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Trial of pIL-12/MK-3475 in Metastatic Melanoma | Clinical Trials | Clareo Health

COMPLETEDPHASE2

Trial of pIL-12/MK-3475 in Metastatic Melanoma

An Open-label, Phase II, Multicenter Study of Enhancing Pembrolizumab Responses in Melanoma Through Intratumoral pIL-12 Electroporation

NCT02493361•University of California, San Francisco

View on ClinicalTrials.gov

Summary

This is a multicenter, Phase II, open-label, 42-patient single-arm trial of intratumoral pIL-12 electroporation (EP) in combination with pembrolizumab in patients with melanoma. Patients will be evaluated in 2 parts. Part A patients will be selected using a flow cytometric assay that quantifies intratumoral PD-1hiCD8+CTLA4+ "exhausted" lymphocytes in the tumor. Part B will enroll patients who have or are failing pembrolizumab at least 12 weeks after starting Programmed cell death protein 1 (PD-1) antibody alone or in combination, or, who have been selected using a flow cytometric assay that quantifies intratumoral PD-1hiCD8+CTLA4+ "exhausted" lymphocytes in the tumor.

Detailed Description

Closed to enrollment earlier than expected due to high response rate in order to advance to phase 2b in proven PD-1-refractory patients. A total of 24 patients were consented instead of the planned enrollment of 42 patients.

Eligibility

Age

18 - No limit years

Sex

ALL

Healthy Volunteers

Inclusion Criteria

•Patients must have histological or cytological diagnosis of melanoma with progressive locally advanced or metastatic disease that is not amenable to definitive local therapy with curative intent.
•At least one measurable tumor accessible for intratumoral injection and EP on investigator's assessment.
•Patients may have had prior chemotherapy or immunotherapy or radiation therapy. All prior therapies must be stopped 4 weeks prior to first dose of study treatment, with the exception of patients who have received ipilimumab, which must be stopped 6 weeks prior to first dose of study treatment. Patients are prohibited from receiving live vaccines within 30 days prior to first dose of study treatment.
•Age \>= 18 years
•Part A: Patient has agreed to two newly obtained tumor biopsies and as required re-biopsies (that can be biopsied on investigator's assessment) and to providing the acquired tissue for biomarker analysis. Analysis of one of the fresh biopsy samples for PD-1hiCD8+CTLA4hi in the CD8+CD45+ gate based on flow cytometry will be done. A second fresh biopsy sample is required for further biomarker analysis and confirmation at a later date of low PD-L1 expression using an Immunohistochemistry (IHC) assay for PD-L1 expression. A valid flow cytometry result is not required for study participation, but repeated biopsy for reanalysis is strongly recommended for patient with insufficient tumor-infiltrating lymphocytes (TIL) in the first tissue sample. Or:
•Part B: Anti-PD-1 non-responders are defined as those showing disease progression according to RECIST v1.1 after at least 12 weeks of therapy with a PD-1 antibody either alone or in combination with approved checkpoint inhibitor or targeted therapies according to their label. There is no serological requirement.
•Life expectancy of at least 6 months.
•Eastern Cooperative Oncology Group (ECOG) performance status 0-1.
•Adequate organ function within 4 weeks of administration of study therapy:
•1. Lactate dehydrogenase (LDH): \<4 x upper limit of normal (ULN)
+15 more criteria

Exclusion Criteria

•Patient is currently participating or has participated in a study of an investigational agent or using an investigational device within 4 weeks of administration of study therapy.
•Patient is expected to require any other form of antineoplastic therapy while on study; including systemic chemotherapy, biological therapy, immunotherapy not specified in this protocol.
•Patient has uveal melanoma.
•Patient has known active central nervous system (CNS) metastases and/or carcinomatous meningitis. Patients with previously treated brain metastases may participate provided they are clinically stable without the use of systemic steroids for at least 8 weeks prior to study entry.
•Patient has risk factors for bowel obstruction or bowel perforation (examples include but not limited to a history of acute diverticulitis, intra-abdominal abscess, and abdominal carcinomatosis).
•Patient previously had a severe hypersensitivity reaction to treatment with another monoclonal antibody (mAb).
•Patient has a history of history of (non-infectious) pneumonitis or interstitial lung disease.
•Patient has active infection at time of study entry that require systemic antibiotics and/or with an oral temperature of \>= 38.3 degrees Celsius (°C)(100.9 degrees Fahrenheit (°F)) within 5 days of first treatment.
•Patients with electronic pacemakers or defibrillators are excluded from this study, as the effect of electroporation on these devices is unknown. Patients with lower extremity lesions may be discussed with the medical monitor.
•Patient has an active autoimmune disease or a documented history of autoimmune disease or syndrome that requires systemic steroids or immunosuppressive agents. Patients with vitiligo or resolved childhood asthma/atopy would be exception to this rule. Patients that require intermittent use of bronchodilators or local steroid injections would not be excluded from the study. Patients with hypothyroidism that is stable on hormone replacement will not be excluded from the study.
+4 more criteria

Locations (2)

University of San Francisco, California

San Francisco, California, United States

Huntsman Cancer Institute, University of Utah

Salt Lake City, Utah, United States

Key Dates

Start Date

August 17, 2015

Primary Completion Date

April 26, 2018

Completion Date

March 2, 2020

Last Updated

January 6, 2021

Enrollment

ACTUAL participants

Conditions

Melanoma

Interventions

Pembrolizumab

DRUG

pIL-12

DRUG

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Data Source & Attribution

This clinical trial information is sourced from ClinicalTrials.gov, a service of the U.S. National Institutes of Health.

ClinicalTrials.gov last update: January 6, 2021Data synced to Clareo: March 29, 2026

Modifications: This data has been reformatted for display purposes. Eligibility criteria have been parsed into inclusion/exclusion sections. Location data has been geocoded to enable distance-based search. For the authoritative and most current information, please visit ClinicalTrials.gov.

Neither the United States Government nor Clareo Health make any warranties regarding the data. Check ClinicalTrials.gov frequently for updates.

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Trial of pIL-12/MK-3475 in Metastatic Melanoma

Inclusion Criteria

Exclusion Criteria

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