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Clinical Trials Search at Vanderbilt-Ingram Cancer Center

Phase I Study of Enadenotucirev and PD-1 Inhibitor in Subjects With Metastatic or Advanced Epithelial Tumors

This is a Phase I multicenter, open label, nonrandomized study of enadenotucirev administered in combination with nivolumab in subjects with metastatic or advanced epithelial tumors (with focus on CRC, SCCHN, UCC, (escalation phase), NSCLC and salivary gland cancer) not responding to standard therapy.
Colon, Head/Neck, Lung, Non Small Cell, Rectal, Urologic
Phase I/II
Mol. targeted/Immunotherapy/Biologics
Enadenotucirev, Nivolumab (BMS-936558)
Not Available
Vanderbilt University


18 Years
Inclusion Criteria:

Adult males or females aged 18 years or over

Disease status:

Dose escalation phase only: Diagnosis of metastatic or advanced CRC, UCC, SCCHN, salivary gland cancer or NSCLC with tumor accessible for biopsy not responding to standard therapy or for whom no standard treatment exists

Dose expansion only: Subjects with pathologically confirmed locally advanced or metastatic disease of the following tumor types:

CRC - MSS or microsatellite MSI-L

SCCHN - Must have received only one line of PDL-1/PD-1 as most recent therapy and Prior radiotherapy must have been completed at least 8 weeks prior to enrolment if radiotherapy was to the head and neck region for curative intent and 2 weeks prior to enrolment if radiotherapy was to other regions

NSCLC - Must have received only one line of prior PDL-1/PD-1 as most recent therapy and no more than two prior lines (for EGFR/ALK wild type) and no more than three prior lines (for EGFR/ALK mutant, including two tyrosine kinase inhibitors)

Dose expansion only: Subjects must have at least one measurable site of disease according to Response Evaluation Criteria in Solid Tumors (RECIST) criteria; this lesion must be outside a previously irradiated area

Prior palliative radiotherapy completed at least 3 weeks before study treatment administration

Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1

Predicted life expectancy of 3 months or more

Ability to comply with study procedures in the Investigator's opinion

Recovered to Grade 1 from the effects (excluding alopecia) of any prior therapy for their malignancies

Non-impaired renal function:

Creatinine ?1.5 mg/dL and estimated glomerular filtration rate (eGFR) ?60 mL/min/1.73m2 or measured creatinine clearance ?60 mL/min

Proteinuria: urine dipstick at screening and baseline negative or trace. Subjects may be included with results of 1+ if they have a spot urinary albumin creatinine ratio (ACR) of either (i) ?3 mg/mmol or (ii) >3 mg-
Adequate hepatic function:

Serum bilirubin
Aspartate aminotransferase and alanine aminotransferase ?3 x upper limit of normal (ULN)

Albumin ?3 g/dL

Lipase: ?1.5 x ULN. Subjects with lipase >1.5 x ULN may enrol if there are neither clinical or radiographic signs of pancreatitis

Amylase: ?1.5 x ULN. Subjects with amylase >1.5 x ULN may enrol if there are neither clinical or radiographic signs of pancreatitis

Adequate bone marrow function:

Absolute neutrophil count ?1.5X10^9/L

Platelets ?100 x 10^9/L

Hemoglobin ?90 g/L

Adequate coagulation tests: international normalized ratio ?1.5

For females of childbearing potential (defined as
Subjects must provide written informed consent to participate

Willing to consent to tumor biopsies during the study

Serum complement (C3/C4 proteins) above the lower limit of normal range

Exclusion Criteria:

Pregnant or breastfeeding females

Known history or evidence of significant immunodeficiency due to underlying illness (e.g. human immunodeficiency virus [HIV]/acquired immunodeficiency syndrome [AIDS]) and/or medication (e.g. systemic corticosteroids or other immunosuppressive medications, including cyclosporine, azathioprine, interferons in the 4 weeks before the first dose of study treatment). Subjects with a condition requiring systemic treatment with either corticosteroids (>10 mg daily prednisolone equivalent) or other immunosuppressive medications within 14 days of the first dose of study treatment. Inhaled or topical steroids and adrenal replacement steroid doses are permitted in the absence of autoimmune disease


Prior allogeneic or autologous bone marrow or organ transplantation

Any history of renal disease, renal injury or auto-immune disease. Subjects with active, known or suspected auto-immune disease or a syndrome that requires systemic or immunosuppressive agents; subjects with vitiligo, type I diabetes mellitus, residual hypothyroidism due to autoimmune disease only requiring hormone replacement, psoriasis not requiring systemic treatment or conditions not expected to recur in the absence of an external trigger are permitted to enrol providing they comply with the other eligibility criteria relating to renal function

History of idiopathic pulmonary fibrosis, drug induced pneumonitis, evidence of active pneumonia or pneumonitis on computed tomography scan

Active infections requiring antibiotics, physician monitoring or recurrent fevers >100.4?F (38.0?C) associated with a clinical diagnosis of active infection

Active viral disease or positive test for hepatitis B virus using hepatitis B surface antigen test or positive test for hepatitis C virus (HCV) using HCV ribonucleic acid or HCV antibody test indicating acute or chronic infection. Positive test for HIV or AIDS; testing is not required in the absence of history

Use of the following antiviral agents: ribavirin, adefovir, lamivudine or cidofovir within 7 days prior to the first dose of study treatment; or pegylated interferon in the 14 days before the first dose of study treatment

Prior treatment with PD-1 and programmed death ligand (PD-L)1 inhibitors

Administration of an investigational drug in the 28 days before the first dose of study treatment

Major surgery or treatment with any chemotherapy, radiation therapy, biologics for cancer or investigational therapy in the 28 days before the first dose of study treatment (subjects with prior cytotoxic or investigational products
Other prior malignancy active within the previous 2 years except for local or organ confined early stage cancer that has been definitively treated with curative intent, does not require ongoing treatment, has no evidence of residual disease and has a negligible risk of recurrence and is therefore unlikely to interfere with the primary and secondary endpoints of the study, including response rate and safety

Symptomatic brain metastases or any leptomeningeal metastasis that is symptomatic and/or requires treatment. Subjects with brain metastases are eligible if these have been locally treated (surgery, radiotherapy). There must also be no requirement for immunosuppressive doses of systemic corticosteroids (>10 mg/day prednisone equivalent) for at least 2 weeks before the first dose of study treatment

Any serious or uncontrolled medical disorder that, in the opinion of the Investigator or the Medical Monitor, may increase the risk associated with study participation or study treatment administration, impair the ability of the subject to receive protocol therapy or interfere with the interpretation of study results

Known allergy to enadenotucirev, nivolumab or their excipients

Any other medical or psychological condition that would preclude participation in the study or compromise ability to give informed consent

Dependence on continuous supplemental oxygen use

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