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

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

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.

Study Overview

• Status: Terminated
• Conditions: Cancer
• Intervention / Treatment: Biological: ETBX-021

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).

• Study Type: Interventional
• Enrollment (Actual): 3
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • El Segundo, California, United States, 90245
      • Chan Soon-Shiong Institute for Medicine
  • South Dakota
    • Sioux Falls, South Dakota, United States, 57104
      • Sanford Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / 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 Names: Ad5 [E1-, E2b-]-HER2/neu Vaccine, Suspension for Injection

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Number of Participants With Treatment-emergent Adverse Events, Number of Participants With Treatment Emergent Serious Adverse Events, and Number of Participants With Dose Limiting Toxicities (DLTs)	Up to 12 months
Determine the Maximum Tolerated Dose (MTD) or Highest Tested Dose (HTD)	Up to 11 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
ORR (Confirmed Complete or Partial Response)	ORR assessed according to the Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1.	Up to 11 months
Disease Control Rate (DCR)	Confirmed response or stable disease lasting for at least 6 months according to RECIST V1.1	Up to 11 months
Duration of Response	The duration of overall response is measured from the time measurement criteria are met for CR or PR (whichever is first recorded) until the first date that recurrence or PD is objectively documented (taking as reference for PD the smallest measurements recorded since the treatment started).	Up to 11 months
Progression Disease Survival	PFS was defined as the time from the date of first treatment to the date of disease progression or death (any cause) whichever occurred first.	Up to 2 years
Overall Survival	OS will be defined as the time from the date of first treatment to the date of death (any cause).	Up to 2 years

Collaborators and Investigators

• Sponsor: NantBioScience, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): March 4, 2017
• Primary Completion (Actual): August 16, 2018
• Study Completion (Actual): August 16, 2018

Study Registration Dates

• First Submitted: April 11, 2016
• First Submitted That Met QC Criteria: April 25, 2016
• First Posted (Estimated): April 26, 2016

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: November 22, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Keywords: Breast Cancer; HER2; Vaccine; Phase 1; Metastatic; Unresectable; Locally Advanced; Solid Tumor; Breast Neoplasms; Cancer Vaccine; Breast Cancer male; Breast Neoplasms male
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Skin Diseases; Breast Diseases; Breast Neoplasms; Immunologic Factors; Physiological Effects of Drugs; Vaccines
• Other Study ID Numbers: QUILT-3.013

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No