Clinical Trials

• 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

• 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

• 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

• Histologically confirmed unilateral adenocarcinoma of the breast
• Positive for ER and/or PgR
• HER2 negative
• Patient has had surgical resection where tumor was removed completely with negative margins
• Anatomic Stage II or III
• Completed neoadjuvant or adjuvant chemotherapy (if indicated)
• Completed adjuvant XRT (if indicated)
• Plan to treat pt with endocrine tx for 5 years
• No prior CDK4/6 inhibitor
• No prior tamoxifen, ralixofene, or AIs for chemoprevention
• No prior tx with anthracycline at cumulative doses of 450mg/m2 or more
• No distant metastatic disease
• No other cancer within 2 years of study enrollment
• No known HIV/HBV/HCV
• No clinically significant cardiac disease

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

• 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 </=150 and HgbA1c </= 7.5%, ALT/AST </= 2.5x ULN
  • PT/PTT </= 1.5x ULN
• 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

• 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

• Histologically confirmed unresectable or metastatic breast cancer
• HER-2 positive (HER2+) by ASCO-CAP guidelines and confirmed by central lab
• Previously treated with T-DM1
• Progression following last treatment (cannot go on after stopping treatment for toxicity alone)
• No prior capecitabine
• No history of insterstitial lung disease or pneumonitis requiring steroids
• No active CNS disease

• Subjects with adenocarcinoma of the breast with evidence of either locally advanced disease not amenable to resection or XRT, or metastatic disease
• Must be appropriate candidates for endocrine monotherapy
• Either measurable disease or bone-only (nonmeasurable) disease
• Post-menopausal women or men
• Must be ER+, HER2 -
• Must have received at least one and no more than two lines of endocrine therapy for advanced/metastatic breast cancer
• Must have received prior treatment with CDK4/6 inhibitor in combination with either fulvestrant or an AI
• No more than one line of chemotherapy in the advanced/metastic setting
• No prior treatment with investigational SERD or ER antagonist
• No presence of symptomatic visceral disease

• 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
•  

• Pathologically confirmed locally advanced unresectable or metastatic breast cancer
• HER2 negative (-) disease
• Hormone receptor (ER and/or PR) positive (+)
• Measurable disease
• CNS disease is allowed provided that patient is neurologically stable on maximum dose of 4mg dexamethosone, no leptomeningeal disease, and no local-directed CNS treatmnt is immediately necessary
• ECOG PS 0-2
• No limit on number of prior endocrine therapies
• No more than 2 prior lines of chemotherapy
• No prior treatment with either capecitabine or any taxane
• No other malignancies within 5 years except with discussion with medical monitor
• No HIV, HBV, HCV
• No Grade 2 or higher neuropathy
•  

• Age 65 or older
• Locally advanced breast cancer not considered curable by surgery or radioation or metastatic breast cancer
• Measurable Disease
• Brain mets are allowed
• ECOG PS 0-2
• If ER/PR+, must have received prior therapy with endocrine therapy (+/- CDK 4/6 therapy).
• Any number of prior endocrine or targeted therapies are permitted
• No prior chemotherapy for metastatic disease
• No known HIV/HBV/HCV
• No Grade >1 neuropathy

• 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
• 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

• Must have diagnosis of endometrial cancer
• Must have received or been intolerant to no more than 2 prior lines of treatment
• Prior treatment should have included platinum containing regimen
• May be PD1 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

• NSCLC with locally advanced, unresectable, Stage III disease
• Must have completed, without progression, definitive chemoradiation within 28 days of randomization
• ECOG PS 0-1
• Must have at least one previously irradiated tumor lesion that is measurable at time of study entry
• No pneumonitis Grade 2 or higher from chemoXRT
• No tuberculosis, HBV, HCV, or HIV
• No mixed histology (small-cell and non-small cell)
• No recent severe cardiac disease
  • No history of other primary malignancy

• 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

• 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

• 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

• Prostate adenocarcinoma
• Post-prostatectomy (within last 10 years)
• Detectable serum PSA (between 0.1 and 1.0 ng/mL) at study entry
• Any of following
  • Gleason score 7-10
  • >= T3a disease
  • PSA never became undetectable following prostatectomy
• No nodal involvement
• KPS 70-100
• Availability of tissue
• Prior ADT allowed if previously given for <90 days
• GFR >35
• No prior invasive malignancy except in-situ disease, stage I resected melanoma, or disease free for at least 2 years
• No prior chemotherapy for prostate cancer
• No prior radiation that would result in overlap
• No history or predisposition to seizures
• No IBD
• No severe CAD

• 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.

• 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

• 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)

• 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

• 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.