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

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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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).

Conditions
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Solid Tumor, Solid Carcinoma, Solid Tumor, Adult, Metastatic Cancer, Advanced Solid Tumor

Intervention / Treatment
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* Biological: CF33-hNIS
* Biological: Pembrolizumab


Participation Criteria
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Eligibility Criteria
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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 an 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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: CF33-hNIS IT Administration Monotherapy<br> | Biological: CF33-hNIS<br>* CF33-hNIS is a chimeric orthopoxvirus (oncolytic virus) engineered to express the human sodium iodide symporter (hNIS)<br>* Other names: HOV2;|
| Experimental: CF33-hNIS IV Administration Monotherapy<br> | Biological: CF33-hNIS<br>* CF33-hNIS is a chimeric orthopoxvirus (oncolytic virus) engineered to express the human sodium iodide symporter (hNIS)<br>* Other names: HOV2;|
| Experimental: CF33-hNIS IT Administration in Combination with Pembrolizumab<br> | Biological: CF33-hNIS<br>* CF33-hNIS is a chimeric orthopoxvirus (oncolytic virus) engineered to express the human sodium iodide symporter (hNIS)<br>* Other names: HOV2;Biological: Pembrolizumab<br>* Pembrolizumab 200mg administrated IV every 3 weeks (Q3W).<br>* Other names: KEYTRUDA®;|
| Experimental: CF33-hNIS IV Administration in Combination with Pembrolizumab<br> | Biological: CF33-hNIS<br>* CF33-hNIS is a chimeric orthopoxvirus (oncolytic virus) engineered to express the human sodium iodide symporter (hNIS)<br>* Other names: HOV2;Biological: Pembrolizumab<br>* Pembrolizumab 200mg administrated IV every 3 weeks (Q3W).<br>* Other names: KEYTRUDA®;|

What is the study measuring?
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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 |
| --- | --- | --- |
| 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. | 
| 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. | 
| 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. | 
| 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. | 
| 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. | 
| 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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oncolytic virus