NCT05346484

Brief Summary

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.

Trial Health

60
Monitor

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
66

participants targeted

Target at P75+ for phase_1

Timeline
Completed

Started May 2022

Typical duration for phase_1

Geographic Reach
2 countries

12 active sites

Status
terminated

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

March 22, 2022

Completed
1 month until next milestone

First Posted

Study publicly available on registry

April 26, 2022

Completed
21 days until next milestone

Study Start

First participant enrolled

May 17, 2022

Completed
3.7 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

January 12, 2026

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

January 12, 2026

Completed
Last Updated

March 6, 2026

Status Verified

June 1, 2025

Enrollment Period

3.7 years

First QC Date

March 22, 2022

Last Update Submit

March 4, 2026

Conditions

Keywords

oncolytic virus

Outcome Measures

Primary Outcomes (2)

  • 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 Outcomes (7)

  • Objective Response Rate (ORR) of CF33-hNIS administered as a monotherapy or in combination with pembrolizumab or modified FOLFOX

    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

    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

    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

    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

    Up to 2 years from first dose of study drug.

  • +2 more secondary outcomes

Other Outcomes (1)

  • To evaluate antiviral immune activation

    Up to 2 years from first dose of study drug.

Study Arms (5)

CF33-hNIS IT Administration Monotherapy

EXPERIMENTAL
Biological: CF33-hNIS

CF33-hNIS IV Administration Monotherapy

EXPERIMENTAL
Biological: CF33-hNIS

CF33-hNIS IT Administration in Combination with Pembrolizumab

EXPERIMENTAL
Biological: CF33-hNISBiological: Pembrolizumab

CF33-hNIS IV Administration in Combination with Pembrolizumab

EXPERIMENTAL
Biological: CF33-hNISBiological: Pembrolizumab

CF33-hNIS IV Administration in Combination with modified FOLFOX

EXPERIMENTAL
Biological: CF33-hNISDrug: Modified FOLFOX

Interventions

CF33-hNISBIOLOGICAL

CF33-hNIS is a chimeric orthopoxvirus (oncolytic virus) engineered to express the human sodium iodide symporter (hNIS)

Also known as: VAXINIA, HOV2
CF33-hNIS IT Administration MonotherapyCF33-hNIS IT Administration in Combination with PembrolizumabCF33-hNIS IV Administration MonotherapyCF33-hNIS IV Administration in Combination with PembrolizumabCF33-hNIS IV Administration in Combination with modified FOLFOX
PembrolizumabBIOLOGICAL

Pembrolizumab 200mg administrated IV every 3 weeks (Q3W).

Also known as: KEYTRUDA®
CF33-hNIS IT Administration in Combination with PembrolizumabCF33-hNIS IV Administration in Combination with Pembrolizumab

28 day cycle of: * Leucovorin calcium/folinic acid * Fluorouracil * oxaliplatin

CF33-hNIS IV Administration in Combination with modified FOLFOX

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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

You may not qualify if:

  • 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

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (12)

University of Arizona Cancer Center

Tucson, Arizona, 85724-5024, United States

Location

Highlands Oncology

Springdale, Arkansas, 72762, United States

Location

City of Hope Medical Center

Duarte, California, 91010, United States

Location

UC San Diego Moores Cancer Center

La Jolla, California, 92093-0698, United States

Location

University of Miami

Miami, Florida, 33136, United States

Location

Barbara Ann Karmanos Cancer Institute

Detroit, Michigan, 48201, United States

Location

Corewell Health

Grand Rapids, Michigan, 49503, United States

Location

University of Cincinnati

Cincinnati, Ohio, 45219, United States

Location

Huntsman Cancer Institute

Salt Lake City, Utah, 84112, United States

Location

NEXT Oncology

Fairfax, Virginia, 22031, United States

Location

Tasman Oncology Research

Southport, Queensland, 4215, Australia

Location

St. Vincent's Hospital

Fitzroy, Victoria, 3065, Australia

Location

Related Links

MeSH Terms

Conditions

Neoplasm MetastasisCholangiocarcinomaBile Duct Neoplasms

Interventions

pembrolizumab

Condition Hierarchy (Ancestors)

Neoplastic ProcessesNeoplasmsPathologic ProcessesPathological Conditions, Signs and SymptomsAdenocarcinomaCarcinomaNeoplasms, Glandular and EpithelialNeoplasms by Histologic TypeBiliary Tract NeoplasmsDigestive System NeoplasmsNeoplasms by SiteBile Duct DiseasesBiliary Tract DiseasesDigestive System Diseases

Study Design

Study Type
interventional
Phase
phase 1
Allocation
NON RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
SEQUENTIAL
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

March 22, 2022

First Posted

April 26, 2022

Study Start

May 17, 2022

Primary Completion

January 12, 2026

Study Completion

January 12, 2026

Last Updated

March 6, 2026

Record last verified: 2025-06

Locations