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QUILT-3.013: Study of Ad5 [E1-, E2b-]-HER2/Neu Vaccine (ETBX-021) in Subjects With Unresectable Locally Advanced or Metastatic HER2-Expressing Breast Cancer

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT02751528
Recruitment Status : Unknown
Verified September 2018 by NantBioScience, Inc..
Recruitment status was:  Active, not recruiting
First Posted : April 26, 2016
Last Update Posted : August 28, 2019
Information provided by (Responsible Party):
NantBioScience, Inc.

Brief Summary:
The purpose of this study is to determine whether ETBX-021 is safe and effective in the treatment of unresectable locally advanced or metastatic HER2-low-expressing breast cancer.

Condition or disease Intervention/treatment Phase
Cancer Biological: ETBX-021 Phase 1

Detailed Description:
This is a Phase I trial in subjects with unresectable locally advanced or metastatic HER2-low expressing (IHC 1+ or 2+) breast cancer. The study will be conducted in two parts: the first part will involve dose escalation using a 3 + 3 design, and the second part will involve the expansion of the MTD or HTD to further evaluate safety, preliminary efficacy, and immunogenicity. In the first part, 3 to 6 subjects will be sequentially enrolled starting at dose cohort 1. Subjects will be assessed for dose-limiting toxicities (DLTs).

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 3 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase I Study of Ad5 [E1-, E2b-]-HER2/Neu Vaccine (ETBX-021) in Subjects With Unresectable Locally Advanced or Metastatic HER2-Low-Expressing (IHC 1+/2+) Breast Cancer
Study Start Date : December 2016
Estimated Primary Completion Date : July 2020
Estimated Study Completion Date : December 2020

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Breast Cancer

Arm Intervention/treatment
Experimental: ETBX-021
Ad5 [E1-, E2b-]-HER2/neu Vaccine, Suspension for Injection
Biological: ETBX-021
ETBX-021 is a HER2-targeting vaccine comprising an Ad5 vector and a modified HER2 gene insert.
Other Name: Ad5 [E1-, E2b-]-HER2/neu Vaccine, Suspension for Injection

Primary Outcome Measures :
  1. Determination of maximum tolerated dose (MTD) or highest tested dose (HTD). [ Time Frame: 2 years ]
  2. Occurrence of dose-limiting toxicities (DLTs). [ Time Frame: 2 years ]
  3. Occurrence of treatment-emergent adverse event (AEs) and serious adverse events (SAEs). [ Time Frame: 2 years ]
  4. Number of subjects with clinically significant changes in laboratory values. [ Time Frame: 2 years ]

    Clinically significant changes in:

    • safety laboratory tests
    • physical examinations
    • electrocardiograms (ECGs)
    • left ventricular ejection fraction (LVEF)
    • vital signs

Secondary Outcome Measures :
  1. Objective response rate (ORR) according to the Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1. [ Time Frame: 2 year ]
    ORR is defined as the proportion of patients with a confirmed complete or partial response.

  2. Disease control rate (DCR). [ Time Frame: up to 2 years ]
    DCR is defined as the proportion of patients with confirmed response or stable disease (SD) lasting for at least 6 months.

  3. Duration of response. [ Time Frame: 2 years ]
  4. Progression free survival (PFS). [ Time Frame: 2 years ]
  5. Overall survival (OS). [ Time Frame: 2 years ]

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  1. Age ≥ 18 years.
  2. Male or female.
  3. Ability to understand and provide signed informed consent that fulfills Institutional Review Board (IRB)'s guidelines.
  4. Histologically confirmed unresectable locally advanced or metastatic breast cancer that expresses HER2 (IHC 1+ or 2+), derived from the most recent metastatic biopsy sample available.
  5. Tumor tissue (block or slides) and whole blood sample available for analysis. Archival tissue is permitted.
  6. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
  7. Concurrent hormone therapy is permitted.
  8. Subjects who have received prior HER2-targeted immunotherapy (vaccine) are eligible for this trial if this treatment was discontinued at least 3 months prior to enrollment.
  9. Resolution of all toxic side effects of prior chemotherapy, radiotherapy, or surgical procedures to NCI CTCAE Grade ≤ 1.
  10. Subjects who are taking medications that do not have a known history of immunosuppression are eligible for this trial.
  11. Adequate hematologic function at screening, as follows:

    • White blood count ≥ 3000/microliter.
    • Hemoglobin ≥ 9 g/dL (may not transfuse or use erythropoietin to achieve this level).
    • Platelets ≥ 75,000/microliter.
    • Prothrombin (PT)-international normalized ratio (INR) < 1.5.
    • Partial thromboplastin time (PTT) < 1.5 x upper limit of normal (ULN).
  12. Adequate renal and hepatic function at screening, as follows:

    • Serum creatinine < 2.0 mg/dL.
    • Bilirubin < 1.5 mg/dL (except for Gilbert's syndrome which will allow bilirubin ≤ 2.0 mg/dL).
    • Alanine aminotransferase (ALT) ≤ 2.5 x ULN.
    • Aspartate aminotransferase (AST) ≤ 2.5 x ULN.
  13. Multigated acquisition (MUGA) scan or echocardiogram with LVEF ≥ institutional LLN. Same imaging modality is to be used throughout the study.
  14. Female subjects of childbearing potential and women < 12 months since the onset of menopause must agree to use acceptable contraceptive methods for the duration of the study and for 7 months following the last injection of study medication. If employing contraception, two of the following precautions must be used: vasectomy of partner, tubal ligation, vaginal diaphragm, intrauterine device, condom and spermicidal (gel/foam/cream/vaginal suppository), or total abstinence. Male subjects must be surgically sterile or must agree to use a condom and acceptable contraceptive method with their partner. Female subjects who are post-menopausal are defined as those with an absence of menses for > 12 consecutive months.
  15. Ability to attend required study visits and return for adequate follow up, as required by this protocol.

Exclusion Criteria:

  1. Subjects with HER2 IHC 3+ tumors, or IHC 2+ with an in situ hybridization (ISH) test result considered positive of HER2 amplification by ASCO-CAP HER2 test guidelines.
  2. Subjects with ongoing HER2-directed therapy, including trastuzumab, pertuzumab, T-DM1, and lapatinib.
  3. Participation in an investigational drug or device study within 30 days of screening for this study.
  4. Pregnant and nursing women.
  5. Subjects with ongoing palbociclib, everolimus, or other breast cancer therapy that interferes with the induction of immune responses.
  6. Subjects with concurrent cytotoxic chemotherapy or radiation therapy. There must be at least 1 month between any other prior chemotherapy (or radiotherapy) and study treatment. Any prior HER2-targeted immunotherapy (vaccine) must have been discontinued at least 3 months before initiation of study treatment. Subjects must have recovered from all acute toxicities from prior treatment prior to screening for this study.
  7. Active brain or central nervous system metastasis, seizures requiring anticonvulsant treatment, cerebrovascular accident (< 6 months), or transient ischemic attack.
  8. Subjects with a history of autoimmune disease (active or past), such as but not restricted to inflammatory bowel disease, systemic lupus erythematosus, ankylosing spondylitis, scleroderma, or multiple sclerosis. Autoimmune-related thyroid disease and vitiligo are permitted.
  9. Subjects with serious intercurrent chronic or acute illness, such as cardiac or pulmonary disease, hepatic disease, or other illness considered by the Investigator as high risk for investigational drug treatment.
  10. Subjects with a history of heart disease, such as congestive heart failure (class II, III, or IV defined by the New York Heart Association functional classification), history of unstable or poorly controlled angina, or history (< 1 year) of ventricular arrhythmia.
  11. Subjects with a medical or psychological impediment that would impair the ability of the subject to receive therapy per protocol or impact ability to comply with the protocol or protocol-required visits and procedures.
  12. History of malignancy except for the following: adequately treated non-melanoma skin cancer, cervical carcinoma in situ, superficial bladder cancer, or other carcinoma that has been in complete remission without treatment for more than 5 years.
  13. Presence of a known active acute or chronic infection, including human immunodeficiency virus (HIV, as determined by enzyme-linked immunosorbent assay [ELISA] and confirmed by western blot) and hepatitis B and hepatitis C virus (HBV/HCV, as determined by HBsAg and hepatitis C serology).
  14. Subjects on systemic intravenous or oral steroid therapy (or other immunosuppressives, such as azathioprine or cyclosporin A) are excluded on the basis of potential immune suppression. Subjects must have had at least 6 weeks of discontinuation of any steroid therapy (except that used as premedication for chemotherapy or contrast-enhanced studies) prior to enrollment.
  15. Subjects with known allergy or hypersensitivity to any component of the investigational product will be excluded.
  16. Subjects with acute or chronic skin disorders that will interfere with injection into the skin of the extremities or subsequent assessment of potential skin reactions will be excluded.
  17. Subjects vaccinated with a live (attenuated) vaccine (e.g., FluMist®) or a killed (inactivated)/subunit vaccine (e.g., PNEUMOVAX®, Fluzone®) within 28 days or 14 days, respectively, of the first planned dose of ETBX-021.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT02751528

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United States, California
Chan Soon-Shiong Institute for Medicine
El Segundo, California, United States, 90245
United States, South Dakota
Sanford Cancer Center
Sioux Falls, South Dakota, United States, 57104
Sponsors and Collaborators
NantBioScience, Inc.
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Responsible Party: NantBioScience, Inc. Identifier: NCT02751528    
Other Study ID Numbers: QUILT-3.013
First Posted: April 26, 2016    Key Record Dates
Last Update Posted: August 28, 2019
Last Verified: September 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Keywords provided by NantBioScience, Inc.:
Breast Cancer
Breast Cancer male
Breast Neoplasms
Breast Neoplasms male
Locally Advanced
Solid Tumor
Phase 1
Cancer Vaccine
Additional relevant MeSH terms:
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Breast Neoplasms
Neoplasms by Site
Breast Diseases
Skin Diseases
Immunologic Factors
Physiological Effects of Drugs