Phase 1b Dose Escalation Study of Intravenous JX-594 in Metastatic, Refractory Colorectal Carcinoma

A Phase 1b Dose Escalation Study of JX-594 (Thymidine Kinase-Inactivated Vaccinia Virus Plus GM-CSF) Administered by Biweekly (Every Two Weeks) Intravenous Infusion in Patients With Metastatic, Refractory Colorectal Carcinoma

The purpose of this pilot safety study is to evaluate the safety and tolerability of JX-594 (Pexa-Vec) administered intravenously every 2 weeks in colorectal carcinoma patients who are refractory to or intolerant of oxaliplatin, irinotecan, and Erbitux treatments.

Study Overview

• Status: Completed
• Conditions: Carcinoma, Colorectal
• Intervention / Treatment: Drug: Recombinant Vaccinia GM-CSF; RAC VAC GM-CSF (JX-594)

Detailed Description

This is a Phase Ib, open-label, dose-escalation study designed to evaluate the safety and tolerability of Pexa-Vec (JX-594), a vaccinia GM-CSF/thymidine kinase-deactivated virus, administered intravenously in patients with advanced/metastatic colorectal carcinoma (CRC) that is refractory to standard therapy. Vaccinia virus, from which Pexa-Vec is derived, shows a natural selectivity toward cancer relative to normal tissues after intravenous (IV) administration.

The study utilizes a sequential dose-escalating design to determine the maximum tolerated dose (MTD) and/or maximum feasible dose (MFD). Patients will receive 4 biweekly treatments of Pexa-Vec administered by IV infusion over 60 minutes on Days 1, 15, 29, and 43. Patients will be sequentially enrolled into one of three dose cohorts:

• Cohort 1: 1 × 10^6 pfu/kg
• Cohort 2: 1 × 10^7 pfu/kg
• Cohort 3: 3 × 10^7 pfu/kg Three patients will be treated at each dose level unless a dose-limiting toxicity (DLT) is observed, at which point the cohort may be expanded. All patients will receive hydration and will be observed in the clinic and/or hospital for a minimum of 24 hours after each infusion.

In addition to safety endpoints, secondary objectives include the evaluation of Pexa-Vec pharmacokinetics (PK), pharmacodynamics, immune response, and preliminary anti-tumoral activity. Tumor response assessments will be conducted using CT or MRI on Days 29 and 57 (±2 days) based on Response Evaluation Criteria in Solid Tumors (RECIST).

• Study Type: Interventional
• Enrollment (Actual): 15
• Phase: Phase 1

Contacts and Locations

Study Locations

• South Korea
  • Seoul, South Korea
    • Samsung Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Histologically-confirmed, advanced/metastatic colorectal carcinoma
• Failed both oxaliplatin and irinotecan based regimens for advanced/metastatic disease (if tumor advanced either immediately or within 3 months of the end of treatment)
• Resistance to Erbitux: patients with Ras mutations, or for whom Erbitux has failed (if tumor advanced either immediately or within 3 months of the end of treatment, or there is no response to Erbitux therapy due to a lack of expression of EGFR (epidermal growth factor))
• Karnofsky Performance Score (KPS) ≥ 70
• Age ≥18 years
• Laboratory Safety: WBC ≥ 3,500 cells/mm3 and ≤ 50,000 cells/mm3, ANC ≥ 1,500 cells/mm3, Hemoglobin ≥ 10 g/dL (transfusion allowed), Platelet count ≥ 100,000 plts/mm3,Total bilirubin ≤ 1.5 X ULN, INR ≤ 1.5, AST, ALT ≤ 2.5x ULN (in case of liver metastasis: AST,ALT ≤5.0 x ULN)
• Serum chemistries within normal limits (WNL) or Grade 1 (excluding alkaline phosphatase) - If patients are diabetic, a fasting glucose must be done and patients must be > 160 mg/dL.
• Patients who, if they are sexually active, are willing and able to refrain from sexual activity for 3 weeks following JX-594 administration. Patients who are willing and able to use a permitted contraceptive for 3 months after the final administration of JX-594.

Exclusion Criteria:

• Significant immunodeficiency due to underlying illness (e.g. HIV/AIDS) and/or medication (e.g. systemic corticosteroids)
• Known myeloproliferative disorders requiring systemic therapy
• History of exfoliative skin condition (e.g. eczema or ectopic dermatitis) requiring systemic therapy
• History of acquiring opportunistic infections.
• Tumor(s) invading a major vascular structure (e.g. carotid artery)
• Tumor(s) in location that would potentially result in significant clinical adverse effects if post-treatment tumor swelling were to occur
• Clinically uncontrolled and/or rapidly accumulating ascites, pericardial and/or pleural effusions
• History of severe or unstable cardiac disease
• Current, known CNS malignancy (history of completely resected or irradiated brain metastases by WBRT or stereotactic radiosurgery allowed)
• Administered anti-cancer therapy within 4 weeks prior to first treatment (6 weeks in case of mitomycin C or nitrosoureas)
• Use of anti-viral, anti-platelet, or anti-coagulation medication [Patients who discontinue such medications within 7 days prior to first treatment may be eligible for this study.] Low dose aspirin (approximately 81 mg) allowed.
• Pulse oximetry O2 saturation <90% Pulse oximetry O2 saturation <90% at rest
• Experienced a severe systemic reaction or side-effect as a result of a previous smallpox vaccination
• Pregnant or nursing
• Household contact exclusions:
• Women who are pregnant or nursing an infant
• Children < 5 years old
• People with skin disease (e.g. eczema, atopic dermatitis, and related diseases
• Immunocompromised hosts (severe deficiencies in cell-mediated immunity, including AIDS, organ transplant recipients, hematologic malignancies)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: single arm; Dose escalation; Dose escalation 1e6 pfu/kg bw, 1e7 pfu/kg bw, 3e7 pfu/kg bw of Recombinant Vaccinia GM-CSF JX-594	Drug: Recombinant Vaccinia GM-CSF; RAC VAC GM-CSF (JX-594); Intravenous Dose Range: 1x10^6 pfu/kg, 1x10^7 pfu/kg, 3x10^7 pfu/kg Up to 4 intravenous infusions administered over 60 minutes every 2 weeks.; Other Names: JX-594

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants Experiencing Dose-Limiting Toxicities (DLTs)	A DLT is defined as any of the following treatment-related adverse events: Grade 4 toxicity, Grade 3 hematologic toxicity for > 5 days, or Grade 3 non-hematologic toxicities persisting for > 7 days except for flu-like symptoms that respond to standard therapies. The number of participants with DLTs was used to determine the Maximally-Tolerated Dose (MTD) and/or Maximum-Feasible Dose (MFD) of JX-594.	Up to Day 57 (assessed through 14 days following the 4th and final biweekly JX-594 infusion, an average of 8 weeks).
Number of Participants With Treatment-Emergent Adverse Events (TEAEs)	Adverse events were collected and assessed to evaluate safety and tolerability. A Treatment-Emergent Adverse Event (TEAE) is defined as an event with a start date on or after the date of the first dose of study treatment, or an event present at baseline that worsened in severity after the first dose.	Up to Day 71 (assessed through 28 days following the 4th and final biweekly JX-594 infusion, an average of 10 weeks).

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants in Each Best Overall Tumor Response Category Based on RECIST	Anti-tumoral response was evaluated using Response Evaluation Criteria in Solid Tumors (RECIST) on CT or MRI. Categories include: Complete Response (CR) = Disappearance of all target lesions; Partial Response (PR) = >=30% decrease in the sum of the longest diameters of target lesions; Progressive Disease (PD) = >=20% increase in the sum of the longest diameters of target lesions or appearance of new lesions; Stable Disease (SD) = Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD.	Up to Day 57 (Week 8)
Overall Survival (OS)	Overall survival (OS) was defined as the time from the first dose of Pexa-Vec until death from any cause. For patients not known to have died at the time of the analysis, OS was censored on the date they were last known to be alive.	From the first dose of Pexa-Vec until death from any cause, assessed up to 24 months

Collaborators and Investigators

• Sponsor: Jennerex Biotherapeutics
• Collaborators: Samsung Medical Center
• Investigators: Principal Investigator: Young Suk Park, MD, Samsung Medical Center

Study record dates

Study Major Dates

• Study Start: September 8, 2010
• Primary Completion (Actual): October 18, 2012
• Study Completion (Actual): October 18, 2012

Study Registration Dates

• First Submitted: June 22, 2011
• First Submitted That Met QC Criteria: June 22, 2011
• First Posted (Estimated): June 27, 2011

Study Record Updates

• Last Update Posted (Actual): July 8, 2026
• Last Update Submitted That Met QC Criteria: June 11, 2026
• Last Verified: June 1, 2026

More Information

Terms related to this study

• Keywords: Colorectal cancer; Rectal Cancer; Colon Cancer; Vaccinia; Vaccinia Virus; JX-594; Jennerex; Colorectal Carcinoma; Pexa-Vec
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Intestinal Diseases; Infections; Virus Diseases; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Colonic Diseases; Poxviridae Infections; DNA Virus Infections; Rectal Neoplasms; Colorectal Neoplasms; Colonic Neoplasms; Vaccinia; Physiological Effects of Drugs; Antineoplastic Agents; Immunologic Factors; Sargramostim; Molgramostim
• Other Study ID Numbers: JX594-IV-CRC014

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No