Clinical Trials /

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

NCT02636036

Description:

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.

Related Conditions:
  • Colorectal Carcinoma
  • Head and Neck Squamous Cell Carcinoma
  • Non-Small Cell Lung Carcinoma
  • Salivary Gland Carcinoma
  • Urothelial Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: Phase I Study of Enadenotucirev and PD-1 Inhibitor in Subjects With Metastatic or Advanced Epithelial Tumors
  • Official Title: A Phase I Multicenter, Open Label Study of Enadenotucirev Combined With PD-1 Inhibitor in Subjects With Metastatic or Advanced Epithelial Tumors

Clinical Trial IDs

  • ORG STUDY ID: ColoAd1-1003
  • NCT ID: NCT02636036

Conditions

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

Interventions

DrugSynonymsArms
enadenotucirevenadenotucirev and nivolumab
nivolumabenadenotucirev and nivolumab

Purpose

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.

Trial Arms

NameTypeDescriptionInterventions
enadenotucirev and nivolumabExperimental
  • enadenotucirev
  • nivolumab

Eligibility Criteria

        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-<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
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Incidence, nature and severity of adverse events (safety and tolerability) in study of enadenotucirev administered in combination with a PD-1 inhibitor
Time Frame:12 months
Safety Issue:
Description:Review of adverse events including serious adverse events (SAEs), adverse events meeting protocol defined DLT criteria, adverse events leading to study treatment or study discontinuation, and adverse events resulting in death

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:PsiOxus Therapeutics Ltd

Last Updated

February 28, 2019