Clinical Trials

• 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

• 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

High risk early breast cancer as defined as follows:
-Post adjuvant chemo withTumor >2cm, N0, Oncotype Dx >25 or
-Post adjuvantchemo with 1-3 positive nodes, OncDx >25 or
-Post adjuvant chemo with >3 positive nodes or
-Post neoadjuvant chemo with >3 positive nodes
HER2 negative, ER/PR positive
Completed standard neoadjuvant or adjuvant taxane or anthracycline therapy
No prior receipt of MTOR inhibitors
ECOG PS 0-2
Fasting cholesterol <300, TG <2.5x ULN
HIV positive allowed if controlled CD4 count and NOT on ART

• Triple negative cancer of the breast, locally advanced or metastatic not amenable to curative resection
• ECOG PS 0-1
• Valid results from central molecular analysis confirming PIK3CA/AKT1/PTEN-altered status by NGS
  • AKT1 missense mutations at E17, L52, or Q79
  • PIK3CA missense mutations at R88, G106, K111, G118, N345, C420, E453, E542, E545, Q546, M1043, H1047, or G1049
  • PTEN homozygous deletion, dominant negative short variant (C124S, G129E, or R130X), less of heterozygosity with copy number 1, double hit 
• No known brain mets
• No prior cancers within 5 years
• No known HIV
• No cirrhosis
• No active steroid use (> or = 10mg prednisone/daily)
• No clinically significant cardiac dysfunction including EF<50%
• No insulin dependent diabetes
• No Grade >=2 uncontrolled or untreated hyperlipidemia/hypertriglyceridemia

• ER+, HEr2- metastatic breast cacner
• Candidate for fulvestrant therapy- patients who ahve started fulvestrant may enter if within 3 months of starting fulvestrant
• ECOG PS 0-2
• Willing to provide fresh tissue biopsies
• Post-menopausal. If pre-menopausal will need to receive concurrent ovarian suppression
• No CNS disease
• No history of seizures
• No prior treatment with anti-androgen agent

• HER2 negative disease
• HR (ER and/or PgR) psoitive disease
• Measurable disease
• ECOG PS 0-2
• Must have received prior taxane containing regimen in the neoadjuvant or adjuvant setting
• If indicated, must have received prior anthracycline containing regimen in neoadjuvant, adjuvant, or metastatic setting
• Unless not indicated (e.g. rapidly progressing disease), must have received prior endocrine therapy. No limit on number of prior endocrine therapies or targeted therapies (CDK4/6, everolimus)
• Documented disease recurrence or progression
• Ability to swallow pills
• No more than 1 prior chemotherapy regimen for advanced disease (not including targeted therapy)
• No prior use of a taxane in the metastatic setting
• No known CNS involvement
• No other cancer within 5 years
• No known HIV/HBV/HCV
• No neuropathy > Grade 1

• Triple negative metastatic breast cancer
• 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

• Any gender

• Single-agent cytotoxic chemotherapy indicated

• Can be measurable or non-measurable disease

• Must have a history of brain metastases that are non-progressing

• In TNBC, must have at least 1 prior lines of metastatic cytotoxic therapy

• In non-TNBC, prior therapy as indicated is required

• Have received prior therapy with anthracycline, taxane, and capecitabine in any setting (neo-adj, adj, or metastatic)

• Most recent anti-cancer therapy within 6 months of randomization

• ECOG PS 0-1

• No prior SCT

• No prior camptothecin-derived agent

• No leptomeningeal disease

• No HBV/HCV/HIV

• No cirrhosis

• No other malignancy within 5 years

• No need for O2 supplementation

• Persistent, recurrent, or metastatic cervical cancer (squamous cell, adenosquamous, or adenocarcinoma) not amenable to curative treatment
• No prior treatment with systemic chemotherapy
• Measurable disease
• ECOG PS 0-1
• No known CNS metastases
• No other malignancy within 3 years (other than NMSC, in situ cancers)
• No chronic steroid therapy
• No autoimmune disease
• No known HBV, HCV, HIV

• 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 

• Metastatic histologically confirmed CRC
• Must have failed treatment with one regimen containing a fluoropyrimidine and oxaliplatin for metastatic disease. All patients must have received a minimum of 6 weeks of the first line therapy. Treatment failure is defined as radiologic progression during or <6 months after the last dose of first-line therapy (including adjuvant)
• ECOG PS 0-1
• Must give access to either archived or new biopsy
• No more than 1 prior chemo regimen in metastatic setting
• No other cancers within 3 years 

• Histologically confirmed endometrial carcinoma
• Radiographic evidence of disease progression after 1 prior platinum-based therapy for metastatic disease
  • Prior adjuvant platinum counts as a prior line if progression occured within 1 year
• Measurable disease (confirmed by central review)
• Adequate organ function
• No significant proteinuria
• ECOG PS 0-1
• No carcinosarcoma, leiomyosarcoma or stromal sarcoma
• No active CNS disease
• No major blood vessel infiltration
• No known HIV, HBV, HCV
• No history of immunodeficiency or chronic immunosuppresant therapy'
• No active autoimmune disease (except psoriasis) that has required systemic therapy within last 2 years.

• Histologically confirmed recurrent epithelial endometrial cancer
  • Patients with germ cell, sex cord stroma, carcinosarcoma, or sarcoma are only eligible if tumor has mixed endometrioid component with documented Wnt signaling alteration
• Refractory or intolerant to at least one prior standard therapy for metastatic or locally advanced disease
  • Prior chemoradiation is considered a line of therapy
• Willing to undergo mandatory pre-treatment and on-treatment biopsies
• ECOG PS 0-1
• No recent prior malignanciy
• No symptomatic CNS metastasis
• No osteoblastic bone mets

• Has undergone 1 allogeneic stem cell transplant from any type of donor and any donor source for hematologic disorder. Recipients of myeloablative and reduced-intesity conditioning regimens are eligible
• Clinically suspected Grade II to IV aGVHD per MAGIC criteria
• Evidence of myeloid engraftment
• Creatinine <2
• No more than 1 prior aHCT
• No more than 2 days of steroids for GVHD
• No presence of GVHD overlap syndrome
• No active HBV or HCV
• No known HIV
• No relapse of underlying malignancy post aHCT

• Confirmed pathologic diagnosis of HCC (from tumor tissue)
• Must not be eligible for locoregional therapy for unresectable HCC. Patients who progressed on local regional therapy are eligible if therapy was >28 days prior
• Barcelona Clinic Liver Cancer (BCLC) stage B or stage C
• Child-Pugh Score class A
• ECOG PS 0-1
• HBV or HCV may be allowed depending on activity (may not have both together)
• Measurable disease
• No prior receipt of durvalumab, tremelimumab, or sorafenib
• No prior receipt of any PD-1, PD-L1, or CTLA-4 antibody
• No autoimmune disease within the last 5 years
• No CNS mets
• No fibrolamellar or sarcomatoid HCC or mixed cholagiocarcinoma with HCC
• No recent steroid use (>10 mg prednisone/day)

• 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

• Extensive stage small-cell lung cancer
• Has progressed within 6 months of receiving platinum based therapy or intolerant of platinum based therapy
• ECOG PS 0-1
• No more than 2 platinum-based regimens for SCLC
• No prior receipt of PD-1/L-1 agents or CTLA-4 inhibitors
• No active CNS mets
  • If history of CNS mets, must be stable for at least 4 weeks, and off steroids for at least 7 days
• No active autoimmune disease requiring treatment in previous 2 years
• Cannot be receiving more than 3 anti-hypertensive agents
• No known HIV/HBV/HCV

• Stage IIB or IIC Melanoma  (T3b, T4a, T4b). Must be node-negative
• No prior treatment for melanoma beyond complete surgical resection of current primary lesion
• Must have received sentinel lymph node biopsy which was negative
• 12 weeks or less from surgical resection and first study treatment
• No evidence of metastatic disease on imaging
• ECOG PS 0-1
• No known additional malignancy within the past 5 years
• Must have recovered adequately from surgery
• No active autoimmune disease requiring systemic treatment in the past 2 years
• No history of non-infectious pneumonitis
• No known HIV/HBV/HCV
•  

• 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

• 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

• 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

• Multiple myeloma either
  • 3rd line after failure of BOTH proteasome inhibitor and IMiD OR
  • 4th line regardless of prior therapies
• Measurable disease activity as indicated by serum or urine M-protein, serum free light chain, biopsy-proven plasmacytoma, >5% bone marrow plasma cells.
• No plasma cell leukemia
• No CNS disease
• No severe autoimmune diseas
• No chronic pulmonary disease
• ANC (>1000/uL), Pplatelet count (>50,000/uL), hemoglobin (>8 g/dL),
• ALT and AST (each <3.0 x upper limit of normal), total bilirubin (<2 mg/dL), creatinine clearance (>30 mL/min),
• Cardiac ejection fraction >45%

• Metastatic renal cell carcinoma with a clear cell component
• Karnofsky PS 70% or higher
• 1-2 lines of prior therapy for advanced or metastaic RCC including at least one antiangiogenic therapy or nivolumab+ipilimumab
• No prior treatment with cabozantinib or other MET inhibitor
• No active CNS malignancies
• No known HIV, HBV, HCV
• No need for Proton -pump inhibitors

• PD-L1 copy number gain/amplification (likely available on Foundation only)
• Patients with MSI-high
  • Using either Foundation 1 or other NGS defined by a shift in the size of 30% or more loci
• Patients with dMMR
  • Defined as loss of at least one of four markers (MLH1, MSH2, PMS2, MSH6)
• Patients with total mutational burden (TMB) high
  • 10 mut/Mb per any CLIA certified test
• Patients with alterations in DNA proofreading/repair genes
  • POLE mutations
  • POLD1 mutations
  • Mutations in genomic instability genes eg. MSH2, MLH1, MSH6
• If testing was not performed by Foundation Medicine, new pretreatment tissue sample is required. Tissue may be submitted within 4 weeks after enrollment
• No metastatic non-small cell lung cancer (no NSCLC)
• No metastatic urothelial carcinoma (no bladder cancer)
• No MSI-high colorectal cancer
• No history of autoimmune disease or immune deficiency
• No HIV/HBV/HCV
• No other malignancy within 5 years
• No need for immunosuppressive medications (including steroids)

• 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 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.
• 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

• One of the following malignancies
  • Biliary cancer
  • Salivary gland cancer
  • Bladder cancer
• HER2 overexpression or amplification
• ECOG PS 0-2
• No prior treatment with any HER-2 directed therapy
• No active or untreated CNS metastastasis
• LVEF must be > or = 50%

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, 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