The goal of this clinical trial is to assess the safety and tolerability of a virus replicon particle (VRP) encapsulated saRNA encoding IL-12 when injected into in head and neck cancer patients. The main questions being addressed are:
The safety and tolerability of intratumoral (IT) injections of VRP-encapsulated saRNA encoding IL-12 (VLPONC-01)
The tumor response to IT injections of VLPONC-01
The tumor response due to the combination of IT injections of VLPONC-01 and system IV administration of neoadjuvant pembrolizumab (anti-PD-1) treatment
Researchers will compare neoadjuvant pembrolizumab alone to the combination therapy to see if the combination enhances tumor responses.
Eligibility criteria
This trial does not accept healthy volunteers
Qualifiers
Eastern Cooperative Oncology Group (ECOG) performance status 0-1, and adequate bone marrow and organ function.
Primary tumors should be amenable to intratumoral (IT) injection >1 cm diameter. This will be determined by the Protocol Director, or the surgeon involved.
Subjects with either a local recurrence or a new primary tumor will be allowed.
Age ≥ 18 years.
Disqualifiers
Tumors which are not feasible for injections include high risk lesions that are near vital organs or important neurovascular structures, as determined by the Protocol Director or involved surgeon.
Women of childbearing potential must have a negative serum β-hCG pregnancy test within 7 days prior to the administration of the first study treatment and/or urine pregnancy 48 hours prior to the administration of the first study treatment. Both sexually active women of childbearing potential and males (and their female partners) patients must agree to use two methods of effective contraception, one of them being a barrier method, or to abstain from sexual activity during the study and for at least 6 months after last dose of study drugs.
Patients expected to receive other anti-cancer medication such as, chemotherapy, immunotherapy, biologic therapy, targeted therapy, monoclonal antibodies, hormonal therapy (other than leuprolide or other GnRH agonists) prior to surgery and where all acute toxicity of prior treatments have not resolved.
Participation in another clinical study with an investigational product during the last 30 days.
Trial design
Design model
Sequential
Treatments tested in this trial
VRP-encapsulated saRNA encoding IL-12 (1 x 10^9 viral particles per injection)
Biological/Vaccine
Weekly IT injections of 1 x 10\^9 viral particles of VLPONC-01
Pembrolizumab (KEYTRUDA®)
Drug
200mg twice 3 weeks apart IV
VRP-encapsulated saRNA encoding IL-12 (3 x 10^8 viral particles per injection)
Biological/Vaccine
Weekly IT injections of 3 x 10\^8 viral particles of VLPONC-01
Treatment groups
41 Participants
are divided into 4 treatment groups
Group A: Cohort A (1 x 10^9 viral particles per injection)Experimental treatment 1 intervention
Group B: Cohort C - Group 1 (1 x 10^9 viral particles per injection plus Pembrolizumab)Experimental treatment 2 interventions
Group C: Cohort C - Group 2 (3 x 10^8 viral particles per injection plus Pembrolizumab)Experimental treatment 2 interventions
Group D: Cohort C - Pembrolizumab onlyExperimental treatment 1 intervention
Trial outcomes
Primary outcomes
1
Safety and tolerability
To assess the safety and tolerability of VLPONC-01. Safety will be based on the occurrence of any grade 3 or higher drug-related adverse events from the VLPONC-01 injections for non-surgery patients and any grade 3 or higher drug-related adverse events that result in a delay to tumor resection surgery.
Time frame
First injection to 90-day follow-up visit post-final injection (Cohort A) or post-surgery (Cohort C)
Secondary outcomes
1
Levels of circulating IL-12
To assess the circulating blood levels of IL-12 after VLPONC-01 treatment compared to baseline to determine the occurrence and safety profile of potential systemic inflammatory responses.
Time frame
First injection to 30-day follow-up visit post-final injection (Cohort A) or post-surgery (Cohort C)
2
VLPONC-01 levels in tumor tissue
To detect levels of VLPONC-01 RNA in surgically resected tissue.
Time frame
First injection to tumor resection surgery
3
Radiological Tumor Response
To assess the primary tumor response by RECIST.
Time frame
First injection to tumor resection surgery (up to 3 months)
4
Pathological Tumor Response
To assess the primary tumor response by pathological analysis.
Time frame
First injection to tumor resection surgery (up to 3 months)
Other outcomes
1
Circulating levels of cytokines, chemokines, and immune markers
To assess the circulating levels cytokines, chemokines, and immune markers using a proteomics assay.
Time frame
First injection to 30-day follow-up visit post-final injection (Cohort A) or post-surgery (Cohort C) through 90-day follow-up visit.
2
ICH Changes in Tumor microenvironment
To assess levels of CD8+ T-cells, macrophages, and other immune cell populations in surgically resected tissue compared to biopsy tissue using immunohistochemistry.
Time frame
First injection to 30-day follow-up visit post-final injection (Cohort A) or post-surgery (Cohort C) through 90-day follow-up visit.
3
Changes in ctDNA related to Neoadjuvant treatment
To assess changes in ctDNA MRD treatment-related molecular response (Cohort C).
Time frame
First injection to 30-day follow-up visit post-final injection (Cohort A) or post-surgery (Cohort C) through 90-day follow-up visit.
4
Changes in cellular populations
To assess the changes in cellular populations in circulating blood using flow cytometry.
Time frame
First injection to 30-day follow-up visit post-final injection (Cohort A) or post-surgery (Cohort C) through 90-day follow-up visit.
Sponsors and contacts
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