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

NCT02636036 | Completed Phase 1 DMC

• 1 other identifier: ColoAd1-1003
• Study Type: interventional
• Target: 51
• Locations: 1 country
• Sites: 6

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, escalation phase), not responding to standard therapy.

Conditions

Colorectal Cancer; Squamous Cell Carcinoma of the Head and Neck; Epithelial Tumor

Keywords

metastatic; epithelial; advanced

Outcome Measures

Primary Outcomes (2)

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

  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

  12 months

• Maximum Tolerated and/or Maximum Feasible Dose

  Maximum tolerated dose (MTD) / maximum feasible dose (MFD) of enadenotucirev administered IV in combination with nivolumab.

  12 months

Study Arms (1)

enadenotucirev and nivolumab

EXPERIMENTAL

Biological: enadenotucirev; Biological: nivolumab

Interventions

enadenotucirev BIOLOGICAL

enadenotucirev and nivolumab

nivolumab BIOLOGICAL

enadenotucirev and nivolumab

Eligibility Criteria

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

You may qualify if:

• Adult males or females aged 18 years or over
• Disease status: - Diagnosis of metastatic or advanced CRC, UCC, SCCHN, salivary gland cancer or NSCLC not responding to standard therapy or for whom no standard treatment exists
• For patients who have received prior PD-1 / PD-L1 therapy (Cohorts 7A and 7B and dose expansion phase only): Prior PD-1 / PD-L1 inhibitor therapy in current line of treatment for ≥6 weeks and ≤4 months, with best response of stable disease or progressive disease
• 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 Adequate lung function
• Adequate renal function
• Adequate hepatic function
• Adequate bone marrow function
• Adequate coagulation tests: PT and aPTT within normal range or international normalized ratio (INR) ≤1.5
• Meeting reproductive status requirements
• Subjects must provide written informed consent to participate
• Willing to consent to tumour biopsies during the study

You may not qualify if:

• Pregnant or breastfeeding females
• Known history or evidence of significant immunodeficiency due to underlying illness
• Splenectomy
• Prior allogeneic or autologous bone marrow or organ transplantation
• Any history of renal disease, renal injury or auto-immune disease.
• History of idiopathic pulmonary fibrosis, drug induced pneumonitis, evidence of active pneumonia or pneumonitis on computed tomography scan
• Clinically or radiologically suspected, or evidence of, lymphangitic carcinomatosis
• 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 4 weeks before the first dose of study treatment
• For Cohort 1 to 6:Prior treatment with PD-1 and programmed death ligand (PD-L)1 inhibitors
• For Cohorts 7A and 7B and dose expansion phase: History of Grade \>2 or currently uncontrolled immune-related AEs while being treated with PD-1 / PD-L1 inhibitors
• For Cohorts 7A and 7B and dose expansion phase: Patients with progressive disease with ≥50% increase in disease burden from start of PD-1 / PD-L1 inhibitor therapy in the most recent line of treatment are excluded
• Major surgery or treatment with any chemotherapy (bisphosphonate therapy or treatment with receptor activator of nuclear factor kappa-Β l(RANK)-ligand inhibitors for metastatic bone disease is permitted), biologics for cancer or investigational therapy in the 28 days before the first dose of study treatment (patients 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 and decision is supported by the half-life of previous therapy). All toxicities attributed to prior anti-cancer therapy other than alopecia must have resolved to Grade 1 or baseline before the first dose of study treatment. Patients 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 enroll Note: This does not apply to anti-PD-1 / PD-L1 if in the patient's current line of therapy, and anti-PD-1 / PD-L1 treatment may continue during screening
• Other prior malignancy active within the previous 3 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

Sponsors & Collaborators

• Akamis Bio: lead
• Bristol-Myers Squibb: collaborator
• Syneos Health: collaborator

Study Sites (6)

University of Arizona Cancer Center, 1515 North Campbell Ave.

Tucson, Arizona, 85724, United States

Location

City of Hope Comprehensive Cancer Center, 1500 E Duarte Str.

Duarte, California, 91010, United States

Location

UCLA Medical Center, 10945 Le Conte Ave, Ste. 3360

Santa Monica, California, 90095, United States

Location

Horizon Oncology Research, 1345 Unity Place, Suite 365

Lafayette, Indiana, 47905, United States

Location

Henry Ford Hospital, 2799 West Grand Blvd.

Detroit, Michigan, 48202, United States

Location

Vanderbilt-Ingram Cancer Center

Nashville, Tennessee, 37232-6307, United States

Location

Related Publications (2)

• Fakih M, Harb W, Mahadevan D, Babiker H, Berlin J, Lillie T, Krige D, Carter J, Cox C, Patel M, Parfitt L, Powell M, Rosen L. Safety and efficacy of the tumor-selective adenovirus enadenotucirev, in combination with nivolumab, in patients with advanced/metastatic epithelial cancer: a phase I clinical trial (SPICE). J Immunother Cancer. 2023 Apr;11(4):e006561. doi: 10.1136/jitc-2022-006561.

  PMID: 37094988 DERIVED

• Khalil DN, Prieto Gonzalez-Albo I, Rosen L, Lillie T, Stacey A, Parfitt L, Soff GA. A tumor-selective adenoviral vector platform induces transient antiphospholipid antibodies, without increased risk of thrombosis, in phase 1 clinical studies. Invest New Drugs. 2023 Apr;41(2):317-323. doi: 10.1007/s10637-023-01345-8. Epub 2023 Mar 10.

  PMID: 36897458 DERIVED

MeSH Terms

Conditions

Colorectal Neoplasms; Squamous Cell Carcinoma of Head and Neck; Carcinoma; Neoplasm Metastasis

Interventions

enadenotucirev; Nivolumab

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases; Carcinoma, Squamous Cell; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Head and Neck Neoplasms; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Tom Lillie, MD

  Psioxus Theraputics

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 20, 2015
• First Posted: December 21, 2015
• Study Start: January 25, 2016
• Primary Completion: October 8, 2021
• Study Completion: October 8, 2021
• Last Updated: November 9, 2021

Record last verified: 2021-11

Data Sharing

• IPD Sharing: Will not share

Locations

US (6)