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

Phase 1TerminatedNCT05346484

Imugene Limited66 enrolled

Overview

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.

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

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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

Locations (12)

University of Arizona Cancer Center

Tucson, Arizona, United States

Highlands Oncology

Springdale, Arkansas, United States

City of Hope Medical Center

Duarte, California, United States

UC San Diego Moores Cancer Center

La Jolla, California, United States

University of Miami

Miami, Florida, United States

Barbara Ann Karmanos Cancer Institute

Detroit, Michigan, United States

Corewell Health

Grand Rapids, Michigan, United States

University of Cincinnati

Cincinnati, Ohio, United States

Huntsman Cancer Institute

Salt Lake City, Utah, United States

NEXT Oncology

Fairfax, Virginia, United States

...and 2 more locations

Outcomes

Primary Outcomes

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.

Time frame: 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.

Time frame: From first dose of study drug through 21-42 days following the first dose of study treatment.

Secondary Outcomes

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.