Clinical Trials

• 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

• 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.

• 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