• Histologically confirmed unresectable locally advanced or metastatic urothelial carcinoma. Subjects with urothelial carcinoma with squamous differentiation or mixed cell types are eligible provided that urothelial is the dominant histology.  Any element of neuroendocrine or small cell histology are excluded
• Must have received prior treatment with a immune checkpoint inhibitor in the locally advanced or metastatic setting
• Must have received prior treatment with platinum containing chemotherapy defined as received in the adjuvant/neoadjuvant setting with recurrent or progressive disease within 12 months of completion OR received treatment with platinum in the locally advanced or metastatic setting
• Must have had progression or recurrence during or following recept of most recent therapy
• ECOG PS 0-1
• Dose escalation cohorts must have available archival or fresh biopsy sample prior to study entry.  Others must have tumor accfessible for sequential biopsy and be willing to provide fresh pre-treatment and on-study tumor tissue biopsies
• No pre-existing sensory or motor neuropathy Grade >/= 2
• No symptomatic or unctrolled CNS metastases
• No prior treatment with enfortumab vedotin
• No prior treatment with any anti-CD47 or anti-SIRPa agent
• No known uncontrolled HBV/HCV/HIV
• No other malignancy within 3 years
• No active autoimmune disease requiring treatment in last year

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

• Patients must have histologically/pathologically confirmed colon adenocarcinoma (T1-3, N1/N1c) with R0 resection accordingly to AJCC 8th edition criteria. NOTE: Patients with pathologic stages II or IIIC colon adenocarcinoma with R0 resection who have a commercially obtained Signatera™ ctDNA+ve assay result post-operatively meeting all timelines and eligibility requirements otherwise, are eligible for enrollment and inclusion in Cohort B.
• No radiographic evidence of overt metastatic disease
• Distal extent of tumor must be greater than or equal to 12cm from the anal verge
• Must have had curative resection (en bloc)
• Resected tumor specimen and blood must have central testing for ctDNA useing the Signatera assay
• Must be microsatellite stable or have intact mismatch proteins
• No more than 60 days post surgery to study entry
• No other invasive malignancy within 5 years
• No known active cardiac disease

• Age 16 or greater
• Histologically or cytologically confirmed Stage IV CRC
• Must contain a BRAF V600E mutation on local (FMI or Caris) or central testing
• No prior systemic treatment in metastatic setting
• Prior adjuvant or neoadjuvant therapy is OK only if relapse/metastasis is 6 months or greater from the end of the neo/adjuvant treatment
• No history of acute or chronic pancreatitis
• No symptomatic brain mets
• Must have measurable disease

• Locally confirmed microsatellite instability-high/ deficient mismatch repair (MSI-H/dMMR) stage IV colorectal carcinoma
• Locally confirmed BRAF V600E mutation in tumor tissue or blood
• ECOG PS 0 or 1
• Have not received prior systemic regimens for metastatic disease.
• Measurable disease
• RAS wt
• No known active central nervous system metastases and/or carcinomatous meningitis; leptomeningeal disease
• No immunodeficiency or active autoimmune disease requiring systemic treatment in the past 2 years
• No presence of acute or chronic pancreatitis
• No previous treatment with any selective BRAF inhibitor (eg, encorafenib, dabrafenib, vemurafenib, XL281/BMS-908662) or any epidermal growth factor receptor (EGFR) inhibitor (eg, cetuximab, panitumumab).
• No previous treatment with an immune checkpoint inhibitor (eg, anti-programmed cell death [PD-1], anti-PD-L1 or anti-PD-L2 agent); or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (eg, CTLA-4, OX 40, CD137).

• Histologically confirmed EC including: endometrioid, serous, undifferentiated, and carcinomsarcoma
• TP53 WT assessed by NGS via central vendor
• Completed a single line, at least 12 weeks, of platinum-based therapy (not including adjuvant or neoadjuvant tx for Stage 1-II disease) adn achieved confirmed PR or CR by RECIST.
• If Primary Stage IV, may have had surgery or not. If surgery, must have had R0 or R1 resection
• Must be able to initiate study drug 3-8 weeks following completion of final dose of chemo
• ECOG PS 0-1
• No uterine sarcoma
• No concurrent systemic steroid therapy above 10mg prednisone or equivalent
• No previous treatment with an XPO1 inhibitor
• No active brain mets

• Unresectable, locally advanced, or metastatic gastric or gastroesophageal junction adenocarcinoma
• Fibroblast growth factor receptor 2b (FGFR2b) overexpression positive by centrally performed IHC testing
• No prior therapy for metastatic or unresectable disease except for up to 1 dose FOLFOX with or withouy nivolumab. Prior adjuvant therapy allowed as long as completed longer than 6 months prior
• ECOG PS 0-1
• Measurable or non-measurable disease allowed
• No symptomatic CNS mets
• No corneal abnormalities
• No known HER2 positive status
• No peripheral sensory neuropathy grade 2 or higher

• Histologic confirmed diagnosis of GBM per WHO classification criteria
• Age >or= 22
• Recovered from maximal debulking surgery, if applicable (gross total resection, partial resection, and biopsy-only patients are all acceptable)
• Planned treatment with RT-TMZ followed by TTFields and maintenance TMZ
• KPS >or= 70%
• Must have stable or decreasing steroid use
• Concomitant RT with TMZ planned to start no later than 8 weeks post surgery
• Able to undergo MRI with contrast of brain
• No infratentorial or leptomeningeal disease
• No plts <100, ANC <1.5, AST/ALT > 3xULN, Tbili >1.5x ULN, creatinine >1.7
• No institutionalized patients
• No active implanted medical devices, bullet fragments, or other skull defects

• Squamous cell cancer (including papillary squamous cell and basaloid, but not neuroendocrine) of the oropharynx.
• Measurable disease at primary site or nodal stations
• P16-positive based on local IHC staining
  • If p16 equivocal, HPV DNA is acceptable
• Clinical stage T1-2N1M0 or T3N0-1M0. Diagnostic w/u negative for mets
• Lifetime cumulative history of smoking cannot exceed 10 years
• ECOG PS 0-1
• No oral cavity, hypopharynx, or larynx cancer
• No supraclavicular nodes
• No prior XRT for H+N CA, no prior PD-1 therapy
•  

• Must have one of the following
  • Disease progression after platinum based chemotherapy (with or without PD-1 therapy) for recurrent or metastatic disease
  • Refractory disease defined as progression or recurrence within six months after the last dose of platinum based chemoradiation for locally advanced disease
• No more than two prior lines of treatment
• ECOG PS 0-1
• Able to swallow and retain oral medications
• No prior taxane
• No symptomatic CNS disease
• No known HIV
• No symptomatic CHF or LVEF <50%
• No active psychiatric illness

• SCCHN
• Must have received prior PD-1 or PD-L1 inhibitor
• ECOG PS 0-1
• No known autoimmune disease
• No need for steroids or other immunsuppressive medicine
• No interstitual lung disease or pulmonary fibrosis

• Histologically confirmed diagnosis of metastatic or unresectable NSCLC (squamous or nonsquamous) not a candidate for definitive therapy
• KRAS G12C mutation
• Known PD-L1 status (can enroll regardless of level)
• 1st line- no prior treatment for metastatic NSCLC
  • OK to have had radiosensitizing chemo >1 year prior
• ECOG PS 0-1
• Measurable disease
• No active CNS mets
• No XRT to the lungs within 6 months prior to first dose of study treatment
• No known autimmune disease

• Eligibility for induction phase (Carbo etoposide)
  • Histologically or cytologically confirmed extensive stage SCLC
  • ECOG PS 0-1
  • No prior therapy for extensive stage disease
  • At least 6 monmths since chemo or XRT for earlier stage disease
  • Measurable disease
  • Negative for HIV and no known HBV/HCV
  • No CNS mets
  • No other malignancies within 5 years
• Eligibilty for maintenance phase (atezolizumab +/- lurbinectidin)
  • Ongoing response or stable disease after 4 cycles of induction therapy
  • All toxicities attributed to prior induction therapy resolved to Grade
  • Not receiving consolidative chest radiation
  • Not receiving antibiotics at the time of randomization

• Diagnosis of relpased or regractory diffuse large B-Cell lymphoma or R/R follicular lymphoma with documented CD20+ mature B-cell neoplasm according to WHO classification 2016 or 2008
  • Can include pts with double-hit or triple-hit DLBCL
  • Must have been previously treated wioth at least 2 prior systemic antineoplastic therapies including at least 1 anti-CD20 monoclonal antibody-containing therapy
  • Measurable disease
  • ECOG PS 0-2
  • No CNS involvement 

• Histologically or cytologically confirmed melanoma
• Clinically detectable and resectable Stage IIIB, IIIC, or IIID melanoma
• Has been untreated for the melanoma with the exception that primary lesion may have been resected or irradiated
• No known CNS mets
• No ocular or mucosal melanoma
• No known HIV/HBV/HCV
• No active autoimmune disease requiring therapy in past 2 years
• Must not have received prior oncolytic viruses

• Must have been diagnosed with either Stage IIIA (>1mm tumor in lymph node), Stage IIIB, Stage IIIC, Stage IIID, or Stage IV melanoma and have histologically confirmed melanoma that is completely surgically resected with negative margins
• ECOG PS 0-1
• Resection must have been performed within 12 weeks prior to randomization
• Tumor tissue available
• No history of uveal melanoma
• No untreated CNS metastases

• Surgically resected and histologically or pathologically confirmed melanoma
• Must be Stage IIB, IIC, III, or IV cutaneous melanoma
• No prior systemic therapy for melanoma
• No more than 12 weeks between final surgical resection and randomization
• HBV/HCV/HIV are allowed if well controlled
• No ocular, conjunctival, or mucosal melanoma
• No diagnosis of immunodeficiency or receiving chronic systemic steroids >10mg prednisone or equivalent
• No active autoimmune disease
• No active CNS disease
• No other malignancy that required active treatment in last 3 years

• Has unresectable Stage III or Stage IV melanoma, not amenable to local therapy
• Has been untreated for advanced disease
• No ocular or mucosal melanoma
• No known additional malignancy that is progressing or requires active treatment within the past two years
• No known CNS metastatses
• No active autoimmune disease requiring systemic treatment in the past two years
• No known HIV/HBV/HCV
• Adequate organ function

• Has unresectable Stage III or Stage IV melanoma not amenable to curative therapy
• Has progressed on treatment with an anti-PD1/L1 monoclonal antibody administered either as monotherapy or in combination with other therapies
• Hsa not received more than 3 lines of therapy
• No known additional malignancy with past 2 years
• No known CNS metastases
• No active autoimmune disease requiring systemic treatment in the last 2 years
• No known HIV/HBV/HCV

• Stage IIIB-IV melanoma, following progression on PD-1 containing regimen
• ECOG PS 0-1
• At least one injectable tumor (visceral or deep nodal lesions may be injectable)
• Measruable disease by RECIST 1.1
• No prior oncolytic virus therapy (no prior T-VEC)
• No active CNS disease
• No history of major autoimmune disease
• No known HBV, HCV, or HIV
• No need for steroids >20mg prednisone daily or equivalent
• No need for chronic use of anti-virals (e.g. acyclovir)
• No prior malignancy in past 3 years except locally curable cancers such as non-melanoma skin cancer, or carcinoma in situ.

• Subject has documented diagnosis of MM and measurable disease, defined as any of the following:
  • M-protein ≥ 0.5 g/dL by serum protein electrophoresis (sPEP) or 
  • M-protein ≥ 200 mg/24-hour urine collection by urine protein electrophoresis (uPEP) or
  • For subjects without measurable disease in sPEP or uPEP: serum free light chain (sFLC) levels > 100 mg/L (10 mg/dL) involved light chain and an abnormal kappa/lambda FLC ratio.
• Subject has received 1 to 3 prior lines of antimyeloma therapy. (Note: One line can contain several phases [eg, induction, (with or without) hematopoietic stem cell transplant, (with or without) consolidation, and/or (with or without) maintenance therapy
• Must have received prior treatment with a lenalidomide-containing regimen
• Must have achieved minimal response or better to at least 1 prior antimyeloma therapy
• Must have documented disease progression during or after their last antimyeloma therapy
• ECOG PS 0-2
• May not have had progression during treatment or within 60 days of the last dose of a proteasome inhibitor
• If prior treatment with a bortezomib containing regimen, must have had a best response of minimal response or better and the subject could not have discontinued bortezomib due to toxicity
• No prior allo transplant
• No plasma cell leukemia, Waldenstrom's macroglobulinemia, POEMS syndrome or clinically significant light-chain amyloidosis
• No known CNS involvement of myeloma
• No grade 2 or higher peripheral neuropathy
• No other malignancy within 5 years
•  

• High grade (grade 3) serous, epithelial ovarian, primary peritoneal, or fallopian tube carcinoma
• Platinum resistant disease (defined progression <6 monhths from completion of a platinum containing therapy)
• Measurable disease
• ECOG PS 0-1
• Received at least 1 but < or = 3 lines of prior systemic anticancer therapy.
• Prior treatment with bevacizumab is required
• No low-grade endometrioid, clear cell, mucinous, or sarcomatous histology, or mixed tumors containing any of these histologies
• No primary platinnum refractory disease
• No requirement of treatment with chronic or frequent use of oral steroids
• No concurrent treatment with mifepristone or other GR modulators
• No peripheral neuropathy
• No symptomatic CNS disease

• Histologically or cytologically confirmed adenocarcinoma of the prostate without small cell features
• Must provide a core or excisional biopsy from soft tissue or bone biopsy from soft tissue within 1 year of screening and after developing mCRPC
• Has prostate cancer progression within 6 months prior to screening by means of one of the following: PSA progression as defined by a minimum of 2 rising PSA levels with an interval of ≥1 week between each assessment where the PSA value at screening should be ≥2 ng/mL; radiographic disease progression in soft tissue based on RECIST criteria with or without PSA progression; radiographic disease progression in bone defined as the appearance of 2 or more new bone lesions on bone scan with or without PSA progression.
• Ongoing androgen deprivation with serum testoterone <50ng/dL
• Stable doses of bone resorptive therapy
• ECOG PS 0-1
• Has previously received docetaxel for mCRPC. Prior treatment with one other chemotherapy is allowed. Up to 2 second-generation hormonal agents (eg. abiraterone, enzalutimide, etc.) are allowed. Prior ketoconazole is allowed. Docetaxel used more than once is considered as 1 therapy.
• No diagnosis of immunodeficiency or systemic steroid therapy
• No autoimmune disease within last 2 years
• No known HBV/HCV/HIV
• No known active CNS mets
• No superscan bone scan
• No active cardiovascular disease
• No gastrointestinal malabsortion
• No active hemoptysis

• Has treated or de novo neuroendocrine  metastatic prostate cancer defined by ≥1% neuroendocrine cells that are located in discrete regions of a recent biopsy specimen from a metastasis as determined by the investigational site and confirmed by central histology review prior to enrollment
• Must provide a core or excisional biopsy from soft tissue or a bone biopsy. For de novo metastatic neuroendocrine prostate participants, biopsies must be performed within 1 year of screening. Participants with bone metastasis only must provide an archival tumor tissue specimen.
• Has prostate cancer progression within 6 months prior to screening, as determined by the investigator, by means of one of the following: PSA progression as defined by a minimum of 2 rising PSA levels with an interval of ≥1 week between each assessment where the PSA value at screening should be ≥2 ng/mL; radiographic disease progression in soft tissue based on RECIST criteria with or without PSA progression; radiographic disease progression in bone defined as the appearance of 2 or more new bone lesions on bone scan with or without PSA progression. Participants with de novo neuroendocrine prostate cancer will not need to provide evidence of progression within 6 months
• Has ongoing androgen deprivation with serum testosterone <50 ng/dL
• Patients receiving bone resorptive therapy must be on stable doses
• ECOG PS 0-1
• Participants must have received prior treatment with androgen deprivation therapy (ADT) for metastatic disease. Participants must also have received prior treatment with an NHA (eg, abiraterone acetate, apalutamide, etc.) or docetaxel for mHSPC or mCRPC. Prior treatment with up to a total of 2 chemotherapies for mCRPC is allowed, as well as up to 2 second-generation hormonal manipulations for mCRPC. Participants who received prior ketoconazole for metastatic disease may be enrolled. Docetaxel for mHSPC is allowed in addition to docetaxel for mCRPC. If docetaxel chemotherapy is used more than once (eg, once for metastatic hormone-sensitive and once for mCRPC), it will be considered as 1 therapy. A limited number of de novo patients may enroll after consultation with the sponsor.
• No prior treatment with Radium or Lutitium
• No immunodeficiency or systemic steroids
• No autoimmune disease within the last 2 years
• No known HIV/HBV/HCV
• No known CNS mets
• No superscan bone scan
• No active cardiovascular disease
• No active hemoptysis

• Has histologically- or cytologically-confirmed adenocarcinoma of the prostate without small cell histology
• Must provide a core or excisional biopsy from soft tissue or bone biopsy within 1 year of screening and after developing mCRPC. Participants with bone metastasis only must provide an archival tumor tissue specimen.
• Has prostate cancer progression within 6 months prior to screening, as determined by the investigator, by means of one of the following: PSA progression as defined by a minimum of 2 rising PSA levels with an interval of ≥1 week between each assessment where the PSA value at screening should be ≥2 ng/mL; radiographic disease progression in soft tissue based on RECIST criteria with or without PSA progression; radiographic disease progression in bone defined as the appearance of 2 or more new bone lesions on bone scan with or without PSA progression. 
• Has ongoing androgen deprivation with serum testosterone <50 ng/dL (<2.0 nM)
• Patients receiving bone resorptive therapy must be on stable doses
• ECOG PS 0-1
• Has received docetaxel for mCRPC. Prior treatment with 1 other chemotherapy for mCRPC is allowed. Up to 2 second-generation hormonal manipulations (eg, abiraterone acetate, enzalutamide, apalutamide, darolutamide or other next-generation hormonal agents [NHA]) are allowed. Participants who received prior ketoconazole for metastatic disease may be enrolled. If docetaxel chemotherapy is used more than once (eg, once for metastatic hormone-sensitive and once for mCRPC), it will be considered as 1 therapy. Prior docetaxel for metastatic hormone-sensitive prostate cancer (mHSPC) is allowed if ≥4 weeks have elapsed from the last dose of docetaxel prior to Day 1 of Cycle 1
• No immunodeficiency or systemic steroid use
• No active autoimmune disease within 2 years
• No known HIV/HBV/HCV
• No known CNS mets
• No superscan bone scan
• No symptomatic ascites or pleural effusion

• Has  treated or de novo metastatic neuroendocrine prostate cancer defined by ≥1% neuroendocrine cells that are located in discrete regions of a recent biopsy specimen from a metastasis as determined by the investigational site and confirmed by central histology review prior to enrollment
• Must provide a core or excisional biopsy from soft tissue or a bone biopsy. For de novo metastatic neuroendocrine prostate participants, biopsies must be performed within 1 year of screening. Participants with bone metastasis only must provide an archival tumor tissue specimen.
• Has prostate cancer progression within 6 months prior to screening, as determined by the investigator, by means of one of the following: PSA progression as defined by a minimum of 2 rising PSA levels with an interval of ≥1 week between each assessment where the PSA value at screening should be ≥2 ng/mL; radiographic disease progression in soft tissue based on RECIST criteria with or without PSA progression; radiographic disease progression in bone defined as the appearance of 2 or more new bone lesions on bone scan with or without PSA progression. Participants with de novo neuroendocrine prostate cancer will not need to provide evidence of progression within 6 months
• Has ongoing androgen deprivation with serum testosterone <50 ng/dL 
• Patients receiving bone resorptive therapy must be on stable doses
• ECOG PS 0-1
• Participants must have received prior treatment with androgen deprivation therapy (ADT) for metastatic disease. Participants must also have received prior treatment with an NHA (eg, abiraterone acetate, apalutamide, darolutamide, enzalutamide, or other NHA) or docetaxel for mHSPC or mCRPC. Prior treatment with up to a total of 2 chemotherapies for mCRPC is allowed, as well as up to 2 second-generation hormonal manipulations for mCRPC. Participants who received prior ketoconazole for metastatic disease may be enrolled. Docetaxel for mHSPC is allowed in addition to docetaxel for mCRPC. If docetaxel chemotherapy is used more than once (eg, once for metastatic hormone-sensitive and once for mCRPC), it will be considered as 1 therapy. A limited number of de novo patients will be allowed to enroll based on consultation with the study team.
• No immunodeficiency or systemic steroid use
• No autoimmune disease within last 2 years
• No known HIV/HBV/HCV
• No known active CNS mets
• No superscan bone scan
• No symptomatic ascited or pleural effusion
• No prior treatment with platinum containing compounds for prostate cancer

• Has treated or de novo neuroendocreine metastatic prostate cancer defined by ≥1% neuroendocrine cells that are located in discrete regions of a recent biopsy specimen from a metastasis as determined by the investigational site and confirmed by central histology review prior to enrollment
• Must provide a core or excisional biopsy from soft tissue or a bone biopsy. For de novo metastatic neuroendocrine prostate participants, biopsies must be performed within 1 year of screening. Participants with bone metastasis only must provide an archival tumor tissue specimen.
• Has prostate cancer progression within 6 months prior to screening, as determined by the investigator, by means of one of the following: PSA progression as defined by a minimum of 2 rising PSA levels with an interval of ≥1 week between each assessment where the PSA value at screening should be ≥2 ng/mL; radiographic disease progression in soft tissue based on Response Evaluation Criteria In Solid Tumors Version 1.1 criteria with or without PSA progression; radiographic disease progression in bone defined as the appearance of 2 or more new bone lesions on bone scan with or without PSA progression. Participants with de novo neuroendocrine prostate cancer will not need to provide evidence of progression within 6 months
• Has ongoing androgen deprivation with serum testosterone <50 ng/dL
• Patients receiving bone resorptive therapy must be on stable doses
• ECOG PS 0-1
• Participants must have received prior treatment with androgen deprivation therapy (ADT) for metastatic disease. Participants must also have received prior treatment with an NHA (eg, abiraterone acetate, apalutamide, darolutamide, enzalutamide, or other NHA) or docetaxel for mHSPC or mCRPC. Prior treatment with up to a total of 2 chemotherapies for mCRPC is allowed, as well as up to 2 second-generation hormonal manipulations for mCRPC. Participants who received prior ketoconazole for metastatic disease may be enrolled. Docetaxel for mHSPC is allowed in addition to docetaxel for mCRPC. If docetaxel chemotherapy is used more than once (eg, once for metastatic hormone-sensitive and once for mCRPC), it will be considered as 1 therapy. A limited number of de novo neuroendrcine CRPC patients will be allowed to enroll with consultation with the study team.
• No immunodeficiency or systemic steroid use
• No autoimmune disease within last 2 years
• No known HIV/HBV/HCV
• No known CNS mets
• No superscan bone scan
• No symptomatic ascites or pleural effusion

• Clinical stage II or III rectal adenoCA defined as T4N0 or any T with node positive disease. T3N0 requiring APR or coloanal astamosis is also allowed
• No prior systemic non-surgical treatment for rectal cancer within last 5 years
• ECOG PS 0-2
• No upper rectal tumors (>12 cm above anal verge)
• No recurrent rectal cancer
• No known MMR deficient cancer

Inclusion Criteria:

• Has a histologically or cytologically confirmed diagnosis of RCC with clear cell component per American Joint Committee on Cancer (AJCC) (8th Edition), with or without sarcomatoid features

• Has intermediate-high risk, high risk, or M1 no evidence of disease (NED) RCC as defined by the following pathological tumor-node metastasis and tumor grading:

  1. Intermediate-high risk RCC: pT2, Grade 4 or sarcomatoid, N0, M0; pT3, any grade, N0, M0
  2. High risk RCC: pT4, any Grade N0, M0; pT any stage, any Grade, N+, M0
  3. M1 NED RCC participants who present not only with the primary kidney tumor but also solid, isolated, soft tissue metastases that can be completely resected at one of the following: the time of nephrectomy (synchronous) or, ≤2 years from nephrectomy (metachronous)
• Has undergone complete resection of the primary tumor (partial or radical nephrectomy) and complete resection of solid, isolated, soft tissue metastatic lesion(s) in M1 NED participants
• Must have undergone a nephrectomy and/or metastasectomy ≤12 weeks prior to randomization
• ECOG PS 0-1
• Must not have a pulse oximeter reading <92% at rest, requires intermittent supplemental oxygen, or requires chronic supplemental oxygen
• No clinically significant cardiovascular disease within 6 months from first dose of study intervention
• No preexisting brain or bone metastatic lesions
• No prior systemic therapy for RCC
• No prior radiotherapy for RCC
• No diagnosis of immunodeficiency or receiving chronic systemic steroid therapy
• No known additional malignancy (other than RCC treated with nephrectomy and/or metastasectomy) that is progressing or has required active treatment within the past 3 years
• No active autoimmune disease that has required systemic treatment in past 2 years (i.e., with use of disease modifying agents, corticosteroids, or immunosuppressive drugs); replacement therapy is allowed
• No history of (noninfectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease
• No known HIV/HBV/HCV

• Patients with recurrent cutaneous SCC histologically confirmed who have failed at least first line standard of care therapy who are not indicated for surgery and standard radiation therapy, or non alpha radiation brachytherapy technologies, and for whom no curative systemic treatment is available
• Histopathological confirmation following previous treatment
• Measurable disease
• One single lesion
• Tumor size </= 7cm
• Targeted lesion must be technically amenable for complete coverage (including margins) by the DaRT seeds.Targets will be deemed technically amenable for complete coverage if there are entry and exit vectors for placement that are not hindered by bone or major vessels or other vital organs (eg. eye)
• ECOG PS 0-2
• No distant or nodal metastatic disease
• No T4 disease or perineural spread
• No previously untreated disease indicated for surgery or radiation
• No mucosal, vulvar, anal, or penile SCC
• No systemic immunosuppresive therapy
• No keratoacanthoma histology
• No clinically significant cardiovascular disease

• Diagnosis of locally advanced or metastatic non-melanoma skin cancer not considered treatable by surgery. Could include;
  • Basal cell carcinoma,
  • Cutaneous squamous cell carcinoma,
  • Merkel cell carcinoma
  • Angiosarcoma of the skin
  • Eccrine carcinoma
  • high grade dermatofibroma protuberans
  • CTCL is NOT allowed
• Must have exhausted or refused currently available therapy
• ECOG PS 0-1
• At least one injectable tumor (visceral or deep nodal lesions may be injectable)
• Measurable disease by RECIST 1.1
• No prior oncolytic virus therapy (no prior T-VEC)
• No active CNS disease
• No history of major autoimmune disease
• No known HBV, HCV, or HIV
• No need for steroids >20mg prednisone daily or equivalent
• No need for chronic use of anti-virals (e.g. acyclovir)
• No prior malignancy in past 3 years except locally curable cancers such as non-melanoma skin cancer, or carcinoma in situ.

Inclusion Criteria:

• ROS1 fusion positive solid malignancies (except for NSCLC)
• Histologically or cytologically confirmed diagnosis of advanced and unresectable or metastatic solid malignancy
• Measurable disease as defined by Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST v1.1), Response Assessment in Neuro-Oncology (RANO) criteria, or International Neuroblastoma Response Criteria (INRC)
• Performance status as follows: Participantss aged >= 18 years: Eastern Cooperative Oncology Group (ECOG) Performance Status 0-2; Participantss aged 16 to < 18 years: Karnofsky score >= 50%; Participants aged < 16 years: Lansky score >= 50%
• For participants aged >= 18 and <18 years: adequate hematologic and end-organ function
• Disease progression on prior treatment, or previously untreated disease with no available acceptable treatment
• Adequate recovery from most recent systemic or local treatment for cancer
• Life expectancy >= 8 weeks
• Ability to comply with the study protocol, in the investigator's judgment
• For female participants of childbearing potential: Negative serum pregnancy test <= 14 days prior to initiating study treatment; agreement to remain abstinent or use single or combined contraception methods that result in a failure rate of < 1% per year for the period defined in the cohort-specific inclusion criteria; and agreement to refrain from donating eggs during the same period
• For male participants: Willingness to remain abstinent or use acceptable methods of contraception as defined in the cohort-specific inclusion criteria
• In addition to the general inclusion criteria above, participants must meet all of the cohort-specific inclusion criteria for the respective cohort

Inclusion Criteria:

• Any Solid Malignancy with NTRK1/2/3 Fusion Positivity
• Histologically or cytologically confirmed diagnosis of advanced and unresectable or metastatic solid malignancy
• Measurable disease as defined by Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST v1.1), Response Assessment in Neuro-Oncology (RANO) criteria, or International Neuroblastoma Response Criteria (INRC)
• Performance status as follows: Participantss aged >= 18 years: Eastern Cooperative Oncology Group (ECOG) Performance Status 0-2; Participantss aged 16 to < 18 years: Karnofsky score >= 50%; Participants aged < 16 years: Lansky score >= 50%
• For participants aged >= 18 and <18 years: adequate hematologic and end-organ function
• Disease progression on prior treatment, or previously untreated disease with no available acceptable treatment
• Adequate recovery from most recent systemic or local treatment for cancer
• Life expectancy >= 8 weeks
• Ability to comply with the study protocol, in the investigator's judgment
• For female participants of childbearing potential: Negative serum pregnancy test <= 14 days prior to initiating study treatment; agreement to remain abstinent or use single or combined contraception methods that result in a failure rate of < 1% per year for the period defined in the cohort-specific inclusion criteria; and agreement to refrain from donating eggs during the same period
• For male participants: Willingness to remain abstinent or use acceptable methods of contraception as defined in the cohort-specific inclusion criteria
• In addition to the general inclusion criteria above, participants must meet all of the cohort-specific inclusion criteria for the respective cohort

Inclusion Criteria:

• Patients with any ALK fusion positive solid malignancy except NSCLC
• Histologically or cytologically confirmed diagnosis of advanced and unresectable or metastatic solid malignancy
• Measurable disease as defined by Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST v1.1), Response Assessment in Neuro-Oncology (RANO) criteria, or International Neuroblastoma Response Criteria (INRC)
• Performance status as follows: Participantss aged >= 18 years: Eastern Cooperative Oncology Group (ECOG) Performance Status 0-2; Participantss aged 16 to < 18 years: Karnofsky score >= 50%; Participants aged < 16 years: Lansky score >= 50%
• For participants aged >= 18 and <18 years: adequate hematologic and end-organ function
• Disease progression on prior treatment, or previously untreated disease with no available acceptable treatment
• Adequate recovery from most recent systemic or local treatment for cancer
• Life expectancy >= 8 weeks
• Ability to comply with the study protocol, in the investigator's judgment
• For female participants of childbearing potential: Negative serum pregnancy test <= 14 days prior to initiating study treatment; agreement to remain abstinent or use single or combined contraception methods that result in a failure rate of < 1% per year for the period defined in the cohort-specific inclusion criteria; and agreement to refrain from donating eggs during the same period
• For male participants: Willingness to remain abstinent or use acceptable methods of contraception as defined in the cohort-specific inclusion criteria
• In addition to the general inclusion criteria above, participants must meet all of the cohort-specific inclusion criteria for the respective cohort

Inclusion Criteria:

• Patients with at metastatic or advanced solid tumors with at least 2 PIK3CA mutations
• Histologically or cytologically confirmed diagnosis of advanced and unresectable or metastatic solid malignancy
• Measurable disease as defined by Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST v1.1), Response Assessment in Neuro-Oncology (RANO) criteria, or International Neuroblastoma Response Criteria (INRC)
• Performance status as follows: Participantss aged >= 18 years: Eastern Cooperative Oncology Group (ECOG) Performance Status 0-2; Participantss aged 16 to < 18 years: Karnofsky score >= 50%; Participants aged < 16 years: Lansky score >= 50%
• For participants aged >= 18 and <18 years: adequate hematologic and end-organ function
• Disease progression on prior treatment, or previously untreated disease with no available acceptable treatment
• Adequate recovery from most recent systemic or local treatment for cancer
• Life expectancy >= 8 weeks
• Ability to comply with the study protocol, in the investigator's judgment
• For female participants of childbearing potential: Negative serum pregnancy test <= 14 days prior to initiating study treatment; agreement to remain abstinent or use single or combined contraception methods that result in a failure rate of < 1% per year for the period defined in the cohort-specific inclusion criteria; and agreement to refrain from donating eggs during the same period
• For male participants: Willingness to remain abstinent or use acceptable methods of contraception as defined in the cohort-specific inclusion criteria
• In addition to the general inclusion criteria above, participants must meet all of the cohort-specific inclusion criteria for the respective cohort

Inclusion Criteria:

• Patients with advanced or solid malignancy with BRAF class II mutation or fusion (ARM I)
• Patients with advanced or solid malignancy with BRAF class III mutation (ARM J)
• Histologically or cytologically confirmed diagnosis of advanced and unresectable or metastatic solid malignancy
• Measurable disease as defined by Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST v1.1), Response Assessment in Neuro-Oncology (RANO) criteria, or International Neuroblastoma Response Criteria (INRC)
• Performance status as follows: Participantss aged >= 18 years: Eastern Cooperative Oncology Group (ECOG) Performance Status 0-2; Participantss aged 16 to < 18 years: Karnofsky score >= 50%; Participants aged < 16 years: Lansky score >= 50%
• For participants aged >= 18 and <18 years: adequate hematologic and end-organ function
• Disease progression on prior treatment, or previously untreated disease with no available acceptable treatment
• Adequate recovery from most recent systemic or local treatment for cancer
• Life expectancy >= 8 weeks
• Ability to comply with the study protocol, in the investigator's judgment
• For female participants of childbearing potential: Negative serum pregnancy test <= 14 days prior to initiating study treatment; agreement to remain abstinent or use single or combined contraception methods that result in a failure rate of < 1% per year for the period defined in the cohort-specific inclusion criteria; and agreement to refrain from donating eggs during the same period
• For male participants: Willingness to remain abstinent or use acceptable methods of contraception as defined in the cohort-specific inclusion criteria
• In addition to the general inclusion criteria above, participants must meet all of the cohort-specific inclusion criteria for the respective cohort

Inclusion Criteria:

• Patients with advanced or malignant solid cancers with RET-fusion positive tumors.
• Histologically or cytologically confirmed diagnosis of advanced and unresectable or metastatic solid malignancy
• Measurable disease as defined by Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST v1.1), Response Assessment in Neuro-Oncology (RANO) criteria, or International Neuroblastoma Response Criteria (INRC)
• Performance status as follows: Participantss aged >= 18 years: Eastern Cooperative Oncology Group (ECOG) Performance Status 0-2; Participantss aged 16 to < 18 years: Karnofsky score >= 50%; Participants aged < 16 years: Lansky score >= 50%
• For participants aged >= 18 and <18 years: adequate hematologic and end-organ function
• Disease progression on prior treatment, or previously untreated disease with no available acceptable treatment
• Adequate recovery from most recent systemic or local treatment for cancer
• Life expectancy >= 8 weeks
• Ability to comply with the study protocol, in the investigator's judgment
• For female participants of childbearing potential: Negative serum pregnancy test <= 14 days prior to initiating study treatment; agreement to remain abstinent or use single or combined contraception methods that result in a failure rate of < 1% per year for the period defined in the cohort-specific inclusion criteria; and agreement to refrain from donating eggs during the same period
• For male participants: Willingness to remain abstinent or use acceptable methods of contraception as defined in the cohort-specific inclusion criteria
• In addition to the general inclusion criteria above, participants must meet all of the cohort-specific inclusion criteria for the respective cohort

• 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

1. Metastatic, recurrent, or unresectable solid tumor with a pathogenic, or presumed pathogenic, somatic mutation of one of the following homologous recombination deficiency (HRD) gene mutations:  BRCA1, BRCA2, ATM, RAD51B, RAD51C, RAD54L, RAD51D, FANC/BRIP1, FANCI, FANCL, FANCN(PALB2), BARD1, CHEK1, CHEK2, CDK12, or PPP2R2A.

2. Participant must have an Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 1
3. Participant must be ≥ 18 years of age

4. Participant must have adequate organ function, defined as follows:

   • Absolute neutrophil count ≥ 1,500/µL
   • Platelets ≥ 100,000/µL
   • Hemoglobin ≥ 9 g/dL
   • Serum creatinine ≤ 1.5 x upper limit of normal (ULN) or calculated creatinine clearance ≥ 60mL/min using the Cockcroft-Gault equation
   • Total bilirubin ≤ 1.5 x ULN (≤2.0 in patients with known Gilberts syndrome) OR direct bilirubin ≤ 1 x ULN
   • Aspartate aminotransferase and alanine aminotransferase ≤ 2.5 x ULN unless liver metastases are present, in which case they must be ≤ 5 x ULN
   • International normalized ratio (INR) or prothrombin time (PT) ≤1.5× ULN unless patient is receiving anticoagulant therapy as long as PT or partial thromboplastin (PTT) is within therapeutic range of intended use of anticoagulants. Activated partial thromboplastin time (aPTT) ≤1.5× ULN unless patient is receiving anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use of anticoagulants
5. Female participant has a negative serum pregnancy test within 72 hours prior to taking study treatment if of childbearing potential and agrees to use a highly effective method of contraception from screening through 180 days after the last dose of study treatment, or is of non-childbearing potential. Non-childbearing potential is defined as follows (by other than medical reasons):
   • ≥45 years of age and has not had menses for >1 year
   • Patients who have been amenorrhoeic for <2 years without history of a hysterectomy and oophorectomy must have a follicle stimulating hormone value in the postmenopausal range upon screening evaluation
   • Post-hysterectomy, post-bilateral oophorectomy, or post-tubal ligation. Documented hysterectomy or oophorectomy must be confirmed with medical records of the actual procedure or confirmed by an ultrasound. Tubal ligation must be confirmed with medical records of the actual procedure, otherwise the patient must be willing to use an adequate barrier method throughout the study, starting with the screening visit through 180 days after the last dose of study treatment. See Section 5.4 for a list of acceptable birth control methods. Information must be captured appropriately within the site's source documents. Note: Abstinence is acceptable if this is the established and preferred contraception for the patient.

h. Male participant agrees to use a highly effective method of contraception (see Section 5.4 for a list of acceptable birth control methods) starting with the first dose of study treatment through 180 days after the last dose of study treatment. Note: Abstinence is acceptable if this is the established and preferred contraception for the patient.

j. If an appropriate archival tumor tissue sample is not available, patient is willing to undergo a pre-treatment tumor biopsy.

Exclusion Criteria:

1. Patients with the following malignancies will be excluded:

   • Prostate cancer
   • Ovarian, breast, and pancreatic patients with known germline BRCA1 or BRCA2 mutation
   • Platinum sensitive ovarian cancer (defined as recurrence > 6 months from last platinum agent), unless platinum intolerant.

• 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

• Histologically confirmed metastatic cancer that is approved to be treated with nivolumab or pembrolizumab
• Must not be eligible for curative resection
• Must be positive for at least 1 of the following human leukocyte antigens:
  • HLA-A*02:01
  • HLA-A*02:06
  • HLA-A*24:02
  • HLA-A*03:01
  • HLA-B*15:01
• ECOG PS 0-1
• No known CNS mets
• No known HIV/HBV/HCV

• Renal cell, NSCLC, or SCCHN
• Must have received prior PD-1 or PD-L1 inhibitor
• ECOG PS 0-1
• No known autoimmune disease
• No need for steroids or other immunsuppressive medicine
• No interstitual lung disease or pulmonary fibrosis