A Study of CF33-hNIS (VAXINIA), an Oncolytic Virus, as Monotherapy or in Combination With Pembrolizumab in Adults With Metastatic or Advanced Solid Tumors (MAST)

A Phase I, Dose Escalation Safety and Tolerability Study of VAXINIA (CF33-hNIS), Administered Intratumorally or Intravenously as a Monotherapy or in Combination With Pembrolizumab in Adult Patients With Metastatic or Advanced Solid Tumors (MAST).

This is an open-label, dose-escalation, multi-center phase I study evaluating the safety of CF33-hNIS (hNIS - human sodium iodide symporter) administered via two routes of administration, intratumoral (IT) or intravenous (IV), either as a monotherapy or in combination with pembrolizumab or mFOLFOX in patients with metastatic or advanced solid tumors.

Study Overview

• Status: Terminated
• Conditions: Solid Tumor; Metastatic Cancer; Cholangiocarcinoma; Bile Duct Cancer; Advanced Solid Tumor; Solid Tumor, Adult; Solid Carcinoma
• Intervention / Treatment: Biological: CF33-hNIS; Biological: Pembrolizumab; Drug: Modified FOLFOX

Detailed Description

CF33-hNIS, a novel chimeric orthopoxvirus, will be administered as a monotherapy or in combination with pembrolizumab or mFOLFOX to assess the safety and efficacy of the treatment regimens as well as immunological changes in the tumour microenvironment.

Patients eligible for treatment in dose escalation IT/IV cohorts include those with any metastatic or advanced solid tumor who have documented radiological progression per RECIST following at least two prior lines of therapy which may have included treatment with an Immune Checkpoint Inhibitor(ICI). For expansion IT and IV cholangiocarcinoma cohort patients, one prior line of systemic chemotherapy in metastatic/advanced setting is required and for patients with targetable tumor mutations, must have also received 1 line of an approved targeted therapy. For expansion IV cholangiocarcinoma cohort, prior treatment with leucovorin calcium, fluorouracil, or oxaliplatin is not permitted.

For IT/IV cohorts, patients will be treated with CF33-hNIS on Day 1 and 8 of Cycle 1 and then on Day 1 of each cycle thereafter. Patients treated with the combination regimen with pembrolizumab will also receive pembrolizumab Day 1 of each cycle beginning with Cycle 2.

For IV cholangiocarcinoma expansion cohort, patients will be treated with CF33-hNIS on Day 3 and Day 17 of each 28 day cycle along with a modified FOLFOX regimen.

• Study Type: Interventional
• Enrollment (Actual): 66
• Phase: Phase 1

Contacts and Locations

Study Locations

• Australia
  • Queensland
    • Southport, Queensland, Australia, 4215
      • Tasman Oncology Research
  • Victoria
    • Fitzroy, Victoria, Australia, 3065
      • St. Vincent's Hospital
• United States
  • Arizona
    • Tucson, Arizona, United States, 85724-5024
      • University of Arizona Cancer Center
  • Arkansas
    • Springdale, Arkansas, United States, 72762
      • Highlands Oncology
  • California
    • Duarte, California, United States, 91010
      • City of Hope Medical Center
    • La Jolla, California, United States, 92093-0698
      • UC San Diego Moores Cancer Center
  • Florida
    • Miami, Florida, United States, 33136
      • University of Miami
  • Michigan
    • Detroit, Michigan, United States, 48201
      • Barbara Ann Karmanos Cancer Institute
    • Grand Rapids, Michigan, United States, 49503
      • Corewell Health
  • Ohio
    • Cincinnati, Ohio, United States, 45219
      • University of Cincinnati
  • Utah
    • Salt Lake City, Utah, United States, 84112
      • Huntsman Cancer Institute
  • Virginia
    • Fairfax, Virginia, United States, 22031
      • NEXT Oncology

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Written informed consent from patient or legally authorized representative
• Age ≥ 18 years old on the date of consent
• IT/IV cohorts: Any metastatic or advanced solid tumor with documented radiological progression following at least two prior lines of treatment (which may have included prior immune checkpoint inhibitor (ICI) treatment). Expansion cholangiocarcinoma IT and IV cohorts: one prior line of chemotherapy in metastatic/advanced setting. Patients with targetable tumor mutations must have also received 1 line of approved targeted therapy.
• Expansion cholangiocarcinoma IV cohort: prior treatment with leucovorin calcium, fluorouracil, or oxaliplatin is not permitted.
• ECOG performance status 0 - 2
• At least one measurable lesion
• For IT administration, ideally < 5 total lesions no greater than 10cm and <33% of liver volume replaced by tumor.
• Adequate renal function
• Adequate liver function
• Adequate hematologic function
• Willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures

Exclusion Criteria:

• Prior treatment with a poxvirus based oncolytic virus.
• Continuous systemic treatment with either corticosteroids (>10 mg daily prednisone equivalents) or other immunosuppressive medications within 4 weeks prior to first dose of study treatment.
• Prior radiotherapy within 2 weeks of start of study treatment.
• Active autoimmune disease
• Prior allogenic tissue/organ transplant or other medical conditions requiring ongoing treatment with immunosuppressive drugs or any condition resulting in a systemic immunosuppressed state
• Inadequate pulmonary function per Investigator assessment.
• Uncontrolled brain or other central nervous system (CNS) metastases.
• History of documented congestive heart failure (New York Heart Association [NYHA] class III - IV), unstable angina, poorly controlled hypertension, clinically significant valvular heart disease or high-risk uncontrolled arrhythmias

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: CF33-hNIS IT Administration Monotherapy	Biological: CF33-hNIS; CF33-hNIS is a chimeric orthopoxvirus (oncolytic virus) engineered to express the human sodium iodide symporter (hNIS); Other Names: VAXINIA; HOV2
Experimental: CF33-hNIS IV Administration Monotherapy	Biological: CF33-hNIS; CF33-hNIS is a chimeric orthopoxvirus (oncolytic virus) engineered to express the human sodium iodide symporter (hNIS); Other Names: VAXINIA; HOV2
Experimental: CF33-hNIS IT Administration in Combination with Pembrolizumab	Biological: CF33-hNIS; CF33-hNIS is a chimeric orthopoxvirus (oncolytic virus) engineered to express the human sodium iodide symporter (hNIS); Other Names: VAXINIA; HOV2; Biological: Pembrolizumab; Pembrolizumab 200mg administrated IV every 3 weeks (Q3W).; Other Names: KEYTRUDA®
Experimental: CF33-hNIS IV Administration in Combination with Pembrolizumab	Biological: CF33-hNIS; CF33-hNIS is a chimeric orthopoxvirus (oncolytic virus) engineered to express the human sodium iodide symporter (hNIS); Other Names: VAXINIA; HOV2; Biological: Pembrolizumab; Pembrolizumab 200mg administrated IV every 3 weeks (Q3W).; Other Names: KEYTRUDA®
Experimental: CF33-hNIS IV Administration in Combination with modified FOLFOX	Biological: CF33-hNIS; CF33-hNIS is a chimeric orthopoxvirus (oncolytic virus) engineered to express the human sodium iodide symporter (hNIS); Other Names: VAXINIA; HOV2; Drug: Modified FOLFOX; 28 day cycle of: Leucovorin calcium/folinic acid; Fluorouracil; oxaliplatin

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Frequency and severity of Adverse Events of IV and IT CF33-hNIS as a monotherapy or in combination with pembrolizumab	Adverse events will be graded according to CTCAE v5.0.	From first dose of study drug through 30 days following the last dose of study treatment.
Recommended Phase 2 Dose (RP2D) of CF33-hNIS as a monotherapy or in combination with pembrolizumab	RP2D determination will be based on evaluation of Dose Limiting Toxicities (DLT) as well as other safety, efficacy and correlative data.	From first dose of study drug through 21-42 days following the first dose of study treatment.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To evaluate viral titers of CF33-hNIS	Viral Plaque Assay (VPA) and polymerase chain reaction (PCR) testing from serum, urine, oral swab, rectal swab, injection site(s) swab and wound dressing swab.	Up to 2 years from first dose of study drug.
To evaluate infection of tumors with CF33-hNIS	hNIS-based imaging via SPECT technetium-99 (99TC).	21 days from first dose of study drug
Objective Response Rate (ORR) of CF33-hNIS administered as a monotherapy or in combination with pembrolizumab or modified FOLFOX	ORR is defined as the proportion of patients in the efficacy population who achieve a radiographic Investigator-assessed confirmed complete response (CR) or partial response (PR), per RECIST v1.1 or confirmed immune complete response (iCR) or immune partial response (iPR) per iRECIST v1.0.	Up to 2 years from first dose of study drug.
Progression-free survival (PFS) of CF33-hNIS administered as a monotherapy or in combination with pembrolizumab or modified FOLFOX	PFS, defined as the time from start of treatment to the first documentation of progressive disease (PD) or death from any cause, whichever occurs first.	Up to 2 years from first dose of study drug.
Overall survival (OS) of CF33-hNIS administered as a monotherapy or in combination with pembrolizumab or modified FOLFOX	defined as the time from the start of treatment until death due to any cause. Median OS and OS rate at 12 months will be reported.	Up to 2 years from first dose of study drug.
Duration of Response (DOR) of CF33-hNIS administered as a monotherapy or in combination with pembrolizumab or modified FOLFOX	DOR is defined as the time from the date a response of PR/iPR or better was first recorded to the date on which progressive disease was first noted or the date of death due to any cause.	Up to 2 years from first dose of study drug.
Disease Control Rate (DCR) of CF33-hNIS administered as a monotherapy or in combination with pembrolizumab or modified FOLFOX	DCR is defined as the proportion of patients who achieve an Investigator-assessed confirmed CR/iCR, PR/iPR, or Stable Disease (SD)/immune SD (iSD) per RECIST v1.1 and iRECIST v1.0.	Up to 2 years from first dose of study drug.

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
To evaluate antiviral immune activation	Up regulation of PD-L1 expression as compared to baseline in tumor tissue and circulating tumor cells (CTC). Analysis of lymphocyte subsets and cytokine profile compared to baseline.	Up to 2 years from first dose of study drug.

Collaborators and Investigators

• Sponsor: Imugene Limited

Publications and helpful links

Helpful Links

• Imugene Limited (ASX: IMU) is a publicly-listed Australian biotechnology company developing cancer immunotherapies.

Study record dates

Study Major Dates

• Study Start (Actual): May 17, 2022
• Primary Completion (Actual): January 12, 2026
• Study Completion (Actual): January 12, 2026

Study Registration Dates

• First Submitted: March 22, 2022
• First Submitted That Met QC Criteria: April 20, 2022
• First Posted (Actual): April 26, 2022

Study Record Updates

• Last Update Posted (Actual): March 6, 2026
• Last Update Submitted That Met QC Criteria: March 4, 2026
• Last Verified: June 1, 2025

More Information

Terms related to this study

• Keywords: oncolytic virus
• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms by Site; Neoplasms; Neoplasms by Histologic Type; Digestive System Neoplasms; Digestive System Diseases; Biliary Tract Diseases; Neoplasms, Glandular and Epithelial; Adenocarcinoma; Neoplastic Processes; Carcinoma; Bile Duct Diseases; Biliary Tract Neoplasms; Pathological Conditions, Signs and Symptoms; Neoplasm Metastasis; Cholangiocarcinoma; Bile Duct Neoplasms; Antineoplastic Agents, Immunological; Immune Checkpoint Inhibitors; Antineoplastic Agents; Molecular Mechanisms of Pharmacological Action; pembrolizumab
• Other Study ID Numbers: CF33-hNIS-002

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No