Optimizing Antitumor Immunity Using Plasmid Electroporation, Pembrolizumab, and Epacadostat

NCT03823131 | Terminated Phase 2 Results DMC FDA Drug FDA Device

• 2 other identifiers: 172021NCI-2018-02901
• Study Type: interventional
• Target: 14
• Locations: 1 country
• Sites: 1

Brief 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. 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.

Conditions

Metastatic Head and Neck Squamous Cell Carcinoma; Recurrent Head and Neck Squamous Cell Carcinoma; Unresectable Head and Neck Squamous Cell Carcinoma

Outcome Measures

Primary Outcomes (1)

• 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.

  Up to 36 months

Secondary Outcomes (7)

• Median Months of Progression-Free Survival (PFS)

  Up to 36 months

• Median Overall Survival (OS)

  Up to 36 months

• Median Time to Response

  Up to 36 months

• Disease Control Rate (DCR)

  Up to 36 months

• Clinical Benefit Rate (CBR)

  Up to 36 months

Study Arms (3)

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.

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.

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.

Device: ImmunoPulse; Drug: Pembrolizumab; Biological: CORVax; Drug: Tavokinogene telseplasmid

Interventions

ImmunoPulse DEVICE

Intratumoral

Also known as: Electroporation, electroporation therapy (EPT)

Arm A: Tavo-EP, pembrolizumab, epacadostat; Arm B: Tavo-EP, pembrolizumab; Arm C: Tavo-EP, pembrolizumab, CORVax

Epacadostat DRUG

Given PO

Also known as: INCB 024360, INCB024360

Arm A: Tavo-EP, pembrolizumab, epacadostat

Pembrolizumab DRUG

Given IV

Also known as: Keytruda, Lambrolizumab, MK-3475, SCH 900475

Arm A: Tavo-EP, pembrolizumab, epacadostat; Arm B: Tavo-EP, pembrolizumab; Arm C: Tavo-EP, pembrolizumab, CORVax

CORVax BIOLOGICAL

Intratumoral

Also known as: DNA-encodable coronaviral vaccine

Arm C: Tavo-EP, pembrolizumab, CORVax

Tavokinogene telseplasmid DRUG

Intratumoral

Also known as: Tavo-EP, DNA plasmid, plasmid IL-12 pUMVC3-hIL-12-NGVL3

Arm A: Tavo-EP, pembrolizumab, epacadostat; Arm B: Tavo-EP, pembrolizumab; Arm C: Tavo-EP, pembrolizumab, CORVax

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• 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.
• 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.

You may not qualify if:

• 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.
• 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.
• 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.

Sponsors & Collaborators

• Chase Heaton, MD: lead
• Incyte Corporation: collaborator
• OncoSec Medical Incorporated: collaborator

Study Sites (1)

University of California, San Francisco

San Francisco, California, 94143, United States

Location

MeSH Terms

Conditions

Squamous Cell Carcinoma of Head and Neck

Interventions

Electroporation; Electroporation Therapies; epacadostat; pembrolizumab

Condition Hierarchy (Ancestors)

Carcinoma, Squamous Cell; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Head and Neck Neoplasms; Neoplasms by Site

Intervention Hierarchy (Ancestors)

Cytological Techniques; Clinical Laboratory Techniques; Investigative Techniques; Electrochemical Techniques; Therapeutics

Limitations and Caveats

The study closed earlier than expected during enrollment into Arm A. Arm B and Arm C were never opened to accrual.

Results Point of Contact

• Title: Dr Chase Heaton, MD
• Organization: University of California, San Francisco

Chase.Heaton@ucsf.edu

(415) 502-1889

Study Officials

• Chase Heaton, MD

  University of California, San Francisco

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Asst Clinical Professor

Study Record Dates

• First Submitted: January 28, 2019
• First Posted: January 30, 2019
• Study Start: May 2, 2019
• Primary Completion: July 31, 2022
• Study Completion: July 31, 2022
• Last Updated: May 9, 2023
• Results First Posted: May 9, 2023

Record last verified: 2023-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)