Breast CancerPhase 1NCT03332797
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
A Phase 1 study testing GDC-9545, Palbociclib and LHRH Agonist in people with Breast Cancer, run by Genentech, Inc. at 23 sites in 5 countries.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 years and older, women only
- Conditions the study is for
- Breast Cancer
- What is being tested?
- GDC-9545, Palbociclib and LHRH Agonist
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 181 participants
- Where
- 23 sitesin 5 countries
- Study dates
- 24 Nov 2017to 31 Jul 2027
- Phase
- Phase 1
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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)
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- 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
- 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 10 days after the last dose of GDC-9545 and 21 days after the last dose of palbociclib, 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
Who cannot join
- 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
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- 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
- 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
Trial locations and contacts
23 sites in 5 countries.
23 sites in 5 countries
Spain8 sites
Hospital Quiron Barcelona
Barcelona, 08023
Hospital Universitari Vall d'Hebron
Barcelona, 08035
ICO L'Hospitalet
L'Hospitalet de Llobregat, Barcelona, 08908
Hospital General Universitario Gregorio Maranon
Madrid, 28007
Centro Oncologioco MD Anderson Internacional
Madrid, 28033
Hospital Universitario Ramón y Cajal
Madrid, 28034
Hospital Universitario HM Sanchinarro
Madrid, 28050
Hospital Clinico Universitario de Valencia
Valencia, 46010
United States6 sites
University of Colorado
Aurora, Colorado, 80045
Massachusetts General Hospital.
Boston, Massachusetts, 02115
Beth Israel Deaconess Medical Center
Boston, Massachusetts, 02215
Dana Farber Cancer Institute
Boston, Massachusetts, 02215
Vanderbilt University Medical Center
Nashville, Tennessee, 37204
Memorial Sloan Kettering Cancer Center
New York, New York, 10065
South Korea5 sites
National Cancer Center
Gyeonggi-do, 410-769
Seoul National University Hospital
Seoul, 03080
Severance Hospital, Yonsei University Health System
Seoul, 03722
Asan Medical Center
Seoul, 05505
Samsung Medical Center
Seoul, 06351
Australia2 sites
St Vincent's Hospital Sydney
Darlinghurst, New South Wales, 2010
Peter Maccallum Cancer Centre
Melbourne, Victoria, 3000
United Kingdom2 sites
Barts Health NHS Trust
London, E1 2ES
The Royal Marsden Hospital
Suttton, SM2 5PT
About this study
Official title: A Phase Ia/Ib, Multicenter, Open-Label, Dose Escalation, Dose Expansion Study Evaluating the Safety, Pharmacokinetics, and Activity of GDC-9545 Alone or in Combination With Palbociclib and/or LHRH Agonist in Patients With Locally Advanced or Metastatic Estrogen Receptor-Positive Breast Cancer
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.
- Conditions
- Breast Cancer
- Being tested
- GDC-9545, Palbociclib, LHRH Agonist
- Medical subject headings
- Breast Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
GDC-9545Drug
Also called Giredestrant, RO7197597, RG6171
GDC-9545 will be administered orally, once daily, on Days 1-28 of each 28-day cycle, until disease progression, unacceptable toxicity, withdrawal of consent, or study termination.
PalbociclibDrug
Palbociclib will be administered orally, once daily, at the label-recommended dose of 125 mg on Days 1-21 of each 28-day cycle, until disease progression, unacceptable toxicity, withdrawal of consent, or study termination.
LHRH AgonistDrug
The LHRH agonist (leuprolide acetate, goserelin acetate, or triptorelin pamoate) will be administered by injection once every 4 weeks on Day 1 of each 28-day cycle, according to the label. The investigator will choose the appropriate LHRH agonist approved for use in breast cancer.
| Study group | Role | What they receive |
|---|---|---|
| Dose Escalation: GDC-9545 | Experimental | During dose escalation, postmenopausal participants will be assigned sequentially to escalating doses of GDC-9545, up to the maximum tolerated dose (MTD) or maximum administered dose (MAD). Receives: Drug: GDC-9545 |
| Dose Escalation: Cohort B0: GDC-9545 + Palbociclib | Experimental | GDC-9545 will be administered to postmenopausal participants, at a dose lower than the MTD or MAD determined in single-agent dose escalation, in combination with the label-recommended dose of palbociclib. Receives: Drug: GDC-9545; Drug: Palbociclib |
| Dose Expansion: Cohort A1: GDC-9545 Dose 1 | Experimental | GDC-9545 will be administered to postmenopausal participants as a single-agent at a dose that is less than or equal to the MTD/MAD (Dose 1). Receives: Drug: GDC-9545 |
| Dose Expansion: Cohort A2: GDC-9545 Dose 1 + LHRH | Experimental | GDC-9545 will be administered to pre- or perimenopausal participants at a dose that is less than or equal to the MTD/MAD (Dose 1) in combination with an approved LHRH agonist. Receives: Drug: GDC-9545; Drug: LHRH Agonist |
| Dose Expansion: Cohort A3: GDC-9545 Dose 2 | Experimental | GDC-9545 will be administered to postmenopausal participants as a single-agent at a dose that is less than or equal to the MTD/MAD (Dose 2). Receives: Drug: GDC-9545 |
| Dose Expansion: Cohort A4: GDC-9545 Dose 2 + LHRH | Experimental | GDC-9545 will be administered to pre- or perimenopausal participants at a dose that is less than or equal to the MTD/MAD (Dose 2) in combination with an LHRH agonist. Receives: Drug: GDC-9545; Drug: LHRH Agonist |
| Dose Expansion: Cohort A5: GDC-9545 Dose 3 | Experimental | GDC-9545 will be administered to postmenopausal participants as a single-agent at a dose that is less than or equal to the MTD/MAD (Dose 3). Receives: Drug: GDC-9545 |
| Dose Expansion: Cohort B1: GDC-9545 + Palbociclib | Experimental | GDC-9545 will be administered to postmenopausal participants, at a dose that is less than or equal to the MTD/MAD, in combination with the label-recommended dose of palbociclib. Receives: Drug: GDC-9545; Drug: Palbociclib |
| Dose Expansion: Cohort B2: GDC-9545 + Palbociclib + LHRH | Experimental | GDC-9545 will be administered to pre- or perimenopausal participants, at a dose that is less than or equal to the MTD/MAD, in combination with the label-recommended dose of palbociclib and an approved LHRH agonist. Receives: Drug: GDC-9545; Drug: Palbociclib; Drug: LHRH Agonist |
| Dose Expansion: Cohort C1: GDC-9545 Dose 2 +/- Palbociclib | Experimental | GDC-9545 will be administered to postmenopausal participants at a pre-defined dose level (Dose 2) as a single agent for 14 days, followed by treatment with either GDC-9545 (Dose 2) plus palbociclib or GDC-9545 (Dose 2) alone for the duration of the study, as determined by the investigator. Receives: Drug: GDC-9545; Drug: Palbociclib |
| Dose Expansion: Cohort C2: GDC-9545 Dose 2 + Palbociclib | Experimental | GDC-9545 will be administered to postmenopausal participants at a pre-defined dose level (Dose 2), in combination with the label-recommended dose of palbociclib. Receives: Drug: GDC-9545; Drug: Palbociclib |
| Dose Expansion: Cohort X: GDC-9545 Dose 3 | Experimental | GDC-9545 will be administered at a pre-defined dose level (Dose 3) to postmenopausal participants currently receiving clinical benefit with GDC-0927 or GDC-0810 on Studies GO29656 (NCT02316509) or GO29642 (NCT01823835), respectively, upon completion of their studies. Receives: Drug: GDC-9545 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants with Adverse Events by Severity, According to National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0 (NCI-CTCAE v4.0)
Measured: From Baseline until 28 days after the last dose of study treatment (up to 84 months)
Dose Escalation: Maximum Tolerated Dose (MTD) or Maximum Administered Dose (MAD) of GDC-9545 When Administered as a Single Agent or in Combination with Palbociclib
Measured: Days -7 to 28 of Cycle 1
Dose Escalation: Number of Participants with Dose-Limiting Toxicities When GDC-9545 is Administered as a Single Agent or in Combination with Palbociclib
Measured: Days -7 to 28 of Cycle 1
Change from Baseline in Systolic Blood Pressure Over Time
Measured: Baseline and at each treatment cycle (1 cycle is 28 days) through to 28 days after the last dose of study treatment
Change from Baseline in Diastolic Blood Pressure Over Time
Measured: Baseline and at each treatment cycle (1 cycle is 28 days) through to 28 days after the last dose of study treatment
Change from Baseline in Body Temperature Over Time
Measured: Baseline and at each treatment cycle (1 cycle is 28 days) through to 28 days after the last dose of study treatment
Change from Baseline in Pulse Rate Over Time
Measured: Baseline and at each treatment cycle (1 cycle is 28 days) through to 28 days after the last dose of study treatment
Change from Baseline in Respiration Rate Over Time
Measured: Baseline and at each treatment cycle (1 cycle is 28 days) through to 28 days after the last dose of study treatment
Change from Baseline in Electrocardiogram (ECG) Results Over Time: Heart Rate
Measured: Baseline and at predefined intervals from Cycle 1 and at each subsequent cycle (1 cycle is 28 days) through to the last dose of study treatment
Change from Baseline in ECG Results Over Time: PR Duration
Measured: Baseline and at predefined intervals from Cycle 1 and at each subsequent cycle (1 cycle is 28 days) through to the last dose of study treatment
Change from Baseline in ECG Results Over Time: QRS Duration
Measured: Baseline and at predefined intervals from Cycle 1 and at each subsequent cycle (1 cycle is 28 days) through to the last dose of study treatment
Change from Baseline in ECG Results Over Time: QT Duration
Measured: Baseline and at predefined intervals from Cycle 1 and at each subsequent cycle (1 cycle is 28 days) through to the last dose of study treatment
Change from Baseline in ECG Results Over Time: QTcF Duration
Measured: Baseline and at predefined intervals from Cycle 1 and at each subsequent cycle (1 cycle is 28 days) through to the last dose of study treatment
Change from Baseline in ECG Results Over Time: RR Duration
Measured: Baseline and at predefined intervals from Cycle 1 and at each subsequent cycle (1 cycle is 28 days) through to the last dose of study treatment
Number of Participants with Clinical Laboratory Abnormalities in Hematology Tests by Highest Grade According to NCI-CTCAE v4.0
Laboratory parameters for hematology will be measured and compared with a standard reference range. Values outside of the standard reference range are considered abnormalities. Not every laboratory abnormality qualifies as an adverse event. A laboratory test result will be reported as an adverse event if it meets any of the following criteria: is accompanied by clinical symptoms; results in a change in study treatment, a medical intervention, or a change in concomitant therapy; or is clinically significant in the investigator's judgment.
Measured: Baseline, Cycle 1, and at each subsequent cycle (1 cycle is 28 days) or at every other cycle starting from Cycle 3 (Cohort X only), up to 28 days after the last dose of study treatment
Number of Participants with Clinical Laboratory Abnormalities in Blood Chemistry Tests by Highest Grade According to NCI-CTCAE v4.0
Laboratory parameters for blood chemistry will be measured and compared with a standard reference range. Values outside of the standard reference range are considered abnormalities. Not every laboratory abnormality qualifies as an adverse event. A laboratory test result will be reported as an adverse event if it meets any of the following criteria: is accompanied by clinical symptoms; results in a change in study treatment, a medical intervention, or a change in concomitant therapy; or is clinically significant in the investigator's judgment.
Measured: Baseline, Cycle 1, and at each subsequent cycle (1 cycle is 28 days) or at every other cycle starting from Cycle 3 (Cohort X only), up to 28 days after the last dose of study treatment
Number of Participants with Clinical Laboratory Abnormalities in Urinalysis Tests by Highest Grade According to NCI-CTCAE v4.0
Laboratory parameters for urinalysis will be measured and compared with a standard reference range. Values outside of the standard reference range are considered abnormalities. Not every laboratory abnormality qualifies as an adverse event. A laboratory test result will be reported as an adverse event if it meets any of the following criteria: is accompanied by clinical symptoms; results in a change in study treatment, a medical intervention, or a change in concomitant therapy; or is clinically significant in the investigator's judgment.
Measured: Baseline, Cycle 3, and at every other cycle (1 cycle is 28 days) up to 28 days after the last dose of study treatment
Secondary outcomes (6)
Plasma Concentration of GDC-9545 Over Time
Measured: At predefined intervals from Cycle 1, Day -7 (Single-Agent Dose Escalation and A1-A5 only) or Cycle 1, Day 1 (B0, B1, and B2) to Cycle 4, Day 1 (1 cycle is 28 days) and at study completion; Cycle 1, Days -7 or 8 (C1 only); Cycle 1, Day 8 (C2 only)
Plasma Concentration of Palbociclib Over Time
Measured: At predefined intervals from Cycle 1, Day 1 to Cycle 4, Day 1 (1 cycle is 28 days) and at study completion (B0, B1, and B2 only); Cycle 1, Day 8 (C2 only)
Plasma Concentration of LHRH Over Time
Measured: At predefined intervals from Cycle 1, Day 1 to Cycle 4, Day 1 (1 cycle is 28 days) and at study completion (B2 only)
Percentage of Participants with Objective Response
Objective response is defined as a complete response or partial response on two consecutive occasions ≥4 weeks apart, as determined by the investigator according to Response Evaluation Criteria In Solid Tumors version 1.1 (RECIST v1.1).
Measured: For all cohorts, except for Cohort X: Baseline and every 8 weeks from Cycle 1, Day 1 until end of study treatment (up to 84 months)
Clinical Benefit Rate
Clinical benefit rate is defined as the percentage of participants achieving either of the following: confirmed complete response or partial response (as determined by the investigator according to RECIST v1.1); or the first occurrence of progressive disease after 24 weeks of study treatment.
Measured: For all cohorts, except for Cohort X: Baseline and every 8 weeks from Cycle 1, Day 1 until end of study treatment (up to 84 months)
Duration of Response
Measured: For all cohorts, except for Cohort X: From the first occurrence of a documented objective response until first observation of disease progression or death from any cause on study, whichever occurs first (up to 84 months)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Nov 2017
- Study start24 Nov 2017
- Primary completion31 Jul 2027 (estimated)
- Study completion31 Jul 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Breast CancerStudies of the same condition, open and under way.
- More trials run by Genentech, Inc.The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 181 participants (actual)
Sponsor and investigators
- Lead sponsor
- Genentech, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Clinical Trials, Study director, Hoffmann-La Roche
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03332797
- Sponsor's protocol ID
- GO39932
- Other IDs
- 2017-002083-41, 2023-506700-12-00, 2023, 2017
- Status last verified
- Aug 2026
- First submitted
- 1 Nov 2017
- Last updated
- 13 Aug 2026
- Results posted
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Malhi V, Agarwal P, Gates MR, Liu L, Wang J, De Bruyn T, Lam S, Eng-Wong J, Perez-Moreno P, Chen YC, Yu J. Optimizing Early-stage Clinical Pharmacology Evaluation to Accelerate Clinical Development of Giredestrant in Advanced Breast Cancer. Cancer Res Commun. 2023 Dec 15;3(12):2551-2559. doi: 10.1158/2767-9764.CRC-23-0324.
PubMed 38019116Jhaveri KL, Bellet M, Turner NC, Loi S, Bardia A, Boni V, Sohn J, Neilan TG, Villanueva-Vazquez R, Kabos P, Garcia-Estevez L, Lopez-Miranda E, Perez-Fidalgo JA, Perez-Garcia JM, Yu J, Fredrickson J, Moore HM, Chang CW, Bond JW, Eng-Wong J, Gates MR, Lim E. Phase Ia/b Study of Giredestrant +/- Palbociclib and +/- Luteinizing Hormone-Releasing Hormone Agonists in Estrogen Receptor-Positive, HER2-Negative, Locally Advanced/Metastatic Breast Cancer. Clin Cancer Res. 2024 Feb 16;30(4):754-766. doi: 10.1158/1078-0432.CCR-23-1796.
PubMed 37921755
Study at a glance
From the registry record, last updated by the sponsor on 13 Aug 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase Ia/Ib, Multicenter, Open-Label, Dose Escalation, Dose Expansion Study Evaluating the Safety, Pharmacokinetics, and Activity of GDC-9545 Alone or in Combination With Palbociclib and/or LHRH Agonist in Patients With Locally Advanced or Metastatic Estrogen Receptor-Positive Breast Cancer
- ClinicalTrials.gov ID
- NCT03332797
- Acronym / sponsor ID
- GO39932
- Conditions
- Breast Cancer
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 181 participants (actual)
- Lead sponsor
- Genentech, Inc.Industry (pharma, biotech, devices)
- Study start
- 24 Nov 2017 (actual)
- Primary completion
- 31 Jul 2027 (estimated)
- Study completion
- 31 Jul 2027 (estimated)
- First posted
- 6 Nov 2017 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 12
| Arm | Type | Receives |
|---|---|---|
| Dose Escalation: GDC-9545 | Experimental | Drug: GDC-9545During dose escalation, postmenopausal participants will be assigned sequentially to escalating doses of GDC-9545, up to the maximum tolerated dose (MTD) or maximum administered dose (MAD). |
| Dose Escalation: Cohort B0: GDC-9545 + Palbociclib | Experimental | Drug: GDC-9545, Drug: PalbociclibGDC-9545 will be administered to postmenopausal participants, at a dose lower than the MTD or MAD determined in single-agent dose escalation, in combination with the label-recommended dose of palbociclib. |
| Dose Expansion: Cohort A1: GDC-9545 Dose 1 | Experimental | Drug: GDC-9545GDC-9545 will be administered to postmenopausal participants as a single-agent at a dose that is less than or equal to the MTD/MAD (Dose 1). |
| Dose Expansion: Cohort A2: GDC-9545 Dose 1 + LHRH | Experimental | Drug: GDC-9545, Drug: LHRH AgonistGDC-9545 will be administered to pre- or perimenopausal participants at a dose that is less than or equal to the MTD/MAD (Dose 1) in combination with an approved LHRH agonist. |
| Dose Expansion: Cohort A3: GDC-9545 Dose 2 | Experimental | Drug: GDC-9545GDC-9545 will be administered to postmenopausal participants as a single-agent at a dose that is less than or equal to the MTD/MAD (Dose 2). |
| Dose Expansion: Cohort A4: GDC-9545 Dose 2 + LHRH | Experimental | Drug: GDC-9545, Drug: LHRH AgonistGDC-9545 will be administered to pre- or perimenopausal participants at a dose that is less than or equal to the MTD/MAD (Dose 2) in combination with an LHRH agonist. |
| Dose Expansion: Cohort A5: GDC-9545 Dose 3 | Experimental | Drug: GDC-9545GDC-9545 will be administered to postmenopausal participants as a single-agent at a dose that is less than or equal to the MTD/MAD (Dose 3). |
| Dose Expansion: Cohort B1: GDC-9545 + Palbociclib | Experimental | Drug: GDC-9545, Drug: PalbociclibGDC-9545 will be administered to postmenopausal participants, at a dose that is less than or equal to the MTD/MAD, in combination with the label-recommended dose of palbociclib. |
| Dose Expansion: Cohort B2: GDC-9545 + Palbociclib + LHRH | Experimental | Drug: GDC-9545, Drug: Palbociclib, Drug: LHRH AgonistGDC-9545 will be administered to pre- or perimenopausal participants, at a dose that is less than or equal to the MTD/MAD, in combination with the label-recommended dose of palbociclib and an approved LHRH agonist. |
| Dose Expansion: Cohort C1: GDC-9545 Dose 2 +/- Palbociclib | Experimental | Drug: GDC-9545, Drug: PalbociclibGDC-9545 will be administered to postmenopausal participants at a pre-defined dose level (Dose 2) as a single agent for 14 days, followed by treatment with either GDC-9545 (Dose 2) plus palbociclib or GDC-9545 (Dose 2) alone for the duration of the study, as determined by the investigator. |
| Dose Expansion: Cohort C2: GDC-9545 Dose 2 + Palbociclib | Experimental | Drug: GDC-9545, Drug: PalbociclibGDC-9545 will be administered to postmenopausal participants at a pre-defined dose level (Dose 2), in combination with the label-recommended dose of palbociclib. |
| Dose Expansion: Cohort X: GDC-9545 Dose 3 | Experimental | Drug: GDC-9545GDC-9545 will be administered at a pre-defined dose level (Dose 3) to postmenopausal participants currently receiving clinical benefit with GDC-0927 or GDC-0810 on Studies GO29656 (NCT02316509) or GO29642 (NCT01823835), respectively, upon completion of their studies. |
Who may qualify
- Ages
- 18 years and older
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (29 listed)
- 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
Key exclusion criteria (20 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| GDC-9545Also: Giredestrant, RO7197597, RG6171GDC-9545 will be administered orally, once daily, on Days 1-28 of each 28-day cycle, until disease progression, unacceptable toxicity, withdrawal of consent, or study termination. | Drug | Dose Escalation: Cohort B0: GDC-9545 + Palbociclib, Dose Escalation: GDC-9545, Dose Expansion: Cohort A1: GDC-9545 Dose 1, Dose Expansion: Cohort A2: GDC-9545 Dose 1 + LHRH, Dose Expansion: Cohort A3: GDC-9545 Dose 2, Dose Expansion: Cohort A4: GDC-9545 Dose 2 + LHRH, Dose Expansion: Cohort A5: GDC-9545 Dose 3, Dose Expansion: Cohort B1: GDC-9545 + Palbociclib, Dose Expansion: Cohort B2: GDC-9545 + Palbociclib + LHRH, Dose Expansion: Cohort C1: GDC-9545 Dose 2 +/- Palbociclib, Dose Expansion: Cohort C2: GDC-9545 Dose 2 + Palbociclib, Dose Expansion: Cohort X: GDC-9545 Dose 3 |
| PalbociclibPalbociclib will be administered orally, once daily, at the label-recommended dose of 125 mg on Days 1-21 of each 28-day cycle, until disease progression, unacceptable toxicity, withdrawal of consent, or study termination. | Drug | Dose Escalation: Cohort B0: GDC-9545 + Palbociclib, Dose Expansion: Cohort B1: GDC-9545 + Palbociclib, Dose Expansion: Cohort B2: GDC-9545 + Palbociclib + LHRH, Dose Expansion: Cohort C1: GDC-9545 Dose 2 +/- Palbociclib, Dose Expansion: Cohort C2: GDC-9545 Dose 2 + Palbociclib |
| LHRH AgonistThe LHRH agonist (leuprolide acetate, goserelin acetate, or triptorelin pamoate) will be administered by injection once every 4 weeks on Day 1 of each 28-day cycle, according to the label. The investigator will choose the appropriate LHRH agonist approved for use in breast cancer. | Drug | Dose Expansion: Cohort A2: GDC-9545 Dose 1 + LHRH, Dose Expansion: Cohort A4: GDC-9545 Dose 2 + LHRH, Dose Expansion: Cohort B2: GDC-9545 + Palbociclib + LHRH |
Primary outcome
Number of Participants with Adverse Events by Severity, According to National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0 (NCI-CTCAE v4.0)
Time frame: From Baseline until 28 days after the last dose of study treatment (up to 84 months)
Dose Escalation: Maximum Tolerated Dose (MTD) or Maximum Administered Dose (MAD) of GDC-9545 When Administered as a Single Agent or in Combination with Palbociclib
Time frame: Days -7 to 28 of Cycle 1
Dose Escalation: Number of Participants with Dose-Limiting Toxicities When GDC-9545 is Administered as a Single Agent or in Combination with Palbociclib
Time frame: Days -7 to 28 of Cycle 1
Change from Baseline in Systolic Blood Pressure Over Time
Time frame: Baseline and at each treatment cycle (1 cycle is 28 days) through to 28 days after the last dose of study treatment
Change from Baseline in Diastolic Blood Pressure Over Time
Time frame: Baseline and at each treatment cycle (1 cycle is 28 days) through to 28 days after the last dose of study treatment
Change from Baseline in Body Temperature Over Time
Time frame: Baseline and at each treatment cycle (1 cycle is 28 days) through to 28 days after the last dose of study treatment
Change from Baseline in Pulse Rate Over Time
Time frame: Baseline and at each treatment cycle (1 cycle is 28 days) through to 28 days after the last dose of study treatment
Change from Baseline in Respiration Rate Over Time
Time frame: Baseline and at each treatment cycle (1 cycle is 28 days) through to 28 days after the last dose of study treatment
Change from Baseline in Electrocardiogram (ECG) Results Over Time: Heart Rate
Time frame: Baseline and at predefined intervals from Cycle 1 and at each subsequent cycle (1 cycle is 28 days) through to the last dose of study treatment
Change from Baseline in ECG Results Over Time: PR Duration
Time frame: Baseline and at predefined intervals from Cycle 1 and at each subsequent cycle (1 cycle is 28 days) through to the last dose of study treatment
Change from Baseline in ECG Results Over Time: QRS Duration
Time frame: Baseline and at predefined intervals from Cycle 1 and at each subsequent cycle (1 cycle is 28 days) through to the last dose of study treatment
Change from Baseline in ECG Results Over Time: QT Duration
Time frame: Baseline and at predefined intervals from Cycle 1 and at each subsequent cycle (1 cycle is 28 days) through to the last dose of study treatment
Change from Baseline in ECG Results Over Time: QTcF Duration
Time frame: Baseline and at predefined intervals from Cycle 1 and at each subsequent cycle (1 cycle is 28 days) through to the last dose of study treatment
Change from Baseline in ECG Results Over Time: RR Duration
Time frame: Baseline and at predefined intervals from Cycle 1 and at each subsequent cycle (1 cycle is 28 days) through to the last dose of study treatment
Number of Participants with Clinical Laboratory Abnormalities in Hematology Tests by Highest Grade According to NCI-CTCAE v4.0
Time frame: Baseline, Cycle 1, and at each subsequent cycle (1 cycle is 28 days) or at every other cycle starting from Cycle 3 (Cohort X only), up to 28 days after the last dose of study treatment
Laboratory parameters for hematology will be measured and compared with a standard reference range. Values outside of the standard reference range are considered abnormalities. Not every laboratory abnormality qualifies as an adverse event. A laboratory test result will be reported as an adverse event if it meets any of the following criteria: is accompanied by clinical symptoms; results in a change in study treatment, a medical intervention, or a change in concomitant therapy; or is clinically significant in the investigator's judgment.
Number of Participants with Clinical Laboratory Abnormalities in Blood Chemistry Tests by Highest Grade According to NCI-CTCAE v4.0
Time frame: Baseline, Cycle 1, and at each subsequent cycle (1 cycle is 28 days) or at every other cycle starting from Cycle 3 (Cohort X only), up to 28 days after the last dose of study treatment
Laboratory parameters for blood chemistry will be measured and compared with a standard reference range. Values outside of the standard reference range are considered abnormalities. Not every laboratory abnormality qualifies as an adverse event. A laboratory test result will be reported as an adverse event if it meets any of the following criteria: is accompanied by clinical symptoms; results in a change in study treatment, a medical intervention, or a change in concomitant therapy; or is clinically significant in the investigator's judgment.
Number of Participants with Clinical Laboratory Abnormalities in Urinalysis Tests by Highest Grade According to NCI-CTCAE v4.0
Time frame: Baseline, Cycle 3, and at every other cycle (1 cycle is 28 days) up to 28 days after the last dose of study treatment
Laboratory parameters for urinalysis will be measured and compared with a standard reference range. Values outside of the standard reference range are considered abnormalities. Not every laboratory abnormality qualifies as an adverse event. A laboratory test result will be reported as an adverse event if it meets any of the following criteria: is accompanied by clinical symptoms; results in a change in study treatment, a medical intervention, or a change in concomitant therapy; or is clinically significant in the investigator's judgment.
6 secondary outcomes
Plasma Concentration of GDC-9545 Over Time
Time frame: At predefined intervals from Cycle 1, Day -7 (Single-Agent Dose Escalation and A1-A5 only) or Cycle 1, Day 1 (B0, B1, and B2) to Cycle 4, Day 1 (1 cycle is 28 days) and at study completion; Cycle 1, Days -7 or 8 (C1 only); Cycle 1, Day 8 (C2 only)
Plasma Concentration of Palbociclib Over Time
Time frame: At predefined intervals from Cycle 1, Day 1 to Cycle 4, Day 1 (1 cycle is 28 days) and at study completion (B0, B1, and B2 only); Cycle 1, Day 8 (C2 only)
Plasma Concentration of LHRH Over Time
Time frame: At predefined intervals from Cycle 1, Day 1 to Cycle 4, Day 1 (1 cycle is 28 days) and at study completion (B2 only)
Percentage of Participants with Objective Response
Time frame: For all cohorts, except for Cohort X: Baseline and every 8 weeks from Cycle 1, Day 1 until end of study treatment (up to 84 months)
Clinical Benefit Rate
Time frame: For all cohorts, except for Cohort X: Baseline and every 8 weeks from Cycle 1, Day 1 until end of study treatment (up to 84 months)
Duration of Response
Time frame: For all cohorts, except for Cohort X: From the first occurrence of a documented objective response until first observation of disease progression or death from any cause on study, whichever occurs first (up to 84 months)
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Aug 2026.
- Derived from this study: PubMed 38019116Malhi V, Agarwal P, Gates MR, Liu L, Wang J, De Bruyn T, Lam S, Eng-Wong J, Perez-Moreno P, Chen YC, Yu J. Optimizing Early-stage Clinical Pharmacology Evaluation to Accelerate Clinical Development of Giredestrant in Advanced Breast Cancer. Cancer Res Commun. 2023 Dec 15;3(12):2551-2559. doi: 10.1158/2767-9764.CRC-23-0324.
- Derived from this study: PubMed 37921755Jhaveri KL, Bellet M, Turner NC, Loi S, Bardia A, Boni V, Sohn J, Neilan TG, Villanueva-Vazquez R, Kabos P, Garcia-Estevez L, Lopez-Miranda E, Perez-Fidalgo JA, Perez-Garcia JM, Yu J, Fredrickson J, Moore HM, Chang CW, Bond JW, Eng-Wong J, Gates MR, Lim E. Phase Ia/b Study of Giredestrant +/- Palbociclib and +/- Luteinizing Hormone-Releasing Hormone Agonists in Estrogen Receptor-Positive, HER2-Negative, Locally Advanced/Metastatic Breast Cancer. Clin Cancer Res. 2024 Feb 16;30(4):754-766. doi: 10.1158/1078-0432.CCR-23-1796.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Clinical Trials study director
Hoffmann-La Roche
23 sites in 5 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing GDC-9545, Palbociclib and LHRH Agonist in people with Breast Cancer, run by Genentech, Inc. at 23 sites in 5 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 29 inclusion and 20 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 13 Aug 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 23 sites in Spain, United States, South Korea, Australia, United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Participants with Adverse Events by Severity, According to National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0 (NCI-CTCAE v4.0) (time frame: From Baseline until 28 days after the last dose of study treatment (up to 84 months)). The study lists 17 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03332797, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 Aug 2026.