A PHASE III, RANDOMIZED, OPEN-LABEL STUDY EVALUATING THE EFFICACY AND SAFETY OF GIREDESTRANT IN COMBINATION WITH PHESGO VERSUS PHESGO AFTER INDUCTION THERAPY WITH PHESGO?TAXANE IN PATIENTS WITH PREVIOUSLY UNTREATED HER2-POSITIVE, ESTROGEN RECEPTOR-POSITIVE LOCALLY-ADVANCED OR METASTATIC BREAST CANCER

Phase 3

Recruiting

• Conditions: PREVIOUSLY UNTREATED HER2-POSITIVE, ESTROGEN RECEPTORPOSITIVE LOCALLY-ADVANCED OR METASTATIC BREAST CANCER; Breast Cancer; D48.6

• Registration Number: LBCTR2024015502
• Lead Sponsor: F. Hoffmann-La Roche Ltd

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2024-08-13
• Last Update Posted: 19 August 2024

Recruitment & Eligibility

• Status: Recruiting
• Sex: All
• Target Recruitment: 812

Inclusion Criteria

?Signed Informed Consent Form
?Participants (females, regardless of menopausal status, and males) who are aged =18 years at the time of signing Informed Consent Form
- For women: postmenopausal or premenopausal status, defined as follows:
A participant is considered postmenopausal if any of the following definitions are met:
Prior bilateral oophorectomy
Age>60 years
Age <60 years and amenorrheic for 12 months or more in the absence of
chemotherapy or ovarian suppression, and FSH and estradiol in the
postmenopausal ranges
-Pre- or perimenopausal (i.e., not meeting the criteria for postmenopausal)
?Ability to comply with the study protocol, in the investigator’s judgment
Histologically or cytologically confirmed and documented adenocarcinoma of the breast with metastatic or locally-advanced disease not amenable to curative resection.
-HER2-positive ABC confirmed by a central laboratory prior to study enrollment. HER2-positive status will be determined based on primary or metastatic lesion and defined as 3? by immunohistochemistry (IHC) and/or positive by HER2 amplification by in situ hybridization (ISH) with a ratio of = 2 for the number of HER2 gene copies to the number of signals for chromosome 17 copies. Participants will be eligible provided that at least one HER2 test (IHC or ISH) yields a positive result
-A representative formalin-fixed, paraffin-embedded (FFPE) tumor specimen in a paraffin block (preferred) or at least 20 slides containing unstained, freshly cut, serial sections that meet the criteria outlined in Section 8.7 must be submitted prior to study enrollment. In exceptional circumstances, 11-19 slides are acceptable provided that other eligibility requirements are met; however, a minimum of 20 slides is highly preferred. For China, the number of slides required for eligibility will be based on Human Genetics Resources Administration of China (HGRAC) specifications.

-Documented ER-positive tumor according to the American Society of Clinical Oncology/College of American Pathologists (ASCO/CAP) guidelines, assessed locally and defined as = 1% of tumor cells staining positive for ER, preferentially based on the same lesion that was used to determine HER2 positivity.
?At least one measurable lesion and/or non-measurable disease evaluable according to RECIST version 1.1
-Note for participants who receive induction therapy off study: baseline tumor assessments must meet the criteria as listed in Section 8.1.1.1 in attached protocol

?Disease-free interval from completion of adjuvant or neoadjuvant systemic non-hormonal treatment to recurrence of = 6 months
?Eastern Cooperative Oncology Group (ECOG) Performance Status 0 or1
?LVEF of at least 50% measured by ECHO or MUGA
?Adequate hematologic and end-organ function, defined by the following laboratory test results, obtained within 7 days prior to enrollment:
- ANC =1.5 x 109 /L (1500 cells/?L) with one exception:
Participants with benign ethnic neutropenia: ANC =1.3?109 /L (1300/?L)
– Platelet count = 100,000 cells/?L
– Hemoglobin =9.0 g/dL
Participants may receive RBC transfusions to obtain this level
– Estimated creatinine clearance = 30mL/min as calculated per institutional guidelines
– INR and aPTT =1.5 ? upper limit of normal (ULN) (except for participants receiving anticoagulation therapy)
For participants receiving warfarin, a stable INR between 2 and 3 is required.
For participants receiving heparin, PTT (or aPTT

Exclusion Criteria

Potential participants are excluded from the study if any of the following criteria apply:

?Previous systemic non-hormonal anti-cancer therapy in the MBC or ABC setting
Note: Up to one line of single-agent ET given in the metastatic or locallyadvanced setting will be allowed.
One or two cycles of Phesgo (or trastuzumab SC with pertuzumab IV, or PH IV) with docetaxel or paclitaxel in the first line ABC setting is allowed prior to enrollment, provided no limiting toxicities or PD have occurred.

?Previous treatment with approved or investigative anti-HER2 agents except Phesgo (or trastuzumab SC with pertuzumab IV, or PH IV), single-agent trastuzumab IV or SC, ado-trastuzumab emtansine, lapatinib, and neratinib in the neoadjuvant or adjuvant setting
?Disease progression within 6 months of receiving trastuzumab, with or without pertuzumab (IV, SC, or fixed-dose combination), or ado-trastuzumab emtansine in the adjuvant setting
?Non-resolution of all acute toxic effects of prior anti-cancer therapy or surgical procedures to NCI CTCAE v5.0 Grade 1 or better (except alopecia, Grade =2 peripheral neuropathy, or other toxicities that are not considered a safety risk for the participant per investigator's judgment)
? History of persistent Grade = 2 (NCI-CTC, Version 5.0) hematological toxicity resulting from previous adjuvant or neo-adjuvant therapy
? History of exposure to the following cumulative doses of anthracyclines
– Doxorubicin ?360 mg/m2
– Liposomal doxorubicin ?500 mg/m2
– Epirubicin ?720 mg/m2
– Mitoxantrone ?120 mg/m2
– Idarubicin ?90 mg/m2 If another anthracycline or more than one anthracycline has been used, then the cumulative dose must not exceed the equivalent of 360 mg/m2 doxorubicin. (See Appendix 10 in protocol for dose conversions).
?Known active uncontrolled or symptomatic central nervous system (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 (e.g., radiotherapy, surgery), are clinically stable, and have not been treated with anticonvulsants or corticosteroids within 2 weeks prior to enrollment.
?Dyspnea at rest due to complications of advanced malignancy, or other disease requiring continuous oxygen therapy
?Pregnant or breastfeeding, or intending to become pregnant during the study or within 7 months after the final dose of Phesgo
o Women of childbearing potential must have a negative serum pregnancy test result within 14 days prior to initiation of induction therapy
?Treated with investigational therapy within 28 days prior to initiation of induction therapy · Treated with localized palliative radiotherapy within 14 days prior to initiation of induction therapy
?Concurrent participation in any other therapeutic clinical trial
?Known hypersensitivity to any of the study medications or to excipients of recombinant human or humanized antibodies
?Current chronic daily treatment (continuous for ?3 months) with corticosteroids (dose of 10 mg/day methylprednisolone or equivalent), excluding inhaled steroids
?Poorly controlled hypertension (e.g., systolic blood pressure ?180 mm Hg or diastolic blood pressure ? 100 mmHg)
?Known clinically significant history of liver disease consistent with Child-Pugh Class B or C, active liver disease including active viral or other hepatitis virus (e.g., hepatitis B or hepatitis

Study & Design

• Study Type: Interventional
• Study Design: Not specified