Cancer
Conditions
Interventions
Arm B Giredestrant plus Phesgo.
Comparator Arm A Maintenance Therapy Phesgo.
Induction Therapy Phesgo plus Taxane Based Chemotherapy
Sponsors
Hoffmann La Roche
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Inclusion Criteria: --Histologically or cytologically confirmed and documented human epidermal growth factor receptor 2 (HER2)-positive/estrogen receptor (ER)-positive 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
Exclusion criteria: Previous systemic non-hormonal anti-cancer therapy in the metastatic breast cancer (MBC) or advanced breast cancer (ABC) setting. Note: Up to one line of single-agent endocrine therapy given in the metastatic or locally advanced setting will be allowed. Prior treatment with a selective estrogen receptor degrader (SERD) Previous treatment with approved or investigative anti-HER2 agents in any breast cancer treatment setting, except Phesgo (or trastuzumab SC with pertuzumab IV, or pertuzumab and trastuzumab IV), ado-trastuzumab emtansine, lapatinib, and neratinib in the neoadjuvant or adjuvant 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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Progression-Free Survival, as Determined by the Investigator According to RECIST v1.1 [ Time Frame: From randomization for maintenance therapy to the first occurrence of disease progression or death from any cause, whichever occurs first (up to 50 months) ] | — |
Secondary
| Measure | Time frame |
|---|---|
| -Overall Survival [ Time Frame: From randomization for maintenance therapy to death from any cause (up to 122 months) ] -Objective Response Rate, as Determined by the Investigator According to RECIST v1.1 [ Time Frame: From randomization for maintenance therapy to disease progression or death (up to 50 months) ] The objective response rate is defined as the percentage of participants with a complete response (CR) or partial response (PR) on two consecutive occasions at least 4 weeks apart. -Duration of Response, as Determined by the Investigator According to RECIST v1.1 [ Time Frame: From first occurrence of documented objective response after randomization for maintenance therapy to disease progression or death from any cause, whichever occurs first (up to 50 months) ] -Clinical Benefit Rate, as Determined by the Investigator According to RECIST v1.1 [ Time Frame: From randomization for maintenance therapy to disease progression or death (up to 50 months) ] The clinical benefit rate is defined as the percentage of participants with stable disease for =24 weeks or a complete response (CR) or partial response (PR). -Mean Role Functioning Score Over Time, as Assessed Using the European Organisation for Research and Treatment of Cancer Quality of Life-Core 30 (EORTC QLQ-C30) Questionnaire [ Time Frame: Maintenance Cycles 1 (Baseline), 3, 6, 9, 12, 15, 18, 24, 30, 36, 39, 48, 57, 66, 75, 84 (1 cycle is 21 days) and to treatment discontinuation, then once every 6 months and once every year for Follow-up Years 1-2 and 3-5, respectively (up to 10 years) ];-Mean Change from Baseline in the Role Functioning Score Over Time, as Assessed Using the European Organisation for Research and Treatment of Cancer Quality of Life-Core 30 (EORTC QLQ-C30) Questionnaire [ Time Frame: Maintenance Cycles 1 (Baseline), 3, 6, 9, 12, 15, 18, 24, 30, 36, 39, 48, 57, 66, 75, 84 (1 cycle is 21 days) and to treatment discontinuation, then once every 6 months and once every year for Follow-up | — |
Countries
Kenya
Contacts
Public ContactGladys Mills
CSM and Start Up Manager Area Africa CONAA
Outcome results
None listed