Inclusion Criteria:

• Female
• Age 18 years or older
• Patients undergoing elective breast conservation surgery for the treatment of Stage 0-III invasive ductal and/or ductal carcinoma in situ
• May include subjects treated with neo-adjuvant therapy (endocrine and/or chemotherapeutic), but not required for study inclusion
• Ability to understand and the willingness to sign a written informed consent document

Exclusion Criteria:

• Male
• Metastatic cancer (Stage IV)
• Lobular carcinoma as primary diagnosis
• Previous ipsilateral breast surgery for benign or malignant disease (this includes implants and breast augmentation)
• Subjects with multi-centric disease (histologically diagnosed cancer in two different quadrants of the breast), unless resected in a single specimen
• Subjects with bilateral disease (diagnosed cancer in both breasts)
• Participating in any other investigational margin assessment study which can influence collection of valid data under this study
• Use of cryo-assisted localization
• Currently lactating
• Current pregnancy
• Subjects undergoing breast conserving surgery whose resected specimen will be evaluated with intraoperative pathology, frozen section, or imprint cytology

• T1c or T2, cN0 or cN1 early breast cancer with plans for surgical resection
• ER/PR <10%, HER2 negative
• ECOG PS 0-1
• ANC >1200, Hgb >10, Plt >100,000
• Tumor determined to have abnormal HER2-driven signaling activity based on the CELx HSF test (to be conducted during screening)
• No T3 or T4 tumors
• No definitive surgical treatment performed yet
• No evidence of metastatic disease
• No prior history of ipsilateral DCIS or breast cancer
• No prior therapy with anthracyclines, taxanes, or anti-HER2 therapy
• No other malignancies within 2 years prior
• No active cardiac disease
• No uncontrolled hypertension
• No known HIV/HBV/HCV
• No neuropathy grade >=2

• HER2 positive invasive breast cancer
• Stage at disease presentation: any cT2-4, any cN1-3, M0
  • Patients with cT1-3N0-1/M0 at presentation must have pathologic evidence of residual cancer in the axilla at time of surgery
  • Patients with T4 or N2-3 disease must have pathologic evidence of residual cancer in either the breast and/or the axilla
• Completion of at least 6 cycles and 16 weeks of pre-operative systemic chemotherapy including 9 weeks of a taxane and 9 weeks of trastuzumab
• Cannot have had a best response to neoadjuvant therapy of progressive disease
• < or = 12 weeks since primary surgery and randomization
• ECOG PS 0-1
• LVEF >or = 50%
• No prior T-DM1 or immune checkpoint inhibitors
• Documentation of PD-L1 status

• Histologically confirmed TNBC, Stage I-III
• Residual invasive disease in the breasat and/or axillary lymph node(s) at surgical resection following neoadjuvant therapy
• Completed at least 6 cycles of neoadjuvant therapy containing an anthracycline and/or a taxane with or without carboplatin, with or without pembrolizumab
• No evidence of locoregional or distant relapse
• Surgical removal of all clinically evident disease
• ECOG PS 0-1
• No adjuvant systemic therapy
• LVEF > 50%
• No known germline BRCA mutation
• No Stage IV disease
• No history of prior invasive breast cancer
• No persistent toxicities from prior anticancer therapies
• No prior autoimmune or inflammatory disorders
• No known HIV

• Metastatic or locally advanced breast cancer not amenable to treatment with curative intent
• ER+, HER2-
• Prior endocrine therapy in combination with CDK 4/6 in either metastatic setting with disease progression after 6 months or in the adjuvant setting with relapsed disease within 12 months of exposure. (patients must have taken at least 12 months of adjuvant endocrine therapy, of which 6 months were in combination with a CDK4/6 inhibitor)
• Measurable disease or evaluable bone mets
• ECOG PS 0-1
• For premenopausal or perimenopausal women or men must have treatment with LHRH agonist therapy for duration of study
• No prior treatment with oral SERD, SERM, or everolimus. Fulvestrant is allowed if tx stopped at least 28 days prior to randomization
• No more than 2 prior lines of systemic endocrine therapy in metastatic setting
• No prior chemotherapy in metasatic setting
• No other malignancy within 5 years except nonmelanoma skin cancer, papillary thyroid cancer, or very low risk of recurrence cancers
• No known active CNS mets

• Histologically or cytologically confirmed and documented human epidermal growth factor receptor 2 (HER2)-positive/estrogen receptor (ER)-positive adenocarcinoma of the breast with metastatic or locally-advanced disease not amenable to curative resection
• Evaluable disease (measurable not required)
• Disease-free interval from completion of adjuvant or neoadjuvant systemic non-hormonal treatment to recurrence of ≥6 months
• ECOG PS 0-1
• LVEF of at least (≥)50%
• No previous systemic non-hormonal anti-cancer therapy in the metastatic breast cancer (MBC) or advanced breast cancer (ABC) setting. Note: Up to one line of single-agent endocrine therapy given in the metastatic or locally advanced setting will be allowed.
• No prior treatment with a selective estrogen receptor degrader (SERD)
• No previous treatment with approved or investigative anti-HER2 agents in any breast cancer treatment setting, except Phesgo (or trastuzumab SC with pertuzumab IV, or pertuzumab and trastuzumab IV), single-agent trastuzumab IV or SC, ado-trastuzumab emtansine, lapatinib, and neratinib in the neoadjuvant or adjuvant setting
• No disease progression within 6 months of receiving trastuzumab, with or without pertuzumab, or ado-trastuzumab emtansine in the adjuvant setting
• No history of exposure to the following cumulative doses of anthracyclines; Doxorubicin >360 mg/m2; Liposomal doxorubicin >500 mg/m2; Epirubucin >720 mg/m2; Mitoxantrone >120 mg/m2; Idarubicin >90 mg/m2.
• No known active uncontrolled or symptomatic central nervous system (CNS) metastases, carcinomatous meningitis, or leptomeningeal disease
• No current chronic daily treatment (continuous for >3 months) with corticosteroids (dose of 10 mg/day methylprednisolone or equivalent)
• No history of malignancy within 5 years prior to screening with the exception of the cancer under investigation in this study and malignancies with a negligible risk of metastasis or death

• Advanced or metastatic breast cancer that is locally assessed and prospectively centrally confirmed as HER2-positive (IHC3+ or ISH+) with known horme receptor status
• No prior chemotherapy or HER2-targeted therapy for advanced or metastatic breast cancer.
• No more than 1 previous line of endorcrine therapy in the metastatic setting
• Adjuvant/neo-adjuvant therapy allowed if >6 months from treatment to metastatic diagnosis
• ECOG PS 0-1
• No clinically active CNS disease
• No active ILD/pneumonitis

• Previously untreated locally advanced, inoperable, or metastatic TNBC (centrally confirmed)
  • Must be PD-L1 negative (centrally confirmed) unless treated in the adjuvant or neoadjuvant setting with PD-1 inhibitors, in which case they can be PD-L1 positive
• Must have had at least 6 months between completion of treatment for curative intent and first documented local or distant disease recurrence (if treated for curative intent in the past)
• Measurable disease
• ECOG PS 0-1
• No HIV
• No active HBV/HCV
• No previous topoisomerase inhibitors

• Locally advanced, inoperable, or metastatic TNBC (centrally confirmed) without prior therapy for advanced disease
• PD-L1 positive (centrally confirmed)
• If patient received treatment for early disease, must have completed treatment at least 6 months prior to development of metastatic disease
• Measurable disease
• ECOG PS 0-1
• No prior topoisomerase inhibitors
• No active autoimmune disease
• If HIV positive may not have had Kaposi's sarcoma or Castleman's disease
• No active HBV/HCV

• Triple negative metastatic breast cancer
• 2nd line
• ECOG PS 0-2
• No prior treatment with any study agents
• No history of autoimmune disease
• Presence of measurable disease
• No symptomatic or untreated CNS disease

• Malignant solid tumor with pathogenic inactivating TSC1 or TSC2 alterations. GEnetic alterations should be identified using NGS in tumor tissue or liquid biopsy
• Metastatic or locally advanced solid tumors
• Must have received all standard therapies appropriate for their tumor type and stage of disease or, in the opinion of the investigator, the patient would b e unlikely to tolerate or derive clinically meaningful benefit from appropriate SOC therapy
• Measurable disease
• ECOG PS 0-1
• Fasting tryglecerid must be < or = 300; fast serus cholesterol must be < or = to 350
• No prior treatment with MTOR inhibitor
• No primary brain tumors
• No known HIV

• Expansion Cohort A (ccRCC): Subjects with previously treated advanced RCC with clear cell histology (including those with a sarcomatoid component) who have radiographically progressed following treatment with at least one prior systemic anticancer regimen for inoperable locally advanced or metastatic disease.
• Expansion Cohorts B and E (nccRCC): Subjects with previously treated advanced RCC with non-clear cell histology who have radiographically progressed following treatment with at least one prior systemic anticancer regimen for inoperable locally advanced or metastatic disease.
• Expansion Cohorts C and F (HR+ BC): Subjects with breast cancer that is hormone receptor positive (ER+ and/or PR+) and negative for human epidermal growth factor receptor 2 (HER-2) and who have radiographically progressed during or following treatment with at least one prior systemic anticancer regimen for inoperable locally advanced or metastatic disease.
• Expansion Cohorts D and G (mCRPC): Subjects with metastatic CRPC (adenocarcinoma of the prostate). Neuroendocrine differentiation and other features permitted if adenocarcinoma is the primary histology.
• Expansion Cohort H (CRC): Subjects with histologically confirmed unresectable, locally advanced, or metastatic adenocarcinoma of the colon or rectum who received prior fluoropyrimidine-containing chemotherapy with oxaliplatin and irinotecan.
  • KRAS/NRAS wild type
  • Must have received all of the following: fluropyridmidine, irinotecan,  oxaliplatin,  EGFR monoclonal antibody, and, for those with BRAF mutation, BRAF inhibitor in combination with cetuximab
  • Must have progression during or within 3 months following the last dose of the most recent regimen
  • Prior therapy with regorafenib or TAS-102 are NOT allowed
• Expansion Cohort I (UC, Maintenance Therapy): Subjects with histologically confirmed, unresectable, locally advanced or metastatic transitional cell carcinoma of the urothelium (including the renal pelvis, ureter, urinary bladder, or urethra) who received first-line chemotherapy of gemcitabine + cisplatin and/or gemcitabine + carboplatin.
• Expansion Cohort J (UC, ICI-refractory): Subjects with histologically confirmed, unresectable, locally advanced or metastatic transitional cell carcinoma of the urothelium (including the renal pelvis, ureter, urinary bladder, or urethra) who progressed on or after PD-1/PD-L1 targeting ICI therapy.
• Expansion Cohort K (UC, platinum-refractory): Subjects with histologically confirmed, unresectable, locally advanced or metastatic transitional cell carcinoma of the urothelium (including the renal pelvis, ureter, urinary bladder, or urethra) who progressed on or after first-line platinum-based combination therapy.
•  Locally advanced, recurrent, or metastatic
• No known untreated CNS mets
• ECOG PS 0-1

• Histologically confirmed locally advanced, recurrent, or metastatic incurable solid tumors
• Must have tumor specimen available
• Measurable disease
• ECOG PS 0-1
• Life expectancy at least 12 weeks
• Phase 1a- must have exhausted all standard therapies for their disease
• Phase 1b- must have disease that has progressed after at least one available standard therapy
• Some cohorts are tumor-type specific- please contact study team to see if tumor type is eligible at any time during the study
• No active HBV/HCV or chronic or acute EBV
• No history of autoimmune disease
• No symptomatic or actively progressing CNS mets

• Histologically or cytologicall confirmed patients with advanced solid tumors
• Must have documented Globo H score of at least 100 from a qualified laboratory IHC assay
• Must have been treated with established standard-f-care therapy or physicians have determined that such established therapy is not sufficiently efficacious or patients have declined to received standard-of-care therapy
• ECOG PS 0-1
• Measurable disease
• Adequate organ function
• No known untreated CNS mets
• No significant clinical cardiac abnormality