Pembrolizumab and Ipilimumab After Prior Immunotherapy for Melanoma

NCT02743819 | Active Not Recruiting Phase 2 Results DMC FDA Drug

• 2 other identifiers: IRB17-0686IRB15-1788
• Study Type: interventional
• Target: 70
• Locations: 1 country
• Sites: 10

Brief Summary

Phase II study evaluating the benefit of the combination of anti-PD1 (pembrolizumab) and anti-CTLA4 (ipilimumab) antibodies in advanced melanoma. The study will determine the response rate of the combination and evaluate other clinical parameters such as progression-free survival and safety of the combination following anti-PD1/L1 antibody. The study will also provide the opportunity to investigate blood or tumor based factors that may predict response to anti-PD1 antibody in combination with anti-CTLA4.

Conditions

Melanoma

Keywords

Melanoma; Pembrolizumab; Ipilimumab

Outcome Measures

Primary Outcomes (1)

• Overall Response Rate (OR) Per irRECIST

  Per Response Evaluation Criteria for use in trials testing immunotherapeutics (iRECIST) for target lesions and assessed by CT or MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR

  16 weeks

Secondary Outcomes (2)

• Progression Free Survival Using the Kaplan Meier Method

  24 months

• Number of Participants With Adverse Events

  30 days after the end of treatment

Study Arms (1)

Treatment

EXPERIMENTAL

Treatment with the combination of pembrolizumab and ipilimumab.

Drug: Pembrolizumab; Drug: Ipilimumab

Interventions

Pembrolizumab DRUG

Pembrolizumab given every 3 weeks (200 mg) by IV infusion.

Also known as: Keytruda

Treatment

Ipilimumab DRUG

Ipilimumab given every 3 weeks (200 mg) by IV infusion for total of 4 doses.

Also known as: Yervoy

Treatment

Eligibility Criteria

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

You may qualify if:

• In order to be eligible for participation in this trial, the subject must:
• Be willing and able to provide written informed consent for the trial.
• Be 18 years of age on day of signing informed consent.
• Have experienced disease progression or stable disease lasting at least 24 weeks during treatment with an anti-PD1/L1 antibody as the treatment regimen immediately prior to accrual to this study or disease progression within 6 months of adjuvant anti-PD1 antibody.
• Have measurable disease based on irRECIST 1.1.
• Have a performance status of 0 or 1 on the ECOG Performance Scale.
• Demonstrate adequate organ function as defined below, all screening labs should be performed within 10 days of treatment initiation.
• Hematological Absolute neutrophil count (ANC) ≥1,500 /mcL Platelets ≥100,000 / mcL Hemoglobin ≥8 g/dL or ≥4.96 mmol/L
• Renal Serum creatinine OR Measured or calculated creatinine clearance ≤1.5 X upper limit of normal (ULN) OR ≥60 mL/min for subject with creatinine levels \> 1.5 X institutional ULN (GFR can also be used in place of creatinine or CrCl)
• Hepatic Serum total bilirubin ≤ 1.5 X ULN OR Direct bilirubin ≤ ULN for subjects with total bilirubin levels \> 1.5 ULN AST (SGOT) and ALT (SGPT) ≤ 2.5 X ULN OR ≤ 5 X ULN for subjects with liver metastases Albumin \>2.5 mg/dL
• Coagulation International Normalized Ratio (INR) or Prothrombin Time (PT) ≤1.5 X ULN unless subject is receiving anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use of anticoagulants
• Activated Partial Thromboplastin Time (aPTT) ≤1.5 X ULN unless subject is receiving anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use of anticoagulants
• Female subject of childbearing potential should have a negative urine or serum pregnancy within 72 hours prior to receiving the first dose of study medication. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.
• Female subjects of childbearing potential should be willing to use 2 methods of birth control or be surgically sterile, or abstain from heterosexual activity for the course of the study through 120 days after the last dose of study medication. Subjects of childbearing potential are those who have not been surgically sterilized or have not been free from menses for \> 1 year.
• Male subjects should agree to use an adequate method of contraception starting with the first dose of study therapy through 120 days after the last dose of study therapy.

You may not qualify if:

• The subject must be excluded from participating in the trial if the subject:
• Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment.
• Has a known history of active TB (Bacillus Tuberculosis)
• Hypersensitivity to pembrolizumab or any of its excipients.
• Has had a prior anti-cancer monoclonal antibody (mAb) within 4 weeks prior to study Day 1 (excluding commercial or investigational anti-PD1 or anti-PD-L1 antibodies as single agents) or who has not recovered (i.e., ≤ Grade 1 or at baseline) from adverse events due to agents administered more than 4 weeks earlier.
• Has had prior chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks prior to study Day 1 or who has not recovered (i.e., ≤ Grade 1 or at baseline) from adverse events due to a previously administered agent.
• Note: Subjects with ≤ Grade 2 neuropathy are an exception to this criterion and may qualify for the study.
• Note: If subject received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy.
• Has a known additional malignancy that is progressing or requires active treatment. Exceptions include basal cell carcinoma of the skin or squamous cell carcinoma of the skin that has undergone potentially curative therapy or in situ cervical cancer.
• Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis. Subjects with previously treated brain metastases may participate provided they are stable (without evidence of progression by imaging for at least four weeks prior to the first dose of trial treatment and any neurologic symptoms have returned to baseline), have no evidence of new or enlarging brain metastases, and are not using steroids for at least 7 days prior to trial treatment. This exception does not include carcinomatous meningitis which is excluded regardless of clinical stability.
• Has active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (eg., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment.
• Patients with uveal/ocular melanoma are excluded.
• Has known history of, or any evidence of active, non-infectious pneumonitis.
• Has an active infection requiring systemic therapy.
• Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the subject's participation for the full duration of the trial, or is not in the best interest of the subject to participate, in the opinion of the treating investigator.

Sponsors & Collaborators

• University of Chicago: lead

Study Sites (10)

University of South Alabama

Mobile, Alabama, 36604, United States

Location

Mount Sinai Medical Center of Florida

Miami Beach, Florida, 33140, United States

Location

H. Lee Moffitt Cancer Center and Research Institute

Tampa, Florida, 33612, United States

Location

University of Chicago

Chicago, Illinois, 60637, United States

Location

Decatur Memorial Hospital

Decatur, Illinois, 62526, United States

Location

NorthShore University HealthSystem

Evanston, Illinois, 60201, United States

Location

Oncology Specialists S.C.

Park Ridge, Illinois, 60068, United States

Location

Illinois Cancer Care

Peoria, Illinois, 61615, United States

Location

Fort Wayne Medical Oncology and Hematology, Inc.

Fort Wayne, Indiana, 46804, United States

Location

Virginia Commonwealth University/ Massey Cancer Center

Richmond, Virginia, 23298, United States

Location

MeSH Terms

Conditions

Melanoma

Interventions

pembrolizumab; Ipilimumab

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)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Results Point of Contact

• Title: Daniel Olson, Clinical Instructor
• Organization: University of Chicago

daniel.olson2@uchospitals.edu

773-834-4183

Study Officials

• Thomas Gajewski, M.D.

  University of Chicago

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 14, 2016
• First Posted: April 19, 2016
• Study Start: June 28, 2016
• Primary Completion: June 1, 2022
• Study Completion (Estimated): June 1, 2026
• Last Updated: June 10, 2025
• Results First Posted: April 21, 2022

Record last verified: 2025-06

Locations

US (10)