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BRIEF TITLE: Study of Enadenotucirev Combined With PD-1 Inhibitor in Subjects With Metastatic or Advanced Epithelial Tumors

A Phase I Multicenter, Open Label Study of Enadenotucirev Combined With PD-1 Inhibitor in Subjects With Metastatic or Advanced Epithelial Tumors

  • Org Study ID: ColoAd1-1003
  • Secondary ID:
  • NCT ID: NCT02636036
  • NCT Alias:
  • Sponsor: PsiOxus Therapeutics Ltd - Industry
  • Source: PsiOxus Therapeutics Ltd

Brief Summary

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.

Overal Status Start Date Phase Study Type
Recruiting January 2016 Phase 1 Interventional

Primary Outcomes:

Primary Outcome 1 - Measure: Incidence, nature and severity of adverse events (safety and tolerability) in study of enadenotucirev administered in combination with a PD-1 inhibitor

Primary Outcome 1 - Time Frame: 12 months

Primary Outcome 2 - Measure: Maximum Tolerated and/or Maximum Feasible Dose

Primary Outcome 2 - Time Frame: 12 months


  • Colorectal Cancer
  • Bladder Carcinoma
  • Squamous Cell Carcinoma of the Head and Neck
  • Salivary Gland Cancer
  • Non Small Cell Lung Cancer


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

- 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

- 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-<70 mg/mmol with a 24 hour
urinary protein <0.2 g/24 hours

- Adequate hepatic function:

- Serum bilirubin <1.5 mg/dL (except subjects with Gilbert's syndrome who may have
total bilirubin <3.0 mg/mL)

- 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 <2 years after last menstruation or
not surgically sterile), a negative serum pregnancy test must be documented within 72
hours of the first dose of study treatment For females who are not postmenopausal (24
months of amenorrhea) or surgically sterile (absence of ovaries and/or uterus):
agreement to use two adequate methods of contraception, during the study treatment
period and for at least 5 months after the last dose of study treatment For males:
agreement to use a barrier method of contraception during the study treatment period
and for at least 7 months after the last dose of study treatment

- 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

- Splenectomy

- 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 <3 weeks prior to
study treatment might be eligible after discussion between the Investigator and
Medical Monitor, if toxicities from the prior treatment have been resolved to NCI
CTCAE Grade 1). All toxicities attributed to prior anti-cancer therapy other than
alopecia and fatigue must have resolved to Grade 1 or baseline before the first dose
of study treatment. Subjects with toxicities attributed to prior anti-cancer therapy
which are not expected to resolve and result in long lasting sequelae, such as
neuropathy after platinum based therapy, are permitted to enrol

- 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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Gender: All

Minimum Age: 18 Years

Maximum Age: N/A

Healthy Volunteers: No

Overall Contact

Name: PsiOxus Therapeutics




Facility Status Contact
University of Arizona Cancer Center, 1515 North Campbell Ave.
Tucson, Arizona 85724
United States
Recruiting Daruka Mahadevan, MD
City of Hope Comprehensive Cancer Center, 1500 E Duarte Str.
Duarte, California 91010
United States
Recruiting Marwan Fakih, MD
UCLA Medical Center, 10945 Le Conte Ave, Ste. 3360
Santa Monica, California 90095
United States
Recruiting Lee Rosen, MD
Horizon Oncology Research, 1345 Unity Place, Suite 345
Lafayette, Indiana 47905
United States
Recruiting Wael Harb, MD
Henry Ford Hospital, 2799 West Grand Blvd.
Detroit, Michigan 48202
United States
Recruiting Ding Wang, MD
Vanderbilt-Ingram Cancer Center
Nashville, Tennessee 37232-6307
United States
Recruiting Jordan Berlin, MD