Metastatic Head and Neck Squamous Cell CarcinomaPhase 2NCT03823131
Optimizing Antitumor Immunity Using Plasmid Electroporation, Pembrolizumab, and Epacadostat
A Phase 2 study testing ImmunoPulse, Epacadostat and Pembrolizumab in people with Metastatic Head and Neck Squamous Cell Carcinoma and Recurrent Head and Neck Squamous Cell Carcinoma, run by Chase Heaton, MD at 1 site in United States.
Trial summary
This phase II trial studies how well tavokinogene telseplasmid with electroporation (tavo-EP), pembrolizumab, and epacadostat work in treating patients with squamous cell carcinoma of the head and neck that cannot be removed by surgery. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Metastatic Head and Neck Squamous Cell Carcinoma, Recurrent Head and Neck Squamous Cell Carcinoma, Unresectable Head and Neck Squamous Cell Carcinoma
- What is being tested?
- ImmunoPulse, Epacadostat and Pembrolizumab
- Type of treatment
- Vaccines, Injection or infusion, Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 14 participants
- Where
- 1 siteUnited States
- Study dates
- 2 May 2019to 31 Jul 2022
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age >= 18 years old.
- Eastern Cooperative Oncology Group (ECOG) performance status 0-2.
- Life expectancy of at least 4 months.
- Patients must have histological or cytological diagnosis of cancer originating in the head and neck that is not amenable to surgical resection or locoregional radiation therapy with curative intent.
- At least one accessible lesion (AL) for intratumoral injection. An AL is defined as meeting the following criteria; (1) at least 0.3 cm x 0.3 cm in longest perpendicular diameters (2) in a suitable location for application of electroporation. Tumors invading the carotid artery or at other sites that the investigator believes to be at high risk of life-threatening hemorrhage should not be injected and these lesions may not be used to meet the inclusion criterion for injectable lesions.
- Measurable disease as defined by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1; at least one lesion where the longest perpendicular diameter is at least 1.0 cm by clinical measurement; or at least 1.0 cm by radiographic imaging for non-nodal lesions; at least 1.5 cm in short axis by radiographic imaging for malignant lymph nodes; If the biopsied lesions were previously irradiated, they must demonstrate either radiographic or pathological evidence of recurrent or residual disease. It is not necessary that this lesion is also an AL.
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- If patient has known brain metastases, they must have stable neurologic status following local therapy (surgery or radiation) for at least 4 weeks without the use of steroids or on stable or decreasing dose of <=10 mg daily prednisone (or equivalent), and must be without neurologic dysfunction that would confound the evaluation of neurologic and other adverse events (AEs) (patients with a history of carcinomatous meningitis are not eligible).
- Patients may have had prior chemotherapy or immunotherapy or radiation therapy. Any drug related adverse events identified during prior therapy must be well controlled (typically resolution to =< grade 1, OR resolved upon investigator review prior to initiation of this therapy.
- No systemic antineoplastic therapy may be received by the patient between the time of the biopsy and the first administration of study treatment.
- Patient must agree to any protocol mandated biopsies of tumor (deemed accessible and safe for biopsy by the investigator's assessment) and they must allow acquired tissue to be used for biomarker analysis.
- For women of childbearing potential, negative serum or urine pregnancy test within 14 days of first dose of study drug(s) and use of birth control from 30 days prior to the first study drug administration and 120 days following last administration of study drug, or for participants in Arm C, 180 days after last dose of CORVax, whichever is longer.
- Male patients must be surgically sterile or must agree to use contraception during the study and at least 120 days following the last administration of study drug, or for participants in Arm C, 180 days after last dose of CORVax, whichever is longer.
Who cannot join
- Active autoimmune disease that has required systemic treatment in past 2 years. Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered a form of systemic treatment.
- Congestive heart failure (New York Heart Association class III to IV)
- History or presence of an abnormal electrocardiogram (ECG) that, in the investigator's opinion, is clinically meaningful. Screening corrected QT (QTc) interval > 480 milliseconds is excluded. In the event that a single QTc is > 480 milliseconds, the subject may enroll if the average QTc for the 3 ECGs is < 480 milliseconds. For subjects with an intraventricular conduction delay (QRS interval > 120 milliseconds), the corrected JT (JTc) interval may be used in place of the QTc with sponsor approval. The JTc must be < 340 milliseconds if JTc is used in place of the QTc. Subjects with left bundle branch block are excluded.
- Uncontrolled or clinically significant conduction abnormalities (e.g., ventricular tachycardia on anti-arrhythmics are excluded), 1st degree atrioventricular (AV) block or asymptomatic left anterior fascicular block (LAFB)/right bundle branch block (RBBB) are eligible.
- Uncontrolled, symptomatic ischemia within 6 months of first dose of study treatment or known myocardial infarction in the previous six months.
- Patients with electronic pacemakers or defibrillators.
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- Has history of (non-infectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease.
- Any other current or previous malignancy within the past 2 years that, in the opinion of the principal investigator will interfere with study-specific endpoints.
- Evidence of significant active infection (e.g., pneumonia, cellulitis, wound abscess, etc.) requiring systemic therapy at time of study enrollment.
- Hepatitis B: Most nasopharyngeal cancer (NPC) patients have been infected with hepatitis B (Cancer Epidemol Biomarkers Prev. 2015. 24:1766-73, N = 711) and, therefore, the inclusion of healthy patients with a history of hepatitis B is a central part of this study. In addition, programmed cell death protein 1 (PD-1) antibodies have been proven to be safe in patients with active hepatitis and hepatocellular carcinoma (e.g. KEYNOTE 224). However, patients with hepatitis B virus (HBV) surface antigen positive (HBSAg) must have aspartate aminotransferase (AST) and total bilirubin < 1.5 x upper limit of normal (ULN) AND
- Negative HBV ribonucleic acid (RNA) polymerase chain reaction (PCR) OR
- On antivirals for HBV AND at least 8 weeks of prior anti-PD-1 antibody therapy AND no history of AST or total bilirubin levels > 1.5 x ULN due to PD-1 antibody therapy
- Hepatitis C (hepatitis C virus (HCV) RNA (qualitative) is detected).
- Presence of a gastrointestinal condition that may affect drug absorption. Administration of epacadostat through a feeding tube is permitted.
- Patients receiving systemic steroid therapy for a chronic inflammatory condition. Topical steroids, nasal and inhaled steroids are permitted. Prednisone or equivalent =< 10 mg/day is permitted as hormone replacement; higher dosage prednisone should be stopped at least 14 days prior to course 1 day 1 (C1D1).
- Receipt of a live vaccine or live attenuated vaccine within 30 days before the first dose of study treatment. Administration of killed vaccines is allowed.
- Subjects receiving monoamine oxidase inhibitors (MAOIs) or drug which has significant MAOI activity (meperidine, linezolid, methylene blue) within the 21 days before screening.
- Any history of serotonin syndrome (SS) after receiving serotonergic drugs.
- Use of any uridine 5'-diphospho-glucuronosyltransferase 1-9 (UGT1A9) inhibitor from screening through follow-up period, including the following: diclofenac, imipramine, ketoconazole, mefenamic acid, and probenecid.
- Known allergy or reaction to any component of study drug formulation.
- Absolute neutrophil count (ANC) < 1.0 x 10^9/L.
- Platelets < 75 x 10^9/L.
- Hemoglobin < 9 g/dL or < 5.6 mmol/L (transfusion is acceptable to meet this criterion).
- Serum creatinine >= 1.5 x institutional upper limit of normal (ULN) OR measured or calculated creatinine clearance [glomerular filtration rate can also be used in place of creatinine or creatinine clearance (CrCl)] < 50 mL/min for subjects with creatinine levels > 1.5 x institutional ULN.
- Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) > 2.5 x institutional ULN.
- Alkaline phosphatase > 2.5 x ULN. Note: Subjects with 1) bone metastases and gamma-glutamyl transpeptidase (GGT) < 2.5 x ULN may enroll if the alkaline phosphatase is < 5 x ULN.
- Total bilirubin above 1.5 x the institutional ULN AND conjugated bilirubin >= 2.0 x ULN.
- International normalized ratio (INR) or prothrombin time (PT) > 1.5 x ULN.
- Activated partial thromboplastin time (aPTT) > 1.5 x ULN.
Trial locations and contacts
1 site in 1 country.
United States1 site
University of California, San Francisco
San Francisco, California, 94143
About this study
Official title: The Trifecta Study: Optimizing Antitumor Immunity Using Plasmid Electroporation, Pembrolizumab, and Epacadostat
This phase II trial studies how well tavokinogene telseplasmid with electroporation (tavo-EP), pembrolizumab, and epacadostat work in treating patients with squamous cell carcinoma of the head and neck that cannot be removed by surgery. Tavokinogene telseplasmid with electroporation is a gene therapy that may delay of tumor growth and which may have less toxicity than other methods of gene delivery. Immunotherapy with monoclonal antibodies, such as pembrolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Epacadostat may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving tavokinogene telseplasmid with electroporation, pembrolizumab, and epacadostat may work better in treating squamous cell carcinoma of the head and neck.
Read the detailed description
PRIMARY OBJECTIVES:
- Dose Escalation Safety Lead-Ins: Assess the safety of tavo-EP and pembrolizumab in combination with epacadostat (CTCAE version 4).
II. Dose Expansion: Determine whether the combination therapy in each arm increases the best overall response rate (BORR) compared with historical data for pembrolizumab monotherapy
SECONDARY OBJECTIVES:
- Dose Expansion: Determine the durability of clinical benefits in participants treated with combination therapy in each arm, as assessed by time to progression, median progression-free survival (PFS), median overall survival (OS).
EXPLORATORY OBJECTIVES:
- Determine the effects of combination therapy on treated and untreated lesions by examining paired biopsy specimens for changes in inflammatory gene expression, relative proportion of effector versus regulatory T cells, evaluation of inflammatory cytokines, T-cell activation, clonality, and other hallmarks of immune activation.
II. Explore systemic markers of immune activation by examining circulating T-cell populations for changes in the frequency and effector function of short-lived effector cells and memory T cells.
III. Explore changes in functional immune responses using Elispot and other assays.
IV. To explore biomarkers that inform scientific understanding of this therapeutic treatment through analysis of specimens retained for Future Biomedical Research.
OUTLINE:
This is a multi-center, open label, 2-stage, double-arm, clinical trial in which participants in Stage 1 will receive either tavo-EP with pembrolizumab, and epacadostat (Arm A), tavo-EP and pembrolizumab (Arm B), or CORVax, tavo-EP and pembrolizumab (Arm C). Arms B and C will only open to enrollment if the treatment is determined to be effective in Arm A.
Participants will be followed at 3-month intervals for toxicity and radiographic imaging (1) until start of a new anti-cancer treatment, (2) until 30 days after documented disease progression, (3) until death, or (4) until 36 months from the initiation of treatment on study, whichever comes first. Each subject will be followed for overall survival until death, withdrawal of consent, or at the time of study closure, whichever occurs first.
- Conditions
- Metastatic Head and Neck Squamous Cell Carcinoma, Recurrent Head and Neck Squamous Cell Carcinoma, Unresectable Head and Neck Squamous Cell Carcinoma
- Being tested
- ImmunoPulse, Epacadostat, Pembrolizumab, CORVax, Tavokinogene telseplasmid
- Medical subject headings
- Squamous Cell Carcinoma of Head and Neck
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ImmunoPulseDevice
Also called Electroporation, electroporation therapy (EPT)
Intratumoral
EpacadostatDrug
Also called INCB 024360, INCB024360
Given PO
PembrolizumabDrug
Also called Keytruda, Lambrolizumab, MK-3475, SCH 900475
Given IV
CORVaxBiological
Also called DNA-encodable coronaviral vaccine
Intratumoral
Tavokinogene telseplasmidDrug
Also called Tavo-EP, DNA plasmid, plasmid IL-12 pUMVC3-hIL-12-NGVL3
Intratumoral
| Study group | Role | What they receive |
|---|---|---|
| Arm A: Tavo-EP, pembrolizumab, epacadostat | Experimental | Tavo-EP will be injected intratumorally on Days 1, 5 and 8 every 6 weeks to up to 7 accessible lesions without exceeding 20 mL per day. Injected lesions will then be electroporated using the ImmunoPulse electroporation device. Pembrolizumab will be administered by a 30 minute IV infusion at a dose of 200 mg every 3 weeks. Epacadostat will be administered at the dose level determined in the dose escalation safety lead-in. Receives: Device: ImmunoPulse; Drug: Epacadostat; Drug: Pembrolizumab; Drug: Tavokinogene telseplasmid |
| Arm B: Tavo-EP, pembrolizumab | Experimental | Tavo-EP will be injected intratumorally on Days 1, 5 and 8 every 6 weeks to up to 7 accessible lesions without exceeding 20 mL per day. Injected lesions will then be electroporated using the ImmunoPulse electroporation device. Pembrolizumab will be administered by a 30 minute IV infusion at a dose of 200 mg every 3 weeks. Receives: Device: ImmunoPulse; Drug: Pembrolizumab; Drug: Tavokinogene telseplasmid |
| Arm C: Tavo-EP, pembrolizumab, CORVax | Experimental | Tavo-EP will be injected intratumorally on Days 1, 5 and 8 every 6 weeks to up to 7 accessible lesions without exceeding 20 mL per day. Injected lesions will then be electroporated using the ImmunoPulse electroporation device. Pembrolizumab will be administered by a 30-minute IV infusion at a dose of 200 mg every 3 weeks. CORVax will be administered at a total dose of 0.2 mg of (S) protein plasmid in 120 microliter (uL) per lesion intratumorally into a maximum of 4 lesions of at least 0.3 mm in diameter for a total plasmid dose of 0.8 mg on treatment days 1 and 29 of cycle 1 followed by electroporation of the plasmid solution in infiltrated regions. On days when both tavo and CORVax is administered to the same lesions, tavo and CORVax will each be injected into the lesion followed by electroporation. Receives: Device: ImmunoPulse; Drug: Pembrolizumab; Biological: CORVax; Drug: Tavokinogene telseplasmid |
What is being measured
The primary outcome is the main question the study is designed to answer.
Best Overall Response Rate
The best overall response (BORR) is defined as the best response recorded from the start of treatment until disease progression/recurrence. Per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1, Complete Response (CR) is defined as the disappearance of all target lesions and any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. Partial Response (PR) is defined as having at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. The combined percentage of participants relative to the total size of the All Treated Subjects population having a demonstrated best response of CR or PR, with a confirmatory scan will be reported.
Measured: Up to 36 months
Secondary outcomes (7)
Median Months of Progression-Free Survival (PFS)
Progression-free survival will be calculated as number of months from the first dosing date until the date of disease progression (i.e the date of the tumor imaging following baseline per central imaging assessment by a radiologist) or death from any cause. Per RECIST version 1.1, Progressive Disease (PD) is defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). Participants who do not have documented disease progression will have their months of PFS censored on the last date of tumor assessment, or death, whichever comes first. Censoring data on date of last tumor imaging to calculate the median PFS will not occur until the overall survival data collection for all participants has been completed.
Measured: Up to 36 months
Median Overall Survival (OS)
Overall survival (OS) is defined as the number of months from the date of enrollment until the date of death regardless of cause, last date of follow-up, or date of study closure (if still alive), whichever comes first. Median months of overall participant survival will be reported using descriptive statistics.
Measured: Up to 36 months
Median Time to Response
Time to response is defined as the number of days from the date of enrollment to the date of the first documented response of CR or PR. The median time to response will be summarized by descriptive statistics.
Measured: Up to 36 months
Disease Control Rate (DCR)
The disease control rate is defined as the best response recorded from the start of treatment including stable disease, until disease progression/recurrence (PD). Per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1, Complete Response (CR) is defined as the disappearance of all target lesions and any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. Partial Response (PR) is defined as having at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. Stable Disease (SD) is defined as having neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study. The proportion of participants relative to the total size of the All Treated Subjects population having a demonstrated response of CR, PR, or SD, with a confirmatory scan will be reported.
Measured: Up to 36 months
Clinical Benefit Rate (CBR)
Clinical benefit rate (CBR) is defined as the percentage of participants who achieved a best overall response of CR, PR and SD with a duration of response lasting at least 6 months or longer.
Measured: Up to 36 months
Median Duration of Response
The duration of response (DOR) will be calculated for participants who achieved a best overall response of CR or PR and calculated as the number of days from the date when CR or PR is first confirmed to the date of progression or death. Participants who do not have a documented progression or death will be censored on the last date of tumor assessment. The median DOR and 95% confidence intervals will be reported.
Measured: Up to 36 months
Proportion of Participants With Reported Treatment-related Adverse Events (AEs)
The proportion of participants with reported treatment-related adverse events, which are adverse events defined as having an attribution of possible, probable, or definite according to NCI Common Terminology Criteria for Adverse Events (CTCAE) v. 4 will be reported.
Measured: Up to 36 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Jan 2019
- Study start2 May 2019
- Primary completion31 Jul 2022
- Study completion31 Jul 2022
Why it stopped: Treatment Ineffective
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Metastatic Head and Neck Squamous Cell CarcinomaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 14 participants (actual)
Sponsor and investigators
- Lead sponsor
- Chase Heaton, MD
- Sponsor type
- University, hospital or other
- Collaborators
- Incyte Corporation, OncoSec Medical Incorporated
- Responsible party
- Sponsor-investigator, Chase Heaton, MD, University of California, San Francisco
- Investigators
- Chase Heaton, MD, Principal investigator, University of California, San Francisco
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03823131
- Sponsor's protocol ID
- 172021
- Other IDs
- NCI-2018-02901
- Status last verified
- Apr 2023
- First submitted
- 28 Jan 2019
- Last updated
- 9 May 2023
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- Yes
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 9 May 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Trifecta Study: Optimizing Antitumor Immunity Using Plasmid Electroporation, Pembrolizumab, and Epacadostat
- ClinicalTrials.gov ID
- NCT03823131
- Acronym / sponsor ID
- 172021
- Conditions
- Metastatic Head and Neck Squamous Cell Carcinoma, Recurrent Head and Neck Squamous Cell Carcinoma, Unresectable Head and Neck Squamous Cell Carcinoma
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Treatment Ineffective
- Enrolment
- 14 participants (actual)
- Lead sponsor
- Chase Heaton, MDUniversity, hospital or other
- Collaborators
- Incyte Corporation, OncoSec Medical Incorporated
- Study start
- 2 May 2019 (actual)
- Primary completion
- 31 Jul 2022 (actual)
- Study completion
- 31 Jul 2022 (actual)
- First posted
- 30 Jan 2019 (actual)
- Results
- Posted 9 May 2023
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This phase II trial studies how well tavokinogene telseplasmid with electroporation (tavo-EP), pembrolizumab, and epacadostat work in treating patients with squamous cell carcinoma of the head and neck that cannot be removed by surgery. Tavokinogene telseplasmid with electroporation is a gene therapy that may delay of tumor growth and which may have less toxicity than other methods of gene delivery. Immunotherapy with monoclonal antibodies, such as pembrolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Epacadostat may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving tavokinogene telseplasmid with electroporation, pembrolizumab, and epacadostat may work better in treating squamous cell carcinoma of the head and neck.
Detailed description
PRIMARY OBJECTIVES:
- Dose Escalation Safety Lead-Ins: Assess the safety of tavo-EP and pembrolizumab in combination with epacadostat (CTCAE version 4).
II. Dose Expansion: Determine whether the combination therapy in each arm increases the best overall response rate (BORR) compared with historical data for pembrolizumab monotherapy
SECONDARY OBJECTIVES:
- Dose Expansion: Determine the durability of clinical benefits in participants treated with combination therapy in each arm, as assessed by time to progression, median progression-free survival (PFS), median overall survival (OS).
EXPLORATORY OBJECTIVES:
- Determine the effects of combination therapy on treated and untreated lesions by examining paired biopsy specimens for changes in inflammatory gene expression, relative proportion of effector versus regulatory T cells, evaluation of inflammatory cytokines, T-cell activation, clonality, and other hallmarks of immune activation.
II. Explore systemic markers of immune activation by examining circulating T-cell populations for changes in the frequency and effector function of short-lived effector cells and memory T cells.
III. Explore changes in functional immune responses using Elispot and other assays.
IV. To explore biomarkers that inform scientific understanding of this therapeutic treatment through analysis of specimens retained for Future Biomedical Research.
OUTLINE:
This is a multi-center, open label, 2-stage, double-arm, clinical trial in which participants in Stage 1 will receive either tavo-EP with pembrolizumab, and epacadostat (Arm A), tavo-EP and pembrolizumab (Arm B), or CORVax, tavo-EP and pembrolizumab (Arm C). Arms B and C will only open to enrollment if the treatment is determined to be effective in Arm A.
Participants will be followed at 3-month intervals for toxicity and radiographic imaging (1) until start of a new anti-cancer treatment, (2) until 30 days after documented disease progression, (3) until death, or (4) until 36 months from the initiation of treatment on study, whichever comes first. Each subject will be followed for overall survival until death, withdrawal of consent, or at the time of study closure, whichever occurs first.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Arm A: Tavo-EP, pembrolizumab, epacadostat | Experimental | Device: ImmunoPulse, Drug: Epacadostat, Drug: Pembrolizumab, Drug: Tavokinogene telseplasmidTavo-EP will be injected intratumorally on Days 1, 5 and 8 every 6 weeks to up to 7 accessible lesions without exceeding 20 mL per day. Injected lesions will then be electroporated using the ImmunoPulse electroporation device. Pembrolizumab will be administered by a 30 minute IV infusion at a dose of 200 mg every 3 weeks. Epacadostat will be administered at the dose level determined in the dose escalation safety lead-in. |
| Arm B: Tavo-EP, pembrolizumab | Experimental | Device: ImmunoPulse, Drug: Pembrolizumab, Drug: Tavokinogene telseplasmidTavo-EP will be injected intratumorally on Days 1, 5 and 8 every 6 weeks to up to 7 accessible lesions without exceeding 20 mL per day. Injected lesions will then be electroporated using the ImmunoPulse electroporation device. Pembrolizumab will be administered by a 30 minute IV infusion at a dose of 200 mg every 3 weeks. |
| Arm C: Tavo-EP, pembrolizumab, CORVax | Experimental | Device: ImmunoPulse, Drug: Pembrolizumab, Biological: CORVax, Drug: Tavokinogene telseplasmidTavo-EP will be injected intratumorally on Days 1, 5 and 8 every 6 weeks to up to 7 accessible lesions without exceeding 20 mL per day. Injected lesions will then be electroporated using the ImmunoPulse electroporation device. Pembrolizumab will be administered by a 30-minute IV infusion at a dose of 200 mg every 3 weeks. CORVax will be administered at a total dose of 0.2 mg of (S) protein plasmid in 120 microliter (uL) per lesion intratumorally into a maximum of 4 lesions of at least 0.3 mm in diameter for a total plasmid dose of 0.8 mg on treatment days 1 and 29 of cycle 1 followed by electroporation of the plasmid solution in infiltrated regions. On days when both tavo and CORVax is administered to the same lesions, tavo and CORVax will each be injected into the lesion followed by electroporation. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (12 listed)
- Age >= 18 years old.
- Eastern Cooperative Oncology Group (ECOG) performance status 0-2.
- Life expectancy of at least 4 months.
- Patients must have histological or cytological diagnosis of cancer originating in the head and neck that is not amenable to surgical resection or locoregional radiation therapy with curative intent.
- At least one accessible lesion (AL) for intratumoral injection. An AL is defined as meeting the following criteria; (1) at least 0.3 cm x 0.3 cm in longest perpendicular diameters (2) in a suitable location for application of electroporation. Tumors invading the carotid artery or at other sites that the investigator believes to be at high risk of life-threatening hemorrhage should not be injected and these lesions may not be used to meet the inclusion criterion for injectable lesions.
Key exclusion criteria (29 listed)
- Active autoimmune disease that has required systemic treatment in past 2 years. Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered a form of systemic treatment.
- Congestive heart failure (New York Heart Association class III to IV)
- History or presence of an abnormal electrocardiogram (ECG) that, in the investigator's opinion, is clinically meaningful. Screening corrected QT (QTc) interval > 480 milliseconds is excluded. In the event that a single QTc is > 480 milliseconds, the subject may enroll if the average QTc for the 3 ECGs is < 480 milliseconds. For subjects with an intraventricular conduction delay (QRS interval > 120 milliseconds), the corrected JT (JTc) interval may be used in place of the QTc with sponsor approval. The JTc must be < 340 milliseconds if JTc is used in place of the QTc. Subjects with left bundle branch block are excluded.
- Uncontrolled or clinically significant conduction abnormalities (e.g., ventricular tachycardia on anti-arrhythmics are excluded), 1st degree atrioventricular (AV) block or asymptomatic left anterior fascicular block (LAFB)/right bundle branch block (RBBB) are eligible.
- Uncontrolled, symptomatic ischemia within 6 months of first dose of study treatment or known myocardial infarction in the previous six months.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| ImmunoPulseAlso: Electroporation, electroporation therapy (EPT)Intratumoral | Device | Arm A: Tavo-EP, pembrolizumab, epacadostat, Arm B: Tavo-EP, pembrolizumab, Arm C: Tavo-EP, pembrolizumab, CORVax |
| EpacadostatAlso: INCB 024360, INCB024360Given PO | Drug | Arm A: Tavo-EP, pembrolizumab, epacadostat |
| PembrolizumabAlso: Keytruda, Lambrolizumab, MK-3475, SCH 900475Given IV | Drug | Arm A: Tavo-EP, pembrolizumab, epacadostat, Arm B: Tavo-EP, pembrolizumab, Arm C: Tavo-EP, pembrolizumab, CORVax |
| CORVaxAlso: DNA-encodable coronaviral vaccineIntratumoral | Biological | Arm C: Tavo-EP, pembrolizumab, CORVax |
| Tavokinogene telseplasmidAlso: Tavo-EP, DNA plasmid, plasmid IL-12 pUMVC3-hIL-12-NGVL3Intratumoral | Drug | Arm A: Tavo-EP, pembrolizumab, epacadostat, Arm B: Tavo-EP, pembrolizumab, Arm C: Tavo-EP, pembrolizumab, CORVax |
Primary outcome
Best Overall Response Rate
Time frame: Up to 36 months
The best overall response (BORR) is defined as the best response recorded from the start of treatment until disease progression/recurrence. Per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1, Complete Response (CR) is defined as the disappearance of all target lesions and any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. Partial Response (PR) is defined as having at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. The combined percentage of participants relative to the total size of the All Treated Subjects population having a demonstrated best response of CR or PR, with a confirmatory scan will be reported.
7 secondary outcomes
Median Months of Progression-Free Survival (PFS)
Time frame: Up to 36 months
Median Overall Survival (OS)
Time frame: Up to 36 months
Median Time to Response
Time frame: Up to 36 months
Disease Control Rate (DCR)
Time frame: Up to 36 months
Clinical Benefit Rate (CBR)
Time frame: Up to 36 months
Median Duration of Response
Time frame: Up to 36 months
Proportion of Participants With Reported Treatment-related Adverse Events (AEs)
Time frame: Up to 36 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 May 2023.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Chase Heaton, MD principal investigator
University of California, San Francisco
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing ImmunoPulse, Epacadostat and Pembrolizumab in people with Metastatic Head and Neck Squamous Cell Carcinoma and Recurrent Head and Neck Squamous Cell Carcinoma, run by Chase Heaton, MD at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 12 inclusion and 29 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 9 May 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 9 May 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Best Overall Response Rate (time frame: Up to 36 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 May 2023.