Breast Cancer Clinical Trial

A Study of GDC-9545 Alone or in Combination With Palbociclib and/or Luteinizing Hormone-Releasing Hormone (LHRH) Agonist in Locally Advanced or Metastatic Estrogen Receptor-Positive Breast Cancer

Summary

This study will evaluate the safety, pharmacokinetic (PK), pharmacodynamic (PD) activity, and preliminary anti-tumor activity of GDC-9545 as a single agent and in combination with palbociclib and/or luteinizing hormone-releasing hormone (LHRH) agonist in participants with advanced or metastatic estrogen receptor (ER)-positive (human epidermal growth factor receptor 2 [HER2]-negative) breast cancer.

View Eligibility Criteria

Eligibility Criteria

Inclusion Criteria for Dose Escalation:

Histologically or cytologically proven diagnosis of adenocarcinoma of the breast with evidence of either locally recurrent disease not amenable to resection or radiation therapy with curative intent or with metastatic disease
Estrogen receptor (ER)-positive tumor
Human epidermal growth factor receptor 2 (HER2)-negative breast cancer as per local laboratory testing
Measurable disease, or evaluable bone disease; that is, bone lesions that are lytic or mixed (lytic + sclerotic) in the absence of measurable lesion
Required paired pre- and on-treatment tumor biopsies for participants with metastases that are safely accessible as determined by the investigator
Advanced or metastatic ER-positive/HER2-negative breast cancer that has recurred or progressed while being treated with adjuvant endocrine therapy for a duration of at least 24 months and/or endocrine therapy in the incurable, locally advanced, or metastatic setting and derived a clinical benefit from therapy (i.e., tumor response or stable disease for at least 6 months)
No more than 2 prior lines of treatment for advanced or metastatic breast cancer
Greater than or equal to (≥)2 weeks must have elapsed from the use of any other endocrine, targeted therapy or chemotherapy
Single-Agent Cohorts (only applies to Dose Escalation): Advanced or metastatic disease that is either refractory to or intolerant of existing standard therapy or for which no effective standard therapy that confers clinical benefit is available
Cohort B0: No prior treatment with cyclin-dependent kinase 4/6 (CDK4/6) inhibitor
For participants undergoing 18F-fluoroestradiol-positron emission tomography (FES-PET) imaging additional restrictions on prior therapy include: ≥2 months must have elapsed from the use of tamoxifen; ≥6 months must have elapsed from the use of fulvestrant
Postmenopausal status
Eastern Cooperative Oncology Group (ECOG) Performance Status less than or equal to (≤)1
Resolution of all acute toxic effects of prior therapy or surgical procedures to baseline or Grade ≤1 (except alopecia or other toxicities not considered to be a safety risk for the patient)
Life expectancy of ≥12 weeks
Adequate organ function

Inclusion Criteria for Dose Expansion:

Same criteria as above for Dose Escalation, except for those that only apply to Dose Escalation, plus the following:

Required paired pre- and on-treatment tumor biopsies for participants in Cohorts A1-A5, B1, and B2 with metastases that are safely accessible as determined by the investigator
In South Korea: Must have received exactly 2 prior lines of treatment for advanced or metastatic breast cancer
In the rest of the world: No more than 1 prior line of treatment for advanced or metastatic breast cancer (not applicable to Cohort X)

Plus the following criteria:

Cohorts B1 and B2: No prior treatment with CDK4/6 inhibitor
Cohorts A1, A3, A5, B1, C1, and C2 only: Postmenopausal status
Cohorts A2, A4, and B2 only: Participants not defined as postmenopausal; Age less than (<)56 years who have medical menopause on LHRH agonist (on stable dose ≥4 weeks)
No prior treatment with an oral selective estrogen receptor degrader (SERD)
For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use non-hormonal contraceptive methods with a failure rate of <1% per year during the treatment period and for 40 days after the last dose of GDC-9545, and agreement to refrain from donating eggs during this same period
Cohort X only: Participants enrolled on Studies GO29656 or GO29642 and received clinical benefit from GDC-0927 or GDC-0810
Hematology, chemistry, and urinalysis collected 72 hours before Cycle 1, Day 1 deemed acceptable for dosing by the investigator
No other endocrine therapy, targeted therapy, or chemotherapy after last dose of GDC-0927 or GDC-0810

Exclusion Criteria for Dose Escalation:

Known brain metastases that are untreated, symptomatic, or require therapy to control symptoms
Current treatment with any systemic anti-cancer therapies for advanced disease (not applicable to Cohort X participants currently receiving GDC-0810 or GDC-0927)
Concurrent treatment with warfarin or phenytoin
Diagnosis of any secondary malignancy within 3 years prior to enrollment, except for appropriately treated carcinoma in situ of the cervix, non-melanoma skin carcinoma, or Stage I uterine cancer
Active inflammatory bowel disease, chronic diarrhea, short bowel syndrome, or major upper gastrointestinal (GI) surgery including gastric resection
Known human immunodeficiency virus (HIV) infection
Known clinically significant history of liver disease consistent with Child-Pugh Class B or C, including active viral or other hepatitis (e.g., hepatitis B or hepatitis C virus), current alcohol abuse, or cirrhosis
Major surgery within 4 weeks prior to enrollment
Radiation therapy within 2 weeks prior to enrollment
Other severe acute or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or investigational product administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the patient inappropriate for entry into this study
Inability or unwillingness to swallow tablets or capsules (only applies to Dose Escalation)
Any serious medical condition or abnormality in clinical laboratory tests that, in the investigator's judgment, precludes the patient's safe participation in and completion of the study (only applies to Dose Escalation)
History or presence of an abnormal electrocardiogram (ECG) that is clinically significant in the investigator's opinion, including complete left bundle branch block, second- or third-degree heart block, or evidence of prior myocardial infarction
QT interval corrected using Fridericia's formula (QTcF) greater than (>)470 milliseconds (ms) demonstrated by at least two ECGs >30 minutes apart
History of ventricular dysrhythmias or risk factors for ventricular dysrhythmias such as structural heart disease coronary heart disease clinically significant electrolyte abnormalities or family history of sudden unexplained death or long QT syndrome
Current treatment with medications that are well known to prolong the QT interval

Exclusion Criteria for Dose Expansion:

Same criteria as above for Dose Escalation, except for those that only apply to Dose Escalation, plus the following criteria:

Pregnant, lactating, or breastfeeding
Additional exclusion criteria for Cohort B (Phase 1b cohort): History of venous thromboembolic event requiring therapeutic anticoagulation
Additional exclusion criteria for Cohorts C1 and C2 only: Current treatment with medications that are well known to decrease heart rate, including beta blockers

Study is for people with:

Breast Cancer

Phase:

Phase 1

Estimated Enrollment:

181

Study ID:

NCT03332797

Recruitment Status:

Active, not recruiting

Sponsor:

Genentech, Inc.

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There are 23 Locations for this study

See Locations Near You

University of Colorado
Aurora Colorado, 80045, United States
Massachusetts General Hospital.
Boston Massachusetts, 02114, United States
Beth Israel Deaconess Medical Center
Boston Massachusetts, 02215, United States
Dana Farber Cancer Institute
Boston Massachusetts, 02215, United States
Memorial Sloan Kettering Cancer Center
New York New York, 10065, United States
Vanderbilt University Medical Center; Vanderbilt University
Nashville Tennessee, 37232, United States
St Vincent's Hospital Sydney
Darlinghurst New South Wales, 2010, Australia
Peter Maccallum Cancer Centre
Melbourne Victoria, 3000, Australia
National Cancer Center; Medical Oncology
Gyeonggi-do , 410-7, Korea, Republic of
Seoul National University Hospital
Seoul , 03080, Korea, Republic of
Severance Hospital, Yonsei University Health System
Seoul , 03722, Korea, Republic of
Asan Medical Center
Seoul , 05505, Korea, Republic of
Samsung Medical Center
Seoul , 06351, Korea, Republic of
ICO L'Hospitalet; Servicio de oncologia medica
L Hospitalet De Llobregat Barcelona, 08908, Spain
Hospital Quiron Barcelona; Servicio de Oncologia
Barcelona , 08024, Spain
Hospital Universitari Vall d'Hebron
Barcelona , 08035, Spain
Centro Oncologioco MD Anderson Internacional; Servicio de Farmacia
Madrid , 28033, Spain
Hospital Universitario Ramón y Cajal
Madrid , 28034, Spain
Hospital General Universitario Gregorio Maranon
Madrid , 28040, Spain
Hospital Universitario HM Sanchinarro; South Texas Accelerated Research Therapeutics
Madrid , 28050, Spain
Hospital Clinico Universitario de Valencia
Valencia , 46010, Spain
Barts Health NHS Trust
London , E1 2E, United Kingdom
The Royal Marsden NHS Foundation Trust; Oncology
London , SW3 6, United Kingdom
The Royal Marsden Hospital
Sutton , SM2 5, United Kingdom

How clear is this clinincal trial information?

Study is for people with:

Breast Cancer

Phase:

Phase 1

Estimated Enrollment:

181

Study ID:

NCT03332797

Recruitment Status:

Active, not recruiting

Sponsor:


Genentech, Inc.

How clear is this clinincal trial information?

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