standard adjuvant ET with an AI (i.e., anastrozole, letrozole, or exemestane) and/or a SERM (i.e., tamoxifenor toremifene), on-treatment after more than or equal to 12 months or off-treatment within 12 months of completion (i.e., treatment-free interval less than 12 months). If neo/adjuvant ET included a CDK4/6i, relapse should have occurred more than or equal to 12 months since completion of CDK4/6i treatment.

9. No history of systemic anti-cancer therapy for locally advanced or metastatic disease.

10. Measurable disease as defined per RECIST v.1.1 or non-measurable bone-only disease which must be evaluable defined as having at least one predominantly lytic bone lesion confirmed by computed tomography (CT) or magnetic resonance imaging (MRI) which can be followed (soft tissue component not required). Tumor lesions previously irradiated or subjected to other locoregional therapy will be deemed measurable only if disease progression at the treated site after completion of therapy is clearly documented.

11. Considered appropriate for treatment with ET (e.g., CDK4/6i in combination with fulvestrant) at time of entry into the study, recommended as per national or local treatment guidelines

12. Life expectancy of more than 6 months

13. ECOG Performance Status 0 to 1

14. Adequate organ function as defined by the following criteria: ANC more than or equal to 1.5x10 to the power of 9/L (1500/microL); Platelet count more than or equal to 100x10 to the power of

Exclusion Criteria

1. Disease recurrence during the first 12 months of adjuvant ET.

2. Prior systemic therapy for metastatic breast cancer eg prior chemotherapy immunotherapy or biologic therapy for locally advanced unresectable or metastatic disease.

3. Prior treatment with a SERD eg fulvestrant novel oral proteolysis targeting chimera complete ER antagonist CERAN or novel SERM other than tamoxifen toremifene.

4. Treatment with any investigational therapy within 28 days prior to randomization or within 5 half lives of the investigational drugs whichever is longer.

5. Radiotherapy or any other anti cancer therapy within 2 weeks before randomization. Participants who received prior radiotherapy to more than or equal to 25 percentage of bone marrow or hematopoietic stem cell or bone marrow transplantation are not eligible regardless of when.

6. Major surgical procedure or significant traumatic injury within 28 days prior to randomization. Anticipation of need for a major surgical procedure during the course of the study.

7. Exposure to strong CYP3A4 inhibitors strong CYP3A4 inducers and moderate CYP3A inducers for participants who will receive abemaciclib only within 14 days or 5 drug elimination half lives whichever is longer prior to initiation of study treatment.

8. Advanced symptomatic, visceral spread that is at risk of life threatening complications in the short term including massive uncontrolled effusions pleural pericardial peritoneal or pulmonary lymphangitis appropriate for treatment with cytotoxic chemotherapy at time of entry into the study as per national or local treatment guidelines.

9. History of other malignancy within 5 years prior to screening except for cancers with very low risk of recurrence including but not limited to appropriately treated carcinoma in situ of the cervix non melanoma skin carcinoma papillary thyroid cancer treated with surgery or Stage I endometrial cancer.

10. Known active uncontrolled or symptomatic CNS metastases carcinomatous meningitis or leptomeningeal disease. Participants with a history of CNS metastases or cord compression are eligible if they have been definitively treated with local therapy eg radiotherapy surgery are clinically stable and have not been treated with anticonvulsants or corticosteroids within 2 weeks prior to randomization.

11. Active cardiac disease or history of cardiac dysfunction including any of the following History within 2 years of screening or presence of idiopathic symptomatic bradycardia or resting heart rate less than 50 bpm at screening. Patients on stable dose of a beta blocker or calcium channel antagonist for preexisting baseline conditions eg hypertension may be eligible if resting heart rate is at least 50 bpm. History of angina pectoris or symptomatic coronary heart disease within 12 months prior to study entry. History of documented congestive heart failure New York Heart Association Class III to IV or cardiomyopathy. QT interval based on mean value of triplicate ECGs corrected through use of Fridericias formula QTcF. More than 470 ms for female participants intended to be treated with palbociclib or abemaciclib. More than 450 ms for male participants intended to be treated with any CDK4 6i and for female participants intended to be treated with ribociclib. History of long or short QT syndrome Brugada syndrome or known history of corrected QT interval prolongation or torsades de pointes. Pres

Study & Design

• Study Type: Interventional
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
To evaluate the efficacy of <br/ ><br>giredestrant compared with <br/ ><br>fulvestrant (both combined with CDK4/6i) in the ESR1m subgroup and FASTimepoint: PFS, defined as time from randomization to first <br/ ><br>occurrence of Progressive disease, as determined by the investigator according to RECIST v1.1, or death from any cause during the study whichever occurs first.