2L CIT-naïve participants will receive doublet combination treatment with atezolizumab plus ipatasertib until unacceptable toxicity or loss of clinical benefit as determined by the investigator.

Participants who progressed on treatment may have the option of receiving atezolizumab + chemo, provided they meet the eligibility criteria.

Enrollment is closed and participant follow-up is complete.

2L CIT-naïve participants will receive doublet combination treatment with atezolizumab plus SGNLIV1A until unacceptable toxicity or loss of clinical benefit as determined by the investigator.

Patients who experience loss of clinical benefit as determined by the investigator or unacceptable toxicity related to SGN-LIV1A will be given the option of receiving Atezolizumab + chemo during Stage 2, provided they meet the eligibility criteria.

Enrollment is closed and participant follow-up is complete.

2L-CIT-naïve participants will receive doublet combination treatment with atezolizumab plus selicrelumab and bevacizumab until unacceptable toxicity or loss of clinical benefit as determined by the investigator.

Participants who progressed on treatment may have the option of receiving atezolizumab + chemo, provided they meet the eligibility criteria.

Enrollment is closed and participant follow-up is complete.

2L CIT-naïve participants enrolled in the active comparator arm who experience disease progression per RECIST v1.1 and 2L CIT-naïve participants enrolled in an experimental arm who experience loss of clinical benefit as determined by the investigator may receive doublet combination treatment with atezolizumab plus chemo (gemcitabine + carboplatin or eribulin) until unacceptable toxicity or loss of clinical benefit as determined by the investigator.

Enrollment is closed and participant follow-up is complete.

HR+ participants will receive treatment with inavolisib plus abemaciclib plus fulvestrant until unacceptable toxicity or disease progression determined by the investigator according to RECIST v1.1.

HR+ participants will receive treatment with inavolisib plus ribociclib plus fulvestrant until unacceptable toxicity or disease progression as determined by the investigator according to RECIST v1.1.

HR+ participants will receive treatment with inavolisib plus ribociclib plus letrozole until unacceptable toxicity or disease progression as determined by the investigator according to RECIST v1.1.

HR+ participants will receive treatment with inavolisib plus ribociclib plus fulvestrant until unacceptable toxicity or disease progression as determined by the investigator according to RECIST v1.1.

HR+ participants will receive treatment with inavolisib plus ribociclib plus letrozole until unacceptable toxicity or disease progression as determined by the investigator according to RECIST v1.1.

HR+ participants will receive treatment with inavolisib plus abemaciclib plus letrozole until unacceptable toxicity or disease progression as determined by the investigator according to RECIST v1.1.

HER2+/HER2-low participants will receive inavolisib + trastuzumab deruxtecan until unacceptable toxicity or disease progression as determined by the investigator according to RECIST v1.1.

Enrollment is closed.

HER2+/HER2-low participants will receive inavolisib + trastuzumab deruxtecan until unacceptable toxicity or disease progression as determined by the investigator according to RECIST v1.1.

Enrollment is closed.

Participants with locally advanced or metastatic, HR+, HER2- participants will receive empagliflozin plus inavolisib plus fulvestrant with or without palbociclib until unacceptable toxicity or disease progression as determined by the investigator according to RECIST v1.1.

Participants with locally advanced or metastatic, HR+, HER2- participants will receive metformin plus inavolisib plus fulvestrant with or without palbociclib until unacceptable toxicity or disease progression as determined by the investigator according to RECIST v1.1.

Participants will receive inavolisib plus atirmociclib plus fulvestrant until unacceptable toxicity or disease progression as determined by the investigator according to RECIST v1.1.

HR+ participants will receive treatment with inavolisib plus abemaciclib plus letrozole until unacceptable toxicity or disease progression as determined by the investigator according to RECIST v1.1.

HR+ participants will receive treatment with inavolisib plus abemaciclib plus giredestrant until unacceptable toxicity or disease progression as determined by the investigator according to RECIST v1.1.

HR+ participants will receive treatment with inavolisib plus abemaciclib plus giredestrant until unacceptable toxicity or disease progression as determined by the investigator according to RECIST v1.1.

HR+ participants will receive treatment with inavolisib plus ribociclib plus giredestrant until unacceptable toxicity or disease progression as determined by the investigator according to RECIST v1.1.

For Atezolizumab + SGN-LIV1A, Atezolizumab + Sacituzumab Govitecan, or Atezolizumab + Chemo arms: atezolizumab will be administered intravenously (IV), 1200 mg, on Day 1 of each 21-day cycle.

For Atezolizumab + Nab-Paclitaxel, Atezolizumab + Selicrelumab + Bevacizumab, Atezolizumab + Ipatasertib, or Atezolizumab + Nab-Paclitaxel + Tocilizumab arms: atezolizumab will be administered IV, 840 mg on Days 1 and 15 of each 28-day cycle.

Ipatasertib will be administered by mouth 400 mg once a day, on Days 1-21 of each 28-day cycle.

SGN-LIV1A will be administered IV, 2.5 milligrams per kilogram (mg/kg) (maximum calculated dose 250 mg), on Day 1 of each 21-day cycle.

Bevacizumab will be administered IV, 10 mg/kg, on Days 1 and 15 of each 28-day cycle.

Gemcitabine will be administered by IV, 1000 mg/m^2, along with carboplatin, by IV, on Days 1 and 8 of each 21-day cycle.

Or

Eribulin will be administered IV, 1.4 mg/m^2 on Days 1 and 8 of each 21-day cycle.

Selicrelumab will be administered by subcutaneous (SC) injection, at a fixed dose of 16 mg on Day 1 of Cycles 1 to 4 and every third cycle thereafter (Cycle = 28 days).

Tocilizumab will be administered IV, 8 mg/kg on Day 1 of each 28-day cycle.

Nab-Paclitaxel will be administered IV, 100 mg/m^2, on Days 1, 8, and 15 of each 28-day cycle.

Sacituzumab govitecan will be administered by IV infusion, 10 mg/kg, on Days 1 and 8 of each 21-day cycle.

Abemaciclib tablets will be administered at a dose of 150 mg twice daily by mouth on Days 1-28 of each 28-day cycle.

For Inavolisib + Abemaciclib + Fulvestrant, Inavolisib + Ribociclib (Dose #1) + Fulvestrant, Inavolisib + Ribociclib (Dose #2) + Fulvestrant, or Inavolisib + Atirmociclib + Fulvestrant arms:

Fulvestrant 500 mg, administered as an IM injection on Days 1 and 15 of Cycle 1, followed by Day 1 of each 28-day cycle thereafter.

For Empa + Inavolisib + Fulvestrant ± Palbociclib, or Metformin + Inavolisib + Fulvestrant ± Palbociclib arms:

Fulvestrant 500 mg, administered as an IM injection on Day 1 and as per local prescribing guidelines thereafter.

Ribociclib tablets will be administered by mouth once daily.

Inavolisib tablets will be administered by mouth once daily.

Trastuzumab Deruxtecan will be administered IV, 5.4 mg/kg on Day 1 of each 21-day cycle.

Ribociclib tablets will be administered by mouth once daily.

Letrozole tablets will be administered at a dose of 2.5 mg once a day by mouth on Days 1-28 of each 28-day cycle.

Inavolisib tablets will be administered by mouth OD.

Empagliflozin, administered orally, once daily (QD)

For Empagliflozin + Inavolisib + Fulvestrant ± Palbociclib arm:

Palbociclib 125 mg administered orally, QD in Cycle 1 followed by 125 mg on Days 1-21 of each cycle.

For Metformin + Inavolisib + Fulvestrant ± Palbociclib arm: Palbociclib 125 mg administered orally, QD in Cycle 1, followed by 125 mg on Days 1-21 of each cycle (Cycle=28 days).

Metf 1000 mg administered orally QD.

Atirmociclib administered orally, BID on Days 1-28 for each 28-day cycle.

Giredestrant 30 mg will be administered by mouth once daily, on Days 1-28 of each 28-day cycle.