Binary Oncolytic Adenovirus in Combination With HER2-Specific Autologous CAR VST, Advanced HER2 Positive Solid Tumors

NCT03740256 | Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: H-43405 VISTA
• Study Type: interventional
• Target: 45
• Locations: 1 country
• Sites: 1

Brief Summary

This study is a first in human Phase 1 study that involves patients with a type of cancer called HER2 (Human Epidermal Growth Factor Receptor 2) positive cancer. This study asks patients to volunteer to take part in a research study investigating the safety and efficacy of using special immune cells called HER2 chimeric antigen receptor specific cytotoxic T lymphocytes (HER2 specific CAR T cells), in combination with intra-tumor injection of CAdVEC, an oncolytic adenovirus that is designed to help the immune system including HER2 specific CAR T cell react to the tumor. The study is looking at combining these two treatments together, because we think that the combination of treatments will work better than each treatment alone. We also hope to learn the best dose level of the treatments and whether or not it is safe to use them together. In this study, CAdVEC will be injected into participants tumor at one tumor site which is most easiest to reach. Once it infects the cancer cells, activation of the immune response will occur so it can attack and kill cancer cells. (This approach may have limited effects on the other tumor sites that have not received the oncolytic virus injection, so, patients will also receive specific T cells following the intratumor CAdVEC injection.) These T cells are special infection-fighting blood cells that can kill cells infected with viruses and tumor cells. Investigators want to see if these cells can survive in the blood and affect the tumor. Both CAdVEC and HER2-specific autologous CAR T are investigational products. They are not approved by the FDA.

Conditions

Bladder Cancer; Head and Neck Squamous Cell Carcinoma; Cancer of the Salivary Gland; Lung Cancer; Breast Cancer; Gastric Cancer; Esophageal Cancer; Colorectal Cancer; Pancreatic Adenocarcinoma; Solid Tumor

Keywords

HER2; Human Epidermal Growth Factor Receptor 2; Bladder; Head and Neck Squamous Cell Carcinoma; Salivary Gland; Lung; Breast; Gastric; Esophageal; Colorectal; Pancreatic; Solid Tumor

Outcome Measures

Primary Outcomes (1)

• Number of patients with dose limiting toxicity (DLT) by CTCAE 5.0

  Incidence of dose limiting toxicities (DLT) of CAdVEC intratumoral injection in combination with HER2.CAR AdVST cells in patients with advanced refractory HER2 positive solid tumors.

  4 weeks after the HER2.CAR AdVST infusion or 4 weeks + 3 days after the CAdVEC injection.

Secondary Outcomes (5)

• Overall Response Rate (ORR) according to RECIST1.1 criteria

  13 weeks

• Disease Control Rate (DCR)

  13 weeks

• Progression Free Survival (PFS)

  15 years

• Overall Survival (OS)

  15 years

• Number of treatment related adverse events with grade 3 or greater severity by CTCAE 5.0

  30 days

Study Arms (1)

Treatment Phase

EXPERIMENTAL

Five dose levels will be evaluated using the BOIN design. Cohorts of size 3 will be enrolled at each dose level until 9 evaluable patients have been studied at a single dose. Each patient will receive an intratumoral injection of CAdVEC alone on Day 1 or combined with an injection of HER2.CAR.T cells on Day 4, according to the following dose levels: Dose Level 1 CAdVEC = 5.00E+9 HER2 specific CAR-T cells = 0 Dose Level 2 CAdVEC = 1.00E+10 HER2 specific CAR-T cells = 0 Dose Level 3 CAdVEC = 1.00E+10 HER2 specific CAR-T cells = 1.00E+06 Dose Level 4 CAdVEC = 1.00E+10 HER2 specific CAR-T cells = 1.00E+07 Dose Level 5 CAdVEC = 1.00E+10 HER2 specific CAR-T cells = 1.00E+08

Biological: CAdVEC

Interventions

CAdVEC BIOLOGICAL

The intratumoral administration of CAdVEC will create a pro-inflammatory tumor microenvironment and will promote the recruitment and expansion of adoptively transferred HER2 specific CAR T cells via CAR (tumor antigen). We expect HER2 CAR T cells expanded at primary tumor sites will re-circulate and target metastasized tumors. The combination we propose to test has the potential to overcome each of the established individual limitations of oncolytic viruses and of CAR T-cells. Testing each element separately would not be beneficial or informative, since the combination therapy is anticipated to have unique profiles of both therapeutic benefit and potential toxicities.

Also known as: HER2-specificCAR- T

Treatment Phase

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• This study will look at solid tumors (as a basket trial for any solid cancer) with HER2 positivity based on IHC
• The patient has a histologically confirmed advanced refractory HER2 positive solid tumor, including but not limited to: head and neck squamous cell carcinoma; cancer of the salivary glands; lung cancer; breast cancer; bladder cancer; gastric cancer; esophageal cancer; colorectal cancer; and pancreatic adenocarcinoma. HER2 positivity is defined as ≥2+ staining by IHC with either the FDA-approved CB11 antibody (Leica) or anti HER2/neu (4B5) (VENTANA), which refers to greater than weak-to-moderate staining intensity in \>10% tumor cells.
• The disease must be deemed unsuitable for curative treatments including surgery, radiotherapy, systemic therapy, including checkpoint inhibitors, or any combination of the above modalities by the referring oncology physician and confirmed by the senior oncologists leading the protocol.
• Disease must have progressed after standard first line therapy, or without available effective treatment options. Patients are still eligible if they have failed more than one line of therapy.
• The patient must have at least one tumor site appropriate for intratumoral injection.
• The patient must have radiographically measurable disease as per RECIST 1.1.
• Life expectancy more than 12 weeks.
• The patient is ≥ 18 years of age, able to understand and give informed consent to study related procedures and treatments.

You may not qualify if:

• History or evidence of active autoimmune disease requiring continuous systemic corticosteroids (with more than 10mg/day prednisone or equivalent dose), immunosuppressants or other disease modifying agents (except palliative radiation).
• Evidence of significant immunosuppressive conditions, such as the following:
• Post organ transplant.
• Diagnosis of HIV or other immunodeficiency disorders.
• Diagnosis of other malignancies within 5 years except for cutaneous basal cell or squamous cell carcinoma, well-differentiated thyroid cancer, or localized prostate cancer.
• Patients with known active hepatitis B or C infection.
• Patient has had acute myocardial infarction within 6 months prior to consent for procurement.
• Injectable tumor site is considered to incur a significant risk of major hemorrhage (e.g. located in the CNS (brain), and proximal to critical neurovascular structures) per investigator's review.
• Uncontrolled intercurrent illness including but not limited to psychiatric illness and or social situations that in the opinion of the investigator would compromise compliance of study requirements or put the patient at unacceptable risk.
• Histologically confirmed advanced refractory HER2 positive solid tumors, including but not limited to: head and neck squamous cell carcinoma; cancer of the salivary glands; lung cancer; breast cancer; bladder cancer; gastric cancer; esophageal cancer; colorectal cancer; and pancreatic adenocarcinoma. HER2 positivity is defined as ≥2+ staining by IHC with either the FDA-approved CB11 antibody (Leica) or anti HER2/neu (4B5) (VENTANA), which refers to greater than weak-to-moderate staining intensity in \>10% tumor cells (HER2 positivity requirement is excluded in DL1 and DL2 as HER2 targeted agents are not used).
• The disease must be deemed unsuitable for curative treatments including surgery, radiotherapy, systemic therapy, including checkpoint inhibitors, or any combination of the above modalities by the referring oncology physician and confirmed by the senior oncologists leading the protocol.
• Disease must have progressed after standard first line therapy, or without available effective treatment options. Patients are still eligible if they have failed more than one line of therapy.
• The patient must have at least one tumor site appropriate for intratumoral injection.
• The patient must have radiographically measurable disease as per RECIST 1.1.
• The patient must have adequate organ function within 7 days prior to treatment as indicated by following measures:

Sponsors & Collaborators

• Baylor College of Medicine: lead
• The Methodist Hospital Research Institute: collaborator

Study Sites (1)

Baylor St. Luke's Medical Center

Houston, Texas, 77030, United States

RECRUITING

MeSH Terms

Conditions

Urinary Bladder Neoplasms; Squamous Cell Carcinoma of Head and Neck; Salivary Gland Neoplasms; Lung Neoplasms; Breast Neoplasms; Stomach Neoplasms; Esophageal Neoplasms; Colorectal Neoplasms

Condition Hierarchy (Ancestors)

Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Urinary Bladder Diseases; Urologic Diseases; Male Urogenital Diseases; Carcinoma, Squamous Cell; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Head and Neck Neoplasms; Mouth Neoplasms; Mouth Diseases; Stomatognathic Diseases; Salivary Gland Diseases; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Diseases; Respiratory Tract Diseases; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Stomach Diseases; Esophageal Diseases; Intestinal Neoplasms; Colonic Diseases; Intestinal Diseases; Rectal Diseases

Study Officials

• Shalini Makawita, MD

  Baylor College of Medicine

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Shalini Makawita, MD

CONTACT

832-957-6500; Shalini.Makawita@bcm.edu

Dustin McFadden

CONTACT

832-824-3855; Dustin.McFadden@bcm.edu

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor, Center for Cell and Gene Therapy

Study Record Dates

• First Submitted: November 9, 2018
• First Posted: November 14, 2018
• Study Start: December 14, 2020
• Primary Completion (Estimated): December 30, 2026
• Study Completion (Estimated): December 30, 2038
• Last Updated: February 6, 2026

Record last verified: 2026-02

Locations

US (1)