• 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

Inclusion Criteria:

1. Patient must have histologically confirmed adenocarcinoma (usual/classic/NOS), squamous cell carcinoma, adenosquamous carcinoma (Including glassy cell)
2. Patient must be FIGO Stage IA2, IBI, IB2 (2018 staging) without evidence of definitive parametrial, vaginal, nodal or distant metastases on exam or imaging. Patients with tumor size less than or equal to 4 cm confirmed on MRI prior to randomization are eligible.
3. Patient must have uterine size <12 cm AND felt to be appropriate for vaginal delivery of the specimen per investigator.
4. Patient must be suitable surgical candidate with preoperative assessments such as labs and EKG performed per institutional standard.
5. Patient must be age 18 years or older.
6. Patient must have ECOG performance status 0-1.
7. Patient must have a negative urine pregnancy test within 30 days of surgery in pre-menopausal women.
8. Patient must have signed an approved informed consent and authorization permitting the release of personal health information.

Exclusion Criteria:

1. Patients with any tumor histology other than those listed above, specifically excluding the following histologies: neuroendocrine, other adenocarcinoma (gastric type, endometrioid, clear cell, serous, signet ring, minimal deviation)
2. Patients with FIGO stage 1A1, IB3, II-IV (2018 staging).
3. Patient with inability to receive an MRI.
4. Patients with a tumor size greater than 4cm or on MRI confirmed prior to randomization are excluded. Patients with definite evidence of vaginal/parametrial involvement on MRI are excluded; if MRI findings are not definitive, then clinical examination must also not reveal parametrial or vaginal extension).
5. Patients with evidence of metastatic disease (imaging or histologically positive lymph nodes).
6. Patients with a history of prior pelvic or abdominal radiotherapy.
7. Patients with a prior malignancy < 5 years from enrollment with the exception of non-melanoma skin cancer.
8. Patients who are unable to withstand prolonged lithotomy or steep trendelenberg.
9. Patient compliance and geographic proximity that do not allow adequate follow-up.
10. Patients with poorly controlled HIV with CD4 counts <500.

• 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.

1. Histologically documented locally advanced or metastatic, unresectable (i.e. surgery morbidity would outweigh potential benefits), progressive or recurrent Dedifferentiated liposarcoma (DDLPS), meeting the criteria for an open study cohort:

   • Cohort A: patient has not received prior systemic therapy for DDLPS in any setting (including adjuvant, neoadjuvant, maintenance, palliative)
   • Cohort B: patient has received any prior systemic therapy for DDLPS in any setting (including adjuvant, neoadjuvant, maintenance, palliative)
2. Written pathology report indicating the diagnosis of DDLPS with positive MDM2 immunohistochemistry or MDM2 amplification as demonstrated by fluorescence in situ hybridisation (FISH) or next-generation sequencing (NGS)
3. Measureable disease
4. ECOG PS 0-1
5. No known mutation in TP53
6. No prior MDM2 inhibitor
7. No prior or concomittant cancers within 2 years except non-melanoma skin cancers, or other treatment curative by local therapy only

• 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.

• 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

• Unresected Stage IIIB, IIIC, or IV melanoma
• No prior therapy for metastatic disease
• At least 6 months from adjuvant therapy
• No clinically active CNS disease
• ECOG PS 0-1
• Measurable (at least 1 lesion >1cm)
• Injectable (total cutaneous/subcut/nodal lesions >1cm in aggregate)
• No prior ipilimumab, PD-1 inhibitors, T-VEC or tumor vaccines
• Previous BRAF or MEK inhibitors allowed if BRAF mutated
• No primary uveal or mucosal melanoma
• No prior intrathoracic XRT

• Histologically documented HER2-positive early breast cancer (EBC) participants, including clinical stage at presentation (based on mammogram or breast MRI assessment): T0-4 (inclusive of inflammatory breast cancer), N1-3, M0 or ≥ T3, N0, M0 as determined by the AJCC staging system, 8th edition

• ECOG PS 0-1
• Adequate organ and bone marrow function
• LVEF ≥ 50% within 28 days before randomization
• FFPE tissue block (2 cores) or 20 freshly-cut, serial tumor slides for HER2 assessment by central lab. If blocks are incomplete or fewer than 20 slides are available, participants may be eligible following discussion with the AstraZeneca Study Physician
• No prior history of invasive breast cancer
• No stage IV breast cancer (determined by AJCC staging system)
• No primary malignancy within 3 years (except resected non-melanoma skin cancer, curatively treated in situ disease) Note: This includes a second current breast primary malignancy (ie, bilateral breast cancer)
• No history of DCIS (except those treated with mastectomy >5 years prior to current diagnosis)
• No history of, or current, ILD/pneumonitis
• No prior systemic therapy for the treatment of breast cancer
• No previous treatment with anthracyclines, cyclophosphamide or taxanes for any malignancy

• Measurable disease

• NSCLC

  • If EGFR mut or ALK positive must have received targeted therapy

  • Must have progressed on both platinum doublet and PD-1 therapy

• Cervical Cancer

  • Persistent, recurrent, or metastatic disease

  • Squamous, adenosquamous or adenocarcinoma histology

  • At least one prior platinum based regimen

  • Confirmation of HPV status

• Bladder cancer

  • Transitional cell carcinoma involving bladder, urethra, ureter, or renal pelvis

  • Minor histologic variants are acceptable

  • Must have progression or recurrence with platinum-containing regimen (in metastatic setting or within 12 months of peri-operative setting)

• SCCHN

  • Must have documented HPV status and subtype

  • Prior treatment with platinum containing regimen with progression or recurrence within 6 months of last dose

  • Cannot be amenable to local therapy with curative intent

• Ovarian

  • Can include epithelial ovarian, primary [peritoneal, or fallopian tube cancer

  • Must have received at least 1 standard systemic therapy for metastatic disease

• HCC

  • Progressive disease to at least one line of therapy or refuse treatment with sorafenib

  • Child-Pugh score of 6 or less. No encephalopathy and Tbili must be <1.5x ULN

  • HBV and HCV must be tested. HBV viral load <100 IU/mL and must be on anti-viral therapy

  • No clinical ascites or variceal bleeding

• No more than 5 prior lines of treatment

• Acceptable lab parameters

• No active CNS metastatases (treated brain mets may be allowed)

• No prior malignancy within 2 years (except for in-situ or non-melanoma skin)

• No autoimmune disease, interstitial lung disease, or requiring immunosuppressive meds

• Metastatic Non-small cell lung cancer
• At least 1 prior line of therapy (2nd line or later)
  • Current arms require patients to be PD-1 naive (this will change)
• Patients with EGFR or ALK alterations must have received targeted therapy
• Measurable disease
• Palliative XRT must be completed at least 2 weeks prior to enrollment
• Biopsies required pre-treatment, on-treatment, and at progression
• No active CNS mets
• No prior malignancy unless CRR achieved at least 2 years prior and no active therapy required
• No systemic therapy within 4 weeks of enrollment
• No active autoimmune disease (except skin disorders, hypothyroidism, T1DM)
• No severe toxicity due to prior immune therapy
• No symptomatic interstitial lung disease
• No known HIV/HBV/HCV

• Females >18 years old

• TNBC defined as ER/PR <1%, HER2 negative

• ECOG PS 0-1

• Labs within standard limits

• No known CNS disease unless adequately treated with XRT or surgery and stable by symptoms for at least 2 months prior

• No other malignancy within 3 years (except non-melanoma skin cancer or in situ cancers)

• No unstable cardiac disease

• No known sensitivity Cremaphor

• Cohort 1- 3rd+ line in African ancestry

  • Must have received prior taxane for metastatic disease but not in most recent treatment

  • Adjuvant therapy counts as therapy if time to recurrence <12 months

• Cohort 2- 1st line in African ancestry- no prior systemic tx for advanced disease

  • Adjuvant therapy only allowd if time to recurrence >12 mo

• Cohort 3- 3rd+ line in non-African ancestry

  • Similar to Cohort 1

• Cohort 4- 1st line in non-African ancestry

  • Similar to cohort 2

• Histologically or cytologically confirmed, locally advanced or metastatic solid malignancy and has exhausted all available standard therapy or not a candidate for standard therapy
• ECOG PS 0-1
• Prior therapy with immune therapy are eligible (except in ovarian cohort)
• In Expansion cohorts patients must either have
  • Advanced epithelial cancer of the ovary, fallopian tube, or peritoneum
  • Advanced MSS endometrial cancer
  • A different malignancy that has high expression of PVRL2
• No active autoimmune disease
• No interstitial lung disease
• No active CNS metastases
• In ovaran cohort, no prior immunotherapy
• No prior therapy with PVRIG inhibitor or anti-TIGIT antibody

• Metastatic or unresectable colorectal cancer.
• KRAS, NRAS, and BRAF wt
• Must have at least 1+ on HER2 testing by central vendor
• Able to provide archival tumor sample
• ECOG PS 0-1
• LVEF > or = 50%
• No surgery or radiation within 4 weeks prior to enrollment
• No MI within 6 months
• No symptomatic CHF or elevated troponins within 4 weeks
• No corneal disease
• No active CNS mets
• No other malignancy within 3 years (except solid tumors curatively treated, in situ dz, or non-melanoma skin cancer)
• No known HIV/HBV/HC

• Intrahepatic cholangiocarcinoma diagnosed by histology
• Unresectable disease
• Less than 50% of liver involved
• No clinically significant extra-hepatic disease (regional nodes 2cm or less are acceptable)
• ECOG PS 0-1
• No history of liver transplantation
• Hepatic vasculature must be compatible with perfusion (prior Whipple is allowed only if anatomy is compatible)
• No prior radiation therapy to the liver (including Y-90, I-131, etc.)
• No prior treatment with percutanous trans-arterial treatment to liver (such as TAE or TACE)
• No Class II or higher CHF
• No prior malignancy within 5 years except in-situ disease or non-melanoma skin cancer
• No active HBV or HCV
• No CNS disease
• Plts >100, Hgb >10 (independent of transfusions), ANC >1500
• Bili <1.5x normal, ALT/AST <5x normal 

• Histologically or cytologically proven ocular melanoma to the liver
• No more than 50% liver parenchema involvement
• Evidence of limited extrahepatic disease allowed as long as life threatening component of disease is in liver
• ECOG PS 0-1
• No Child Class B or C cirrhosis
• No active HBV or HCV
• No active CNS mets

• Metastatic solid tumor
• ALK alterations as follows
  • ALK gene rearrangements by NGS or FISH using Vysis ALK Break Apart FISH Probe Kit
  • Activating non-synonymous mutations in and around the ALK kinase domain by NGS
  • ALK copy number gains by NGS
  • Patients with melanoma and high ALK expression by IHC
• ECOG PS 0-2
• No prior treatment with any ALK inhibitor
• Following tumor types are not eligible
  • Non-small cell lung cancer (NSCLC)
  • Neuroblastoma
  • Childhood tumors

• Histologically or cytologically confirmed advanced unresectable or metastatic solid malignancy
• Positive biomarker results from a CLIA certified lab, either tissue or blood sample
• ROS1 gene fusion positivity
• No non-small lung cancer (NSCLC)
• ECOG PS 0-2
• No symptomatic CNS metastases
• No known HIV/HBV/HCV
• No other malignancy within 3 years of study
• No prior treatment with crizotinib

• Histologically or cytologically confirmed advanced unresectable or metastatic solid malignancy
• Positive biomarker results from a CLIA certified lab, either tissue or blood sample
• No primary CNS malignancy
• One of the following PIK3CA mutations:
  • R88Q
  • ​G106A/D/R/S/V
  • K111N/R/E
  • G118D
  • N345D/H/I/K/S/T/Y
  • C420R
  • E453A/D/G/K/Q/R/V
  • E542A/D/G/K/Q/R/V
  • E545A/D/G/K/L/Q/R/V
  • Q546E/H/L/P/R
  • M1043I/T/V
  • H1047D/I/L/M/P/Q/R/T/Y
  • G1049A/C/D/R/S
  • Others only with study medical monitor approval
• ECOG PS 0-2
• No symptomatic CNS metastases
• No known HIV/HBV/HCV
• No other malignancy within 3 years of study
• No anti-hyperglycemic medication (no treated T2DM or T1DM)

• Histologically or cytologically confirmed advanced unresectable or metastatic solid malignancy
• Positive biomarker results from a CLIA certified lab, either tissue or blood sample
• No breast cancer (breast cancer is excluded)
• Either ERBB2 (HER2) amplification defined as a copy number of 6 or higher via FISH, CISH or DNA NGS assay OR
• Any of the following ERBB2 mutations:
  • 222C; R226S; E265K; D277H; G292R; G309A/E; S310F/Y; C311R/S; E321G; C334S; S418T; A440T; P551L; R552S; S653C; V659E; G660D; R678Q; T733I; L755P/S_T759del; I767M; L768S; D769H/N/Y; Y772_A775dup; A775_G776ins(SVMA/VVMA/YAMA/YVMA/YVMD); G776delins(VC/VV/LC); V777L; G778_P780dup; V779A/L; T798M; L841V; V842I; N857S; T862A; L869R; H878Y; R896C​​G
• ​TMB must be <10 mutations/megabase
• ECOG PS 0-2
• No symptomatic CNS metastases
• No known HIV/HBV/HCV
• No other malignancy within 3 years of study
• No prior treatment with crizotinib
• No active autoimmune disease

• Histologically or cytologically confirmed advanced unresectable or metastatic solid malignancy
• Positive biomarker results from a CLIA certified lab, either tissue or blood sample
• No breast cancer (breast cancer is excluded)
• Either ERBB2 (HER2) amplification defined as a copy number of 6 or higher via FISH, CISH or DNA NGS assay OR
• Any of the following ERBB2 mutations:
  • 222C; R226S; E265K; D277H; G292R; G309A/E; S310F/Y; C311R/S; E321G; C334S; S418T; A440T; P551L; R552S; S653C; V659E; G660D; R678Q; T733I; L755P/S_T759del; I767M; L768S; D769H/N/Y; Y772_A775dup; A775_G776ins(SVMA/VVMA/YAMA/YVMA/YVMD); G776delins(VC/VV/LC); V777L; G778_P780dup; V779A/L; T798M; L841V; V842I; N857S; T862A; L869R; H878Y; R896C​​G
• Must ALSO have one of the following alterations
  • ​TMB > or =10 mutations/megabase
  • MSI-h
  • dMMR (negative IHC for MLH1, MSH2, MSH6, or PMS2_
• ECOG PS 0-2
• No symptomatic CNS metastases
• No known HIV/HBV/HCV
• No other malignancy within 3 years of study
• No prior treatment with crizotinib
• No active autoimmune disease

• Histologically or cytologically confirmed advanced unresectable or metastatic solid malignancy
• Positive biomarker results from a CLIA certified lab, either tissue or blood sample
• Not Non-small cell lung cancer (NO NSCLC)
• ALK gene fusion positivety defined as a 3' AALK fusion with a protein coding 5' gene fusion partner, predicted to be in frame with an intact kinase domain
• ECOG PS 0-2
• No symptomatic CNS metastases
• No known HIV/HBV/HCV
• No other malignancy within 3 years of study
• No prior treatment with crizotinib

• Histologically or cytologically confirmed advanced unresectable or metastatic solid malignancy
• Positive biomarker results from a CLIA certified lab, either tissue or blood sample
• Either PTEN protein loss as determined by a CLIA or equivalently certified immunohistochemistry assay OR
• PTEN loss of function defined as PTEN dominant negative missense mutations or deleterious in-frame and missense mutations affecting protein function
• ECOG PS 0-2
• No symptomatic CNS metastases
• No known HIV/HBV/HCV
• No other malignancy within 3 years of study
• No prior treatment with crizotinib
• No insuline dependent diabetes

• Histologically or cytologically confirmed advanced unresectable or metastatic solid malignancy
• Positive biomarker results from a CLIA certified lab, either tissue or blood sample
• One of the following mutations in AKT:
  • ​AKT 1 : E17K, L52R, or Q79K
  • AKT 2 : E17K
  • AKT 3: E17K, L51R, or Q78K
• ECOG PS 0-2
• No symptomatic CNS metastases
• No known HIV/HBV/HCV
• No other malignancy within 3 years of study
• No prior treatment with crizotinib
• No insulin dependent diabetes

• Histologically or cytologically confirmed advanced unresectable or metastatic solid malignancy
• Positive biomarker results from a CLIA certified lab, either tissue or blood sample
• Tumor mutational burden-high (TMB-H) determined by CLIA opr quivalently certified assay, via tissue or blood
• No prior treatment with anti-PD1 or anti-PD-L1 agents
• ECOG PS 0-2
• No symptomatic CNS metastases
• No known HIV/HBV/HCV
• No other malignancy within 3 years of study
• No prior treatment with crizotinib
• No active autoimmune disease

• Histologically or cytologically confirmed advanced unresectable or metastatic solid malignancy
• Positive biomarker results from a CLIA certified lab, either tissue or blood sample
• Microsatellite instability high (MSI-h) or deficient mismatch repair dMMR
• No prior treatment with anti-PD1 or anti-PD-L1 agents
• ECOG PS 0-2
• No symptomatic CNS metastases
• No known HIV/HBV/HCV
• No other malignancy within 3 years of study
• No prior treatment with crizotinib
• No active autoimmune disease

• Triple-negative adenocarcinoma of the breast either unresectable with curative intent and either locally advanced or metastatic 
  • Most recent biopsy shows ER and PR levels <1%, HER2 <3+
• No prior systemic therapy for metastatic disease
  • No chemotherapy for early disease in last 12 months
• Appropriate candidate for paclitaxel monotherapy if PD-L1 negative (or unknown)
• Appropriate candidate for paclitaxel and atezolizumab if PD-L1 status is positive
• Appropriate lab values
  • CBC: ANC >/= 1500, Hgb >/= 9, plts >/= 100
  • Chem: CrCl >/=50, Alb >/=3, Gluc
  • PT/PTT
• No known HIV/HBV/HCV
• No LVEF <50%
• No requirement for steroids >10mg prednisone or equivalent
• No known CNS disease or spinal cord mets
• No other malignancies in last 5 years except in-situ cervical, non-melanoma skin, or stage I endometrial
• No history of diabetes
• No Grade 2 or higher neuropathy
• No active or history of autoimmune disease

• Histologically or cytologically confirmed TNBC based on the most recent analyzed biopsy or other pathology specimen. TNBC determination as per local institution as per standard guidelines.
• Refractory to or relapsed after at least two prior standard therapeutic regimens for advanced/metastatic TNBC. Prior use of cisplatin (or carboplatin) is permitted.
• Prior exposure to a taxane (paclitaxel or docetaxel)-based regimen in localized or advanced/metastatic setting.
• Eligible for one of the chemotherapy options listed as TPC (Eribulin, capecitabine, gemcitabine, or vinorelbine) as per investigator assessment.
• ECOG performance score of 0 or 1 .
• Measurable disease by CT or MRI as per RECIST 1.1. Bone-only disease is not permitted.
• Patients with treated, non-progressive brain metastases, off high-dose steroids (>20 mg prednisone or equivalent) for at least 4 weeks can be enrolled in the trial.
• No Presence of bulky disease (defined as any single mass > 7 cm in its greatest dimension). Patients with a mass over 7 cm, but otherwise eligible, may be considered for enrollment after discussion and approval with the medical monitor.
• No Patients with active ≥ grade 2 anorexia, nausea or vomiting, and/or signs of intestinal obstruction.
• Patients with non-melanoma skin cancer or carcinoma in situ of the cervix are eligible, while patients with other prior malignancies must have had at least a 3-year disease-free interval.
• No patients known to be HIV positive, hepatitis B positive, or hepatitis C positive.

• Metastatic or surgically unresectable solid tumor
• Measurable disease
• Documentation of an FGFR1-3 gene mutation or translocation
• At least 1 prior line of therapy with progression
• No other therapy available likely to provide clinical benefit
• ECOG PS 0-2
• No other FGFR inhibitors within last 6 months
• No clinically significant corneal or retinal disorder
• No untreated CNS disease (except primary brain cancer)
• No additional malignancy at current time requiring active treatment
• No history of calcium or phosphate disorder or systemic mineral imbalance
• No clinically significant cardiac disease
• No active HBV/HCV
• No known HIV

• Pathologically confirmed Stage II, III, or IVA SCC of oral cavity (excluding lip)
• Disease surgically resectable with curative intent
• Karnofsky PS > or = 70%
• No prior surgery, XRT, or chemo for this disease other than emergency procedure required for supportive care
• No oropharynx tumor
• Heme labs wnl
• PT/PTT <1.4 uln
• Creatinine clearance >50mL/min
• No T4b disease as follows:
  • No involvement of pterygopalatine fossa, maxillary sinus, or facial skin
  • No gross extension of tumor to skull base, no pterygoid plate erosion
  • No sphenoid bone or foramen ovale involvement
  • No direct extension to prevertebral fascia
  • No extension to superior nasopharynx or Eustachian tube
  • No direct extension into neck with deep neck musculature involvement
  • No suspected invasion or encasement of carotid arteries
  • No direct extension of neck disease to involve skin
  • No direct extension to mediastinal structures
  • No regional metastases to supraclavicular neck
• No need for daily immunosuppression (eg. steroids)
• No need for continued systemic anticoagulation
• No symptomatic cardiopulmonary disease
• No prior diagnosis of cancer that has required treatment in last 5 years
• No prior axillary dissection

• Has histologically confirmed cutaneous squamous cell carcinoma (cSCC) as the primary site of malignancy (metastatic skin involvement from another primary cancer or from an unknown primary cancer is not permitted)
• Has histologically confirmed LA cSCC with ≥1 high-risk feature(s) as the primary site of malignancy
• Has undergone complete macroscopic resection of all known cSCC disease with or without microscopic positive margins
• Has completed adjuvant radiotherapy (RT) for LA cSCC with last dose of RT ≥4 weeks and ≤16 weeks from randomization
• Has completed at least 50 Gray (Gy) 25 fractions of adjuvant RT for LA cSCC prior to study entry
• Is disease free as assessed by the investigator with complete radiographic staging assessment ≤28 days from randomization
• Has provided an archival or newly-obtained tumor tissue sample adequate for Programmed Cell Death Ligand 1 (PD-L1) testing as determined by central laboratory testing
• ECOG PS 0-1
• No other histologic type of skin cancer other than invasive cSCC (eg, basal cell carcinoma) that has not been definitively treated with surgery or radiation, Merkel cell carcinoma; or melanoma
• No prior immunotherapy
• Must have recovered from all radiation-related toxicities; must have not required corticosteroids; and has not had radiation pneumonitis
• No active autoimmune disease that has required systemic treatment in past 2 years (ie, with use of disease modifying agents, corticosteroids or immunosuppressive drugs)
• No known HIV/HBV/HCV

• Previously untreated locally advanced non-metastatic TNBC definedn as one of the following TNM classifications:
  • T1c, N1-N2
  • T2, N0-N2
  • T3, N0-N2
  • T4a-d, N0-N2
• ECOG Performance Status 0-1
• No history of other malignancy within 5 years except cervical CIS, or non-melanoma skin cancer
• No prior therapy with anti-PD-1
• No active autoimmune disease that required systemic treatment in past 2 years

Major Inclusion Criteria:

• Previously untreated patients with local biopsy-proven, CD20-positive DLBCL, including one of the following diagnoses by 2016 World Health Organization (WHO) classification of lymphoid neoplasms are eligible:

  1. DLBCL, NOS including GCB type, ABC type
  2. T-cell rich large BCL
  3. Epstein-Barr virus-positive DLBCL, NOS
  4. Anaplastic lymphoma kinase (ALK)-positive large BCL
  5. Human herpes virus-8 (HHV8)-positive DLBCL, NOS
  6. High-grade BCL with MYC and B-cell lymphoma 2 (BCL2) and/or B-cell lymphoma 6 (BCL6) rearrangements (double-hit or triple-hit lymphoma). Please note: Patients must be appropriate candidates for R-CHOP. If an investigator deems a patient with a known double- or triple-hit lymphoma (HGBL) should be treated more aggressively (e.g. dose-adjusted etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin and rituximab [DA-EPOCH-R] or cyclophosphamide, vincristine, doxorubicin and dexamethasone (CVAD) followed by methotrexate and cytarabine [Hyper CVAD]), this patient would not be considered eligible for this study
  7. DLBCL coexistent with either follicular lymphoma (FL) of any grade, gastric MALT lymphoma or non-gastric MALT lymphoma
  8. FL grade 3b
• Availability of archival or freshly collected tumor tissue sent for retrospective central pathology review
• IPI status of 3 to 5 (for patients > 60 years of age) or aaIPI 2 to 3 (for patients ≤ 60 years of age)
• Diagnosis to treatment interval, defined as the time between the date of DLBCL diagnosis (date of the first biopsy specimen containing lymphoma according to the local pathology report) and the start of treatment (C1D1) ≤ 28 days
• ECOG performance status of 0, 1, or 2
• Left ventricular ejection fraction equal to or greater than lower limit of institutional normal range, assessed by local echocardiography or cardiac multi-gated acquisition (MUGA) scan
• Adequate hematologic function
•  

Major Exclusion Criteria:

• Any other histological type of lymphoma according to WHO 2016 classification of lymphoid neoplasms, e.g., primary mediastinal (thymic) large B-cell lymphoma, Burkitt's lymphoma, BCL, unclassifiable, with features intermediate between DLBCL and classical Hodgkin lymphoma (grey-zone lymphoma); primary effusion lymphoma; primary cutaneous DLBCL, leg type; primary DLBCL of the CNS; DLBCL arising from CLL or indolent lymphoma

• History of prior non-hematologic malignancy except for the following:

  1. Malignancy treated with curative intent and with no evidence of active disease present for more than 2 years before screening
  2. Adequately treated lentigo maligna melanoma without current evidence of disease or adequately controlled non-melanomatous skin cancer
  3. Adequately treated carcinoma in situ without current evidence of disease
• Any systemic anti-lymphoma and/or investigational therapy prior to the start of C1D1, except for permitted pre-phase treatment
• Contraindication to any of the individual components of R-CHOP, including prior receipt of anthracyclines
• Known CNS lymphoma involvement
• Known active systemic bacterial, viral, fungal, or other infection at screening, including patients with suspected active or latent tuberculosis (as confirmed by a positive interferon-gamma release assay)
• History or evidence of clinically significant cardiovascular, CNS and/or other systemic disease that in the investigator's opinion would preclude participation in the study or compromise the patient's ability to give informed consent

• Histological diagnosis of squamous cell carcinoma of hte oral cavity, oropharynx, hypopharynx, or larynx
• Eligible for the following stages:
  • For HPV negative disease
    • Stage III, IVA, or IVB
  • For HPV positive disease that is not oropharyngeal
    • Stage III, IVA, or IVB
  • For oropharyngeal HPV positive disease
    • T4 or N2c or N3
• No prior therapy for advanced stage SCCHN, must be eligible for CRT with curative intent
• ECOG PS 0-1
• No prior immunotherapy
• No other malignancy within 5 years except CIS or non-melanoma skin cancer
• No active autoimmune disease
• No severe cardiac issues with preiouvs 6 months
• No known HBV/HCV/HIV

• Postmenopausal women with locally advanced or metastatic breast cancer
• Progression on an aromatase inhibitor (AI) in combination with a CDK4/6 inhibitor
• Demonstrated prior sensitivity to endocrine therapy (recurrence or progression after at least 12 months of treatment in metastatic setting)
• Measurable or non-measurable disease allowed
• One of the following ESR point mutations in cell-free DNA:
  • Y537S, Y537C, D538G, E380Q, S463P, V534E, P535H, L536H, L536P, L536R, L536Q, or Y537N
• May have received up to one chemothearpy regimen in adjuvant or neoadjuvant setting
• ECOG PS 0-1
• No prior use of any SERM with following exception
  • OK if tamoxifen previously used in adjuvant setting with relapse at least 1 year after stopping tamoxifen
• No prior everolimus or PI3K inhibitors
• No presence of CNS disease
• No immediate need for chemotherapy
• No HIV, HBV, HCV
• No prior malignancy in last 5 years except non-melanoma skin cancer or early stage cervical cancer
• No uncontrolled HTN
•  

• Completely resected cutaneous or mucosal melanoma (or unknown primary)

• Stage IIIB, IIIC, or IV (M1a, M1b, or M1c allowed). IIIA allowed only if N2a

• May be eligible either at initial presentation or following resection of recurrence

• Must have undergone wide excision of primary lesion (if present)

• Full lymphadenectomy required for all patients with positive sentinel nodes

• Must be registered within 98 days of final surgery for melanoma

• Must have 5 unstained slides available from original or current tumor

• Must be disease free on scans within 42 days of therapy

• ECOG PS 0-1

• No prior systemic therapy for melanoma

• Prior radiation is allowed

• No brain mets (or history of brain mets)

• No autoimmune disease

• No HBV or HCV

• HIV allowed if CD4 counts >350, viral load <25,000

• Stage 4 or unresectable Stage III melanoma
• Must have had prior treatment with PD-1 or PD-L1 antibody
  • Must have had best response of SD (no PR or CR) on PD-1 or PD-L1 antibody
  • Must have documented disease progression either while on PD-1 or PD-L1 agents or since stopping therapy with these agents with no intervening treatment
• No prior therapy with ipilimumab or other anti-CTLA-4 agents
• No systemic therapy between progression on the PD(L)-1 therapy and registration
• ECOG PS 0-2
• No active CNS disease
  • Patients with history of CNS disease must have been treated with XRT or surgery and have no evidence of CNS progression, and been off steroids for at least 14 days
• No history of autoimmune pneumonitis or colitis that required interruption fo therapy or steroid treatment
• No known HBV or HCV. HIV is allowed if CD4 count is normal.
• No ocular melanoma

• High-grade serous ovarian, fallopian tube, or primary peritoneal cancer who have recurrent disease and have been previously treated with chemotherapy for advanced/metastatic disease and who experience a response lasting at least 6 months to first-line platinum based-therapy but currently considered platinum-resistant
• Up to 4 lines of prior therapy allowed in Phase 1 portion, Up to 3 lines allowed in Phase 2 portion
• May not have progressed while on platinum treatment or within 1 month from completion of platinum-containing regimen in any line
• Measurable disease by RECIST 1.1
• ECOG PS 0-1
• No active CNS mets (stable for at least 4 weeks and resolution of symptoms are allowed)
• No additional malignancy within 5 years (except non-melanoma skin, in situ of  cervix)
• No chronic systemic steroid use
• No active autoimmune disease that has required treatment in last 2 years
• No history of interstitial lung disease
• No history of platelet transfusion for chemo-induced thrombocytopenia
• No prior anti-PD1 or PARP therapy

• TNBC who have been treated with at least 1 prior regimen for advanced/metastatic disease or who relapsed/progressed while on or within 1 month from completion of adjuvant chemotherapy
• Up to 3 lines of prior therapy allowed in Phase 1 portion, Up to 2 lines allowed in Phase 2 portion
• May not have progressed while on platinum treatment or within 1 month from completion of platinum-containing regimen in any line
• Measurable disease by RECIST 1.1
• ECOG PS 0-1
• No active CNS mets (stable for at least 4 weeks and resolution of symptoms are allowed)
• No additional malignancy within 5 years (except non-melanoma skin, in situ of  cervix)
• No chronic systemic steroid use
• No active autoimmune disease that has required treatment in last 2 years
• No history of interstitial lung disease
• No history of platelet transfusion for chemo-induced thrombocytopenia
• No prior anti-PD1 or PARP therapy

• Radiographic findings c/w and biopsy proven NSCLC
• Tumor <4 cm maximum diameter (clinical stage IA and selected IB within 60 days of tx)
• All clinically suspicious mediastinal nodes confirmed negative for cancer histologically
• Tumor verified by thoracic surgeon to be in a location that will permit sublobar resection
• Tumor must be peripheral (not touching any surface within 2 cm of proximal bronchial tree)
• Patient must be at high risk for surgery by meeting 1 major or 2 minor criteria
• No prior malignancy unless disease free for >3 years (except skin CA and in-situ disease)
• No evidence of distant mets
• No prior intrathoracic radiation therapy
• ECOG PS 0-2

• Age >18 years at the time of informed consent
• Histologically confirmed diagnosis of melanoma
• Primary or recurrent Stage IIIB to IV M1c disease for whom surgery is not recommended
• Must have an activating BRAF mutation (limited to V600E or V600K mutations if subject is being treated first line, but can include any well-defined BRAF mutation after failure of prior immunotherapy)
• Measurable disease per RECIST 1.1
• Injectable disease defined as either of the following:
  • At least one injectable cutaneous, subcutaneous, or nodal melanoma lesion >10mm in longest diameter
  • Multiple injectable melanoma lesions that in aggregate have a longest diameter of >10mm
• ECOG Performance Status 0-1
• Any number of prior treatment regimens, provided that subject has not previously received T-VEC or combination of dabrafenib/trametinib
• No clinically active CNS mets
• No active herpes infection or prior complications of herpetic infections
• No known HIV, HBV, HCV
• No known severe autoimmune disease

Unresectable IIIB, IIIC, or IV�disease._
Cutaneous, subcutaneous, or nodal disease amenable to intralesional therapy
ECOG PS 0-1
No primary ocular or mucosal melanoma
No symptomatic autoimmune disease
At least one injectable lesion below the waist

Adenocarcinoma without neuroendocrine or small cell features
PSADT of < /=10 months (3 rising values during ADT, last >2ng/ml)
No evidence of metastasis (pelvic nodes up to 2cm allowed)
Castrate levels of testosterone x 4 weeks prior
Stable doses of bone resorptive agents x4 weeks prior
No anti-androgen x 4 weeks prior (ie. bicalutamide)
No surgery x 4 weeks prior
ECOG PS 0-1
No prior tx with 2nd gen anti-androgens
No hx of seizures
No prior malignancy (except skin and superficial bladder) within 5 years
No cardiac disease within 5years