Clinical Trials List
Protocol NumberWO43571
NCT Number(ClinicalTrials.gov Identfier)NCT05296798
Active
2022-06-01 - 2032-12-31
Phase III
Recruiting5
ICD-10C50.011
Malignant neoplasm of nipple and areola, right female breast
ICD-10C50.012
Malignant neoplasm of nipple and areola, left female breast
ICD-10C50.019
Malignant neoplasm of nipple and areola, unspecified female breast
ICD-10Z51.12
Encounter for antineoplastic immunotherapy
ICD-9174.0
Malignant neoplasm of female breast, nipple and areola
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
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Trial Applicant
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Sponsor
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Trial scale
Multi-Regional Multi-Center
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Update
2026/02/01
Investigators and Locations
Co-Principal Investigator
- 羅喬 Division of General Surgery
- 林柏翰 Division of General Internal Medicine
- YEN-SHEN LU Division of Hematology & Oncology
- 林季宏 Division of Hematology & Oncology
- MING-YANG WANG Division of General Surgery
- Wei-Wu Chen Division of Radiation Therapy
- 黃柏翔 Division of Hematology & Oncology
- 張端瑩 Division of Hematology & Oncology
- 陳怡君 Division of Hematology & Oncology
The Actual Total Number of Participants Enrolled
0 Recruiting
Co-Principal Investigator
- Chun-Yu Liu Division of General Surgery
- 馮晉榮 Division of General Surgery
- 邱仁輝 Division of General Surgery
- 鄭涵方 Division of General Surgery
- 賴亦貞 Division of General Surgery
- 陳彥蓁 Division of General Surgery
- 林燕淑 Division of General Surgery
- Jiun-I Lai Division of General Surgery
- Yi-Fang Tsai Division of General Surgery
- 陳柏方 Division of General Surgery
- Chi-Cheng Huang Division of General Surgery
- Ta-Chung Chao Division of General Surgery
The Actual Total Number of Participants Enrolled
0 Recruiting
Co-Principal Investigator
- Yao-Chung Wu Division of General Surgery
- Chen-Teng Wu Division of General Surgery
- Chih-Jung Chen Division of General Surgery
- Liang-Chih Liu Division of General Surgery
- 黃至豪 Division of General Surgery
The Actual Total Number of Participants Enrolled
0 Recruiting
The Actual Total Number of Participants Enrolled
0 Recruiting
Co-Principal Investigator
- 楊舜如 Division of Hematology & Oncology
- Yao-Lung Kuo Division of General Surgery
- Kuo-Ting Lee Division of General Surgery
- Jui-Hung Tsai Division of Hematology & Oncology
- Chun-Hui Lee Division of Hematology & Oncology
- Zhu-Jun Loh Division of General Surgery
The Actual Total Number of Participants Enrolled
0 Recruiting
Condition/Disease
Locally Advanced or Metastatic Breast Cancer
Objectives
The purpose of this trial is to evaluate the efficacy and safety of giredestrant, a novel oral selective estrogen receptor degrader (SERD), combined with Phesgo? (pertuzumab, trastuzumab, and HuPH20, subcutaneous injection) after 4 to 6 cycles of Phesgo+taxane induction therapy (i.e., docetaxel or paclitaxel according to standard of care) in subjects with previously untreated locally advanced unresectable or metastatic estrogen receptor (ER)-positive, human epidermal growth factor receptor type 2 (HER2)-positive breast cancer (BC). Despite advances in early diagnosis and curative multi-therapy approaches, some patients may experience metastatic recurrence or “new” metastatic breast cancer (MBC). There is a continuing need for treatments with improved benefit-risk profiles to prolong progression-free survival (PFS) and other survival endpoints in patients with ER-positive, HER2-positive advanced breast cancer (ABC).
Test Drug
GiredestrantPhesgo (1200/600 mg)Phesgo (600/600 mg)
Active Ingredient
Giredestrant
pertuzumab
trastuzumab
rHuPH20
pertuzumab
trastuzumab
rHuPH20
pertuzumab
trastuzumab
rHuPH20
pertuzumab
trastuzumab
rHuPH20
Dosage Form
Capsule
Solution for injection
Solution for injection
Solution for injection
Solution for injection
Dosage
30 mg/capsule
80 mg/mL
60 mg/mL
2,000 U/mL
60 mg/mL
60 mg/mL
2,000 U/mL
80 mg/mL
60 mg/mL
2,000 U/mL
60 mg/mL
60 mg/mL
2,000 U/mL
Endpoints
PFS, defined as the time from randomization to the first disease progression or death from any cause, whichever occurred first, as assessed by the trial sponsor according to Response Evaluation Criteria in Solid Tumors, version 1.1 (RECIST v1.1)
Inclution 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
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
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), 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 adjuvant anti-HER2 therapy (such as trastuzumab, with or without pertuzumab [IV, SC, or fixed-dose combination], or ado-trastuzumab emtansine, or neratinib)
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 consistent with Child-Pugh Class B or C, active liver disease including active viral or other hepatitis virus, autoimmune hepatic disorders, or sclerosing cholangitis, current alcohol abuse, or cirrhosis
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 for ≥4 weeks, have a CD4 count ≥350 cells/uL, and have an undetectable viral load and no history of AIDS-defining opportunistic infections within 12 months prior to enrollment.
Serious COVID-19 infection within 14 days prior to enrollment; however, no screening testing for SARS-CoV-2 is required
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
Treatment with strong CYP3A4 inhibitors or inducers within 14 days or 5 drug-elimination half-lives, whichever is longer, prior to initiation of giredestrant treatment in Arm B
A documented history of hemorrhagic diathesis, coagulopathy, or thromboembolism, including deep vein thrombosis, unless the condition is adequately treated and under control
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), 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 adjuvant anti-HER2 therapy (such as trastuzumab, with or without pertuzumab [IV, SC, or fixed-dose combination], or ado-trastuzumab emtansine, or neratinib)
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 consistent with Child-Pugh Class B or C, active liver disease including active viral or other hepatitis virus, autoimmune hepatic disorders, or sclerosing cholangitis, current alcohol abuse, or cirrhosis
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 for ≥4 weeks, have a CD4 count ≥350 cells/uL, and have an undetectable viral load and no history of AIDS-defining opportunistic infections within 12 months prior to enrollment.
Serious COVID-19 infection within 14 days prior to enrollment; however, no screening testing for SARS-CoV-2 is required
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
Treatment with strong CYP3A4 inhibitors or inducers within 14 days or 5 drug-elimination half-lives, whichever is longer, prior to initiation of giredestrant treatment in Arm B
A documented history of hemorrhagic diathesis, coagulopathy, or thromboembolism, including deep vein thrombosis, unless the condition is adequately treated and under control
The Estimated Number of Participants
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Taiwan
65 participants
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Global
922 participants
