Clinical trial NCT05346484: A Study of CF33-hNIS (VAXINIA), an Oncolytic Virus, as Monotherapy or in Combination With Pembrolizumab in Adults With Metastatic or Advanced Solid Tumors
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).
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Solid Tumor
Solid Carcinoma
Solid Tumor, Adult
Metastatic Cancer
Advanced Solid Tumor
Cholangiocarcinoma
Bile Duct Cancer
Keywords: oncolytic virus
Lead sponsor: Imugene Limited
Sponsor class: INDUSTRY
First posted: 2022-04-26
Enrollment: 100
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Frequency and severity of Adverse Events of IV and IT CF33-hNIS as a monotherapy or in combination with pembrolizumab
timeFrame: From first dose of study drug through 30 days following the last dose of study treatment.
measure: Recommended Phase 2 Dose (RP2D) of CF33-hNIS as a monotherapy or in combination with pembrolizumab
timeFrame: From first dose of study drug through 21-42 days following the first dose of study treatment.
Secondary outcomes:
measure: Objective Response Rate (ORR) of CF33-hNIS administered as a monotherapy or in combination with pembrolizumab or modified FOLFOX
timeFrame: Up to 2 years from first dose of study drug.
measure: Progression-free survival (PFS) of CF33-hNIS administered as a monotherapy or in combination with pembrolizumab or modified FOLFOX
timeFrame: Up to 2 years from first dose of study drug.
measure: Overall survival (OS) of CF33-hNIS administered as a monotherapy or in combination with pembrolizumab or modified FOLFOX
timeFrame: Up to 2 years from first dose of study drug.
measure: Duration of Response (DOR) of CF33-hNIS administered as a monotherapy or in combination with pembrolizumab or modified FOLFOX
timeFrame: Up to 2 years from first dose of study drug.
measure: Disease Control Rate (DCR) of CF33-hNIS administered as a monotherapy or in combination with pembrolizumab or modified FOLFOX
timeFrame: Up to 2 years from first dose of study drug.
measure: To evaluate viral titers of CF33-hNIS
timeFrame: Up to 2 years from first dose of study drug.
measure: To evaluate infection of tumors with CF33-hNIS
timeFrame: 21 days from first dose of study drug
Other outcomes:
measure: To evaluate antiviral immune activation
timeFrame: Up to 2 years from first dose of study drug.
Locations:
city: Tucson
country: United States
facility: University of Arizona Cancer Center
state: Arizona
city: Springdale
country: United States
facility: Highlands Oncology
state: Arkansas
city: Duarte
country: United States
facility: City of Hope Medical Center
state: California
city: La Jolla
country: United States
facility: UC San Diego Moores Cancer Center
state: California
city: Miami
country: United States
facility: University of Miami
state: Florida
city: Detroit
country: United States
facility: Barbara Ann Karmanos Cancer Institute
state: Michigan
city: Grand Rapids
country: United States
facility: Corewell Health
state: Michigan
city: Cincinnati
country: United States
facility: University of Cincinnati
state: Ohio
city: Salt Lake City
country: United States
facility: Huntsman Cancer Institute
state: Utah
city: Fairfax
country: United States
facility: NEXT Oncology
state: Virginia
city: Southport
country: Australia
facility: Tasman Oncology Research
state: Queensland
city: Fitzroy
country: Australia
facility: St. Vincent's Hospital
state: Victoria
Study officials:
References: