A Study to Evaluate the Efficacy and Safety of Giredestrant in Combination With Phesgo (Pertuzumab, Trastuzumab, and Hyaluronidase-zzxf) Versus Phesgo in Participants With Locally Advanced or Metastatic Breast Cancer (heredERA Breast Cancer)

• Status: Not yet recruiting
• Trial end date: 2032-09-30
• Target enrollment: 0
• Participant gender: All

Summary

This Phase III, randomized, two-arm, open-label, multicenter study will evaluate the efficacy and safety of giredestrant plus Phesgo compared with Phesgo after induction therapy with Phesgo plus taxane in participants with human epidermal growth factor receptor 2 (HER2)-positive, estrogen receptor (ER)-positive advanced breast cancer (metastatic or locally advanced disease not amenable to curative treatment) who have not previously received a systemic non-hormonal anti-cancer therapy in the advanced setting.

• Phase: Phase 3
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Hoffmann-La Roche
• Treatments: Docetaxel; Paclitaxel; Pertuzumab; Trastuzumab

Criteria

Inclusion Criteria:

• Histologically or cytologically confirmed and documented adenocarcinoma of the breast with metastatic or locally-advanced disease not amenable to curative resection

• At least one measurable lesion and/or non-measurable disease evaluable according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1

• 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 or 1

• Left ventricular ejection fraction (LVEF) of at least (≥)50% measured by echocardiogram (ECHO) or multiple-gated acquisition scan (MUGA)

• Adequate hematologic and end-organ function

• For women of childbearing potential: Participants who agree to remain abstinent (refrain from heterosexual intercourse) or use contraception, and agree to refrain from donating eggs, during the treatment period and for 7 months after the final dose of Phesgo

• For men: participants who agree to remain abstinent (refrain from heterosexual intercourse) or use a condom, and agree to refrain from donating sperm, during the treatment period and for 7 months after the final dose of Phesgo to avoid exposing the embryo

Maintenance Phase Inclusion Criteria

• Complete a minimum of four cycles of induction therapy

• Achieve a minimum of stable disease (SD) (or Non-complete response [CR]/Non-progressive disease [PD] for participants with non-measurable disease) (i.e., did not experience PD) according to RECIST v1.1 at the last tumor assessment during the induction therapy phase

• LVEF of ≥50% at the last assessment during the induction therapy phase

Exclusion Criteria:

• Previous systemic non-hormonal anti-cancer therapy in the metastatic breast cancer (MBC) or advanced breast cancer (ABC) setting

• Prior treatment with a selective estrogen receptor degrader (SERD)

• Previous treatment with approved or investigative anti- human epidermal growth factor receptor 2 (HER2) agents in any breast cancer (BC) treatment setting

• Disease progression within 6 months of receiving trastuzumab, with or without pertuzumab, or ado-trastuzumab emtansine in the adjuvant setting

• Non-resolution of all acute toxic effects of prior anti-cancer therapy or surgical procedures to National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0 (NCI CTCAE v5.0) Grade 1 or better

• 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; Epirubucin >720 mg/m2; Mitoxantrone >120 mg/m2; Idarubicin >90 mg/m2.

• Known active uncontrolled or symptomatic central nervous system (CNS) metastases, carcinomatous meningitis, or leptomeningeal disease

• 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

• 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)

• Poorly controlled hypertension

• Known clinically significant history of liver disease

• Active cardiac disease or history of cardiac dysfunction

• Major surgical procedure or significant traumatic injury within 14 days prior to enrollment or anticipation of need for major surgery during induction therapy

• Active inflammatory bowel disease, chronic diarrhea, short bowel syndrome, or major upper gastrointestinal surgery

• Concurrent, serious, uncontrolled infections, or known infection with HIV with the following exception: Individuals who are HIV positive are eligible provided they are stable on anti-retroviral therapy, have a CD4 count ≥200 cells/uL, and have an undetectable viral load and no history of AIDS-defining opportunistic infections within 12 months prior to enrollment.

• Serious infection requiring oral or IV antibiotics within 7 days prior to screening

• Any serious medical condition or abnormality in clinical laboratory tests that precludes an individual's safe participation in the study

• History of malignancy within 5 years prior to screening with the exception of the cancer under investigation in this study and malignancies with a negligible risk of metastasis or death

• For pre- and perimenopausal women, and men: Known hypersensitivity to luteinizing hormone-releasing hormone agonist (LHRHa); Not willing to undergo and maintain treatment with approved LHRHa therapy for the duration of endocrine therapy that requires gonadal function suppression