Metastatic ER - PR Positive

Key Eligibility:
1. New diagnosis of metastatic TNBC
2. PD-L1 testing by SP142 assay; currently only accepting PD-L1+ patients
3. No prior immunotherapy exposure
4. Patients are randomized to Abraxane + atezolizumab or Abraxane + Sacituzumab govitecan
5. Visits: Day 1 of each 21 day cycle

ER/PR+, No blastic only mets. Recurrence after 12 months on adjuvant tx if recurrent

Key Eligibility Criteria:

Inclusion:
1. For Phase 1b: locally advanced, recurrent, or metastatic, incurable, and histologically or cytologically confirmed HR+/HER2- breast cancer by ASCO/CAP criteria (based on most recent assessment):
a) Must have received CDK4/6i in the adjuvant or metastatic setting, unless patient was unable or unwilling to receive standard of care CDK4/6i treatment; or must be able to receive it on protocol, AND,
b) Received no more than 1 prior line of therapy containing chemotherapy (including cytotoxic antibody-drug conjugates) given in the metastatic setting; AND,
c) Must have received no more than 3 lines of therapy in total for metastatic disease.
d) May have received a prior PI3Ka inhibitor

NOTE: If the patient progressed on the PI3K inhibitor a sample (tissue or liquid) must have been obtained following progression, or at study screening, to be analyzed at a CAP/CLIA-certified or equivalently accredited diagnostic laboratory, determine the resistance mutation(s) and Sponsor approval for study inclusion obtained. If the patient was intolerant to the drug, then mutational analysis and Sponsor approval are not required for enrollment.

Exclusion:
1. Has had tumor evaluated for PTEN and AKT and has known mutations or deletions in PTEN, or, activating mutations in AKT (E17K) determined at a CAP/CLIA-certified or equivalently accredited diagnostic laboratory (e.g., ISO15189-certified, in-house clinical testing).
2. Metaplastic breast cancer
3. Possible allergies to TOS-358 or excipients


For pre-screening, please contact: Message Basket: P VICC RESEARCH BREAST OHO

Endocrine Therapy vs Capecitabine after progression on CDK4/6 inhibitor
1. Clinical stage IV invasive mammary carcinoma or unresectable locoregional recurrence of invasive mammary carcinoma that is:
a) ER/PR-positive (> 1% cells) by IHC and HER2 negative (by IHC or FISH)
b) Previously exposed to an aromatase inhibitor (AI) or a selective estrogen-receptor modulator/ downregulator (SERM; SERD) + a CDK4/6 inhibitor
2. 2nd line and above (no prior chemo in metastatic)
3. PIK3CA negative

2nd line only, no prior chemo, evaluable okay

Key Eligibility Criteria:

Inclusion:
1. For Phase 1b: locally advanced, recurrent, or metastatic, incurable, and histologically or cytologically confirmed HR+/HER2- breast cancer by ASCO/CAP criteria (based on most recent assessment):
a) Must have received CDK4/6i in the adjuvant or metastatic setting, unless patient was unable or unwilling to receive standard of care CDK4/6i treatment; or must be able to receive it on protocol, AND,
b) Received no more than 1 prior line of therapy containing chemotherapy (including cytotoxic antibody-drug conjugates) given in the metastatic setting; AND,
c) Must have received no more than 3 lines of therapy in total for metastatic disease.
d) May have received a prior PI3Ka inhibitor

NOTE: If the patient progressed on the PI3K inhibitor a sample (tissue or liquid) must have been obtained following progression, or at study screening, to be analyzed at a CAP/CLIA-certified or equivalently accredited diagnostic laboratory, determine the resistance mutation(s) and Sponsor approval for study inclusion obtained. If the patient was intolerant to the drug, then mutational analysis and Sponsor approval are not required for enrollment.

Exclusion:
1. Has had tumor evaluated for PTEN and AKT and has known mutations or deletions in PTEN, or, activating mutations in AKT (E17K) determined at a CAP/CLIA-certified or equivalently accredited diagnostic laboratory (e.g., ISO15189-certified, in-house clinical testing).
2. Metaplastic breast cancer
3. Possible allergies to TOS-358 or excipients


For pre-screening, please contact: Message Basket: P VICC RESEARCH BREAST OHO

Key Eligibility:
1. New diagnosis of metastatic TNBC
2. PD-L1 testing by SP142 assay; currently only accepting PD-L1+ patients
3. No prior immunotherapy exposure
4. Patients are randomized to Abraxane + atezolizumab or Abraxane + Sacituzumab govitecan
5. Visits: Day 1 of each 21 day cycle

Endocrine Therapy vs Capecitabine after progression on CDK4/6 inhibitor
1. Clinical stage IV invasive mammary carcinoma or unresectable locoregional recurrence of invasive mammary carcinoma that is:
a) ER/PR-positive (> 1% cells) by IHC and HER2 negative (by IHC or FISH)
b) Previously exposed to an aromatase inhibitor (AI) or a selective estrogen-receptor modulator/ downregulator (SERM; SERD) + a CDK4/6 inhibitor
2. 2nd line and above (no prior chemo in metastatic)
3. PIK3CA negative