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

• 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

• 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

• 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

• Hormone receptor positive, HER2 negative metastatic breast cancer
• Refractory to or relapsed after at least 2, and no more than 4, prior systemic therapies including;
  • At least 1 prior anticancer hormonal treatment
  • At least 1 CDK4/6 in the metastatic settting
• Eligible to receive at least 1 of the following chemotherapies; eribulin, capecitabine, gemcitabine, vinorelbine
• Disease progression after most recent therapy
• No potential therapy available with curative intent (e.g. surgery)
• No prior Topo1 inhibitors

• 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

• Metastatic colorectal cancer
• Presence of BRAF V600E mutation in tumor tissue determined by local assay at any time prior to screening
• No prior therapy for metastatic disease (this trial is a 1st line trial)
• Measurable disease
• ECOG PS 0-1
• No uncontrolled BP (SBP>149 or DBP >99) despite optimal antihypertensives
• No symptomatic CNS involvement
• No history of Inflammatory Bowel Disease (IBD) requiring treatment in last 12 months
• No thromboembolic events, cerebrovascular events, acute coronary snydromes, or CHF in the past 6 months
• No known contraindication to cetuximab administration
• No uncontrolled glaucoma, hyperviscosity syndrome, or hypercoagulability syndrome
• No other malignancy within 3 years (if definitively treated and not recurrent) or 5 years (if not definitively treated)
• No known HIV/HBV/HCV

• 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

• 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.

• 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

• 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

• 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
• 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

• 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
•  

• 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

• Currently open cohorts must have documented Wnt signaling alteration
• Histologically confirmed recurrent platinum-resistant/regractory epithelial ovarian 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

• 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

• 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

• 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.

• 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

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