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

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 exclusion criteria, plus:

* Cohort C1 (palbociclib combination cohorts): history of venous thromboembolic event requiring therapeutic anticoagulation; vaginal bleeding within 2 months prior to enrollment

Phase IIa portion - all above exclusion criteria, plus:

* Cohort A1, A2, and Cohort B2 only: more than 1 prior chemotherapy in the advanced/metastatic setting
* Cohort B1 only: prior chemotherapy in the advanced/metastatic setting