Clinical Trials

• Histologically confirmed intrahepatic cholangiocarcinoma, extrahepatic cholangiocarcinoma, or gallbladder cancer
• Must have metastatic or unresectable disease and no prior therapy for metastatic disease
• Does not need to be measurable disease
• No ampullary cancer
• No adjuvant therapy within 6 months prior to registration
• ECOG PS 0-1
• No other prior malignancy within 2 years

• Biliary Tract Cancer with 1 prior line of therapy
• Adjuvant therapy only counts as prior line if recurrence within 6 months of completing tx
• Measurable Disease per RECIST 1.1
• Archival tissue or newly obtained tissue available
• ECOG PS 0-1
• BP < or = 150/90 at screening without change in antihypertensives within 1 week before C1D1
• No evidence of malabsorption syndrome
• No evidence of major blood vessel involvement
• No clinically significant hemoptysis or tumor bleeding
• No arterial thromboembolism within 12 months
• No significant CAD within 12 months
• No prior lenvatinib or checkpoint inhibitor therapy
• Prior bevacizumab is allowed
• No proteinuria defined as Uprotein >1g/24 hours
• LVEF must be 55% or greater
• No chronic systemic steroid or immunosuppressive therapy
• No diagnosis of immunodeficiency
• No active CNS metastases
• No tumor involving the brain stem
• No active autoimmune disease that has required treatment within last 2 years
• No known HIV/HBV/HCV

• ECOG PS 0-2
• Histological or cytological evidence of urothelial (transitional cell) carcinoma of the renal pelvis, ureter, bladder or urethra
• Locally advanced/unresectable disease as determined by site attending urologic oncologist or metastatic disease
• Evaluable untreated tumor tissue for biomarker analysis.
• Willing to undergo a core needle or excisional biopsy on-treatment.
• Measurable disease
• No prior chemotherapy for locally advanced or metastatic urothelial cancer
  • Perioperative chemotherapy previously administered in the neoadjuvant and/or adjuvant setting is permitted
• Ineligible for cisplatin as defined by presence of one or more of the following:
  • Impaired renal function [GFR ≥ 30 but ≤ 60 cc/min].
  • Grade ≥ 2 Hearing Loss (hearing loss measured by audiometry of 25 dB at two contiguous frequencies)
  • Grade ≥ 2 peripheral neuropathy
  • ECOG Performance Status of 2
  • Solitary Kidney
• No Active or untreated central nervous system (CNS) metastases. Patients with treated asymptomatic CNS metastases are eligible, provided they meet all of the following criteria:
  • Evaluable or measurable disease outside the CNS
  • No metastases to midbrain, pons, medulla, cerebellum, or within 10 mm of the optic apparatus (optic nerves and chiasm)
  • No history of intracranial or spinal cord hemorrhage
  • No evidence of significant vasogenic edema
  • No ongoing requirement for dexamethasone as therapy for CNS disease; anticonvulsants at a stable dose allowed
  • No stereotactic radiation, whole-brain radiation within 4 weeks prior to Cycle 1 Day 1
  • Patients with central nervous system (CNS) metastases treated by neurosurgical resection or brain biopsy within 3 months prior to Cycle 1 Day 1 will be excluded
• No malignancies other than urothelial cancer within 5 years prior
• No history of autoimmune disease
• Known HIV, HBV, or HCV
• No inadequately controlled hypertension (defined as persistent systolic blood pressure (SBP) > 150 and/or diastolic blood pressure (DBP) > 100 mmHg)

• Unresectable or metastatic transitional cell carcinoma or the urothelium (renal pelvis, ureters, urinary bladder, or urethra)
  • Both transitional cell and mixed transitional/non-transitional cell histologies are permitted
• No prior 1st line therapy for metastatic disease
  • Prior adjuvant therapy allowed if it has been >12 months since last therapy
  • Prior local intervesical chemo or immune therapy is allowed if at least 28 days before study treatment
• Either cisplatin-eligible or cisplatin-ineligible but carboplatin eligible patients are allowed
• Measurable disease
• ECOG PS 0-1
• No prior immunotherapy with exception of BCG or antitumor vaccines
• No autoimmune disease requiring immunosuppression
• No untreated CNS disease
• No contraindications to platinum-based doublet chemotherapy

• ER positive breast cancer
• Tumor stage at least T2
• Plan to receive local surgery
• Post-menopausal or if premenopausal will need to have concurrent ovarian suppression
• ECOG PS 0-2
• No history of seizures
• Not on full dose anticoagulation
• No prior treatment with anti-androgen agents
• No history of CNS metastases

• 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

• Invasive breast cancer (ductal, lobular, tubular, mammary, medullary)
• If received neoadjuvant therapy, pre treatment staging must have N1 or N2 disease pre-chemo or are T3N0
• If did not receive neoadjuvant, must be T0N1-2a, T1N1-2a, T2N1-2a, or T3N0-2a.
• No prior therapeutic radiation to the chest, neck, or axilla
• No prior history of ipsilateral breast cancer
  • DCIS or LCIS are allowed
• Negative margins following mastectomy
• No significant post mastectomy complications in the ipsilateral breast requiring unplanned re-operation or admission for IV antibiotics.
  • Reoperation for margins or lymph node dissection is allowed
• Radiation oncologist is NOT planning to use a chest wall/scar boost
• Radiation oncologist is planning to treat regional lymph nodes including internal mammary nodes and meet acceptable protocol dosimetric requirements
• No co-existing medical conditions with a life expectancy <5 years
• ECOG PS 0-1

• Stage T1-3 N1 M0 at diagnosis (prior to start of neoadjuvant chemotherapy)
• No inflammatory breast cancer
• No other malignancy within 5 years
• Must have received axillary ultrasound with bx or axillary lymph nodes prior to or within 14 days of starting neoadjuvant therapy
• Must have documented ER/PR/HER2 status before neoadjuvant therapy
• Must have completed all planned chemotherapy prior to trial (ie. no planned adjuvant therapy)
• Must have completed at least 4 cycles of neoadjuvant chemotherapy consisting of an anthracycline and/or taxane based regimen
• HER2 positive patients must have received anti-HER2 therapy as part of neoadjuvant regimen
• Must have clinically negative axilla documented on physical exam at the completion of neoadjuvant chemotherapy (no imaging needed)
• No neoadjuvant endocrine or radiation therapy
• No history of prior breast cancer
• ECOG PS 0-1
• Must complete surgery within 56 days of finish of neoadjuvant therapy
• At least 1 sentinel lymph node identified intra-operatively with at least micromets

• Patients must have pathologic confirmation of axillary nodal involvement at presentation (before neoadjuvant therapy) based on a positive FNA (demonstrating malignant cells) or positive core needle biopsy (demonstrating invasive adenocarcinoma).  Patients may not have had documentation of axillary nodal positivity by sentinel node biopsy (before neoadjuvant therapy).

• Patient must have clinically T1-3, N1 breast cancer at the time of diagnosis (before neoadjuvant chemotherapy)

• Hormone receptor status must be performed on the primary breast tumor before neoadjuvant chemotherapy.

• HER2 status must be performed on the primary breast tumor before neoadjuvant chemotherapy. Patients who have a primary tumor that is either HER2-positive or HER2-negative are eligible)

• Patients must have completed a minimum of 8 weeks of standard neoadjuvant chemoterahyp consisting of an anthracycline and/or taxane-based regimen

• For patients who receive adjuvant chemotherapy after surgery a maximum of 12 weeks of intended chemotherapy may be administered but must be completed before randomization

• Patients with HER2-positive tumors must have received neoadjuvant anti-HER2 therapy (with all or with a portion of the neoadjuvant chemotherapy regimen), unless medically contraindicated.

• At the time of definitive surgery, all removed axillary nodes must be histologically free of cancer

• ECOG PS 0-1

• Postmenopausal or pre-menopausal but treated with LHRH agonist therapy for the duration of study treatment
• Locally advanced or metastatic adenocarcinoma of the breast not curable
• Documented ER-positive and HER2-negative
• No prior systemic anti-cancer therapy for metastatic disease
• Measurable disease
• ECOG PS 0-1
• No disease recurrence within 12 months of treatment with an AI or a CDK4/6 inhibitor in adjuvant/neoadjuvant setting
• No prior SERD
• No active CNS disease

• Must have measurable disease by RECIST 1.1
• Diagnosis of TNBC
• Must have received or been intolerant to not more than 2 lines of therapy for metastatic disease
• Prior therapy should have included anthracycline and/or taxane
• LDH must be <2x ULN at screening
• May be PD-L1 treatment refractory (number capped)
• ECOG PS 0-1
• No 2nd malignancy within 2 years
• No active CNS involvement
• No history of interstitial lung disease
• No active pneumonitis or history of non-infectious pneumonitis that required steroids
• No active autoimmune disease that required systemic tx in past 2 years (other than replacement therapy)
• No known HIV, HBV, HCV
• No need for steroids at dose of greater than 10mg prednisone or equivalent daily
• No recent history of substance abuse

• 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
•  

• ER -, PR-, HER2 - biopsy proven breast cancer
• Locally advanced (not curable by surgery or radiation) or metastatic
• No prior chemotherapy for metastatic disease
• (Neo)Adjuvant therapy allowed if disease free interval of at least 12 months after completion
• No prior therapy with PD-1, PD-L1, or CTLA-4 inhibitors
• Tissue available for PD-1 level determination
• ECOG PS 0-2
• No known HIV/HBV/HCV
• No history of active autoimmune disease
• No Grade 2 or higher neuropathy

• 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

• 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

• Metastatic or unresectable colorectal adenocarcinoma
• Has not progressed after first-line induction of at least 6 cycles of FOLFOX with bevacizumab
  • May have received prior adjuvant/neoadjuvant chemo for CRC as long as it was completed at least 6 months prior to initiation of metastatic FOLFOX-bev
• Has experienced unacceptable toxicity to oxaliplatin that required the discontinuation of oxaliplatin (such as neurotoxicity)
• Must be randomized within a minimum of 2 weeks and a maximum of 6 weeks after their last dose of FOLFOX+bev
• ECOG PS 0-1
• No known CNS disease
• No known HIV/HBV/HCV
• No clinically significant bleeding within 28 days
• No uncontrolled hypertension, nephrotic syndrome, GI perforation
• No prior tx with olaparib or other PARP inhibitor

• Female age 18 or greater
• Histologicall confirmed diagnosis of epithelial endometrial carcinoma. All histologies, including carcinosarcoma, are allowed
• Disease in one of the following categories
  • Newly diagnosed Stage III disease (with measurable disease following surgery or biopsy)
  • Newly diagnosed Stage IV disease (with or without disease following surgery or diagnostic biopsy)
  • Recurrence of disease where the potential for cure by surgery alone or in combination is poor
• Naive to first line systemic anti-cancer treatment.  For patients with recurrent disease only, prior chemo is allowed only if administered in the adjuvant setting and there is at least 12 months from the date of the last dose of chemo to the date of subsequent relapse
• ECOG PS 0-1
• No CNS disease
• No prior treatment with PARP inhibitors or immunotherapy

• Histologically confirmed WHO Grade IV glioblastoma
• Failed initial systemic tx
• At least 3 weeks from prior surgical resection
• At least 6 months from previous radiation unless new area of enhancement outside the 80% isodose line of originial radiation field
• At least 6 weeks from prior mAbs
• Has not required escalting doses of steroids or had progression of neurologic symptoms in last 2 weeks
• No carcinomatous meningitis
• No extracranial disease
• No multifocal tumor
• No recurrent tumor greater than 6cm
• No intra- or pertumoral hemorrhage greater than grade 1
• Measurable Disease per RECIST and RANO
• Archival tissue or newly obtained tissue available
• ECOG PS 0-1
• BP < or = 150/90 at screening without change in antihypertensives within 1 week before C1D1
• No evidence of malabsorption syndrome
• No evidence of major blood vessel involvement
• No clinically significant hemoptysis or tumor bleeding
• No arterial thromboembolism within 12 months
• No significant CAD within 12 months
• No prior lenvatinib or checkpoint inhibitor therapy
• Prior bevacizumab is allowed
• No proteinuria defined as Uprotein >1g/24 hours
• LVEF must be 55% or greater
• No diagnosis of immunodeficiency
• No active CNS metastases
• No tumor involving the brain stem
• No active autoimmune disease that has required treatment within last 2 years
• No known HIV/HBV/HCV

• Squamous cell carcinoma of the oropharynx
• Measurable disease either in primary or lymph node
• P16 posotive locally
• T1-2N1M0 or T3N0-1M0
• No more than 10 pack years of smoking history
• ECOG PS 0-1
• No T4 or N2
• No recurrent disease
• No supraclavicular nodes
• No prior malignancy unless disease free for at least 3 years
• No allergy to cisplatin

• 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

• Advanced SCCHN
  • eligible to receive single agent pembrolizumab as standard-of-care OR
  • eligible to receive single-agent docetaxel as standard of care 
• Measurable disease
• ECOG PS 0-1
• No history of severe autoimmune disease
• Not receiving high-dose systemic steorid therapy or any other form of immunosuppressive therapy

• Histologically or cytologically confirmed metastatic nonsquamous NSCLC
• EGFR wt, ALK-wt, ROS1-wt
• Measurable disease per RECIST 1.1
• ECOG PS 0-1
• No prior PD-(L)1 therapy in adjuvant setting
• First line metastatic:
  • Prior adjuvant therapy with radiation/surgery/chemo allowed if completed >6 months prior to relapse.
• Adequately controlled BP defined as BP <150/90 with no change in antihypertensive meds within 1 week prior to randomization
• No known untreated CNS mets
• No history of pneumonitis that required steroids
• No major blood vessel invastion or large volume hemoptysis
• No known HIV/HBV/HCV
• No active autoimmune disease
• No prior hypersensitivity to monoclonal antibodies

• Histologically or cytologicall confirmed Stage IV (M1a or M1b) non-squamous NSCLC
  • Mixed histologies allowed if predominant type non-squamous
  • No small cell allowed (even if non-predominant part of mixed histology)
  • May be untreated or could have received 1 prior regimen
  • EGFR or ALK positive should have had prior treatment with TKI
• No prior radiation therapy to the lung >30Gy within past 6 months
• Must have measurable disease by RECIST 1.1
• ECOG PS 0-1
• No 2nd malignancy within 2 years
• No active CNS involvement
• No history of interstitial lung disease
• No active pneumonitis or history of non-infectious pneumonitis that required steroids
• No active autoimmune disease that required systemic tx in past 2 years (other than replacement therapy)
• No known HIV, HBV, HCV
• No need for steroids at dose of greater than 10mg prednisone or equivalent daily
• No recent history of substance abuse

• New diagnosis of brain mets from a histologically or cytological confirmed primary or metastatic NSCLC tumor. If original histologic proof of malignancy is >5 years, new pathologic confirmation is needed
• KPS >70
• 1 inoperable brain mets or 2-10 brain lesions per screening MRI, confirmed by contrast enhanced MRI amenable to SRS according to following criteria
  • Largest tumor volume < 10cc
  • Longest tumor diameter < 3cm
  • Cumulative volume of all tumors < 15cc
• At least one measurable lesion per RANO-BM
• May continue on systemic therapy during trial. Should be receiving optimal systemic therapy.
• Patient must be able to operate NovoTTF-100M device independently or with caregiver
• No ALK/ROS-1 alterations. No BRAF, EGFR mutations
• No significant edema with risk of brain herniation
• No midline shift > 10mm
• No intractable seizures
• No infratentorial or leptomeningeal mets
• No recurrent brain mets or brain mets previously treated with surgery/XRT/radiosurgery
• No implantable electronic medical devices in the brain
• No other concurrent brain directed therapy

• 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

• 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.

• 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

• Histologic diagnosis of epithelial ovarian, fallopian tube, or primary peritoneal carcinoma per pre-treatment biopsies (laparoscopic or percutaneous)
• Histologic documentation of the original primary tumor is required
• FIGO Stage III-IV
• Following histologic subtypes eligible: high grade serous adenocarcinoma, endometrioid adenocarcinoma, undifferentiated carcinoma, clear cell adenocarcinoma, mixed epithelial carcinoma, or adenocarcinoma NOS.
• ECOG PS 0-2
• No need for treatment with immunosuppressive medication
• No patients receiving treatment for active autoimmune disease
• No known CNS involvement
• No prior abdominal radiation or chemotherapy for abdominal or pelvic tumor

• Recurrent high-grade serous, endometrioid, or clear-cell ovarian, fallopian tube, or primary peritoneal cancer
• Must be considered resistant to the last administered platinum therapy
• Must be 2nd, 3rd, or 4th line
• Must have been previously treated with platinu-based regimen, taxane, and bevacizumab
• Measurable disease
• ECOG PS 0-1
• Did not have disease progression within 3 months of starting first-line platinum therapy
• No known BRCA mutation
• No prior therapy with PD-1 or PD-L1 agent
• No known immunodeficiency or on steroids >10mg/day prednisone or equivalent
• No uncontrolled CNS disease
• No other cancers within 2 years
• No known HIV, HBV, HCV

• Histologically confirmed adenocarcinoma of pancreas not previously treated in metastatic setting
• Initial diagnosis of metastatic disease < or = 6 weeks prior to screening
• Measurable disease
• ECOG PS 0-1
• Adequate hepatic, hemtologic, and renal function
• No prior therapy in adjuvant setting unless adjuvant therapy was completed at least 12 months prior to metastatic diagnosis
• No CNS metastases

• Histologic confirmation of adenocarcinoma of the prostate without small cell features
• Current evidence of metastatic disease documented by either bone lesions on bone scan and/or soft tissue lesions on CT/MRI
• ECOG PS 0-1
• Ongoing androgen deprivation therapy (ADT) with a GnRH analogue or bilateral orchiectomy
• Documented disease progression per PCWG3 criteria within 6 months prior to screening
• Only one prior 2nd generation hormonal therapy in the metastatic setting
  • Patients may have received two prior 2nd gen HT (abi + enza or apalutamide or darolutamide) if and only if the first drug had been used in the non-metastatic setting
• Chemotherapy naive for metastatic CRPC
• Must have progressed during or after 2nd gen hormonal therapy or have documented intolerance to 2nd gen HT
• No active brain mets
• No known or suspected autoimmune disease
• No condition requiring systemic corticosteroids (>10 mg prednisone or equivalent)
• No prior treatment with PD-1 or PD-L1 antibodies
•  

• Histologically confirmed diagnosis of locally advanced/metastatic RCC with clear cell component
• Has had disease progression on or after having received 1st line systemic treatment for RCC with CTLA4+PD1 or VEGF-TKI+PD1
• No more than 3 prior lines of therapy
• KPS >/= 70
• No requirement for supplemental oxygen at baseline
• No prior cancer within 3 years
• No known CNS mets
• No significant cardiac disease
• No receipt of GCSF or EPO within 28 days prior to first dose
• No known HBV/HCV/HIV

• 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.

• 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
• 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

• 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

• 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

• Histologically confirmed cancer for which no curative therapy exists
• Documented HER2 (ERBB2) or HER4 (ERBB4)  mutation in any malignancy or EGFR ex 18 mutations in lung cancer.
  • Currently CLOSED cohorts include: HER2mt lung, colorectal, and biliary
• At least one measurable or evaluable lesion
• LVEF >/=50%
• ECOG PS 0-2
• No prior treatment with ERBB2 (HER2) directed TKIs (eg lapatinib, afatinib, neratinib)
• No symptomatic or unstable brain mets (stable are allowed)
• No cumulative prior anthracycline dose >450mg/m2 doxorubicin or equivalent
• No uncontrolled cardiac disease
• No chronic diarrheal disorder

Part 1:

• Locally advanced or metastatic NSCLC, melanoma, SCCHN, RCC, or GC/GEJ cancer
  • NSCLC and SCCHN must have received prior platinum-based therapy
  • Patients with targetable mutations (e.g. ALK, ROS, EGFR, etc.) must have had prior treatment with approved targeted therapy
• May have had prior therapy with anti-CTLA-4 or anti-PD-1/L1 therapy
• Prior treatments limited to no more than 3
• ECOG PS 0-1
• LVEF 50% or higher
• No known CNS mets
• No history of pneumonitis
• No prior cancer within 3 years (except locally curable cancers)
• No history of life-threatening toxicity to immunotherapy
• No known HBV/HCV/HIV

• Histologically or cytologically confirmed patients with advanced or metastatic solid tumors
• Measurable disease
• Must have been treated with all estrablished standard-of-care therapy or determined by the physician that such established therapy is not sufficiently efficacious, or patients have declined to receive standard of care therapy
• ECOG PS 0-1
• Must have Globo-H overexpression as measured by central lab
• No known active autoimmune or inflammatory disease
• Not receiving systemic steroids of >10mg prednisone per day or equivalent

• 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

• One of the following malignancies
  • Small cell lung cancer: locally recurrent or metastatic SCLC whose disease has progressed after at least 1 prior line of chemo
  • Gastric or GEJ adenoCA: Disease that has progressed after at least 1 prior line of chemo
  • SCC of genitalia (anus, cervix, vulva, or penis): disease that has progressed after at least 1 prior line (adjuvant counts as prior line)
  • Pancreatic CA: Disease that has progressed after at least 1 line of prior therapy (adjuvant tx counts as a line if recurrence is within 6 months)
  • Endometrial CA: Disease that has progressed after at least 1 line of prior therapy (adjuvant tx counts as a line if recurrence is within 6 months)
• ECOG PS 0-1
• Measurable disease
• No prior topoisomerase I inhibitor
• No symptomatic CNS involvement
• No known HIV/HBV/HCV

• Advanced solid tumor or relapsed/refractory lymphoma OR
  • eligible to receive single agent pembrolizumab as standard-of-care OR
  • eligible to receive single-agent docetaxel as standard of care OR
    ​advanced pancreatic adenocarcinoma and eligible to receive gemcitabine plus nab-paclitaxel as standard of care
• Measurable disease
• ECOG PS 0-1
• No history of severe autoimmune disease
• Not receiving high-dose systemic steorid therapy or any other form of immunosuppressive therapy

• Advanced Solid Malignancy
• Fresh and/or archival tumor tissue
• Evidence of measurable disease (except for prostate)
• Life expectancy >12 weeks
• ECOG PS 0-1
• No therapeutic anticoagulation
• no history of autoimmune disease
• No uncontrolled intercurrent illness
• No HTN >150/90 despite optimal management
• No active CNS mets
• No other malignancies within 3 years
• No autoimmune toxicity >Grade 3 from prior immunotherapy

• 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

• Histologically or cytologically confirmed, metastatic solid malignancy
• Has exhausted all available standard therapy or not a candidate for standard therapy
• ECOG PS 0-1
• Prior PD-1/PD-L1 allowed
• No other malignancy within 2 years prior
• No active autoimmune disease requiring systemic therapy within last 2 years
• No chronic steroids or immunosuppressants.

• ECOG PS 0-1
• No active CNS disease (controlled brain mets are allowed)
• Must have one of the five malignancies below
  • Clear-cell RCC
  • Triple-negative Breast Cancer
  • Squamous cell carcinoma of the head and neck
  • Colorectal cancer
  • Non-small cell lung cancer
• No other malignancies within 2 years
• No active, known, or suspected autoimmune disease (except asthma, vitiligo, T1DM, hypothyroidism, Graves disease, or psoriasis not requiring treatment)
• No severe autoimmune reactions to immunotherapy
• No need for active steroid therapy
• No significant cardiac disease
• No chronic hepatitis
• No active interstitial lung disease
• RCC specific eligibility criteria
  • Previously received one or two anti-VEGFR therapies
  • No more than 3 total prior systemic tx in metastatic setting
  • Must have evidence of progression on or after last treatment received and within 6 months of starting study
• CRC specific eligibilty criteria
  • Must have received and progressed on at least 1 standard therapy for metastatic disease
  • Must have known MSI status
• NSCLC specific eligibility criteria
  • Must have progressed on or been refractory to platinum doublet
  • Must have known EGFR, ALK, ROS1 status.
    • Those with EGFR or ALK alterations must have previously received TKI therapy
• SCCHN specific eligibility criteria
  • Not amenable ot local therapy with curative intent
  • Must have progressed on or been intolerant of platinum containing regimen
• TNBC specific eligibility criteria
  • Must have received and progressed on or been intolerant to at least 1 standard chemotherapy with anthracycline and taxane