A Study of GDC-0810 Single Agent or in Combination With Palbociclib and/or a Luteinizing Hormone-Releasing Hormone (LHRH) Agonist in Women With Locally Advanced or Metastatic Estrogen Receptor Positive Breast Cancer

An Open-Label, Phase Ia/Ib/IIa Study of GDC-0810 Single Agent or in Combination With Palbociclib and/or an LHRH Agonist in Women With Locally Advanced or Metastatic Estrogen Receptor Positive Breast Cancer

Status

Terminated

Phases

Phase 1Phase 2

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT01823835

Enrollment

152

Registered

2013-04-04

Start date

2014-12-29

Completion date

2020-03-13

Last updated

2021-06-18

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Breast Cancer

Brief summary

This study is a multi-institution, Phase Ia/Ib/IIa open-label, dose-finding, safety, pharmacokinetics (PK), and proof-of-concept study of GDC-0810 as a single agent and in combination with palbociclib and/or LHRH agonist. The study is divided into 3 phases: Phase Ia, Phase Ib, and Phase IIa. During Phase Ia (dose escalation phase), GDC-0810 single agent will be administered orally on a continuous daily dosing regimen with a Day -7 lead-in period for single dose PK evaluation prior to the start of daily treatment. The incidence of dose-limiting toxicities (DLTs) will be evaluated from Day -7 through the first cycle (28 days) of treatment (35 days total). Depending on safety and tolerability, participants will be assigned sequentially to escalating doses of GDC-0810 using standard 3 + 3 design. During Phase Ib (dose escalation and expansion phase), participants will receive GDC-0810 with palbociclib and/or LHRH agonist to determine the recommended Phase II dose (RP2D) and assess the safety and tolerability of concomitant administration. During Phase IIa (dose expansion phase), participants previously treated with an aromatase inhibitor (AI) will be treated at the RP2D to further characterize the safety, PK, pharmacodynamics, and anti-tumor activity of GDC-0810.

Interventions

DRUGGDC-0810

GDC-0810 administered orally once daily until disease progression, unacceptable toxicity, withdrawal of consent, GDC-0810 drug supply exhausted, or study termination (up to 3 years).

DRUGLHRH Agonist

LHRH agonist administered once monthly until disease progression, unacceptable toxicity, withdrawal of consent, GDC-0810 drug supply exhausted, or study termination (up to 3 years). Choice of LHRH agonist will be an institutional choice approved for use in breast cancer.

DRUGPalbociclib

Palbociclib administered orally once daily until disease progression, unacceptable toxicity, withdrawal of consent, GDC-0810 drug supply exhausted, or study termination (up to 3 years).

Study design

Allocation

NON_RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

NONE

Eligibility

Sex/Gender

FEMALE

Age

18 Years to No maximum

Healthy volunteers

Inclusion criteria

Phase 1a portion * 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 metastatic disease, both progressing after at least 6 months of hormonal therapy for estrogen receptor (ER) positive breast cancer * ER-positive, human epidermal growth factor 2 (HER2) negative * At least 2 months must have elapsed from the use of tamoxifen * At least 6 months must have elapsed from the use of fulvestrant * At least 2 weeks must have elapsed from the use of any other anticancer hormonal therapy * At least 3 weeks must have elapsed from the use of any chemotherapy * Postmenopausal status * Eastern Cooperative Oncology Group (ECOG) performance status less than or equal to 2 * Adequate organ function Phase Ib portion * All above inclusion criteria, except: * Postmenopausal status, pre- and peri-menopausal participants will also be included * ECOG performance status less than 2 * At least 2 months must have elapsed from the use of tamoxifen not applicable * At least 6 months must have elapsed from the use of fulvestrant not applicable and plus: * Documented sensitivity to prior hormonal therapy * Cohort C1 (palbociclib combination cohorts): no prior treatment with cyclin-dependent kinase (CDK) 4/6 inhibitor Phase IIa portion * All above inclusion criteria for Phase Ia, except: * Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1 * At least 6 months must have elapsed from the use of fulvestrant not applicable and plus: * Cohort A only: confirmed estrogen receptor alpha (ESR1) mutation and presence of measurable disease as per RECIST v1.1 or evaluable bone disease * Cohort A1 only: no prior fulvestrant allowed; at least 2 months must have elapsed from the use of tamoxifen * Cohort A2 only: prior fulvestrant allowed * Cohort B only: disease progression following no more than 1 prior treatment with an aromatase inhibitor in the advanced/metastatic setting * Cohort B1 only: no prior fulvestrant allowed * Cohort B2 only: prior fulvestrant allowed

Exclusion criteria

Phase 1a portion * Untreated or symptomatic central nervous system (CNS) metastases * Endometrial disorders * More than 2 prior chemotherapy in the advanced/metastatic setting (prior adjuvant chemotherapy is allowed so long as it occurred greater than or equal to 12 months prior to enrollment) * Current treatment with any systemic anticancer therapies for advanced disease * Any significant cardiac dysfunction within 12 months prior to enrollment * Active inflammatory bowel disease or chronic diarrhea, short bowel syndrome, or upper gastrointestinal surgery including gastric resection * Known human immunodeficiency virus (HIV) infection * Known clinically significant history of liver disease * Major surgery within 4 weeks prior to enrollment * Radiation therapy within 2 weeks prior to enrollment Phase Ib portion - all above

Design outcomes

Primary

Measure	Time frame	Description
Phase Ia: Maximum Tolerated Dose of GDC-0810 When Used as a Single Agent	Day -7 through the first cycle (28 days) of treatment (35 days total)	Maximum Tolerated Dose (MTD) is determined based on the number of Dose Limiting Toxicities (DLTs) experienced by the participants. DLTs were defined as any of the following adverse events (AEs) that are deemed by the investigator or the Sponsor to be related to study drug (toxicities will be attributed to single agent GDC-0810 unless they are clearly related to disease progression or can clearly be attributed to a cause other than GDC-0810 administration): * Any grade ≥ 3 non-hematologic toxicity (excluding alopecia) * Any grade ≥ 3 hematologic toxicity of \> 7 days' duration * Any grade toxicity that leads to study drug interruption of \> 7 days' duration
Phase Ia: RP2D of GDC-0810 When Used as a Single Agent	Day -7 through the first cycle (28 days) of treatment (35 days total)	The recommended Phase II dose (RP2D) was based on the overall safety/tolerability and pharmacokinetic profile of GDC-0810.
Phase IIa: Percentage of Participants With Confirmed Objective Tumor Response of GDC-0810 According to RECIST v1.1	Screening and every 8 weeks from Cycle 1 Day 1 until Cycle 12, thereafter every 3 months until disease progression (up to 3 years)	Objective response (OR) is defined as a complete response (CR) or partial response (PR) as determined by investigator assessment according to RECIST v1.1. OR was based on criteria related to changes in size of target lesions. CR was the disappearance of all target lesions. PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters.
Phase IIa: Percentage of Participants With Clinical Benefit Response of GDC-0810 According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1)	Screening and every 8 weeks from Cycle 1 Day 1 until Cycle 12, thereafter every 3 months until disease progression (up to 3 years)	Clinical Benefit Response (CBR) is defined as the percentage of participants achieving confirmed RECIST v1.1 defined CR, PR, and/or stable disease. CR was the disappearance of all target lesions. PR was defined as at least a 30% decrease in the sum of diameters of target lesions. Stable disease was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease.
Phase Ib: RP2D of GDC-0810 When Used in Combination With Palbociclib and/or LHRH	first cycle (Days 1 to 28 of a 28-day schedule)	The RP2D of GDC-0810 When Used in Combination With Palbociclib and/or LHRH RP2D was not determined since the development of the GDC-0810 was discontinued before enrolling Cohort C2. The RP2D would have been based on the overall safety and PK/PD profile of GDC-0810 and palbociclib, and not necessarily the MTD.

Secondary

Measure	Time frame	Description
Area Under the Concentration-Time Curve From Time 0 to Infinity (AUC0-Inf)	Day-7 at 0 (predose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 24, and 48 hours postdose	Area under the concentration-time curve from time 0-infinity (AUC0-inf) has been calculated using PK samples collected after administration of a single dose (on Day -7) of GDC-0810.
Phase Ia: Plasma Half-life (t1/2) of GDC-0810 Single Agent	Day -7 at 0 (predose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 24, 48 hours postdose	Half-life (t1/2) was calculated after single dose administration and not at steady state.
Phase Ia: Apparent Clearance (Cl/F)	Day -7 at 0 (predose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 24, 48 hours postdose	Apparent Clearance (CL/F) was estimated using PK samples collected following administration of a single dose (on Day -7) of GDC-0810
Phase IIa: Effect of GDC-0810 Single Agent on Ventricular Repolarization as Measured by Corrected QT Intervals (QTc) Using Fridericia's Formula	Screening; on Cycle 2 Day 1 predose and at 1, 2, 3, 4, and 6 hours postdose; Cycle 3 Day 1 predose, and at 1, 3, and 6 hours post dose	The corrected QT interval (QTc) was calculated using Fridericia's formula from electrocardiogram (ECG) data. Changes in ECG intervals from baseline were calculated. Triplicate ECG measurements were collected throughout the study. The averaged triplicate ECG measurements were used for analysis.
Phase Ib: Cmax of GDC-0810 in Combination With Palbociclib and/or an LHRH Agonist	C1: Predose and at 1, 2, 3, 4, and 6 hours postdose on Cycle 1 Day 1 and Cycle 1 Day 8; D1: Predose and at 1, 2, 3, 4, and 6 hours postdose on Cycle 1 Day 1 and Cycle 2 Day 1	Cmax has been calculated using PK samples collected after GDC-0810 administration.
Phase Ib: Tmax of GDC-0810 in Combination With Palbociclib and/or an LHRH Agonist	C1: Predose and at 1, 2, 3, 4, and 6 hours postdose on Cycle 1 Day 1 and Cycle 1 Day 8; D1: Predose and at 1, 2, 3, 4, and 6 hours postdose on Cycle 1 Day 1 and Cycle 2 Day 1	Tmax has been calculated using PK samples collected after GDC-0810 administration.
Phase Ib: AUC0-6 of GDC-0810 in Combination With Palbociclib and/or an LHRH Agonist	C1: Predose and at 1, 2, 3, 4, and 6 hours postdose on Cycle 1 Day 1 and Cycle 1 Day 8; D1: Predose and at 1, 2, 3, 4, and 6 hours postdose on Cycle 1 Day 1 and Cycle 2 Day 1	AUC0-6 has been calculated using PK samples collected after GDC-0810 administration.
Phase Ib: t/2 of GDC-0810 in Combination With Palbociclib and/or an LHRH Agonist	C1: Predose and at 1, 2, 3, 4, and 6 hours postdose on Cycle 1 Day 1 and Cycle 1 Day 8; D1: Predose and at 1, 2, 3, 4, and 6 hours postdose on Cycle 1 Day 1 and Cycle 2 Day 1	Half-life (t1/2) can be estimated only when the PK sample collection following a dose is long enough to characterize the elimination phase. The PK samples in these cohorts were only collected up to 6 hours following the dose, hence, t1/2 could not be estimated.
All Phases: Percentage of Participants With Adverse Events (AEs)	up to 3 years	An adverse event (AE) is any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product and that does not necessarily have a causal relationship with this treatment.
Phase Ib: Tmax of Palbociclib in Combination With GDC-0810 and/or an LHRH Agonist	Predose and at 1, 2, 3, 4, and 6 hours postdose on Cycle 1 Day 1 and Cycle 1 Day 8	Tmax has been calculated using PK samples collected after GDC-0810 administration.
Phase Ib: AUC0-6 of Palbociclib in Combination With GDC-0810 and/or an LHRH Agonist	Predose and at 1, 2, 3, 4, and 6 hours postdose on Cycle 1 Day 1 and Cycle 1 Day 8	AUC0-6 has been calculated using PK samples collected after GDC-0810 administration.
Phase Ib: t/2 of Palbociclib in Combination With GDC-0810 and/or an LHRH Agonist	Cohort C1: Predose and at 1, 2, 3, 4, and 6 hours postdose on Cycle 1 Day 1 and Cycle 1 Day 8	Half-life (t1/2) can be estimated only when the PK sample collection following a dose is long enough to characterize the elimination phase. The PK samples in these cohorts were only collected up to 6 hours following the dose, hence, t1/2 could not be estimated.
Phase Ib: Cmax of LHRH Agonist in Combination With GDC-0810 and/or Palbociclib	Predose and at 1, 2, 3, 4, and 6 hours postdose on Cycle 1 Day 1 and Cycle 2 Day 1	Cmax has been calculated using PK samples collected after GDC-0810 administration.
Phase Ib: Tmax of LHRH Agonist in Combination With GDC-0810 and/or Palbociclib	Predose and at 1, 2, 3, 4, and 6 hours postdose on Cycle 1 Day 1 and Cycle 2 Day 1	Tmax has been calculated using PK samples collected after GDC-0810 administration.
Phase Ib: AUC0-6 of LHRH Agonist in Combination With GDC-0810 and/or an Palbociclib	Predose and at 1, 2, 3, 4, and 6 hours postdose on Cycle 1 Day 1 and Cycle 2 Day 1	AUC0-6 has been calculated using PK samples collected after GDC-0810 administration.
Phase Ib: t/2 of LHRH Agonist in Combination With GDC-0810 and/or Palbociclib	Cohort D1: Predose and at 1, 2, 3, 4, and 6 hours postdose on Cycle 1 Day 1 and Cycle 2 Day 1	Half-life (t1/2) can be estimated only when the PK sample collection following a dose is long enough to characterize the elimination phase. The PK samples in these cohorts were only collected up to 6 hours following the dose, hence, t1/2 could not be estimated.
Phase Ib: Cmax of Palbociclib in Combination With GDC-0810 and/or an LHRH Agonist	Predose and at 1, 2, 3, 4, and 6 hours postdose on Cycle 1 Day 1 and Cycle 1 Day 8	Cmax has been calculated using PK samples collected after GDC-0810 administration.
Phase Ia: Maximum Plasma Concentration (Cmax) of GDC-0810 Single Agent and Its Glucuronide Metabolites	Single Dose: Day-7 at 0 (predose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 24, 48 hours postdose; Multiple Doses: Day 29 (Cycle 2 Day 1) at 0 (predose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 24, hours postdose	Maximum Plasma Concentration (Cmax) has been calculated using PK samples collected after administration of a single dose (on Day -7) and also following once-daily multiple doses (at steady state on Day 29) of GDC-0810.
Phase Ia: Time to Maximum Concentration (Tmax) of GDC-0810 Single Agent and Its Glucuronide Metabolites	Single Dose: Day-7 at 0 (predose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 24, 48 hours postdose; Multiple Doses: Day 29 (Cycle 2 Day 1) at 0 (predose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 24, hours postdose	Time to Maximum Concentration (Tmax) has been calculated using PK samples collected after administration of a single dose (on Day -7) and also following once-daily multiple doses (at steady state on Day 29) of GDC-0810.
Phase Ia: Area Under the Concentration-time Curves at 6 Hours (AUC0-6) of GDC-0810 Single Agent and Its Glucuronide Metabolites	Single Dose: Day-7 at 0 (predose), 0.5, 1, 1.5, 2, 3, 4, 6 hours postdose; Multiple Doses: Day 29 (Cycle 2 Day 1) at 0 (predose), 0.5, 1, 1.5, 2, 3, 4, 6 hours postdose	Area under the concentration-time curves from time 0 to 6 hours (AUC0-6) has been calculated using PK samples collected after administration of a single dose (on Day -7) and also following once-daily multiple doses (at steady state on Day 29) of GDC-0810.
Phase Ia: Area Under the Concentration-time Curves at 24 Hours (AUC0-24) of GDC-0810 Single Agent and Its Glucuronide Metabolites	Single Dose: Day-7 at 0 (predose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 24 hours postdose; Multiple Doses: Day 29 (Cycle 2 Day 1) at 0 (predose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 24 hours postdose	Area under the concentration-time curves from time 0 to 24 hours (AUC0-24) has been calculated using PK samples collected after administration of a single dose (on Day -7) and also following once-daily multiple doses (at steady state on Day 29) of GDC-0810.

Countries

Netherlands, South Korea, Spain, United States

Participant flow

Participants by arm

Arm	Count
Phase Ia - Cohort 1 100 mg GDC-0810 once daily (QD) in fasting state.	3
Phase Ia - Cohort 2 200 mg GDC-0810 QD in fasting state.	4
Phase Ia - Cohort 3 400 mg GDC-0810 QD in fasting state.	4
Phase Ia - Cohort 4 600 mg GDC-0810 QD in fasting state.	6
Phase Ia - Cohort 5 600 mg GDC-0810 QD in non-fasting state.	6
Phase Ia - Cohort 6 300 mg GDC-0810 twice daily (BID) in fasting state.	6
Phase Ia - Cohort 7 800 mg GDC-0810 QD in fasting state.	6
Phase Ia - Cohort 8 800 mg GDC-0810 QD in non-fasting state.	3
Phase Ia - Cohort 9 400 mg GDC-0810 BID in fasting state.	3
Phase IIa - Cohort A1 600 mg GDC-0810 QD. Additionally, participants in this arm did not receive any prior treatment with fulvestrant and had confirmed ER-a (ESR1) mutation of the ligand binding domain (LBD).	19
Phase IIa - Cohort A2 600 mg GDC-0810 QD. Additionally, participants in this arm had prior treatment with fulvestrant and confirmed ER-a (ESR1) mutation of the LBD.	10
Phase IIa - Cohort B1 600 mg GDC-0810 QD. Additionally, participants in this arm did not receive any prior treatment with fulvestrant and had progressed following ≤1 prior therapy with an aromatase inhibitor (AI).	53
Phase IIa - Cohort B2 600 mg GDC-0810 QD. Additionally, participants in this arm had prior treatment with fulvestrant and progressed following ≤1 prior therapy with an AI.	19
Phase Ib - Cohort C1 400 mg GDC-0810 + 125 mg Palbociclib QD.	4
Phase Ib - Cohort D1 ≤600 mg GDC-0810 QD + LHRH agonist once monthly.	6
Total	152

Withdrawals & dropouts

Period	Reason	FG000	FG001	FG002	FG003	FG004	FG005	FG006	FG007	FG008	FG009	FG010	FG011	FG012	FG013	FG014
Overall Study	Adverse Event	0	0	0	0	1	0	1	0	0	0	1	2	0	0	0
Overall Study	Physician Decision	0	0	0	0	0	0	0	0	0	0	0	2	0	0	0
Overall Study	Progressive Disease	3	4	3	6	4	6	5	3	3	18	8	46	18	4	6
Overall Study	Study Termination	0	0	0	0	1	0	0	0	0	0	0	1	0	0	0
Overall Study	Withdrawal by Subject	0	0	1	0	0	0	0	0	0	1	1	2	1	0	0

Baseline characteristics

Characteristic	Phase Ia - Cohort 1	Phase Ia - Cohort 2	Phase Ia - Cohort 3	Phase Ia - Cohort 4	Phase Ia - Cohort 5	Phase Ia - Cohort 6	Phase Ia - Cohort 7	Phase Ia - Cohort 8	Phase Ia - Cohort 9	Phase IIa - Cohort A1	Phase IIa - Cohort A2	Phase IIa - Cohort B1	Phase IIa - Cohort B2	Phase Ib - Cohort C1	Phase Ib - Cohort D1	Total
Age, Continuous	66.3 Years STANDARD_DEVIATION 5.7	63.5 Years STANDARD_DEVIATION 9.6	60.8 Years STANDARD_DEVIATION 6.9	55.3 Years STANDARD_DEVIATION 8.5	69.3 Years STANDARD_DEVIATION 7.2	56.2 Years STANDARD_DEVIATION 12.8	50.5 Years STANDARD_DEVIATION 14.6	58.3 Years STANDARD_DEVIATION 3.5	64.7 Years STANDARD_DEVIATION 4	55.4 Years STANDARD_DEVIATION 12.2	63.4 Years STANDARD_DEVIATION 8.9	61.9 Years STANDARD_DEVIATION 9.3	62.6 Years STANDARD_DEVIATION 12.2	58.5 Years STANDARD_DEVIATION 13.1	41.7 Years STANDARD_DEVIATION 8.9	59.8 Years STANDARD_DEVIATION 11.2
Race/Ethnicity, Customized Asian	0 Participants	0 Participants	0 Participants	0 Participants	1 Participants	1 Participants	0 Participants	0 Participants	0 Participants	2 Participants	1 Participants	2 Participants	0 Participants	0 Participants	3 Participants	10 Participants
Race/Ethnicity, Customized Black or African American	0 Participants	0 Participants	1 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	2 Participants	0 Participants	0 Participants	3 Participants
Race/Ethnicity, Customized Other	1 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	1 Participants
Race/Ethnicity, Customized Unknown	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	1 Participants	0 Participants	0 Participants	0 Participants	0 Participants	1 Participants	5 Participants	2 Participants	0 Participants	2 Participants	11 Participants
Race/Ethnicity, Customized White	2 Participants	4 Participants	3 Participants	6 Participants	5 Participants	4 Participants	6 Participants	3 Participants	3 Participants	17 Participants	8 Participants	46 Participants	15 Participants	4 Participants	1 Participants	127 Participants
Sex: Female, Male Female	3 Participants	4 Participants	4 Participants	6 Participants	6 Participants	6 Participants	6 Participants	3 Participants	3 Participants	19 Participants	10 Participants	53 Participants	19 Participants	4 Participants	6 Participants	152 Participants
Sex: Female, Male Male	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk	EG002 affected / at risk	EG003 affected / at risk	EG004 affected / at risk	EG005 affected / at risk	EG006 affected / at risk	EG007 affected / at risk	EG008 affected / at risk	EG009 affected / at risk	EG010 affected / at risk	EG011 affected / at risk	EG012 affected / at risk	EG013 affected / at risk	EG014 affected / at risk
deaths Total, all-cause mortality	1 / 3	1 / 4	0 / 4	1 / 6	2 / 6	0 / 6	1 / 6	0 / 3	0 / 3	0 / 19	0 / 10	3 / 53	0 / 19	0 / 4	0 / 6
other Total, other adverse events	3 / 3	4 / 4	4 / 4	6 / 6	6 / 6	6 / 6	6 / 6	3 / 3	3 / 3	18 / 19	10 / 10	51 / 53	19 / 19	4 / 4	6 / 6
serious Total, serious adverse events	1 / 3	1 / 4	1 / 4	1 / 6	3 / 6	4 / 6	1 / 6	1 / 3	0 / 3	4 / 19	1 / 10	11 / 53	1 / 19	1 / 4	2 / 6

Outcome results

Primary

Phase Ia: Maximum Tolerated Dose of GDC-0810 When Used as a Single Agent

Maximum Tolerated Dose (MTD) is determined based on the number of Dose Limiting Toxicities (DLTs) experienced by the participants. DLTs were defined as any of the following adverse events (AEs) that are deemed by the investigator or the Sponsor to be related to study drug (toxicities will be attributed to single agent GDC-0810 unless they are clearly related to disease progression or can clearly be attributed to a cause other than GDC-0810 administration): * Any grade ≥ 3 non-hematologic toxicity (excluding alopecia) * Any grade ≥ 3 hematologic toxicity of \> 7 days' duration * Any grade toxicity that leads to study drug interruption of \> 7 days' duration

Time frame: Day -7 through the first cycle (28 days) of treatment (35 days total)

Population: All participants that were enrolled in Phase Ia of the study.

Arm	Measure	Value (NUMBER)
Phase Ia - All Cohorts	Phase Ia: Maximum Tolerated Dose of GDC-0810 When Used as a Single Agent	NA milligram (mg)

Primary

Phase Ia: RP2D of GDC-0810 When Used as a Single Agent

The recommended Phase II dose (RP2D) was based on the overall safety/tolerability and pharmacokinetic profile of GDC-0810.

Time frame: Day -7 through the first cycle (28 days) of treatment (35 days total)

Population: All participants that were enrolled in Phase Ia of the study.

Arm	Measure	Value (NUMBER)
Phase Ia - All Cohorts	Phase Ia: RP2D of GDC-0810 When Used as a Single Agent	600 milligram (mg)

Primary

Phase Ib: RP2D of GDC-0810 When Used in Combination With Palbociclib and/or LHRH

The RP2D of GDC-0810 When Used in Combination With Palbociclib and/or LHRH RP2D was not determined since the development of the GDC-0810 was discontinued before enrolling Cohort C2. The RP2D would have been based on the overall safety and PK/PD profile of GDC-0810 and palbociclib, and not necessarily the MTD.

Time frame: first cycle (Days 1 to 28 of a 28-day schedule)

Population: All participants that were enrolled in Phase Ib of the study.

Arm	Measure	Value (NUMBER)
Phase Ia - All Cohorts	Phase Ib: RP2D of GDC-0810 When Used in Combination With Palbociclib and/or LHRH	NA mg
Phase IIa - Cohort A2	Phase Ib: RP2D of GDC-0810 When Used in Combination With Palbociclib and/or LHRH	NA mg

Primary

Phase IIa: Percentage of Participants With Clinical Benefit Response of GDC-0810 According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1)

Clinical Benefit Response (CBR) is defined as the percentage of participants achieving confirmed RECIST v1.1 defined CR, PR, and/or stable disease. CR was the disappearance of all target lesions. PR was defined as at least a 30% decrease in the sum of diameters of target lesions. Stable disease was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease.

Time frame: Screening and every 8 weeks from Cycle 1 Day 1 until Cycle 12, thereafter every 3 months until disease progression (up to 3 years)

Population: All participants that were enrolled in Phase IIa of the study.

Arm	Measure	Value (NUMBER)
Phase Ia - All Cohorts	Phase IIa: Percentage of Participants With Clinical Benefit Response of GDC-0810 According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1)	5.3 percentage of participants
Phase IIa - Cohort A2	Phase IIa: Percentage of Participants With Clinical Benefit Response of GDC-0810 According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1)	10.0 percentage of participants
Phase IIa - Cohort B1	Phase IIa: Percentage of Participants With Clinical Benefit Response of GDC-0810 According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1)	28.3 percentage of participants
Phase IIa - Cohort B2	Phase IIa: Percentage of Participants With Clinical Benefit Response of GDC-0810 According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1)	15.8 percentage of participants

Primary

Phase IIa: Percentage of Participants With Confirmed Objective Tumor Response of GDC-0810 According to RECIST v1.1

Objective response (OR) is defined as a complete response (CR) or partial response (PR) as determined by investigator assessment according to RECIST v1.1. OR was based on criteria related to changes in size of target lesions. CR was the disappearance of all target lesions. PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters.

Time frame: Screening and every 8 weeks from Cycle 1 Day 1 until Cycle 12, thereafter every 3 months until disease progression (up to 3 years)

Population: All participants that were enrolled in Phase IIa of the study.

Arm	Measure	Group	Value (NUMBER)
Phase Ia - All Cohorts	Phase IIa: Percentage of Participants With Confirmed Objective Tumor Response of GDC-0810 According to RECIST v1.1	Partial Response	0 percentage of participants
Phase Ia - All Cohorts	Phase IIa: Percentage of Participants With Confirmed Objective Tumor Response of GDC-0810 According to RECIST v1.1	Complete Response	0 percentage of participants
Phase IIa - Cohort A2	Phase IIa: Percentage of Participants With Confirmed Objective Tumor Response of GDC-0810 According to RECIST v1.1	Complete Response	0 percentage of participants
Phase IIa - Cohort A2	Phase IIa: Percentage of Participants With Confirmed Objective Tumor Response of GDC-0810 According to RECIST v1.1	Partial Response	0 percentage of participants
Phase IIa - Cohort B1	Phase IIa: Percentage of Participants With Confirmed Objective Tumor Response of GDC-0810 According to RECIST v1.1	Complete Response	0 percentage of participants
Phase IIa - Cohort B1	Phase IIa: Percentage of Participants With Confirmed Objective Tumor Response of GDC-0810 According to RECIST v1.1	Partial Response	7.5 percentage of participants
Phase IIa - Cohort B2	Phase IIa: Percentage of Participants With Confirmed Objective Tumor Response of GDC-0810 According to RECIST v1.1	Partial Response	0 percentage of participants
Phase IIa - Cohort B2	Phase IIa: Percentage of Participants With Confirmed Objective Tumor Response of GDC-0810 According to RECIST v1.1	Complete Response	0 percentage of participants

Secondary

All Phases: Percentage of Participants With Adverse Events (AEs)

An adverse event (AE) is any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product and that does not necessarily have a causal relationship with this treatment.

Time frame: up to 3 years

Arm	Measure	Value (NUMBER)
Phase Ia - All Cohorts	All Phases: Percentage of Participants With Adverse Events (AEs)	100 percentage of participants
Phase IIa - Cohort A2	All Phases: Percentage of Participants With Adverse Events (AEs)	100 percentage of participants
Phase IIa - Cohort B1	All Phases: Percentage of Participants With Adverse Events (AEs)	100 percentage of participants
Phase IIa - Cohort B2	All Phases: Percentage of Participants With Adverse Events (AEs)	100 percentage of participants
Phase Ia - Cohort 5	All Phases: Percentage of Participants With Adverse Events (AEs)	100 percentage of participants
Phase Ia - Cohort 6	All Phases: Percentage of Participants With Adverse Events (AEs)	100 percentage of participants
Phase Ia - Cohort 7	All Phases: Percentage of Participants With Adverse Events (AEs)	100 percentage of participants
Phase Ia - Cohort 8	All Phases: Percentage of Participants With Adverse Events (AEs)	100 percentage of participants
Phase Ia - Cohort 9	All Phases: Percentage of Participants With Adverse Events (AEs)	100 percentage of participants
Phase IIa - Cohort A1	All Phases: Percentage of Participants With Adverse Events (AEs)	100 percentage of participants
Phase IIa - Cohort A2	All Phases: Percentage of Participants With Adverse Events (AEs)	100 percentage of participants
Phase IIa - Cohort B1	All Phases: Percentage of Participants With Adverse Events (AEs)	100 percentage of participants
Phase IIa - Cohort B2	All Phases: Percentage of Participants With Adverse Events (AEs)	100 percentage of participants
Phase Ib - Cohort C1	All Phases: Percentage of Participants With Adverse Events (AEs)	100 percentage of participants
Phase Ib - Cohort D1	All Phases: Percentage of Participants With Adverse Events (AEs)	100 percentage of participants

Secondary

Area Under the Concentration-Time Curve From Time 0 to Infinity (AUC0-Inf)

Area under the concentration-time curve from time 0-infinity (AUC0-inf) has been calculated using PK samples collected after administration of a single dose (on Day -7) of GDC-0810.

Time frame: Day-7 at 0 (predose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 24, and 48 hours postdose

Population: All participants that were enrolled in Phase Ia of the study, provided sufficient blood samples for analysis and received once daily dosing.

Arm	Measure	Value (MEAN)	Dispersion
Phase Ia - All Cohorts	Area Under the Concentration-Time Curve From Time 0 to Infinity (AUC0-Inf)	5.3 hr*ug/ml	Standard Deviation 1.96
Phase IIa - Cohort A2	Area Under the Concentration-Time Curve From Time 0 to Infinity (AUC0-Inf)	10 hr*ug/ml	Standard Deviation 2.8
Phase IIa - Cohort B1	Area Under the Concentration-Time Curve From Time 0 to Infinity (AUC0-Inf)	30.8 hr*ug/ml	Standard Deviation 16.3
Phase IIa - Cohort B2	Area Under the Concentration-Time Curve From Time 0 to Infinity (AUC0-Inf)	40.5 hr*ug/ml	Standard Deviation 11.3
Phase Ia - Cohort 5	Area Under the Concentration-Time Curve From Time 0 to Infinity (AUC0-Inf)	114 hr*ug/ml	Standard Deviation 57.4
Phase Ia - Cohort 7	Area Under the Concentration-Time Curve From Time 0 to Infinity (AUC0-Inf)	65.7 hr*ug/ml	Standard Deviation 28
Phase Ia - Cohort 8	Area Under the Concentration-Time Curve From Time 0 to Infinity (AUC0-Inf)	101 hr*ug/ml	Standard Deviation 78.5

Secondary

Phase Ia: Apparent Clearance (Cl/F)

Apparent Clearance (CL/F) was estimated using PK samples collected following administration of a single dose (on Day -7) of GDC-0810

Time frame: Day -7 at 0 (predose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 24, 48 hours postdose

Population: All participants that were enrolled in Phase Ia of the study and provided sufficient blood samples for analysis.

Arm	Measure	Value (MEAN)	Dispersion
Phase Ia - All Cohorts	Phase Ia: Apparent Clearance (Cl/F)	20.4 L/hr	Standard Deviation 6.43
Phase IIa - Cohort A2	Phase Ia: Apparent Clearance (Cl/F)	21 L/hr	Standard Deviation 4.94
Phase IIa - Cohort B1	Phase Ia: Apparent Clearance (Cl/F)	15.1 L/hr	Standard Deviation 5.56
Phase IIa - Cohort B2	Phase Ia: Apparent Clearance (Cl/F)	15.7 L/hr	Standard Deviation 4.13
Phase Ia - Cohort 5	Phase Ia: Apparent Clearance (Cl/F)	8.21 L/hr	Standard Deviation 8.38
Phase Ia - Cohort 6	Phase Ia: Apparent Clearance (Cl/F)	NA L/hr	—
Phase Ia - Cohort 7	Phase Ia: Apparent Clearance (Cl/F)	15.1 L/hr	Standard Deviation 9.45
Phase Ia - Cohort 8	Phase Ia: Apparent Clearance (Cl/F)	11.1 L/hr	Standard Deviation 6.23
Phase Ia - Cohort 9	Phase Ia: Apparent Clearance (Cl/F)	NA L/hr	—

Secondary

Phase Ia: Area Under the Concentration-time Curves at 24 Hours (AUC0-24) of GDC-0810 Single Agent and Its Glucuronide Metabolites

Area under the concentration-time curves from time 0 to 24 hours (AUC0-24) has been calculated using PK samples collected after administration of a single dose (on Day -7) and also following once-daily multiple doses (at steady state on Day 29) of GDC-0810.

Time frame: Single Dose: Day-7 at 0 (predose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 24 hours postdose; Multiple Doses: Day 29 (Cycle 2 Day 1) at 0 (predose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 24 hours postdose

Population: All participants that were enrolled in Phase Ia of the study and provided sufficient blood samples for analysis.

Arm	Measure	Group	Value (MEAN)	Dispersion
Phase Ia - All Cohorts	Phase Ia: Area Under the Concentration-time Curves at 24 Hours (AUC0-24) of GDC-0810 Single Agent and Its Glucuronide Metabolites	GDC-0810 (Single Dose)	3.58 hr*ug/mL	Standard Deviation 1.75
Phase Ia - All Cohorts	Phase Ia: Area Under the Concentration-time Curves at 24 Hours (AUC0-24) of GDC-0810 Single Agent and Its Glucuronide Metabolites	GDC-0810-N-Glucuronide (Multiple Doses)	0.13 hr*ug/mL	Standard Deviation 0.0141
Phase Ia - All Cohorts	Phase Ia: Area Under the Concentration-time Curves at 24 Hours (AUC0-24) of GDC-0810 Single Agent and Its Glucuronide Metabolites	GDC-0810 (Multiple Doses)	5.34 hr*ug/mL	Standard Deviation 2.99
Phase Ia - All Cohorts	Phase Ia: Area Under the Concentration-time Curves at 24 Hours (AUC0-24) of GDC-0810 Single Agent and Its Glucuronide Metabolites	GDC-0810-N-Glucuronide (Single Dose)	0.13 hr*ug/mL	Standard Deviation 0.0197
Phase IIa - Cohort A2	Phase Ia: Area Under the Concentration-time Curves at 24 Hours (AUC0-24) of GDC-0810 Single Agent and Its Glucuronide Metabolites	GDC-0810-N-Glucuronide (Single Dose)	0.224 hr*ug/mL	Standard Deviation 0.109
Phase IIa - Cohort A2	Phase Ia: Area Under the Concentration-time Curves at 24 Hours (AUC0-24) of GDC-0810 Single Agent and Its Glucuronide Metabolites	GDC-0810 (Single Dose)	8.81 hr*ug/mL	Standard Deviation 2.52
Phase IIa - Cohort A2	Phase Ia: Area Under the Concentration-time Curves at 24 Hours (AUC0-24) of GDC-0810 Single Agent and Its Glucuronide Metabolites	GDC-0810-N-Glucuronide (Multiple Doses)	0.132 hr*ug/mL	Standard Deviation 0.0253
Phase IIa - Cohort A2	Phase Ia: Area Under the Concentration-time Curves at 24 Hours (AUC0-24) of GDC-0810 Single Agent and Its Glucuronide Metabolites	GDC-0810 (Multiple Doses)	7.36 hr*ug/mL	Standard Deviation 1.32
Phase IIa - Cohort B1	Phase Ia: Area Under the Concentration-time Curves at 24 Hours (AUC0-24) of GDC-0810 Single Agent and Its Glucuronide Metabolites	GDC-0810-Acyl-Glucuronide (Single Dose)	3.76 hr*ug/mL	Standard Deviation 2.13
Phase IIa - Cohort B1	Phase Ia: Area Under the Concentration-time Curves at 24 Hours (AUC0-24) of GDC-0810 Single Agent and Its Glucuronide Metabolites	GDC-0810 (Single Dose)	28.5 hr*ug/mL	Standard Deviation 15.6
Phase IIa - Cohort B1	Phase Ia: Area Under the Concentration-time Curves at 24 Hours (AUC0-24) of GDC-0810 Single Agent and Its Glucuronide Metabolites	GDC-0810-Acyl-Glucuronide (Multiple Doses)	4.42 hr*ug/mL	Standard Deviation 2.27
Phase IIa - Cohort B1	Phase Ia: Area Under the Concentration-time Curves at 24 Hours (AUC0-24) of GDC-0810 Single Agent and Its Glucuronide Metabolites	GDC-0810-N-Glucuronide (Single Dose)	0.413 hr*ug/mL	Standard Deviation 0.152
Phase IIa - Cohort B1	Phase Ia: Area Under the Concentration-time Curves at 24 Hours (AUC0-24) of GDC-0810 Single Agent and Its Glucuronide Metabolites	GDC-0810-N-Glucuronide (Multiple Doses)	0.413 hr*ug/mL	Standard Deviation 0.121
Phase IIa - Cohort B1	Phase Ia: Area Under the Concentration-time Curves at 24 Hours (AUC0-24) of GDC-0810 Single Agent and Its Glucuronide Metabolites	GDC-0810 (Multiple Doses)	22.8 hr*ug/mL	Standard Deviation 6.14
Phase IIa - Cohort B2	Phase Ia: Area Under the Concentration-time Curves at 24 Hours (AUC0-24) of GDC-0810 Single Agent and Its Glucuronide Metabolites	GDC-0810-Acyl-Glucuronide (Single Dose)	11.4 hr*ug/mL	Standard Deviation 7.43
Phase IIa - Cohort B2	Phase Ia: Area Under the Concentration-time Curves at 24 Hours (AUC0-24) of GDC-0810 Single Agent and Its Glucuronide Metabolites	GDC-0810 (Single Dose)	44.7 hr*ug/mL	Standard Deviation 19.5
Phase IIa - Cohort B2	Phase Ia: Area Under the Concentration-time Curves at 24 Hours (AUC0-24) of GDC-0810 Single Agent and Its Glucuronide Metabolites	GDC-0810 (Multiple Doses)	66.9 hr*ug/mL	Standard Deviation 46.8
Phase IIa - Cohort B2	Phase Ia: Area Under the Concentration-time Curves at 24 Hours (AUC0-24) of GDC-0810 Single Agent and Its Glucuronide Metabolites	GDC-0810-N-Glucuronide (Single Dose)	1.54 hr*ug/mL	Standard Deviation 1.08
Phase IIa - Cohort B2	Phase Ia: Area Under the Concentration-time Curves at 24 Hours (AUC0-24) of GDC-0810 Single Agent and Its Glucuronide Metabolites	GDC-0810-N-Glucuronide (Multiple Doses)	2.63 hr*ug/mL	Standard Deviation 2.21
Phase IIa - Cohort B2	Phase Ia: Area Under the Concentration-time Curves at 24 Hours (AUC0-24) of GDC-0810 Single Agent and Its Glucuronide Metabolites	GDC-0810-Acyl-Glucuronide (Multiple Doses)	21.8 hr*ug/mL	Standard Deviation 21.2
Phase Ia - Cohort 5	Phase Ia: Area Under the Concentration-time Curves at 24 Hours (AUC0-24) of GDC-0810 Single Agent and Its Glucuronide Metabolites	GDC-0810-N-Glucuronide (Single Dose)	2.08 hr*ug/mL	Standard Deviation 1.02
Phase Ia - Cohort 5	Phase Ia: Area Under the Concentration-time Curves at 24 Hours (AUC0-24) of GDC-0810 Single Agent and Its Glucuronide Metabolites	GDC-0810-Acyl-Glucuronide (Single Dose)	8.59 hr*ug/mL	Standard Deviation 3.82
Phase Ia - Cohort 5	Phase Ia: Area Under the Concentration-time Curves at 24 Hours (AUC0-24) of GDC-0810 Single Agent and Its Glucuronide Metabolites	GDC-0810-Acyl-Glucuronide (Multiple Doses)	10.4 hr*ug/mL	Standard Deviation 4.07
Phase Ia - Cohort 5	Phase Ia: Area Under the Concentration-time Curves at 24 Hours (AUC0-24) of GDC-0810 Single Agent and Its Glucuronide Metabolites	GDC-0810 (Single Dose)	101 hr*ug/mL	Standard Deviation 49.9
Phase Ia - Cohort 5	Phase Ia: Area Under the Concentration-time Curves at 24 Hours (AUC0-24) of GDC-0810 Single Agent and Its Glucuronide Metabolites	GDC-0810 (Multiple Doses)	102 hr*ug/mL	Standard Deviation 35.9
Phase Ia - Cohort 5	Phase Ia: Area Under the Concentration-time Curves at 24 Hours (AUC0-24) of GDC-0810 Single Agent and Its Glucuronide Metabolites	GDC-0810-N-Glucuronide (Multiple Doses)	2.64 hr*ug/mL	Standard Deviation 1.4
Phase Ia - Cohort 6	Phase Ia: Area Under the Concentration-time Curves at 24 Hours (AUC0-24) of GDC-0810 Single Agent and Its Glucuronide Metabolites	GDC-0810 (Multiple Doses)	44.2 hr*ug/mL	Standard Deviation 14.5
Phase Ia - Cohort 6	Phase Ia: Area Under the Concentration-time Curves at 24 Hours (AUC0-24) of GDC-0810 Single Agent and Its Glucuronide Metabolites	GDC-0810 (Single Dose)	41.2 hr*ug/mL	Standard Deviation 15.9
Phase Ia - Cohort 6	Phase Ia: Area Under the Concentration-time Curves at 24 Hours (AUC0-24) of GDC-0810 Single Agent and Its Glucuronide Metabolites	GDC-0810-N-Glucuronide (Single Dose)	1.07 hr*ug/mL	Standard Deviation 0.786
Phase Ia - Cohort 6	Phase Ia: Area Under the Concentration-time Curves at 24 Hours (AUC0-24) of GDC-0810 Single Agent and Its Glucuronide Metabolites	GDC-0810-N-Glucuronide (Multiple Doses)	1.09 hr*ug/mL	Standard Deviation 0.594
Phase Ia - Cohort 6	Phase Ia: Area Under the Concentration-time Curves at 24 Hours (AUC0-24) of GDC-0810 Single Agent and Its Glucuronide Metabolites	GDC-0810-Acyl-Glucuronide (Multiple Doses)	4.61 hr*ug/mL	Standard Deviation 1.34
Phase Ia - Cohort 6	Phase Ia: Area Under the Concentration-time Curves at 24 Hours (AUC0-24) of GDC-0810 Single Agent and Its Glucuronide Metabolites	GDC-0810-Acyl-Glucuronide (Single Dose)	6.03 hr*ug/mL	Standard Deviation 4.89
Phase Ia - Cohort 7	Phase Ia: Area Under the Concentration-time Curves at 24 Hours (AUC0-24) of GDC-0810 Single Agent and Its Glucuronide Metabolites	GDC-0810 (Multiple Doses)	80.4 hr*ug/mL	Standard Deviation 26.8
Phase Ia - Cohort 7	Phase Ia: Area Under the Concentration-time Curves at 24 Hours (AUC0-24) of GDC-0810 Single Agent and Its Glucuronide Metabolites	GDC-0810-Acyl-Glucuronide (Multiple Doses)	18.1 hr*ug/mL	Standard Deviation 16.3
Phase Ia - Cohort 7	Phase Ia: Area Under the Concentration-time Curves at 24 Hours (AUC0-24) of GDC-0810 Single Agent and Its Glucuronide Metabolites	GDC-0810-N-Glucuronide (Single Dose)	5.67 hr*ug/mL	Standard Deviation 7.17
Phase Ia - Cohort 7	Phase Ia: Area Under the Concentration-time Curves at 24 Hours (AUC0-24) of GDC-0810 Single Agent and Its Glucuronide Metabolites	GDC-0810-N-Glucuronide (Multiple Doses)	3.72 hr*ug/mL	Standard Deviation 1.81
Phase Ia - Cohort 7	Phase Ia: Area Under the Concentration-time Curves at 24 Hours (AUC0-24) of GDC-0810 Single Agent and Its Glucuronide Metabolites	GDC-0810 (Single Dose)	61.8 hr*ug/mL	Standard Deviation 25.5
Phase Ia - Cohort 7	Phase Ia: Area Under the Concentration-time Curves at 24 Hours (AUC0-24) of GDC-0810 Single Agent and Its Glucuronide Metabolites	GDC-0810-Acyl-Glucuronide (Single Dose)	30.6 hr*ug/mL	Standard Deviation 44
Phase Ia - Cohort 8	Phase Ia: Area Under the Concentration-time Curves at 24 Hours (AUC0-24) of GDC-0810 Single Agent and Its Glucuronide Metabolites	GDC-0810-N-Glucuronide (Single Dose)	1.83 hr*ug/mL	Standard Deviation 2.04
Phase Ia - Cohort 8	Phase Ia: Area Under the Concentration-time Curves at 24 Hours (AUC0-24) of GDC-0810 Single Agent and Its Glucuronide Metabolites	GDC-0810-Acyl-Glucuronide (Single Dose)	7.64 hr*ug/mL	Standard Deviation 5.51
Phase Ia - Cohort 8	Phase Ia: Area Under the Concentration-time Curves at 24 Hours (AUC0-24) of GDC-0810 Single Agent and Its Glucuronide Metabolites	GDC-0810-Acyl-Glucuronide (Multiple Doses)	12 hr*ug/mL	Standard Deviation 5.44
Phase Ia - Cohort 8	Phase Ia: Area Under the Concentration-time Curves at 24 Hours (AUC0-24) of GDC-0810 Single Agent and Its Glucuronide Metabolites	GDC-0810 (Multiple Doses)	75.2 hr*ug/mL	Standard Deviation 15.4
Phase Ia - Cohort 8	Phase Ia: Area Under the Concentration-time Curves at 24 Hours (AUC0-24) of GDC-0810 Single Agent and Its Glucuronide Metabolites	GDC-0810 (Single Dose)	95.1 hr*ug/mL	Standard Deviation 76.4
Phase Ia - Cohort 8	Phase Ia: Area Under the Concentration-time Curves at 24 Hours (AUC0-24) of GDC-0810 Single Agent and Its Glucuronide Metabolites	GDC-0810-N-Glucuronide (Multiple Doses)	2.35 hr*ug/mL	Standard Deviation 1.57
Phase Ia - Cohort 9	Phase Ia: Area Under the Concentration-time Curves at 24 Hours (AUC0-24) of GDC-0810 Single Agent and Its Glucuronide Metabolites	GDC-0810-N-Glucuronide (Multiple Doses)	2.66 hr*ug/mL	Standard Deviation 1.58
Phase Ia - Cohort 9	Phase Ia: Area Under the Concentration-time Curves at 24 Hours (AUC0-24) of GDC-0810 Single Agent and Its Glucuronide Metabolites	GDC-0810-Acyl-Glucuronide (Single Dose)	7.1 hr*ug/mL	Standard Deviation 1.96
Phase Ia - Cohort 9	Phase Ia: Area Under the Concentration-time Curves at 24 Hours (AUC0-24) of GDC-0810 Single Agent and Its Glucuronide Metabolites	GDC-0810-Acyl-Glucuronide (Multiple Doses)	20.8 hr*ug/mL	Standard Deviation 14.9
Phase Ia - Cohort 9	Phase Ia: Area Under the Concentration-time Curves at 24 Hours (AUC0-24) of GDC-0810 Single Agent and Its Glucuronide Metabolites	GDC-0810 (Single Dose)	47.7 hr*ug/mL	Standard Deviation 11.4
Phase Ia - Cohort 9	Phase Ia: Area Under the Concentration-time Curves at 24 Hours (AUC0-24) of GDC-0810 Single Agent and Its Glucuronide Metabolites	GDC-0810-N-Glucuronide (Single Dose)	0.649 hr*ug/mL	Standard Deviation 0.055
Phase Ia - Cohort 9	Phase Ia: Area Under the Concentration-time Curves at 24 Hours (AUC0-24) of GDC-0810 Single Agent and Its Glucuronide Metabolites	GDC-0810 (Multiple Doses)	109 hr*ug/mL	Standard Deviation 73.3

Secondary

Phase Ia: Area Under the Concentration-time Curves at 6 Hours (AUC0-6) of GDC-0810 Single Agent and Its Glucuronide Metabolites

Area under the concentration-time curves from time 0 to 6 hours (AUC0-6) has been calculated using PK samples collected after administration of a single dose (on Day -7) and also following once-daily multiple doses (at steady state on Day 29) of GDC-0810.

Time frame: Single Dose: Day-7 at 0 (predose), 0.5, 1, 1.5, 2, 3, 4, 6 hours postdose; Multiple Doses: Day 29 (Cycle 2 Day 1) at 0 (predose), 0.5, 1, 1.5, 2, 3, 4, 6 hours postdose

Population: All participants that were enrolled in Phase Ia of the study and provided sufficient blood samples for analysis.

Arm	Measure	Group	Value (MEAN)	Dispersion
Phase Ia - All Cohorts	Phase Ia: Area Under the Concentration-time Curves at 6 Hours (AUC0-6) of GDC-0810 Single Agent and Its Glucuronide Metabolites	GDC-0810-N-Glucuronide (Multiple Doses)	0.105 hr*ug/mL	Standard Deviation 0.0724
Phase Ia - All Cohorts	Phase Ia: Area Under the Concentration-time Curves at 6 Hours (AUC0-6) of GDC-0810 Single Agent and Its Glucuronide Metabolites	GDC-0810 (Multiple Doses)	4.83 hr*ug/mL	Standard Deviation 2.3
Phase Ia - All Cohorts	Phase Ia: Area Under the Concentration-time Curves at 6 Hours (AUC0-6) of GDC-0810 Single Agent and Its Glucuronide Metabolites	GDC-0810 (Single Dose)	3.18 hr*ug/mL	Standard Deviation 1.65
Phase Ia - All Cohorts	Phase Ia: Area Under the Concentration-time Curves at 6 Hours (AUC0-6) of GDC-0810 Single Agent and Its Glucuronide Metabolites	GDC-0810-N-Glucuronide (Single Dose)	0.0401 hr*ug/mL	Standard Deviation 0.0197
Phase IIa - Cohort A2	Phase Ia: Area Under the Concentration-time Curves at 6 Hours (AUC0-6) of GDC-0810 Single Agent and Its Glucuronide Metabolites	GDC-0810-N-Glucuronide (Multiple Doses)	0.103 hr*ug/mL	Standard Deviation 0.0335
Phase IIa - Cohort A2	Phase Ia: Area Under the Concentration-time Curves at 6 Hours (AUC0-6) of GDC-0810 Single Agent and Its Glucuronide Metabolites	GDC-0810 (Multiple Doses)	6.19 hr*ug/mL	Standard Deviation 2.18
Phase IIa - Cohort A2	Phase Ia: Area Under the Concentration-time Curves at 6 Hours (AUC0-6) of GDC-0810 Single Agent and Its Glucuronide Metabolites	GDC-0810 (Single Dose)	6.78 hr*ug/mL	Standard Deviation 1.19
Phase IIa - Cohort A2	Phase Ia: Area Under the Concentration-time Curves at 6 Hours (AUC0-6) of GDC-0810 Single Agent and Its Glucuronide Metabolites	GDC-0810-N-Glucuronide (Single Dose)	0.116 hr*ug/mL	Standard Deviation 0.0729
Phase IIa - Cohort B1	Phase Ia: Area Under the Concentration-time Curves at 6 Hours (AUC0-6) of GDC-0810 Single Agent and Its Glucuronide Metabolites	GDC-0810-Acyl-Glucuronide (Single Dose)	3.18 hr*ug/mL	Standard Deviation 1.77
Phase IIa - Cohort B1	Phase Ia: Area Under the Concentration-time Curves at 6 Hours (AUC0-6) of GDC-0810 Single Agent and Its Glucuronide Metabolites	GDC-0810-N-Glucuronide (Single Dose)	0.321 hr*ug/mL	Standard Deviation 0.149
Phase IIa - Cohort B1	Phase Ia: Area Under the Concentration-time Curves at 6 Hours (AUC0-6) of GDC-0810 Single Agent and Its Glucuronide Metabolites	GDC-0810-Acyl-Glucuronide (Multiple Doses)	3.72 hr*ug/mL	Standard Deviation 1.91
Phase IIa - Cohort B1	Phase Ia: Area Under the Concentration-time Curves at 6 Hours (AUC0-6) of GDC-0810 Single Agent and Its Glucuronide Metabolites	GDC-0810 (Single Dose)	23.7 hr*ug/mL	Standard Deviation 11.3
Phase IIa - Cohort B1	Phase Ia: Area Under the Concentration-time Curves at 6 Hours (AUC0-6) of GDC-0810 Single Agent and Its Glucuronide Metabolites	GDC-0810-N-Glucuronide (Multiple Doses)	0.321 hr*ug/mL	Standard Deviation 0.105
Phase IIa - Cohort B1	Phase Ia: Area Under the Concentration-time Curves at 6 Hours (AUC0-6) of GDC-0810 Single Agent and Its Glucuronide Metabolites	GDC-0810 (Multiple Doses)	18.8 hr*ug/mL	Standard Deviation 4.76
Phase IIa - Cohort B2	Phase Ia: Area Under the Concentration-time Curves at 6 Hours (AUC0-6) of GDC-0810 Single Agent and Its Glucuronide Metabolites	GDC-0810-Acyl-Glucuronide (Single Dose)	8.25 hr*ug/mL	Standard Deviation 4.54
Phase IIa - Cohort B2	Phase Ia: Area Under the Concentration-time Curves at 6 Hours (AUC0-6) of GDC-0810 Single Agent and Its Glucuronide Metabolites	GDC-0810 (Single Dose)	34.3 hr*ug/mL	Standard Deviation 14.4
Phase IIa - Cohort B2	Phase Ia: Area Under the Concentration-time Curves at 6 Hours (AUC0-6) of GDC-0810 Single Agent and Its Glucuronide Metabolites	GDC-0810 (Multiple Doses)	41.1 hr*ug/mL	Standard Deviation 27.5
Phase IIa - Cohort B2	Phase Ia: Area Under the Concentration-time Curves at 6 Hours (AUC0-6) of GDC-0810 Single Agent and Its Glucuronide Metabolites	GDC-0810-N-Glucuronide (Multiple Doses)	1.37 hr*ug/mL	Standard Deviation 1.21
Phase IIa - Cohort B2	Phase Ia: Area Under the Concentration-time Curves at 6 Hours (AUC0-6) of GDC-0810 Single Agent and Its Glucuronide Metabolites	GDC-0810-Acyl-Glucuronide (Multiple Doses)	13 hr*ug/mL	Standard Deviation 11.1
Phase IIa - Cohort B2	Phase Ia: Area Under the Concentration-time Curves at 6 Hours (AUC0-6) of GDC-0810 Single Agent and Its Glucuronide Metabolites	GDC-0810-N-Glucuronide (Single Dose)	1.16 hr*ug/mL	Standard Deviation 0.815
Phase Ia - Cohort 5	Phase Ia: Area Under the Concentration-time Curves at 6 Hours (AUC0-6) of GDC-0810 Single Agent and Its Glucuronide Metabolites	GDC-0810-N-Glucuronide (Single Dose)	1.36 hr*ug/mL	Standard Deviation 0.917
Phase Ia - Cohort 5	Phase Ia: Area Under the Concentration-time Curves at 6 Hours (AUC0-6) of GDC-0810 Single Agent and Its Glucuronide Metabolites	GDC-0810 (Single Dose)	58.2 hr*ug/mL	Standard Deviation 28.9
Phase Ia - Cohort 5	Phase Ia: Area Under the Concentration-time Curves at 6 Hours (AUC0-6) of GDC-0810 Single Agent and Its Glucuronide Metabolites	GDC-0810 (Multiple Doses)	74.9 hr*ug/mL	Standard Deviation 30.1
Phase Ia - Cohort 5	Phase Ia: Area Under the Concentration-time Curves at 6 Hours (AUC0-6) of GDC-0810 Single Agent and Its Glucuronide Metabolites	GDC-0810-N-Glucuronide (Multiple Doses)	1.83 hr*ug/mL	Standard Deviation 1.01
Phase Ia - Cohort 5	Phase Ia: Area Under the Concentration-time Curves at 6 Hours (AUC0-6) of GDC-0810 Single Agent and Its Glucuronide Metabolites	GDC-0810-Acyl-Glucuronide (Single Dose)	5.29 hr*ug/mL	Standard Deviation 2.71
Phase Ia - Cohort 5	Phase Ia: Area Under the Concentration-time Curves at 6 Hours (AUC0-6) of GDC-0810 Single Agent and Its Glucuronide Metabolites	GDC-0810-Acyl-Glucuronide (Multiple Doses)	8.25 hr*ug/mL	Standard Deviation 3.47
Phase Ia - Cohort 6	Phase Ia: Area Under the Concentration-time Curves at 6 Hours (AUC0-6) of GDC-0810 Single Agent and Its Glucuronide Metabolites	GDC-0810-Acyl-Glucuronide (Multiple Doses)	2.03 hr*ug/mL	Standard Deviation 0.669
Phase Ia - Cohort 6	Phase Ia: Area Under the Concentration-time Curves at 6 Hours (AUC0-6) of GDC-0810 Single Agent and Its Glucuronide Metabolites	GDC-0810-N-Glucuronide (Multiple Doses)	0.409 hr*ug/mL	Standard Deviation 0.23
Phase Ia - Cohort 6	Phase Ia: Area Under the Concentration-time Curves at 6 Hours (AUC0-6) of GDC-0810 Single Agent and Its Glucuronide Metabolites	GDC-0810-N-Glucuronide (Single Dose)	0.486 hr*ug/mL	Standard Deviation 0.36
Phase Ia - Cohort 6	Phase Ia: Area Under the Concentration-time Curves at 6 Hours (AUC0-6) of GDC-0810 Single Agent and Its Glucuronide Metabolites	GDC-0810 (Multiple Doses)	19.3 hr*ug/mL	Standard Deviation 7.01
Phase Ia - Cohort 6	Phase Ia: Area Under the Concentration-time Curves at 6 Hours (AUC0-6) of GDC-0810 Single Agent and Its Glucuronide Metabolites	GDC-0810-Acyl-Glucuronide (Single Dose)	2.76 hr*ug/mL	Standard Deviation 2.23
Phase Ia - Cohort 6	Phase Ia: Area Under the Concentration-time Curves at 6 Hours (AUC0-6) of GDC-0810 Single Agent and Its Glucuronide Metabolites	GDC-0810 (Single Dose)	18.8 hr*ug/mL	Standard Deviation 7.38
Phase Ia - Cohort 7	Phase Ia: Area Under the Concentration-time Curves at 6 Hours (AUC0-6) of GDC-0810 Single Agent and Its Glucuronide Metabolites	GDC-0810 (Multiple Doses)	65.7 hr*ug/mL	Standard Deviation 20.6
Phase Ia - Cohort 7	Phase Ia: Area Under the Concentration-time Curves at 6 Hours (AUC0-6) of GDC-0810 Single Agent and Its Glucuronide Metabolites	GDC-0810-Acyl-Glucuronide (Multiple Doses)	14 hr*ug/mL	Standard Deviation 11.1
Phase Ia - Cohort 7	Phase Ia: Area Under the Concentration-time Curves at 6 Hours (AUC0-6) of GDC-0810 Single Agent and Its Glucuronide Metabolites	GDC-0810-N-Glucuronide (Multiple Doses)	2.63 hr*ug/mL	Standard Deviation 1.01
Phase Ia - Cohort 7	Phase Ia: Area Under the Concentration-time Curves at 6 Hours (AUC0-6) of GDC-0810 Single Agent and Its Glucuronide Metabolites	GDC-0810 (Single Dose)	51.1 hr*ug/mL	Standard Deviation 18
Phase Ia - Cohort 7	Phase Ia: Area Under the Concentration-time Curves at 6 Hours (AUC0-6) of GDC-0810 Single Agent and Its Glucuronide Metabolites	GDC-0810-Acyl-Glucuronide (Single Dose)	21.1 hr*ug/mL	Standard Deviation 26.9
Phase Ia - Cohort 7	Phase Ia: Area Under the Concentration-time Curves at 6 Hours (AUC0-6) of GDC-0810 Single Agent and Its Glucuronide Metabolites	GDC-0810-N-Glucuronide (Single Dose)	3.81 hr*ug/mL	Standard Deviation 4.15
Phase Ia - Cohort 8	Phase Ia: Area Under the Concentration-time Curves at 6 Hours (AUC0-6) of GDC-0810 Single Agent and Its Glucuronide Metabolites	GDC-0810 (Multiple Doses)	70.5 hr*ug/mL	Standard Deviation 22
Phase Ia - Cohort 8	Phase Ia: Area Under the Concentration-time Curves at 6 Hours (AUC0-6) of GDC-0810 Single Agent and Its Glucuronide Metabolites	GDC-0810-Acyl-Glucuronide (Single Dose)	3.99 hr*ug/mL	Standard Deviation 2.29
Phase Ia - Cohort 8	Phase Ia: Area Under the Concentration-time Curves at 6 Hours (AUC0-6) of GDC-0810 Single Agent and Its Glucuronide Metabolites	GDC-0810-N-Glucuronide (Single Dose)	0.938 hr*ug/mL	Standard Deviation 0.983
Phase Ia - Cohort 8	Phase Ia: Area Under the Concentration-time Curves at 6 Hours (AUC0-6) of GDC-0810 Single Agent and Its Glucuronide Metabolites	GDC-0810-N-Glucuronide (Multiple Doses)	2.08 hr*ug/mL	Standard Deviation 1.15
Phase Ia - Cohort 8	Phase Ia: Area Under the Concentration-time Curves at 6 Hours (AUC0-6) of GDC-0810 Single Agent and Its Glucuronide Metabolites	GDC-0810-Acyl-Glucuronide (Multiple Doses)	10.2 hr*ug/mL	Standard Deviation 3.61
Phase Ia - Cohort 8	Phase Ia: Area Under the Concentration-time Curves at 6 Hours (AUC0-6) of GDC-0810 Single Agent and Its Glucuronide Metabolites	GDC-0810 (Single Dose)	48.3 hr*ug/mL	Standard Deviation 28.4
Phase Ia - Cohort 9	Phase Ia: Area Under the Concentration-time Curves at 6 Hours (AUC0-6) of GDC-0810 Single Agent and Its Glucuronide Metabolites	GDC-0810 (Multiple Doses)	43 hr*ug/mL	Standard Deviation 26
Phase Ia - Cohort 9	Phase Ia: Area Under the Concentration-time Curves at 6 Hours (AUC0-6) of GDC-0810 Single Agent and Its Glucuronide Metabolites	GDC-0810 (Single Dose)	22.1 hr*ug/mL	Standard Deviation 5.43
Phase Ia - Cohort 9	Phase Ia: Area Under the Concentration-time Curves at 6 Hours (AUC0-6) of GDC-0810 Single Agent and Its Glucuronide Metabolites	GDC-0810-Acyl-Glucuronide (Single Dose)	3.27 hr*ug/mL	Standard Deviation 1.03
Phase Ia - Cohort 9	Phase Ia: Area Under the Concentration-time Curves at 6 Hours (AUC0-6) of GDC-0810 Single Agent and Its Glucuronide Metabolites	GDC-0810-N-Glucuronide (Single Dose)	0.29 hr*ug/mL	Standard Deviation 0.0295
Phase Ia - Cohort 9	Phase Ia: Area Under the Concentration-time Curves at 6 Hours (AUC0-6) of GDC-0810 Single Agent and Its Glucuronide Metabolites	GDC-0810-Acyl-Glucuronide (Multiple Doses)	8.45 hr*ug/mL	Standard Deviation 5.79
Phase Ia - Cohort 9	Phase Ia: Area Under the Concentration-time Curves at 6 Hours (AUC0-6) of GDC-0810 Single Agent and Its Glucuronide Metabolites	GDC-0810-N-Glucuronide (Multiple Doses)	0.974 hr*ug/mL	Standard Deviation 0.605

Secondary

Phase Ia: Maximum Plasma Concentration (Cmax) of GDC-0810 Single Agent and Its Glucuronide Metabolites

Maximum Plasma Concentration (Cmax) has been calculated using PK samples collected after administration of a single dose (on Day -7) and also following once-daily multiple doses (at steady state on Day 29) of GDC-0810.

Time frame: Single Dose: Day-7 at 0 (predose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 24, 48 hours postdose; Multiple Doses: Day 29 (Cycle 2 Day 1) at 0 (predose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 24, hours postdose

Population: All participants that were enrolled in Phase Ia of the study and provided sufficient blood samples for analysis.

Arm	Measure	Group	Value (MEAN)	Dispersion
Phase Ia - All Cohorts	Phase Ia: Maximum Plasma Concentration (Cmax) of GDC-0810 Single Agent and Its Glucuronide Metabolites	GDC-0810 (Single Dose)	2.29 micrograms per milliliter (ug/mL)	Standard Deviation 1.24
Phase Ia - All Cohorts	Phase Ia: Maximum Plasma Concentration (Cmax) of GDC-0810 Single Agent and Its Glucuronide Metabolites	GDC-0810-N-Glucuronide (Multiple Doses)	0.067 micrograms per milliliter (ug/mL)	Standard Deviation 0.055
Phase Ia - All Cohorts	Phase Ia: Maximum Plasma Concentration (Cmax) of GDC-0810 Single Agent and Its Glucuronide Metabolites	GDC-0810-N-Glucuronide (Single Dose)	0.0171 micrograms per milliliter (ug/mL)	Standard Deviation 0.021
Phase Ia - All Cohorts	Phase Ia: Maximum Plasma Concentration (Cmax) of GDC-0810 Single Agent and Its Glucuronide Metabolites	GDC-0810 (Multiple Doses)	2.59 micrograms per milliliter (ug/mL)	Standard Deviation 1.43
Phase IIa - Cohort A2	Phase Ia: Maximum Plasma Concentration (Cmax) of GDC-0810 Single Agent and Its Glucuronide Metabolites	GDC-0810 (Single Dose)	3.76 micrograms per milliliter (ug/mL)	Standard Deviation 0.599
Phase IIa - Cohort A2	Phase Ia: Maximum Plasma Concentration (Cmax) of GDC-0810 Single Agent and Its Glucuronide Metabolites	GDC-0810-N-Glucuronide (Single Dose)	0.0535 micrograms per milliliter (ug/mL)	Standard Deviation 0.015
Phase IIa - Cohort A2	Phase Ia: Maximum Plasma Concentration (Cmax) of GDC-0810 Single Agent and Its Glucuronide Metabolites	GDC-0810-N-Glucuronide (Multiple Doses)	0.061 micrograms per milliliter (ug/mL)	Standard Deviation 0.0271
Phase IIa - Cohort A2	Phase Ia: Maximum Plasma Concentration (Cmax) of GDC-0810 Single Agent and Its Glucuronide Metabolites	GDC-0810 (Multiple Doses)	3.26 micrograms per milliliter (ug/mL)	Standard Deviation 1.11
Phase IIa - Cohort B1	Phase Ia: Maximum Plasma Concentration (Cmax) of GDC-0810 Single Agent and Its Glucuronide Metabolites	GDC-0810-N-Glucuronide (Single Dose)	0.177 micrograms per milliliter (ug/mL)	Standard Deviation 0.1
Phase IIa - Cohort B1	Phase Ia: Maximum Plasma Concentration (Cmax) of GDC-0810 Single Agent and Its Glucuronide Metabolites	GDC-0810 (Multiple Doses)	9.08 micrograms per milliliter (ug/mL)	Standard Deviation 3.43
Phase IIa - Cohort B1	Phase Ia: Maximum Plasma Concentration (Cmax) of GDC-0810 Single Agent and Its Glucuronide Metabolites	GDC-0810-Acyl-Glucuronide (Multiple Doses)	1.89 micrograms per milliliter (ug/mL)	Standard Deviation 1.34
Phase IIa - Cohort B1	Phase Ia: Maximum Plasma Concentration (Cmax) of GDC-0810 Single Agent and Its Glucuronide Metabolites	GDC-0810-Acyl-Glucuronide (Single Dose)	1.46 micrograms per milliliter (ug/mL)	Standard Deviation 0.997
Phase IIa - Cohort B1	Phase Ia: Maximum Plasma Concentration (Cmax) of GDC-0810 Single Agent and Its Glucuronide Metabolites	GDC-0810-N-Glucuronide (Multiple Doses)	0.184 micrograms per milliliter (ug/mL)	Standard Deviation 0.0832
Phase IIa - Cohort B1	Phase Ia: Maximum Plasma Concentration (Cmax) of GDC-0810 Single Agent and Its Glucuronide Metabolites	GDC-0810 (Single Dose)	9.4 micrograms per milliliter (ug/mL)	Standard Deviation 2.53
Phase IIa - Cohort B2	Phase Ia: Maximum Plasma Concentration (Cmax) of GDC-0810 Single Agent and Its Glucuronide Metabolites	GDC-0810-N-Glucuronide (Multiple Doses)	0.416 micrograms per milliliter (ug/mL)	Standard Deviation 0.346
Phase IIa - Cohort B2	Phase Ia: Maximum Plasma Concentration (Cmax) of GDC-0810 Single Agent and Its Glucuronide Metabolites	GDC-0810 (Single Dose)	12.7 micrograms per milliliter (ug/mL)	Standard Deviation 5.36
Phase IIa - Cohort B2	Phase Ia: Maximum Plasma Concentration (Cmax) of GDC-0810 Single Agent and Its Glucuronide Metabolites	GDC-0810-Acyl-Glucuronide (Multiple Doses)	3.64 micrograms per milliliter (ug/mL)	Standard Deviation 2.96
Phase IIa - Cohort B2	Phase Ia: Maximum Plasma Concentration (Cmax) of GDC-0810 Single Agent and Its Glucuronide Metabolites	GDC-0810 (Multiple Doses)	11.8 micrograms per milliliter (ug/mL)	Standard Deviation 6.61
Phase IIa - Cohort B2	Phase Ia: Maximum Plasma Concentration (Cmax) of GDC-0810 Single Agent and Its Glucuronide Metabolites	GDC-0810-N-Glucuronide (Single Dose)	0.468 micrograms per milliliter (ug/mL)	Standard Deviation 0.388
Phase IIa - Cohort B2	Phase Ia: Maximum Plasma Concentration (Cmax) of GDC-0810 Single Agent and Its Glucuronide Metabolites	GDC-0810-Acyl-Glucuronide (Single Dose)	3 micrograms per milliliter (ug/mL)	Standard Deviation 0.827
Phase Ia - Cohort 5	Phase Ia: Maximum Plasma Concentration (Cmax) of GDC-0810 Single Agent and Its Glucuronide Metabolites	GDC-0810 (Multiple Doses)	25 micrograms per milliliter (ug/mL)	Standard Deviation 8.35
Phase Ia - Cohort 5	Phase Ia: Maximum Plasma Concentration (Cmax) of GDC-0810 Single Agent and Its Glucuronide Metabolites	GDC-0810-N-Glucuronide (Single Dose)	0.691 micrograms per milliliter (ug/mL)	Standard Deviation 0.526
Phase Ia - Cohort 5	Phase Ia: Maximum Plasma Concentration (Cmax) of GDC-0810 Single Agent and Its Glucuronide Metabolites	GDC-0810-Acyl-Glucuronide (Single Dose)	2.26 micrograms per milliliter (ug/mL)	Standard Deviation 1.24
Phase Ia - Cohort 5	Phase Ia: Maximum Plasma Concentration (Cmax) of GDC-0810 Single Agent and Its Glucuronide Metabolites	GDC-0810-N-Glucuronide (Multiple Doses)	0.723 micrograms per milliliter (ug/mL)	Standard Deviation 0.338
Phase Ia - Cohort 5	Phase Ia: Maximum Plasma Concentration (Cmax) of GDC-0810 Single Agent and Its Glucuronide Metabolites	GDC-0810 (Single Dose)	22.2 micrograms per milliliter (ug/mL)	Standard Deviation 11.6
Phase Ia - Cohort 5	Phase Ia: Maximum Plasma Concentration (Cmax) of GDC-0810 Single Agent and Its Glucuronide Metabolites	GDC-0810-Acyl-Glucuronide (Multiple Doses)	3.16 micrograms per milliliter (ug/mL)	Standard Deviation 1.2
Phase Ia - Cohort 6	Phase Ia: Maximum Plasma Concentration (Cmax) of GDC-0810 Single Agent and Its Glucuronide Metabolites	GDC-0810 (Multiple Doses)	8.89 micrograms per milliliter (ug/mL)	Standard Deviation 3.96
Phase Ia - Cohort 6	Phase Ia: Maximum Plasma Concentration (Cmax) of GDC-0810 Single Agent and Its Glucuronide Metabolites	GDC-0810-Acyl-Glucuronide (Multiple Doses)	0.993 micrograms per milliliter (ug/mL)	Standard Deviation 0.435
Phase Ia - Cohort 6	Phase Ia: Maximum Plasma Concentration (Cmax) of GDC-0810 Single Agent and Its Glucuronide Metabolites	GDC-0810-N-Glucuronide (Multiple Doses)	0.181 micrograms per milliliter (ug/mL)	Standard Deviation 0.0846
Phase Ia - Cohort 6	Phase Ia: Maximum Plasma Concentration (Cmax) of GDC-0810 Single Agent and Its Glucuronide Metabolites	GDC-0810-Acyl-Glucuronide (Single Dose)	1.35 micrograms per milliliter (ug/mL)	Standard Deviation 0.876
Phase Ia - Cohort 6	Phase Ia: Maximum Plasma Concentration (Cmax) of GDC-0810 Single Agent and Its Glucuronide Metabolites	GDC-0810-N-Glucuronide (Single Dose)	0.299 micrograms per milliliter (ug/mL)	Standard Deviation 0.171
Phase Ia - Cohort 6	Phase Ia: Maximum Plasma Concentration (Cmax) of GDC-0810 Single Agent and Its Glucuronide Metabolites	GDC-0810 (Single Dose)	9.73 micrograms per milliliter (ug/mL)	Standard Deviation 4.5
Phase Ia - Cohort 7	Phase Ia: Maximum Plasma Concentration (Cmax) of GDC-0810 Single Agent and Its Glucuronide Metabolites	GDC-0810-N-Glucuronide (Single Dose)	1.38 micrograms per milliliter (ug/mL)	Standard Deviation 1.19
Phase Ia - Cohort 7	Phase Ia: Maximum Plasma Concentration (Cmax) of GDC-0810 Single Agent and Its Glucuronide Metabolites	GDC-0810 (Single Dose)	15.9 micrograms per milliliter (ug/mL)	Standard Deviation 3.13
Phase Ia - Cohort 7	Phase Ia: Maximum Plasma Concentration (Cmax) of GDC-0810 Single Agent and Its Glucuronide Metabolites	GDC-0810 (Multiple Doses)	18.4 micrograms per milliliter (ug/mL)	Standard Deviation 4.84
Phase Ia - Cohort 7	Phase Ia: Maximum Plasma Concentration (Cmax) of GDC-0810 Single Agent and Its Glucuronide Metabolites	GDC-0810-N-Glucuronide (Multiple Doses)	0.74 micrograms per milliliter (ug/mL)	Standard Deviation 0.327
Phase Ia - Cohort 7	Phase Ia: Maximum Plasma Concentration (Cmax) of GDC-0810 Single Agent and Its Glucuronide Metabolites	GDC-0810-Acyl-Glucuronide (Single Dose)	7.02 micrograms per milliliter (ug/mL)	Standard Deviation 8.19
Phase Ia - Cohort 7	Phase Ia: Maximum Plasma Concentration (Cmax) of GDC-0810 Single Agent and Its Glucuronide Metabolites	GDC-0810-Acyl-Glucuronide (Multiple Doses)	3.37 micrograms per milliliter (ug/mL)	Standard Deviation 2.34
Phase Ia - Cohort 8	Phase Ia: Maximum Plasma Concentration (Cmax) of GDC-0810 Single Agent and Its Glucuronide Metabolites	GDC-0810-N-Glucuronide (Multiple Doses)	1.17 micrograms per milliliter (ug/mL)	Standard Deviation 0.893
Phase Ia - Cohort 8	Phase Ia: Maximum Plasma Concentration (Cmax) of GDC-0810 Single Agent and Its Glucuronide Metabolites	GDC-0810-N-Glucuronide (Single Dose)	0.369 micrograms per milliliter (ug/mL)	Standard Deviation 0.338
Phase Ia - Cohort 8	Phase Ia: Maximum Plasma Concentration (Cmax) of GDC-0810 Single Agent and Its Glucuronide Metabolites	GDC-0810-Acyl-Glucuronide (Multiple Doses)	4.62 micrograms per milliliter (ug/mL)	Standard Deviation 2.19
Phase Ia - Cohort 8	Phase Ia: Maximum Plasma Concentration (Cmax) of GDC-0810 Single Agent and Its Glucuronide Metabolites	GDC-0810-Acyl-Glucuronide (Single Dose)	1.29 micrograms per milliliter (ug/mL)	Standard Deviation 0.617
Phase Ia - Cohort 8	Phase Ia: Maximum Plasma Concentration (Cmax) of GDC-0810 Single Agent and Its Glucuronide Metabolites	GDC-0810 (Multiple Doses)	25.5 micrograms per milliliter (ug/mL)	Standard Deviation 9.3
Phase Ia - Cohort 8	Phase Ia: Maximum Plasma Concentration (Cmax) of GDC-0810 Single Agent and Its Glucuronide Metabolites	GDC-0810 (Single Dose)	15.6 micrograms per milliliter (ug/mL)	Standard Deviation 4.97
Phase Ia - Cohort 9	Phase Ia: Maximum Plasma Concentration (Cmax) of GDC-0810 Single Agent and Its Glucuronide Metabolites	GDC-0810-N-Glucuronide (Multiple Doses)	0.308 micrograms per milliliter (ug/mL)	Standard Deviation 0.148
Phase Ia - Cohort 9	Phase Ia: Maximum Plasma Concentration (Cmax) of GDC-0810 Single Agent and Its Glucuronide Metabolites	GDC-0810 (Single Dose)	10.1 micrograms per milliliter (ug/mL)	Standard Deviation 4.23
Phase Ia - Cohort 9	Phase Ia: Maximum Plasma Concentration (Cmax) of GDC-0810 Single Agent and Its Glucuronide Metabolites	GDC-0810 (Multiple Doses)	13.9 micrograms per milliliter (ug/mL)	Standard Deviation 4.87
Phase Ia - Cohort 9	Phase Ia: Maximum Plasma Concentration (Cmax) of GDC-0810 Single Agent and Its Glucuronide Metabolites	GDC-0810-N-Glucuronide (Single Dose)	0.153 micrograms per milliliter (ug/mL)	Standard Deviation 0.0421
Phase Ia - Cohort 9	Phase Ia: Maximum Plasma Concentration (Cmax) of GDC-0810 Single Agent and Its Glucuronide Metabolites	GDC-0810-Acyl-Glucuronide (Multiple Doses)	2.82 micrograms per milliliter (ug/mL)	Standard Deviation 1.43
Phase Ia - Cohort 9	Phase Ia: Maximum Plasma Concentration (Cmax) of GDC-0810 Single Agent and Its Glucuronide Metabolites	GDC-0810-Acyl-Glucuronide (Single Dose)	1.36 micrograms per milliliter (ug/mL)	Standard Deviation 0.421

Secondary

Phase Ia: Plasma Half-life (t1/2) of GDC-0810 Single Agent

Half-life (t1/2) was calculated after single dose administration and not at steady state.

Time frame: Day -7 at 0 (predose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 24, 48 hours postdose

Population: All participants that were enrolled in Phase Ia of the study and provided sufficient blood samples for analysis.

Arm	Measure	Value (MEAN)	Dispersion
Phase Ia - All Cohorts	Phase Ia: Plasma Half-life (t1/2) of GDC-0810 Single Agent	40.7 hr	Standard Deviation 3.47
Phase IIa - Cohort A2	Phase Ia: Plasma Half-life (t1/2) of GDC-0810 Single Agent	15.2 hr	Standard Deviation 2.35
Phase IIa - Cohort B1	Phase Ia: Plasma Half-life (t1/2) of GDC-0810 Single Agent	24.1 hr	Standard Deviation 17.3
Phase IIa - Cohort B2	Phase Ia: Plasma Half-life (t1/2) of GDC-0810 Single Agent	9.58 hr	Standard Deviation 3.41
Phase Ia - Cohort 5	Phase Ia: Plasma Half-life (t1/2) of GDC-0810 Single Agent	7.91 hr	Standard Deviation 2.67
Phase Ia - Cohort 6	Phase Ia: Plasma Half-life (t1/2) of GDC-0810 Single Agent	NA hr	—
Phase Ia - Cohort 7	Phase Ia: Plasma Half-life (t1/2) of GDC-0810 Single Agent	10.1 hr	Standard Deviation 1.59
Phase Ia - Cohort 8	Phase Ia: Plasma Half-life (t1/2) of GDC-0810 Single Agent	7.09 hr	Standard Deviation 3.23
Phase Ia - Cohort 9	Phase Ia: Plasma Half-life (t1/2) of GDC-0810 Single Agent	NA hr	—

Secondary

Phase Ia: Time to Maximum Concentration (Tmax) of GDC-0810 Single Agent and Its Glucuronide Metabolites

Time to Maximum Concentration (Tmax) has been calculated using PK samples collected after administration of a single dose (on Day -7) and also following once-daily multiple doses (at steady state on Day 29) of GDC-0810.

Time frame: Single Dose: Day-7 at 0 (predose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 24, 48 hours postdose; Multiple Doses: Day 29 (Cycle 2 Day 1) at 0 (predose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 24, hours postdose

Population: All participants that were enrolled in Phase Ia of the study and provided sufficient blood samples for analysis.

Arm	Measure	Group	Value (MEDIAN)
Phase Ia - All Cohorts	Phase Ia: Time to Maximum Concentration (Tmax) of GDC-0810 Single Agent and Its Glucuronide Metabolites	GDC-0810-N-Glucuronide (Multiple Doses)	2 hour (hr)
Phase Ia - All Cohorts	Phase Ia: Time to Maximum Concentration (Tmax) of GDC-0810 Single Agent and Its Glucuronide Metabolites	GDC-0810 (Single Dose)	1.5 hour (hr)
Phase Ia - All Cohorts	Phase Ia: Time to Maximum Concentration (Tmax) of GDC-0810 Single Agent and Its Glucuronide Metabolites	GDC-0810-N-Glucuronide (Single Dose)	0.5 hour (hr)
Phase Ia - All Cohorts	Phase Ia: Time to Maximum Concentration (Tmax) of GDC-0810 Single Agent and Its Glucuronide Metabolites	GDC-0810 (Multiple Doses)	1.47 hour (hr)
Phase IIa - Cohort A2	Phase Ia: Time to Maximum Concentration (Tmax) of GDC-0810 Single Agent and Its Glucuronide Metabolites	GDC-0810-N-Glucuronide (Single Dose)	1.95 hour (hr)
Phase IIa - Cohort A2	Phase Ia: Time to Maximum Concentration (Tmax) of GDC-0810 Single Agent and Its Glucuronide Metabolites	GDC-0810 (Multiple Doses)	0.9 hour (hr)
Phase IIa - Cohort A2	Phase Ia: Time to Maximum Concentration (Tmax) of GDC-0810 Single Agent and Its Glucuronide Metabolites	GDC-0810 (Single Dose)	1.71 hour (hr)
Phase IIa - Cohort A2	Phase Ia: Time to Maximum Concentration (Tmax) of GDC-0810 Single Agent and Its Glucuronide Metabolites	GDC-0810-N-Glucuronide (Multiple Doses)	1 hour (hr)
Phase IIa - Cohort B1	Phase Ia: Time to Maximum Concentration (Tmax) of GDC-0810 Single Agent and Its Glucuronide Metabolites	GDC-0810 (Multiple Doses)	1.55 hour (hr)
Phase IIa - Cohort B1	Phase Ia: Time to Maximum Concentration (Tmax) of GDC-0810 Single Agent and Its Glucuronide Metabolites	GDC-0810 (Single Dose)	2 hour (hr)
Phase IIa - Cohort B1	Phase Ia: Time to Maximum Concentration (Tmax) of GDC-0810 Single Agent and Its Glucuronide Metabolites	GDC-0810-Acyl-Glucuronide (Multiple Doses)	1.84 hour (hr)
Phase IIa - Cohort B1	Phase Ia: Time to Maximum Concentration (Tmax) of GDC-0810 Single Agent and Its Glucuronide Metabolites	GDC-0810-Acyl-Glucuronide (Single Dose)	2 hour (hr)
Phase IIa - Cohort B1	Phase Ia: Time to Maximum Concentration (Tmax) of GDC-0810 Single Agent and Its Glucuronide Metabolites	GDC-0810-N-Glucuronide (Multiple Doses)	1.64 hour (hr)
Phase IIa - Cohort B1	Phase Ia: Time to Maximum Concentration (Tmax) of GDC-0810 Single Agent and Its Glucuronide Metabolites	GDC-0810-N-Glucuronide (Single Dose)	2 hour (hr)
Phase IIa - Cohort B2	Phase Ia: Time to Maximum Concentration (Tmax) of GDC-0810 Single Agent and Its Glucuronide Metabolites	GDC-0810-Acyl-Glucuronide (Single Dose)	2.85 hour (hr)
Phase IIa - Cohort B2	Phase Ia: Time to Maximum Concentration (Tmax) of GDC-0810 Single Agent and Its Glucuronide Metabolites	GDC-0810 (Single Dose)	2.99 hour (hr)
Phase IIa - Cohort B2	Phase Ia: Time to Maximum Concentration (Tmax) of GDC-0810 Single Agent and Its Glucuronide Metabolites	GDC-0810 (Multiple Doses)	2.48 hour (hr)
Phase IIa - Cohort B2	Phase Ia: Time to Maximum Concentration (Tmax) of GDC-0810 Single Agent and Its Glucuronide Metabolites	GDC-0810-N-Glucuronide (Single Dose)	2.85 hour (hr)
Phase IIa - Cohort B2	Phase Ia: Time to Maximum Concentration (Tmax) of GDC-0810 Single Agent and Its Glucuronide Metabolites	GDC-0810-N-Glucuronide (Multiple Doses)	3.49 hour (hr)
Phase IIa - Cohort B2	Phase Ia: Time to Maximum Concentration (Tmax) of GDC-0810 Single Agent and Its Glucuronide Metabolites	GDC-0810-Acyl-Glucuronide (Multiple Doses)	3.53 hour (hr)
Phase Ia - Cohort 5	Phase Ia: Time to Maximum Concentration (Tmax) of GDC-0810 Single Agent and Its Glucuronide Metabolites	GDC-0810 (Multiple Doses)	2.95 hour (hr)
Phase Ia - Cohort 5	Phase Ia: Time to Maximum Concentration (Tmax) of GDC-0810 Single Agent and Its Glucuronide Metabolites	GDC-0810-Acyl-Glucuronide (Multiple Doses)	2.95 hour (hr)
Phase Ia - Cohort 5	Phase Ia: Time to Maximum Concentration (Tmax) of GDC-0810 Single Agent and Its Glucuronide Metabolites	GDC-0810 (Single Dose)	3.01 hour (hr)
Phase Ia - Cohort 5	Phase Ia: Time to Maximum Concentration (Tmax) of GDC-0810 Single Agent and Its Glucuronide Metabolites	GDC-0810-N-Glucuronide (Single Dose)	3.51 hour (hr)
Phase Ia - Cohort 5	Phase Ia: Time to Maximum Concentration (Tmax) of GDC-0810 Single Agent and Its Glucuronide Metabolites	GDC-0810-Acyl-Glucuronide (Single Dose)	3.51 hour (hr)
Phase Ia - Cohort 5	Phase Ia: Time to Maximum Concentration (Tmax) of GDC-0810 Single Agent and Its Glucuronide Metabolites	GDC-0810-N-Glucuronide (Multiple Doses)	2.95 hour (hr)
Phase Ia - Cohort 6	Phase Ia: Time to Maximum Concentration (Tmax) of GDC-0810 Single Agent and Its Glucuronide Metabolites	GDC-0810-Acyl-Glucuronide (Single Dose)	1.98 hour (hr)
Phase Ia - Cohort 6	Phase Ia: Time to Maximum Concentration (Tmax) of GDC-0810 Single Agent and Its Glucuronide Metabolites	GDC-0810-N-Glucuronide (Single Dose)	1.72 hour (hr)
Phase Ia - Cohort 6	Phase Ia: Time to Maximum Concentration (Tmax) of GDC-0810 Single Agent and Its Glucuronide Metabolites	GDC-0810 (Multiple Doses)	1.65 hour (hr)
Phase Ia - Cohort 6	Phase Ia: Time to Maximum Concentration (Tmax) of GDC-0810 Single Agent and Its Glucuronide Metabolites	GDC-0810-Acyl-Glucuronide (Multiple Doses)	1.65 hour (hr)
Phase Ia - Cohort 6	Phase Ia: Time to Maximum Concentration (Tmax) of GDC-0810 Single Agent and Its Glucuronide Metabolites	GDC-0810-N-Glucuronide (Multiple Doses)	1.65 hour (hr)
Phase Ia - Cohort 6	Phase Ia: Time to Maximum Concentration (Tmax) of GDC-0810 Single Agent and Its Glucuronide Metabolites	GDC-0810 (Single Dose)	1.48 hour (hr)
Phase Ia - Cohort 7	Phase Ia: Time to Maximum Concentration (Tmax) of GDC-0810 Single Agent and Its Glucuronide Metabolites	GDC-0810 (Multiple Doses)	1.59 hour (hr)
Phase Ia - Cohort 7	Phase Ia: Time to Maximum Concentration (Tmax) of GDC-0810 Single Agent and Its Glucuronide Metabolites	GDC-0810-Acyl-Glucuronide (Multiple Doses)	2.27 hour (hr)
Phase Ia - Cohort 7	Phase Ia: Time to Maximum Concentration (Tmax) of GDC-0810 Single Agent and Its Glucuronide Metabolites	GDC-0810-N-Glucuronide (Single Dose)	3.54 hour (hr)
Phase Ia - Cohort 7	Phase Ia: Time to Maximum Concentration (Tmax) of GDC-0810 Single Agent and Its Glucuronide Metabolites	GDC-0810 (Single Dose)	3.04 hour (hr)
Phase Ia - Cohort 7	Phase Ia: Time to Maximum Concentration (Tmax) of GDC-0810 Single Agent and Its Glucuronide Metabolites	GDC-0810-N-Glucuronide (Multiple Doses)	2.27 hour (hr)
Phase Ia - Cohort 7	Phase Ia: Time to Maximum Concentration (Tmax) of GDC-0810 Single Agent and Its Glucuronide Metabolites	GDC-0810-Acyl-Glucuronide (Single Dose)	3.54 hour (hr)
Phase Ia - Cohort 8	Phase Ia: Time to Maximum Concentration (Tmax) of GDC-0810 Single Agent and Its Glucuronide Metabolites	GDC-0810-Acyl-Glucuronide (Single Dose)	3 hour (hr)
Phase Ia - Cohort 8	Phase Ia: Time to Maximum Concentration (Tmax) of GDC-0810 Single Agent and Its Glucuronide Metabolites	GDC-0810-Acyl-Glucuronide (Multiple Doses)	2.93 hour (hr)
Phase Ia - Cohort 8	Phase Ia: Time to Maximum Concentration (Tmax) of GDC-0810 Single Agent and Its Glucuronide Metabolites	GDC-0810-N-Glucuronide (Single Dose)	3 hour (hr)
Phase Ia - Cohort 8	Phase Ia: Time to Maximum Concentration (Tmax) of GDC-0810 Single Agent and Its Glucuronide Metabolites	GDC-0810 (Multiple Doses)	2.93 hour (hr)
Phase Ia - Cohort 8	Phase Ia: Time to Maximum Concentration (Tmax) of GDC-0810 Single Agent and Its Glucuronide Metabolites	GDC-0810 (Single Dose)	2 hour (hr)
Phase Ia - Cohort 8	Phase Ia: Time to Maximum Concentration (Tmax) of GDC-0810 Single Agent and Its Glucuronide Metabolites	GDC-0810-N-Glucuronide (Multiple Doses)	2.93 hour (hr)
Phase Ia - Cohort 9	Phase Ia: Time to Maximum Concentration (Tmax) of GDC-0810 Single Agent and Its Glucuronide Metabolites	GDC-0810-N-Glucuronide (Multiple Doses)	2.05 hour (hr)
Phase Ia - Cohort 9	Phase Ia: Time to Maximum Concentration (Tmax) of GDC-0810 Single Agent and Its Glucuronide Metabolites	GDC-0810 (Single Dose)	1.88 hour (hr)
Phase Ia - Cohort 9	Phase Ia: Time to Maximum Concentration (Tmax) of GDC-0810 Single Agent and Its Glucuronide Metabolites	GDC-0810-Acyl-Glucuronide (Single Dose)	2.98 hour (hr)
Phase Ia - Cohort 9	Phase Ia: Time to Maximum Concentration (Tmax) of GDC-0810 Single Agent and Its Glucuronide Metabolites	GDC-0810-Acyl-Glucuronide (Multiple Doses)	2.05 hour (hr)
Phase Ia - Cohort 9	Phase Ia: Time to Maximum Concentration (Tmax) of GDC-0810 Single Agent and Its Glucuronide Metabolites	GDC-0810-N-Glucuronide (Single Dose)	1.88 hour (hr)
Phase Ia - Cohort 9	Phase Ia: Time to Maximum Concentration (Tmax) of GDC-0810 Single Agent and Its Glucuronide Metabolites	GDC-0810 (Multiple Doses)	2.05 hour (hr)

Secondary

Phase Ib: AUC0-6 of GDC-0810 in Combination With Palbociclib and/or an LHRH Agonist

AUC0-6 has been calculated using PK samples collected after GDC-0810 administration.

Time frame: C1: Predose and at 1, 2, 3, 4, and 6 hours postdose on Cycle 1 Day 1 and Cycle 1 Day 8; D1: Predose and at 1, 2, 3, 4, and 6 hours postdose on Cycle 1 Day 1 and Cycle 2 Day 1

Population: All participants that were enrolled in Phase Ib of the study.

Arm	Measure	Group	Value (MEAN)	Dispersion
Phase Ia - All Cohorts	Phase Ib: AUC0-6 of GDC-0810 in Combination With Palbociclib and/or an LHRH Agonist	C1D1	18.9 hr*ug/ml	Standard Deviation 9.19
Phase Ia - All Cohorts	Phase Ib: AUC0-6 of GDC-0810 in Combination With Palbociclib and/or an LHRH Agonist	C1D8	18.2 hr*ug/ml	Standard Deviation 10.4
Phase IIa - Cohort A2	Phase Ib: AUC0-6 of GDC-0810 in Combination With Palbociclib and/or an LHRH Agonist	C1D1	33.6 hr*ug/ml	Standard Deviation 7.91
Phase IIa - Cohort A2	Phase Ib: AUC0-6 of GDC-0810 in Combination With Palbociclib and/or an LHRH Agonist	C2D1	38.8 hr*ug/ml	Standard Deviation 3.53

Secondary

Phase Ib: AUC0-6 of LHRH Agonist in Combination With GDC-0810 and/or an Palbociclib

AUC0-6 has been calculated using PK samples collected after GDC-0810 administration.

Time frame: Predose and at 1, 2, 3, 4, and 6 hours postdose on Cycle 1 Day 1 and Cycle 2 Day 1

Population: All participants that were enrolled in Phase Ib of the study, Cohort D1 and provided sufficient samples for analysis.

Arm	Measure	Group	Value (MEAN)	Dispersion
Phase Ia - All Cohorts	Phase Ib: AUC0-6 of LHRH Agonist in Combination With GDC-0810 and/or an Palbociclib	C1D1	118 hr*ug/ml	Standard Deviation 76.4
Phase Ia - All Cohorts	Phase Ib: AUC0-6 of LHRH Agonist in Combination With GDC-0810 and/or an Palbociclib	C2D1	106 hr*ug/ml	—

Secondary

Phase Ib: AUC0-6 of Palbociclib in Combination With GDC-0810 and/or an LHRH Agonist

AUC0-6 has been calculated using PK samples collected after GDC-0810 administration.

Time frame: Predose and at 1, 2, 3, 4, and 6 hours postdose on Cycle 1 Day 1 and Cycle 1 Day 8

Population: All participants that were enrolled in Phase Ib of the study, Cohort C1 and provided sufficient samples for analysis.

Arm	Measure	Group	Value (MEAN)	Dispersion
Phase Ia - All Cohorts	Phase Ib: AUC0-6 of Palbociclib in Combination With GDC-0810 and/or an LHRH Agonist	C1D1	200 hr*ug/ml	Standard Deviation 41.4
Phase Ia - All Cohorts	Phase Ib: AUC0-6 of Palbociclib in Combination With GDC-0810 and/or an LHRH Agonist	C1D8	464 hr*ug/ml	Standard Deviation 106

Secondary

Phase Ib: Cmax of GDC-0810 in Combination With Palbociclib and/or an LHRH Agonist

Cmax has been calculated using PK samples collected after GDC-0810 administration.

Time frame: C1: Predose and at 1, 2, 3, 4, and 6 hours postdose on Cycle 1 Day 1 and Cycle 1 Day 8; D1: Predose and at 1, 2, 3, 4, and 6 hours postdose on Cycle 1 Day 1 and Cycle 2 Day 1

Population: All participants that were enrolled in Phase Ib of the study and provided sufficient samples for analysis.

Arm	Measure	Group	Value (MEAN)	Dispersion
Phase Ia - All Cohorts	Phase Ib: Cmax of GDC-0810 in Combination With Palbociclib and/or an LHRH Agonist	Cycle 1 Day 1 (C1D1)	10.2 ug/ml	Standard Deviation 2.98
Phase Ia - All Cohorts	Phase Ib: Cmax of GDC-0810 in Combination With Palbociclib and/or an LHRH Agonist	Cycle 1 Day 8 (C1D8)	9.95 ug/ml	Standard Deviation 5.85
Phase IIa - Cohort A2	Phase Ib: Cmax of GDC-0810 in Combination With Palbociclib and/or an LHRH Agonist	Cycle 1 Day 1 (C1D1)	8.96 ug/ml	Standard Deviation 1.87
Phase IIa - Cohort A2	Phase Ib: Cmax of GDC-0810 in Combination With Palbociclib and/or an LHRH Agonist	Cycle 2 Day 1 (C2D1)	9.62 ug/ml	Standard Deviation 0.0354

Secondary

Phase Ib: Cmax of LHRH Agonist in Combination With GDC-0810 and/or Palbociclib

Cmax has been calculated using PK samples collected after GDC-0810 administration.

Time frame: Predose and at 1, 2, 3, 4, and 6 hours postdose on Cycle 1 Day 1 and Cycle 2 Day 1

Population: All participants that were enrolled in Phase Ib of the study, Cohort D1 and provided sufficient samples for analysis.

Arm	Measure	Group	Value (MEAN)	Dispersion
Phase Ia - All Cohorts	Phase Ib: Cmax of LHRH Agonist in Combination With GDC-0810 and/or Palbociclib	C1D1	39.6 ug/ml	Standard Deviation 9.85
Phase Ia - All Cohorts	Phase Ib: Cmax of LHRH Agonist in Combination With GDC-0810 and/or Palbociclib	C2D1	32.4 ug/ml	—

Secondary

Phase Ib: Cmax of Palbociclib in Combination With GDC-0810 and/or an LHRH Agonist

Cmax has been calculated using PK samples collected after GDC-0810 administration.

Time frame: Predose and at 1, 2, 3, 4, and 6 hours postdose on Cycle 1 Day 1 and Cycle 1 Day 8

Population: All participants that were enrolled in Phase Ib of the study, Cohort C1 and provided sufficient samples for analysis.

Arm	Measure	Group	Value (MEAN)	Dispersion
Phase Ia - All Cohorts	Phase Ib: Cmax of Palbociclib in Combination With GDC-0810 and/or an LHRH Agonist	C1D1	54.8 ug/ml	Standard Deviation 9.04
Phase Ia - All Cohorts	Phase Ib: Cmax of Palbociclib in Combination With GDC-0810 and/or an LHRH Agonist	C1D8	97.8 ug/ml	Standard Deviation 27.1

Secondary

Phase Ib: t/2 of GDC-0810 in Combination With Palbociclib and/or an LHRH Agonist

Half-life (t1/2) can be estimated only when the PK sample collection following a dose is long enough to characterize the elimination phase. The PK samples in these cohorts were only collected up to 6 hours following the dose, hence, t1/2 could not be estimated.

Time frame: C1: Predose and at 1, 2, 3, 4, and 6 hours postdose on Cycle 1 Day 1 and Cycle 1 Day 8; D1: Predose and at 1, 2, 3, 4, and 6 hours postdose on Cycle 1 Day 1 and Cycle 2 Day 1

Population: No data from any participants could be used for analysis.

Secondary

Phase Ib: t/2 of LHRH Agonist in Combination With GDC-0810 and/or Palbociclib

Time frame: Cohort D1: Predose and at 1, 2, 3, 4, and 6 hours postdose on Cycle 1 Day 1 and Cycle 2 Day 1

Population: No data from any participants could be used for analysis.

Secondary

Phase Ib: t/2 of Palbociclib in Combination With GDC-0810 and/or an LHRH Agonist

Time frame: Cohort C1: Predose and at 1, 2, 3, 4, and 6 hours postdose on Cycle 1 Day 1 and Cycle 1 Day 8

Population: No data from any participants could be used for analysis.

Secondary

Phase Ib: Tmax of GDC-0810 in Combination With Palbociclib and/or an LHRH Agonist

Tmax has been calculated using PK samples collected after GDC-0810 administration.

Time frame: C1: Predose and at 1, 2, 3, 4, and 6 hours postdose on Cycle 1 Day 1 and Cycle 1 Day 8; D1: Predose and at 1, 2, 3, 4, and 6 hours postdose on Cycle 1 Day 1 and Cycle 2 Day 1

Population: All participants that were enrolled in Phase Ib of the study and provided sufficient samples for analysis.

Arm	Measure	Group	Value (MEDIAN)
Phase Ia - All Cohorts	Phase Ib: Tmax of GDC-0810 in Combination With Palbociclib and/or an LHRH Agonist	C1D1	2 hr
Phase Ia - All Cohorts	Phase Ib: Tmax of GDC-0810 in Combination With Palbociclib and/or an LHRH Agonist	C1D8	2.5 hr
Phase IIa - Cohort A2	Phase Ib: Tmax of GDC-0810 in Combination With Palbociclib and/or an LHRH Agonist	C1D1	3 hr
Phase IIa - Cohort A2	Phase Ib: Tmax of GDC-0810 in Combination With Palbociclib and/or an LHRH Agonist	C2D1	3 hr

Secondary

Phase Ib: Tmax of LHRH Agonist in Combination With GDC-0810 and/or Palbociclib

Tmax has been calculated using PK samples collected after GDC-0810 administration.

Time frame: Predose and at 1, 2, 3, 4, and 6 hours postdose on Cycle 1 Day 1 and Cycle 2 Day 1

Population: All participants that were enrolled in Phase Ib of the study, Cohort D1 and provided sufficient samples for analysis.

Arm	Measure	Group	Value (MEDIAN)
Phase Ia - All Cohorts	Phase Ib: Tmax of LHRH Agonist in Combination With GDC-0810 and/or Palbociclib	C1D1	3 hr
Phase Ia - All Cohorts	Phase Ib: Tmax of LHRH Agonist in Combination With GDC-0810 and/or Palbociclib	C1D8	3 hr

Secondary

Phase Ib: Tmax of Palbociclib in Combination With GDC-0810 and/or an LHRH Agonist

Tmax has been calculated using PK samples collected after GDC-0810 administration.

Time frame: Predose and at 1, 2, 3, 4, and 6 hours postdose on Cycle 1 Day 1 and Cycle 1 Day 8

Population: All participants that were enrolled in Phase Ib of the study, Cohort C1 and provided sufficient samples for analysis.

Arm	Measure	Group	Value (MEDIAN)
Phase Ia - All Cohorts	Phase Ib: Tmax of Palbociclib in Combination With GDC-0810 and/or an LHRH Agonist	C1D1	4 hr
Phase Ia - All Cohorts	Phase Ib: Tmax of Palbociclib in Combination With GDC-0810 and/or an LHRH Agonist	C1D8	6 hr

Secondary

Phase IIa: Effect of GDC-0810 Single Agent on Ventricular Repolarization as Measured by Corrected QT Intervals (QTc) Using Fridericia's Formula

The corrected QT interval (QTc) was calculated using Fridericia's formula from electrocardiogram (ECG) data. Changes in ECG intervals from baseline were calculated. Triplicate ECG measurements were collected throughout the study. The averaged triplicate ECG measurements were used for analysis.

Time frame: Screening; on Cycle 2 Day 1 predose and at 1, 2, 3, 4, and 6 hours postdose; Cycle 3 Day 1 predose, and at 1, 3, and 6 hours post dose

Population: All participants enrolled in Phase IIa of the study and with post baseline ECG measurements

Arm	Measure	Group	Value (NUMBER)
Phase Ia - All Cohorts	Phase IIa: Effect of GDC-0810 Single Agent on Ventricular Repolarization as Measured by Corrected QT Intervals (QTc) Using Fridericia's Formula	≤ 450 milliseconds (msec)	100 percentage of participants
Phase Ia - All Cohorts	Phase IIa: Effect of GDC-0810 Single Agent on Ventricular Repolarization as Measured by Corrected QT Intervals (QTc) Using Fridericia's Formula	>450 and ≤480 msec	0 percentage of participants
Phase Ia - All Cohorts	Phase IIa: Effect of GDC-0810 Single Agent on Ventricular Repolarization as Measured by Corrected QT Intervals (QTc) Using Fridericia's Formula	Increase from baseline ≤30 msec	100 percentage of participants
Phase Ia - All Cohorts	Phase IIa: Effect of GDC-0810 Single Agent on Ventricular Repolarization as Measured by Corrected QT Intervals (QTc) Using Fridericia's Formula	Increase from baseline >30 and ≤60 msec	0 percentage of participants
Phase IIa - Cohort A2	Phase IIa: Effect of GDC-0810 Single Agent on Ventricular Repolarization as Measured by Corrected QT Intervals (QTc) Using Fridericia's Formula	>450 and ≤480 msec	33.3 percentage of participants
Phase IIa - Cohort A2	Phase IIa: Effect of GDC-0810 Single Agent on Ventricular Repolarization as Measured by Corrected QT Intervals (QTc) Using Fridericia's Formula	Increase from baseline ≤30 msec	100 percentage of participants
Phase IIa - Cohort A2	Phase IIa: Effect of GDC-0810 Single Agent on Ventricular Repolarization as Measured by Corrected QT Intervals (QTc) Using Fridericia's Formula	Increase from baseline >30 and ≤60 msec	0 percentage of participants
Phase IIa - Cohort A2	Phase IIa: Effect of GDC-0810 Single Agent on Ventricular Repolarization as Measured by Corrected QT Intervals (QTc) Using Fridericia's Formula	≤ 450 milliseconds (msec)	66.7 percentage of participants
Phase IIa - Cohort B1	Phase IIa: Effect of GDC-0810 Single Agent on Ventricular Repolarization as Measured by Corrected QT Intervals (QTc) Using Fridericia's Formula	Increase from baseline ≤30 msec	93.9 percentage of participants
Phase IIa - Cohort B1	Phase IIa: Effect of GDC-0810 Single Agent on Ventricular Repolarization as Measured by Corrected QT Intervals (QTc) Using Fridericia's Formula	>450 and ≤480 msec	8.8 percentage of participants
Phase IIa - Cohort B1	Phase IIa: Effect of GDC-0810 Single Agent on Ventricular Repolarization as Measured by Corrected QT Intervals (QTc) Using Fridericia's Formula	Increase from baseline >30 and ≤60 msec	6.1 percentage of participants
Phase IIa - Cohort B1	Phase IIa: Effect of GDC-0810 Single Agent on Ventricular Repolarization as Measured by Corrected QT Intervals (QTc) Using Fridericia's Formula	≤ 450 milliseconds (msec)	91.2 percentage of participants
Phase IIa - Cohort B2	Phase IIa: Effect of GDC-0810 Single Agent on Ventricular Repolarization as Measured by Corrected QT Intervals (QTc) Using Fridericia's Formula	Increase from baseline >30 and ≤60 msec	0 percentage of participants
Phase IIa - Cohort B2	Phase IIa: Effect of GDC-0810 Single Agent on Ventricular Repolarization as Measured by Corrected QT Intervals (QTc) Using Fridericia's Formula	>450 and ≤480 msec	0 percentage of participants
Phase IIa - Cohort B2	Phase IIa: Effect of GDC-0810 Single Agent on Ventricular Repolarization as Measured by Corrected QT Intervals (QTc) Using Fridericia's Formula	≤ 450 milliseconds (msec)	100 percentage of participants
Phase IIa - Cohort B2	Phase IIa: Effect of GDC-0810 Single Agent on Ventricular Repolarization as Measured by Corrected QT Intervals (QTc) Using Fridericia's Formula	Increase from baseline ≤30 msec	100 percentage of participants

Source: ClinicalTrials.gov · Data processed: Mar 10, 2026

A Study of GDC-0810 Single Agent or in Combination With Palbociclib and/or a Luteinizing Hormone-Releasing Hormone (LHRH) Agonist in Women With Locally Advanced or Metastatic Estrogen Receptor Positive Breast Cancer

Conditions

Brief summary

Related papers

Interventions

Sponsors

Study design

Eligibility

Inclusion criteria

Exclusion criteria

Design outcomes

Primary

Secondary

Countries

Participant flow

Participants by arm

Withdrawals & dropouts

Baseline characteristics

Adverse events

Outcome results

Phase Ia: Maximum Tolerated Dose of GDC-0810 When Used as a Single Agent

Phase Ia: RP2D of GDC-0810 When Used as a Single Agent

Phase Ib: RP2D of GDC-0810 When Used in Combination With Palbociclib and/or LHRH

Phase IIa: Percentage of Participants With Clinical Benefit Response of GDC-0810 According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1)

Phase IIa: Percentage of Participants With Confirmed Objective Tumor Response of GDC-0810 According to RECIST v1.1

All Phases: Percentage of Participants With Adverse Events (AEs)

Area Under the Concentration-Time Curve From Time 0 to Infinity (AUC0-Inf)

Phase Ia: Apparent Clearance (Cl/F)

Phase Ia: Area Under the Concentration-time Curves at 24 Hours (AUC0-24) of GDC-0810 Single Agent and Its Glucuronide Metabolites

Phase Ia: Area Under the Concentration-time Curves at 6 Hours (AUC0-6) of GDC-0810 Single Agent and Its Glucuronide Metabolites

Phase Ia: Maximum Plasma Concentration (Cmax) of GDC-0810 Single Agent and Its Glucuronide Metabolites

Phase Ia: Plasma Half-life (t1/2) of GDC-0810 Single Agent

Phase Ia: Time to Maximum Concentration (Tmax) of GDC-0810 Single Agent and Its Glucuronide Metabolites

Phase Ib: AUC0-6 of GDC-0810 in Combination With Palbociclib and/or an LHRH Agonist

Phase Ib: AUC0-6 of LHRH Agonist in Combination With GDC-0810 and/or an Palbociclib

Phase Ib: AUC0-6 of Palbociclib in Combination With GDC-0810 and/or an LHRH Agonist

Phase Ib: Cmax of GDC-0810 in Combination With Palbociclib and/or an LHRH Agonist

Phase Ib: Cmax of LHRH Agonist in Combination With GDC-0810 and/or Palbociclib

Phase Ib: Cmax of Palbociclib in Combination With GDC-0810 and/or an LHRH Agonist

Phase Ib: t/2 of GDC-0810 in Combination With Palbociclib and/or an LHRH Agonist

Phase Ib: t/2 of LHRH Agonist in Combination With GDC-0810 and/or Palbociclib

Phase Ib: t/2 of Palbociclib in Combination With GDC-0810 and/or an LHRH Agonist

Phase Ib: Tmax of GDC-0810 in Combination With Palbociclib and/or an LHRH Agonist

Phase Ib: Tmax of LHRH Agonist in Combination With GDC-0810 and/or Palbociclib

Phase Ib: Tmax of Palbociclib in Combination With GDC-0810 and/or an LHRH Agonist

Phase IIa: Effect of GDC-0810 Single Agent on Ventricular Repolarization as Measured by Corrected QT Intervals (QTc) Using Fridericia's Formula