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

Solid Tumor Clinical Trial

— MAST  

Official title:

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).

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05346484
• Other study ID #: CF33-hNIS-002
• Status: Recruiting
• Phase: Phase 1
• Start date: May 17, 2022
• Est. completion date: January 2025

Study information

• Verified date: May 2024
• Source: Imugene Limited
• Contact: Lisa Guttman
• Phone: 61 2 9423 0881
• Email: info[@]imugene.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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 in patients with metastatic or advanced solid tumors.

Description:

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

Patients eligible for treatment 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.

All enrolled 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 will also received pembrolizumab beginning on Day 1 of each cycle beginning with Cycle 2.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 100
• Est. completion date: January 2025
• Est. primary completion date: December 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Written informed consent from patient or legally authorized representative

• Age = 18 years old on the date of consent

• 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 treatment)

• ECOG performance status 0 - 2

• At least one measurable lesion

• 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

Related Conditions & MeSH terms

• Advanced Solid Tumor
• Bile Duct Cancer
• Bile Duct Neoplasms
• Cholangiocarcinoma
• Metastatic Cancer
• Neoplasms
• Solid Carcinoma
• Solid Tumor
• Solid Tumor, Adult

Intervention

Biological:
• CF33-hNIS
CF33-hNIS is a chimeric orthopoxvirus (oncolytic virus) engineered to express the human sodium iodide symporter (hNIS)
• Pembrolizumab
Pembrolizumab 200mg administrated IV every 3 weeks (Q3W).

Locations

Country	Name	City	State
Australia	St. Vincent's Hospital	Fitzroy	Victoria
Australia	Tasman Oncology Research	Southport	Queensland
United States	University of Cincinnati	Cincinnati	Ohio
United States	Barbara Ann Karmanos Cancer Institute	Detroit	Michigan
United States	City of Hope Medical Center	Duarte	California
United States	NEXT Oncology	Fairfax	Virginia
United States	Corewell Health	Grand Rapids	Michigan
United States	UC San Diego Moores Cancer Center	La Jolla	California
United States	University of Miami	Miami	Florida
United States	Huntsman Cancer Institute	Salt Lake City	Utah
United States	Highlands Oncology	Springdale	Arkansas
United States	University of Arizona Cancer Center	Tucson	Arizona

Sponsors (1)

Lead Sponsor	Collaborator
Imugene Limited

Countries where clinical trial is conducted

United States,  Australia, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	To evaluation 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.
Primary	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.
Primary	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	Objective Response Rate (ORR) of CF33-hNIS administered as a monotherapy or in combination with pembrolizumab	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.
Secondary	Progression-free survival (PFS) of CF33-hNIS administered as a monotherapy or in combination with pembrolizumab.	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.
Secondary	Overall survival (OS) of CF33-hNIS administered as a monotherapy or in combination with pembrolizumab.	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.
Secondary	Duration of Response (DOR) of CF33-hNIS administered as a monotherapy or in combination with pembrolizumab.	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.
Secondary	Disease Control Rate (DCR) of CF33-hNIS administered as a monotherapy or in combination with pembrolizumab.	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.
Secondary	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.
Secondary	To evaluate infection of tumors with CF33-hNIS	hNIS-based imaging via SPECT technetium-99 (99TC).	21 days from first dose of study drug

External Links

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