Treatment of Advanced Melanoma With MK-3475 and Peginterferon

NCT02112032 | Completed Phase 1 DMC

• 1 other identifier: 13-105
• Study Type: interventional
• Target: 43
• Locations: 1 country
• Sites: 1

Brief Summary

This study is to test how safe it is to give the combination of PEG IFN-α2b (SYLATRON) and MK-3475, an investigational drug, to patients with advanced melanoma. Its effectiveness against melanoma will also be evaluated.

Conditions

Melanoma

Keywords

melanoma; advanced

Outcome Measures

Primary Outcomes (1)

• Number of Participants with Serious and Non-Serious Adverse Events

  29 days

Secondary Outcomes (1)

• Time to Disease Progression

  6 months

Study Arms (3)

Dose Level 1

EXPERIMENTAL

MK-3475: 2 mg/kg every 3 weeks by intravenous infusion for up to 2 years Peginterferon alfa-2b: 1 µg/kg every week by subcutaneous injection for up to 2 years

Drug: MK-3475; Drug: Peginterferon alfa-2b

Dose Level 2

EXPERIMENTAL

MK-3475: 2 mg/kg every 3 weeks by intravenous infusion for up to 2 years Peginterferon alfa-2b: 2 µg/kg every week by subcutaneous injection for up to 2 years

Drug: MK-3475; Drug: Peginterferon alfa-2b

Dose Level 3

EXPERIMENTAL

MK-3475: 2 mg/kg every 3 weeks by intravenous infusion for up to 2 years Peginterferon alfa-2b: 3 µg/kg every week by subcutaneous injection for up to 2 years

Drug: MK-3475; Drug: Peginterferon alfa-2b

Interventions

MK-3475 DRUG

This is a dose escalation study to determine the serious and non-serious adverse events that occur as the dose increases.

Also known as: Anti-PD-1, SCH 900475, 1374853-91-4, Humanized X PD-1_mAb (H409A11) IgG4

Dose Level 1; Dose Level 2; Dose Level 3

Peginterferon alfa-2b DRUG

This is a dose escalation study to determine the serious and non-serious adverse events that occur from the combination of Peginterferon and MK-3475 as the doses increase.

Also known as: Sylatron, 215647-85-1, Pegintron

Dose Level 1; Dose Level 2; Dose Level 3

Eligibility Criteria

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

You may qualify if:

• Patient must have a histologically or cytologically confirmed diagnosis of unresectable stage III or IV melanoma. Patient may not have a diagnosis of uveal melanoma.
• Patients may be previously untreated or have received up to 3 prior systemic therapies for metastatic disease. Prior radiation therapy (any number) and interferon use in the adjuvant or metastatic disease settings is permitted (in this trial interferon is mainly used to enhance or initiate immune responses to MK-3475). Vaccine therapy will not be counted as systemic therapy. All prior therapies must have been discontinued for at least 4 weeks. A 2 week washout for kinase inhibitors is acceptable.
• Patients can be either ipilimumab naïve or refractory to ipilimumab, defined as received at least two doses of ipilimumab and documented disease progression. Patients who were re-treated with ipilimumab and patients who were on maintenance ipilimumab will be allowed to enter the trial as long as there is documented PD. Progressive disease will be defined as increase in tumor burden \> 25% relative to nadir (minimum recorded tumor burden) which is confirmed by repeat assessment no less than four weeks from the date of the first documented PD. Once PD is confirmed, initial date of PD documentation will be considered as the date of disease progression.
• Full resolution of ipilimumab related AEs to baseline (including irAEs) off of steroid treatment (\> 10 mg/day prednisone or equivalent dose) for irAEs for at least two weeks prior to first dose of study drug.
• No history of severe irAEs from ipilimumab of CTCAE Grade 4 requiring steroid treatment; no history of CTCAE Grade 3 requiring steroid treatment (\> 10mg/day prednisone or equivalent dose) for \> 12 weeks.
• Minimum of four weeks (wash out period) from the last dose of ipilimumab.
• Patients must consent to participate in the correlative studies and should have available tumor tissue for tumor biopsies.
• Patient must have measurable disease as per RECIST version 1.1. At least 1 of the tumor sites must be amenable to biopsy and this may not be the site of disease used to measure antitumor response.
• Patient is ≥ 18 years of age on day of signing informed consent.
• Patient must have a performance status of 0 or 1 on the ECOG Performance Scale
• Patient must have adequate organ function as indicated by the following laboratory values (within 4 weeks prior to starting the study drugs):
• Absolute neutrophil count (ANC) ≥ 1,500/uL
• Platelets ≥ 100,000/uL
• Hemoglobin ≥ 9 g/dL or ≥ 5.6 mmol/L
• Serum creatinine ≤ 1.5 X upper limit of normal (ULN)

You may not qualify if:

• Patient who has had chemotherapy, radioactive, or biological cancer therapy within four weeks prior to the first dose of study drug, or who has not recovered to CTCAE Grade 1 or better from the AEs due to cancer therapeutics administered more than four weeks earlier. Subjects with ≤ grade 2 neuropathy are an exception to this criterion and may qualify for the study.
• Note: If patient received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy.
• Patient is currently participating or has participated in a study of an investigational agent or using an investigational device within 4 weeks of the first dose of study drug.
• Patient is expected to require any other form of systemic or localized antineoplastic therapy while on study.
• Patient is on chronic systemic steroid therapy (\> 10 mg/kg prednisone or equivalent) within two weeks before the planned date for first dose randomized treatment or on any other form of immunosuppressive medication (Premedication with corticosteroid for nausea is permitted.)
• Patient has a known history of a hematologic malignancy, primary brain tumor or sarcoma, or of another primary solid tumor, unless the patient has undergone potentially curative therapy with no evidence of that disease for five years.
• Note: The time requirement also does not apply to patients who underwent successful definitive resection of basal or squamous cell carcinoma of the skin, superficial bladder cancer, in situ cancers including cervical cancer, breast cancer, melanoma, or other in situ cancers.
• Patient has known active central nervous system (CNS) metastases and/or carcinomatous meningitis. Patients with previously treated brain metastases may participate provided they are stable (without evidence of progression by MRI for at least four weeks prior to the first dose of study drug), have no evidence of new or enlarging brain metastases and are off systemic steroids (≤ 10 mg/day prednisone or equivalent) for at least two weeks prior to enrollment.
• Patient previously had a severe hypersensitivity reaction to treatment with another mAb or IFN-α2b.
• 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, type I diabetes, resolved childhood asthma/atopy would be exceptions to this rule. Patients who require intermittent use of bronchodilators or local steroid injections would not be excluded from the study. Patients with hypothyroidism stable on hormone replacement will also not be excluded from the study.
• Patient has evidence of interstitial lung disease.
• Serious illnesses, such as: cardiovascular disease (uncontrolled congestive heart failure, hypertension, cardiac ischemia, myocardial infarction, and severe cardiac arrhythmia), bleeding disorders, autoimmune diseases, severe obstructive or restrictive pulmonary diseases, active systemic infections, and inflammatory bowel disorders. This includes HIV or AIDS-related illness, or active HBV and HCV.
• Patient had prior treatment with any other anti-PD-1, or PD-L1 or PD-L2 agent.
• Patient has an active infection requiring systemic therapy.
• Patient has known history of human Immunodeficiency virus (HIV) (HIV 1/2 antibodies).

Sponsors & Collaborators

• Hassane M. Zarour, MD: lead
• Merck Sharp & Dohme LLC: collaborator
• Melanoma Research Alliance: collaborator

Study Sites (1)

Hillman Cancer Center

Pittsburgh, Pennsylvania, 15232, United States

Location

MeSH Terms

Conditions

Melanoma

Interventions

pembrolizumab; spartalizumab; Immunoglobulin G; peginterferon alfa-2b

Condition Hierarchy (Ancestors)

Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Neoplasms by Site; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Immunoglobulin Isotypes; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Hassane Zarour, MD

  UPMC Hillman Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor of Medicine, Immunology, and Dermatology

Study Record Dates

• First Submitted: April 9, 2014
• First Posted: April 11, 2014
• Study Start: July 24, 2014
• Primary Completion: April 12, 2019
• Study Completion: July 17, 2020
• Last Updated: May 5, 2021

Record last verified: 2021-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)