Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Also known as GDC-9545, [14C]-GDC-9545, RO7197597, RG6171, GDC-9545 Solution for Infusion
Giredestrant · 12 trials · 10 indications
PFS is defined as the time from randomization to the first occurrence of PD, as determined by the investigator according to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1), or death from any cause during the study.
The Intent-to-Treat (ITT) population consists of all randomized participants, and the ESR1m subpopulation is defined as participants in the ITT population whose tumors harbor a detectable Estrogen Receptor 1 (ESR1) mutation at baseline as measured in circulating tumor DNA (ctDNA).
The percentage of participants who have regression is defined as participants who have a decrease in the proportion of cancer in their endometrial biopsy or the proportion of cancer is not increased, but there is an increase in non-cancer/non-atypical hyperplasia at the 6-month assessment compared with baseline.
PFS was defined as the Kaplan-Meier estimate of time from randomization to the first occurrence of disease progression as determined by the investigator according to RECIST v1.1, or death from any cause (whichever occurs first). Disease progression was defined as ≥20% increase in the sum of diameters of target lesions, unequivocal progression in non-target lesions, and/or appearance of new lesions. Kaplan-Meier methodology was used to estimate median PFS. The 95% confidence interval for the median was computed using the method of Brookmeyer and Crowley. Participants without the occurrence of disease progression or death as of the clinical cutoff were censored at the time of the last tumor assessment prior to the clinical cutoff or at the time of randomization plus 1 day for those without post-baseline assessment.
Ki67 is a proliferation biomarker with prognostic value in ER-positive breast cancer. Ki67 scores were centrally assessed with immunohistochemistry and defined as a percentage of positively stained tumor cell nuclei among the total number of tumor cells assessed, with a potential range of 0-100%. A score of 0% indicates no tumor cell nuclei with Ki67 staining and a score of 100% indicates all tumor cell nuclei are positively stained with Ki67. The relative percentage change was calculated using Ki67 scores at Baseline and Week 2. Relative Percent Change was defined as Week 2 Ki67 percentage score/Baseline Ki67 percentage score\*100. A smaller value of relative percentage change indicates improvement.
The biological response to the study treatment was assessed by measuring changes in cell proliferation (Ki67 expression) using formalin-fixed paraffin-embedded histopathology sections of the tumor biopsy specimens taken at baseline and at day of surgery. Baseline was defined as a sample taken prior to initiation of study drug. The results show the proportion of nuclei staining Ki67-positive (Ki67+) in the tumor biopsy sample taken post-treatment (at surgery) relative to that in the pre-treatment sample (at baseline).
The biological response to the study treatment was assessed by measuring changes in cell proliferation (Ki67 expression) using formalin-fixed paraffin-embedded histopathology sections of the tumor biopsy specimens taken at baseline and at day of surgery. Baseline was defined as a sample taken prior to initiation of study drug. The results show the percentage of nuclei staining Ki67-positive (Ki67+) in the pre- and post-treatment tumor biopsy samples (taken at baseline and surgery, respectively) and the absolute difference in the percentage of Ki67+ nuclei between the two samples (calculated as surgery minus baseline).
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.
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.
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.
| Arm | Type | Description |
|---|---|---|
| Cohort A: Upfront Adjuvant Endocrine Therapy Population | EXPERIMENTAL | Participants will receive giredestrant. |
| Cohort B: Switch Adjuvant Endocrine Therapy Population | EXPERIMENTAL | Participants will receive giredestrant. |
| Giredestrant | EXPERIMENTAL | - |
| Giredestrant + Investigator's Choice of CDK4/6i | EXPERIMENTAL | Participants in the experimental arm will receive giredestrant plus the investigator's choice of CDK4/6 inhibitor (CDK4/6i): palbociclib, ribociclib, or abemaciclib. |
| Fulvestrant + Investigator's Choice of CDK4/6i | ACTIVE_COMPARATOR | Participants in the control arm will receive fulvestrant plus the investigator's choice of CDK4/6 inhibitor (CDK4/6i): palbociclib, ribociclib, or abemaciclib. |
| Giredestrant plus Everolimus | EXPERIMENTAL | - |
| Physician's Choice of Endocrine Therapy plus Everolimus | ACTIVE_COMPARATOR | The physician's choice of endocrine therapy is defined as either exemestane, fulvestrant, or tamoxifen. |
| Arm A: Giredestrant | EXPERIMENTAL | - |
| Arm B: Physician's Choice of Endocrine Therapy | ACTIVE_COMPARATOR | - |
| Giredestrant + Letrozole-matched Placebo + Palbociclib | EXPERIMENTAL | - |
| Letrozole + Giredestrant-matched Placebo + Palbociclib | ACTIVE_COMPARATOR | - |
| Physician Choice of Endocrine Monotherapy | ACTIVE_COMPARATOR | The physician choice of endocrine monotherapy will be limited to fulvestrant or an aromatase inhibitor. |
| Giredestrant + Palbociclib | EXPERIMENTAL | - |
| Anastrozole + Palbociclib | ACTIVE_COMPARATOR | - |
| Cohort 1: Giredestrant Monotherapy | ACTIVE_COMPARATOR | - |
| Cohort 1: Giredestrant + Abemaciclib | EXPERIMENTAL | - |
| Cohort 1: Giredestrant + Ipatasertib | EXPERIMENTAL | - |
| Cohort 1: Giredestrant + Inavolisib | EXPERIMENTAL | - |
| Cohort 1: Giredestrant + Ribociclib | EXPERIMENTAL | - |
| Cohort 1: Giredestrant + Everolimus | EXPERIMENTAL | - |
| Cohort 1: Giredestrant + Samuraciclib | EXPERIMENTAL | - |
| Cohort 1: Giredestrant + Atezolizumab | EXPERIMENTAL | - |
| Cohort 1: Giredestrant + Abemaciclib + Atezolizumab | EXPERIMENTAL | - |
| Cohort 1: Giredestrant + Inavolisib (ESR1m enriched) | EXPERIMENTAL | ESR1m stands for estrogen receptor mutation. |
| Cohort 2: Giredestrant + PH FDC SC | ACTIVE_COMPARATOR | - |
| Cohort 2: Giredestrant + PH FDC SC + Abemaciclib | EXPERIMENTAL | - |
| Cohort 2: Giredestrant + PH FDC SC + Palbociclib | EXPERIMENTAL | - |
| Cohort 3: Giredestrant + Inavolisib + Palbociclib | EXPERIMENTAL | - |
| Cohort 3: Giredestrant + Inavolisib + Abemaciclib | EXPERIMENTAL | - |
| Cohort 3: Giredestrant + Inavolisib + Ribociclib | EXPERIMENTAL | - |
| Giredestrant 10 mg | EXPERIMENTAL | - |
| Giredestrant 30 mg | EXPERIMENTAL | - |
| Giredestrant 100 mg | EXPERIMENTAL | - |
| 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). |
| 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. |
| 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). |
| 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. |
| 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). |
| 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. |
| 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). |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| Name | Type | Description |
|---|---|---|
| Giredestrant | DRUG | Participants will receive giredestrant 30 mg orally once a day for up to 5 years. |
| Fulvestrant | DRUG | Fulvestrant 500 mg intramuscularly (IM) on Days 1 and 15 of Cycle 1 and on Day 1 of each subsequent 28-day cycle until PD or unacceptable toxicity. |
| Abemaciclib | DRUG | If chosen by the investigator as the CDK4/6i, participants will receive abemaciclib 150 mg PO twice per day (BID) on Days 1-28 of each 28-day cycle until PD or unacceptable toxicity. |
| Palbociclib | DRUG | If chosen by the investigator as the CDK4/6i, participants will receive palbociclib 125 mg PO QD on Days 1-21 of each 28-day cycle until PD or unacceptable toxicity. |
| Ribociclib | DRUG | If chosen by the investigator as the CDK4/6i, participants will receive ribociclib 600 mg PO QD on Days 1-21 of each 28-day cycle until PD or unacceptable toxicity. |
| LHRH Agonist | DRUG | Only pre/perimenopausal female participants and male participants will receive a luteinizing hormone-releasing hormone (LHRH) agonist locally approved for use in breast cancer on Day 1 of each 28-day treatment cycle. |
| FoundationOne Liquid CDx Assay (F1LCDx) | DIAGNOSTIC_TEST | F1LCDx is a next-generation sequencing (NGS)-based in vitro diagnostic test that detects and analyses genomic alterations in circulating cell-free DNA (cfDNA) isolated from plasma derived from the anti-coagulated peripheral whole blood of cancer patients. It will be used to determine the eligibility of participants requiring confirmation of ESR1 mutation status (mutation detected \[ESR1m\] vs. no mutation detected \[ESR1nmd\]). |
| Exemestane | DRUG | If exemestane is chosen as the physician's choice of endocrine therapy, the participant will receive exemestane at a dose of 25 mg orally once a day (QD) on Days 1-28 of each 28-day cycle or as per local label, until unacceptable toxicity or disease progression as determined by investigator according to RECIST v1.1. |
| Tamoxifen | DRUG | If tamoxifen is chosen as the physician's choice of endocrine therapy, the participant will receive tamoxifen at a dose of 20 mg orally QD on Days 1-28 of each 28-day cycle or as per local prescribing information, until unacceptable toxicity or disease progression as determined by investigator according to RECIST v1.1. |
| Everolimus | DRUG | Participants will receive treatment with everolimus 10 mg orally QD during each 28-day cycle until unacceptable toxicity or disease progression as determined by the investigator according to RECIST v1.1. |
| Dexamethasone Mouth Rinse | DRUG | A compounded alcohol-free mouthwash of dexamethasone (0.5 mg in 5 mL) will be supplied, where feasible. It is strongly recommended for prophylaxis or treatment of stomatitis/mucositis. Participants should use the alcohol-free mouthwash of dexamethasone four times QD for 8 weeks started concurrently with study treatment, and use it reactively thereafter with the first appearance of symptoms. |
| Physician's Choice of Endocrine Therapy | DRUG | The physician's choice of endocrine therapy (PCET) is limited to tamoxifen or one of the specified third generation aromatase inhibitors: letrozole, anastrozole, or exemestane. Participants will receive PCET daily on Days 1-28 of each 28-day cycle for 5 years or until disease recurrence or unacceptable toxicity (whichever occurs first). Continuing PCET after 5 years is at the discretion of the investigator and per local standard of care. Dose administration of PCET should be performed in accordance with the local prescribing information for the respective product. |
| Giredestrant-matched Placebo | DRUG | Giredestrant-matched placebo is taken orally once per day on Days 1-28 of each 28-day treatment cycle. |
| Letrozole | DRUG | Letrozole 2.5 milligrams (mg) is taken orally once per day on Days 1-28 of each 28-day treatment cycle. |
| Letrozole-matched Placebo | DRUG | Letrozole-matched placebo is taken orally once per day on Days 1-28 of each 28-day treatment cycle. |
| Fulvestrant or an Aromatase Inhibitor (Physician Choice) | DRUG | Physician choice of endocrine monotherapy (fulvestrant or an aromatase inhibitor) is taken in accordance with the local prescribing information for the respective product. |
| Anastrozole | DRUG | During the window-of-opportunity phase (first 2 weeks), anastrozole 1 mg will be taken orally QD as a single agent. During the neoadjuvant treatment phase, anastrozole 1 mg will be taken orally QD on Days 1-28 of each 28-day cycle for a total of 4 cycles, in combination with palbociclib. |
| Surgery | PROCEDURE | Surgery must be performed within a maximum of 14 days after the final cycle in the neoadjuvant treatment phase and ideally should occur as soon as possible after the last dose of study treatment. |
| Ipatasertib | DRUG | 400 mg orally once a day on Days 1-21 of each 28-day cycle until unacceptable toxicity or disease progression |
| Inavolisib | DRUG | 9 mg orally once a day during each 28-day cycle until unacceptable toxicity or disease progression |
| Samuraciclib | DRUG | 360 mg orally once a day during each 28-day cycle until unacceptable toxicity or disease progression |
| PH FDC SC | DRUG | On Day 1 of Cycle 1 (1 cycle is 21 days), pertuzumab and trastuzumab fixed-dose combination for subcutaneous use (PH FDC SC) will be administered SC as a fixed dose formulation of 1200 mg pertuzumab, 600 mg trastuzumab, and 30,000 units hyaluronidase. On Day 1 of Cycles 2 and beyond, PH FDC SC will be administered SC once every 21 days as a fixed dose of 600 mg pertuzumab, 600 mg trastuzumab, and 20,000 units hyaluronidase. |
| Atezolizumab | DRUG | 840 mg by intravenous (IV) infusion on Days 1 and 15 each 28-day cycle. |
| GDC-9545 | DRUG | 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. |
Inclusion Criteria: * Histologically confirmed diagnosis of ER-positive, HER2-negative, Stage I-III, breast cancer * Definitive surgery of primary breast tumor(s) and axillary lymph nodes (axillary lymph node dissection and/or sentinel lymph node biopsy) * Participants must have completed any prior...
Giredestrant is an investigational oral medicine being studied for estrogen receptor (ER)-positive, HER2-negative breast cancer, including early breast cancer and locally advanced or metastatic disease, and for grade 1 endometrial cancer. It is being developed as an endocrine therapy for hormone receptor-driven tumors.
Giredestrant targets ESR1, the estrogen receptor alpha. It is a degrader, meaning it binds the receptor and promotes its breakdown rather than only blocking it. This targeted degradation is intended to reduce estrogen receptor signaling that drives ER-positive tumor growth.
Giredestrant is being developed by Roche Holding AG, which trades over the counter in the United States under the ticker RHHBY. Roche is running the clinical program across early and advanced breast cancer and endometrial cancer.
Giredestrant is investigational and remains in clinical development. Its program spans Phase 1 through Phase 3, with Phase 3 studies in ER-positive, HER2-negative early and advanced breast cancer, a completed Phase 2 study in grade 1 endometrial cancer, and earlier-phase work. It is not an approved therapy.
Giredestrant trials include NCT07827573 in early breast cancer, NCT07541079 in patients intolerant to adjuvant aromatase inhibitors, NCT06065748 comparing it with fulvestrant plus a CDK4/6 inhibitor in advanced breast cancer, and the completed Phase 2 NCT05634499 in grade 1 endometrial cancer. Total enrollment across these studies is about 6,191 participants.
Yes. Giredestrant is also known as GDC-9545, and the name GDC-9545 appears in study listings and tablet formulations, including fasted treatment arms and a carbon-14 labeled version used in pharmacokinetic work. Searches for GDC-9545 refer to the same Roche compound.