A PHASE Ib/II MULTICENTER, OPEN-LABEL, RANDOMIZED STUDY EVALUATING THE SAFETY, PHARMACOKINETICS, AND ACTIVITY OF GDC-4198 ALONE AND IN COMBINATION WITH GIREDESTRANT IN COMPARISON WITH ABEMACICLIB AND GIREDESTRANT IN PARTICIPANTS WITH LOCALLY ADVANCED OR METASTATIC ESTROGEN RECEPTOR-POSITIVE, HER2-NEGATIVE BREAST CANCER WHO HAVE PREVIOUSLY PROGRESSED DURING OR AFTER A CDK4/6 INHIBITOR

Inclusion Criteria: - Histologically and/or cytologically confirmed adenocarcinoma of the breast that is locally advanced or metastatic. - Previously documented ER+ and HER2- tumor according to American Society of Clinical Oncology (ASCO)/ College of American Pathologists (CAP) or European Society of Medical Oncology (ESMO) guidelines or any national guidelines with criteria conforming to ASCO/CAP or ESMO guidelines. - Disease progression during or after treatment with an approved cyclin-dependent kinase 4/6 (CDK4/6) inhibitor and endocrine therapy (ET) in the locally advanced or metastatic setting. - Measurable or non-measurable evaluable, disease per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1) - Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1 - Life expectancy ≥ 6 months Exclusion Criteria: - Advanced, symptomatic, visceral spread that is at risk of life-threatening complications in the short term appropriate for treatment with cytotoxic chemotherapy at time of entry into the study, as per national or local treatment guidelines. - Have received more than one-line of therapy for locally advanced or metastatic disease. - Have received prior chemotherapy for metastatic breast cancer - Treatment with anti-cancer therapies, including investigational therapies, within 28 days or 5 drug elimination half -lives, whichever is shorter, prior to initiation of study drug. Treatment with an approved oral endocrine therapy (ET) within 7 days prior to initiation of study drug; treatment with fulvestrant or an approved CDK4/6 inhibitor within 21 days prior to initiation of study drug. - Poor peripheral venous access - Malabsorption condition or other gastrointestinal (GI) conditions/surgeries that the investigator assesses may significantly interfere with enteral absorption - History of malignancy within 3 years prior to screening, except for cancer under investigation in this study and malignancies with a negligible risk of metastasis or death.