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HER2CLIMB (ONT-380-206): Phase 2 Randomized, Double-Blinded, Controlled Study of ONT-380 vs. Placebo in Combination with Capecitabine and Trastuzumab in Patients with Pretreated Unresectable Locally Advanced or Metastatic HER2+ Breast Carcinoma
Contact Treatment Inclusion Criteria Exclusion Criteria Informed Consent

Courtney Frederick Office Ph: 203-737-7992, Fax: 203-785-5792 , e-mail:

If you are eligible to participate, you will be “randomized” into one of two study groups: One group will receive ONT-380, capecitabine and trastuzumab. The other group will receive a placebo (a placebo is something that looks like medicine but is not actually medicine), capecitabine and trastuzumab. Twice as many subjects will be assigned to the ONT-380 group as will be assigned to the placebo.

1. Have histologically confirmed HER2+ breast carcinoma, with HER2+ defined by FISH and/or 3+ staining by IHC

a. Tissue blocks or slides must be submitted to confirm HER2 positivity (FISH-positive or
IHC 3+) by a sponsor-designated central laboratory prior to randomization. Centrally

confirmed HER2 results (either IHC or FISH) from a previous study can be used to

determine eligibility for this study with approval from the sponsor

2. Have received previous treatment with a taxane, trastuzumab, pertuzumab, and T-DM1

3. If pertuzumab and/or T-DM1 were given in the neo-adjuvant or adjuvant

setting, must have completed that treatment at least 12 months prior to start

of treatment

4. Have progression of unresectable locally advanced or metastatic breast cancer after last systemic therapy (as confirmed by investigator)

5. Have measurable or non-measureable disease assessable by RECIST 1.1

6. Be at least 18 years of age at time of consent

7. Have Eastern Cooperative Oncology Group Performance Status (ECOG PS) 0 or 1

8. Have a life expectancy of at least 6 months, in the opinion of the investigator

9. Have adequate hepatic function as defined by the following:
a. Total bilirubin ≤1.5 X ULN, except for patients with known Gilbert’s disease, who may

enroll if the conjugated bilirubin is ≤1.5 X ULN

b. AST and ≤ 2.5 X ULN (≤ 5 X ULN if liver metastases are present)

Inclusion Criteria

(must all be answered Yes)

11. Have adequate baseline hematological parameters as defined by:

Date of Test


≥ 9.0 g/dl




≥ 1500 cells/μL


≥ 100,000/μL



12. Have creatinine clearance ≥ 50 mL/min as calculated per institutional guidelines

13. INR and aPTT ≤ 1.5 X ULN unless on medication known to alter INR and aPTT. (Note: Warfarin is a prohibited concomitant therapy.)

14. Have LVEF ≥ 50% as assessed by ECHO or MUGA documented within 4 weeks prior to first dose of study treatment

15. If female of childbearing potential, must have a negative result of serum pregnancy test performed within 7 days prior to first dose of study treatment. (Females of childbearing potential are those who have not undergone surgical sterilization with a hysterectomy and/or bilateral oophorectomy; or, are not postmenopausal, as defined as ≥ 12 months of amenorrhea
16. Women of childbearing potential (as defined above) and men with partners of childbearing potential must agree to use a highly effective hormonal form of contraception or two effective forms of non-hormonal contraception. [Effective methods of contraception include oral, transdermal, injectable, or implantable contraceptives; IUD; female condom; diaphragm with spermicide; cervical cap; use of a condom by the sexual partner; or a sterile sexual partner.] Male pts with partners of childbearing potential must use barrier contraception. All study subjects should practice effective contraception, as described above, starting from the signing of informed consent until 6 months after the last dose of study medication or investigational medicinal product.
17. Pt or legally authorized representative of a pt must provide signed informed consent per a consent document that has been approved by an institutional review board or independent ethics committee (IRB/IEC) prior to initiation of any study-related tests or procedures that are not part of standard-of-care for the patient’s disease.
18. Patients must also be willing and able to comply with study procedures
CNS Inclusion – Based on screening brain MRI, patients must have one of the following:
18. No evidence of Brain metastases
19. Untreated Brain metastases not needing immediate local therapy. For pts with untreated CNS lesions > 2.0 cm on screening MRI, discussion with and approval from medical monitor is required prior to enrollment.
Inclusion Criteria
(must all be answered Yes)
20. Previously treated Brain metastases
a. Brain metastases previously treated with local therapy may either be stable since
treatment or may have progressed since prior local CNS therapy, provided that there is no
clinical indication for immediate re-treatment with local therapy in the opinion of the
b. Pts treated with Brain local therapy for newly identified lesions found on initial MRI
performed during screening for this study may be eligible to enroll if all of the following
criteria are met:
i. Time since whole brain radiation therapy (WBRT) is > 21 days prior to first dose of
treatment, time since stereotactic radiosurgery (SRS) is > 14 days prior to first dose of
treatment, or time since surgical resection is > 28 days
ii. Other sites of evaluable disease are present
c. Relevant records of any Brain treatment must be available to allow for classification of target and non-target lesions

1. Have previously been treated with:
a. Lapatinib with 12 months of starting study treatment or

b. Neratinib, afarinib or other investigation HER2/ epidermal growth factor receptors (EGFR) or HER2 TKI at any time previously

2. Have previously been treated with capecitabine for metastatic disease. Note: patients who have received capecitabine for adjuvant or neoadjuvant treatment at least 12 months prior to starting study treatment are eligible.

3. History of exposure to the following cumulative doses of anthracyclines:
a. Doxorubicin or liposomal doxorubicin > 360 mg/m2

b. Epirubicin > 720 mg/m2

c. Mitoxantrone > 120 mg/m2

d. Idarubicin > 90 mg/m2

e. Other anthracyclines (e.g., liposomal doxorubicin) > the equivalent of 360 mg/m2 of doxorubicin

f. If more than one anthracycline has been used, then the cumulative dose must not exceed the equivalent of 360 mg/m2 of doxorubicin

4. Have history of allergic reactions to trastuzumab, capecitabine, or ONT-380 (or compounds chemically or biologically similar), except for Grade 1 or 2 infusion related reactions to trastuzumab that were successfully managed

5. Have received treatment with any systemic anti-cancer therapy (including hormonal therapy), non-CNS radiation, or experimental agent ≤ 3 weeks of first dose of study treatment

6. Have any toxicity related to prior cancer therapies that has not resolved to ≤ Grade 1, with the following exceptions: alopecia and neuropathy, which must have resolved to ≤ Grade 2; and CHF, which must have been ≤ Grade 1 in severity at the time of occurrence, and must have resolved completely

7. Have clinically significant cardiac disease such as ventricular arrhythmia requiring therapy, uncontrolled hypertension (defined as persistent SBP > 150 mm Hg and/or DBP > 100 mm Hg on antihypertensive medications), or any history of symptomatic CHF

8. Have known MI or unstable angina within 6 months prior to first dose of study treatment

Exclusion Criteria

(must all be answered No)

9. Are known carriers of Hepatitis B or Hepatitis C or have other known chronic liver disease

10. Are known to be positive for human immunodeficiency virus (HIV)

11. Are pregnant, breastfeeding, or planning a pregnancy

12. Require warfarin therapy or other coumarin derivatives

13. Have inability to swallow pills or any significant GI disease which would preclude the adequate oral absorption of medications

14. Have used a strong CYP3A4 inducer or inhibitor, or strong CYP2C8 inducer or inhibitor within 3 elimination half-lives of the inhibitor or inducer prior to first dose of study treatment (see Appendix C and Appendix D)

15. Have known dihydropyrimidine dehydrogenase deficiency

16. Unable for any reason to undergo MRI of the brain

17. Have any other medical, social, or psychosocial factors that, in the opinion of the investigator, could impact safety or compliance with study procedures

18. History of other malignancy within the previous 3 years, except for

appropriately treated carcinoma in situ of the cervix, non-melanoma skin

carcinoma, Stage 1 uterine cancer, synchronous or previously diagnosed

HER2-positive breast cancer, or cancers with a similar curative outcome as

those mentioned above.

CNS Exclusion – Based on screening brain MRI, patients must not have any of the following:
19. Any untreated lesions > 2.0 cm in size, unless discussed with medical monitor and approval for enrollment is given

20. Ongoing use of systemic corticosteroids for control of symptoms of brain

metastases at a total daily dose of >4mg of dexamethasone (or equivalent).

However, patients on chronic stable dose of ≤ 4 mg total daily of

dexamethasone (or equivalent) may be eligible with discussion and approval

by the medical monitor.

21. Any lesion thought to require immediate local therapy, including (but not limited to) a lesion in an anatomic site where increase in size or possible treatment-related edema may pose risk to patient (e.g. brain stem lesions). Pts who undergo local treatment for such lesions identified by screening MRI may still be eligible for the study based on criteria described

under CNS inclusion criteria 20b

22. Known leptomeningeal disease (LMD). Patient must be free of neurological

symptoms of LMD as documented by the investigator

23. Have poorly controlled seizures

Main CAF

Pre-screen CAF

HIC: 1603017423

A phase I/II clinical trial evaluating the safety and clinical activity of radioiodide (131I-) as a novel targeted therapy for metastatic breast cancer that overexpresses functional Na/I symporter
Contact Treatment Inclusion Criteria Exclusion Criteria Informed Consent

Courtney Frederick

Tel: 203-737-7992

Fax: 203-785-4069

The trial includes a screening phase with I-124 to identify patients whose cancer enriches iodine. Those who meet enrichment criteria will be treated with a I-131 that is used to treat metastatic thyroid cancer, where it is highly effective. The treatment is a ONE TIME ORAL THERAPY with I-131 capsules AT THE MAIN CAMPUS that are dosed based on the I-124 uptake level.

1. All breast cancer subtypes (TNBC, ER+, HER2+) are eligible but have to have disease progression after treatment with all available therapies known to confer clinical benefit and have.

2. Radiological evidence of measurable or evaluable metastatic disease by Response Evaluation in Solid Tumors (RECIST) 1.1

3. There is no restriction on the number of prior lines of therapy.

4. Less than 70 years of age (patients older than age 70 are at an increased risk of thyrotoxicosis)

5. Eastern Cooperative Oncology Group (ECOG) Performance Status score of < 2.

6. Recovery to Grade ≤ 2 from any prior side effects of prior therapy for cancer.

7. Adequate bone marrow function defined as white blood cells (WBCs) ≥ 3.0 × 109/L, neutrophils ≥ 1.5 × 109/L, platelets ≥ 100 × 109/L. Adequate renal function defined as serum creatinine < 1.5 mg/dL or creatinine clearance (GFR) > 40 mL/min calculated using the following formula: GFR = 175 x Serum Cr-1.154 x age-0.203 x 0.742 (female) and x 1.212 (if patient is African American).

8. Adequate liver function defined as AST, ALT ≤ 3 × upper limit of normal (UNL) in the absence of liver metastasis and ≤ 5 × UNL with liver metastases; bilirubin < 1.5 × UNL; alkaline phosphatase ≤ 2.5 × UNL in the absence of bone metastasis and ≤ 5 × UNL in case of bone metastases.

9. TSH, T3 and free T4 must be within normal range.

10. The patient should not have had intravenous or intrathecal iodinated contrast agents (IVP, CT with contrast, myelogram, and angiogram) for 4 weeks prior to screening 124I- PET/CT scans and/or 131I- treatment.

11. Patients with treated brain metastases are eligible if the brain metastases have remained stable for more than 4 weeks after completing therapy to the brain.

12. Normal urine or serum Beta-HCG in premenopausal women of childbearing potential.

13. Women of childbearing potential must agree to use effective contraception during the treatment period and for at least 6 months after the last dose of 124I- and/or 131I- as these agents interfere with radioactive iodide uptake

1. Concurrent anti-tumor treatment including radiation therapy, hormonal and chemotherapy.

2. Patients with underlying symptomatic cardiac disease such as coronary artery disease, congestive heart failure, or atrial fibrillation.

3. Significant gastrointestinal abnormalities, including: ulcerative colitis, chronic diarrhea associated with intestinal malabsorption, Crohn's disease, and prior surgical procedures affecting absorption.

4. Women who are nursing or pregnant




Contact Treatment Inclusion Criteria Exclusion Criteria Informed Consent

Courtney Frederick

Office Phone: 203-737-7992

Fax: 203-785-5792


Orteronel 300mg po BID (total daily dose of 600mg).

1.Androgen Reveptor positive (AR+) breast cancer defined as ≥10% staining by immunohisto-chemistry. Tumor tissue from a primary biopsy or metastatic lesion is mandatory. Submision of tissue for AR assessment confirmation at the central laboratory.

2.In addition to having AR+ tumors, patients must fit into 1 of the 2 following categories:

◦Triple Negative Breast Cancer : Must have received at least 1 and up to 3 prior chemotherapy regimens for metastatic disease.

◦HER2+ patients in this group must have received a minimum of 2 lines of HER2-directed therapy for metastatic cancer.

3.Patients with bone only metastasis are eligible.

4.Both female and male patients are eligible.

5. Lab:

  • ANC ≥ 1.25 x 109/L
  • Platelet count ≥ 75 x 109/L
  • Hemoglobin ≥ 9.0 g/dL
  • Serum creatinine ≤1.5 x ULN or creatinine clearance ≥40 mL/min as calculated by the Cockcroft-Gault method
  • Serum AST and ALT ≤ 2.5 x the upper limit of normal (ULN), if no liver involvement
  • Serum total bilirubin (TBILI) ≤ 1.5 ×ULN patients with known Gilbert Syndrome, a total bilirubin ≤3.0 x ULN, with direct bilirubin ≤1.5 x ULN)
  • AST and ALT ≤5 ULN in case of liver metastases

6.Screening calculated LVEF of ≥50% by echocardiogram (ECHO) or multiple-gated acquisition (MUGA) scan

7. Life expectancy of ≥3 months

1.Known hypersensitivity to orteronel or to orteronel excipients

2.Patients receiving other anticaner treatment for breast cancer (Receiving chronic bisphosphonate or denosumab therapy are eligible).

3.Prior anti-androgen therapy

4.Use of an investigational drug ≤21 days or 5 half-lives (whichever is shorter) prior to the first dose of orteronel, or concurrent treatment. For investigational drugs for which 5 half-lives is less than 21 days, a minimum of 10 days between termination of the investigational drug and administration of orteronel is required.

5.Active brain metastases or leptomeningeal disease. Previously treatedbrain metastases that are stable for at least 3 months are allowed. Patients must be off steroids, but anti-convulsants are allowed.

6.Adrenal insufficiency, or patients receiving treatment with ketoconazole, abiraterone, or aminoglutethimide.

7.Wide field RT (including therapeutic radioisotopes such as strontium 89) administered ≤28 days or limited field RT for palliation ≤7 days prior to study drug

8.Major surgical procedures ≤28 days of beginning study treatment or minor surgical procedures ≤7 days.

9.Active gastrointestinal disease or other condition that will interfere significantly with the absorption, distribution, metabolism, or excretion of oral therapy.

10.Active/serious cardiac disease, thromboembolic events, or any other cardiac condition within 6 months prior to study drug. Chronic stable atrial fibrillation on stable anticoagulant therapy is allowed.

11.ECG abnormalities of Q-wave infarction, unless identified 6 or more months prior to screening or QTc Fridericia (F) interval >460 msec

12.Inadequately controlled hypertension

13.HIV, active chronic HBV, or HCV, life-threatening illness unrelated to cancer, or any serious medical or psychiatric illness.

14.Uncontrolled DM (Type II DM are eligible if they require only oral hypoglycemic agents and fasting blood glucose level is ≤120. Type I DM are eligible if HbAlc is ≤7).

CAF - main



Contact Treatment Inclusion Criteria Exclusion Criteria Informed Consent

Noelle Sowers

Office Ph: 203-737-3472

Fax: 203-785-4069 ,


All patients will receive SGN-LIV1A. Patients enrolled in Part B will receive SGN-LIV1A in combination with trastuzumab. This study will be conducted in 2 parts (Part A: monotherapy, Part B: combination therapy). SGN-LIV1A will be administered on Day 1 of of 3-week cycles as a 30-minute IV infusion. Research biopsy has to be obtained on Cycle 1 Day 5 (window Day 47).

1. Pathologically confirmed diagnosis of breast cancer with radiographic evidence of incurable, unresectable, locally advanced or metastatic disease.

2. Part A: Patients with triple-negative disease must have received at least 2 prior cytotoxic regimens in the incurable, unresectable, LA/MBC setting.

Patients with ER- and/or PR-positive/HER2-negative disease must have received at least 2 prior cytotoxic regimens in the incurable, unresectable, LA/MBC setting, and are no longer a candidate for hormonal therapy.

Part B: Patients with HER2-positive disease must have received at least 2 prior cytotoxic regimens in the incurable, unresectable LA/MBC setting.

HER2-positivity will be determined by the local lab.

3. Positive for LIV-1 expression on newly obtained tumor tissue biopsy. Archived tumor tissue, if available, is also required for LIV-1 expression analysis. 80-90% of patients are expected to be positive.

4. Measureable disease as defined in RECIST Version 1.1: at least 1 tumor lesion 10 mm in the longest diameter or a lymph node 15 mm in short axis measurement assessed by CT scan.

5. Females18 years of age.

6. ECO 0 or 1

7. Patients must have completed treatment with chemotherapy, radiotherapy, hormonal therapy, or other treatment with an investigational agent 2 weeks prior to first dose of study drug, unless disease progression is documented, and have recovered from any clinically significant toxicity associated with the treatment.

8. Patients must have completed treatment with a biologic agent or immunotherapy 4 weeks prior to the first dose of study drug, unless disease progression is documented, and have recovered from any clinically significant toxicity associated with the treatment. An exception to this requirement is treatment with denosumab, which is permitted on study.

9. Lab evaluation: absolute neutrophil count (ANC) 1500/?L, platelet count 100,000/?L, hemoglobin 8.0 g/dL, serum bilirubin 1.5x upper limit of normal (ULN), serum creatinine 1.5x ULN, alanine aminotransferase (ALT) and aspartate aminotransferase (AST) 1.5x ULN or 3x ULN if liver metastases present

10. Negative pregnancy test resultand must agree to use 2 effective contraception methods during the study and for an extended time following the last dose of study drug.

11. Part B only: LVEF 50% as determined by echocardioggram or MUGA scan.

1. Pre-existing neuropathy ≥Grade 2.

2. Another primary invasive malignancy that has not been in remission for at least 3 years with the exception of carcinoma in situ of the cervix, squamous or basal cell skin cancer, or thyroid cancer.

3. Cerebral/meningeal disease related to breast cancer and has not been definitively treated.

4. Any active Grade 3 or higher toxicity within 2 weeks prior to the first dose of SGN-LIV1A.

5. Positive HBsAg, active hepatitis C infection, or a known history of being seropositive for HIV.

6. Documented history of a cerebral vascular event, unstable angina, myocardial infarction, or cardiac symptoms consistent with New York Heart Association Class III-IV within 6 months prior to their first dose of SGN-LIV1A.

7. Any P-gp inducers/inhibitors or strong CYP3A inducers/inhibitors within 2 weeks prior to the first dose of study drug.

8. Females who are breastfeeding.

9. Known hypersensitivity to any excipient contained in the drug formulation of SGN-LIV1A.

10. Major surgery ≤3 weeks of study treatment.

Part B only: known hypersensitivity to Trastuzumab

Main Consent

Optional Tests Consent

Contact for the above HER2 Clinical Trials

Courtney Frederick, RN, BSN

Clinical Trials Research Nurse

Tel: 203-737-7992