Pembrolizumab and Ipilimumab After Prior Immunotherapy for Melanoma
|The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.|
|ClinicalTrials.gov Identifier: NCT02743819|
Recruitment Status : Active, not recruiting
First Posted : April 19, 2016
Results First Posted : April 21, 2022
Last Update Posted : March 6, 2023
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|Condition or disease||Intervention/treatment||Phase|
|Melanoma||Drug: Pembrolizumab Drug: Ipilimumab||Phase 2|
To determine the irRECIST* response rate of pembrolizumab with ipilimumab following initial progression or stable disease to anti-PD1/L1 antibody (or combination not containing anti-CTLA4) in subjects with advanced melanoma.
- To summarize the progression-free survival (RECIST v1.1 and irRC) of the combination following prior treatment with anti-PD1/L1 antibody.
- To assess the safety of the combination following prior treatment with anti-PD1/L1 antibody.
To evaluate changes in the tumor microenvironment and other biospecimens before and after adding ipilimumab to pembrolizumab.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||70 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Phase II Study of Pembrolizumab and Ipilimumab Following Initial Anti-PD1/L1 Antibody|
|Actual Study Start Date :||June 28, 2016|
|Actual Primary Completion Date :||June 1, 2022|
|Estimated Study Completion Date :||June 2026|
Treatment with the combination of pembrolizumab and ipilimumab.
Pembrolizumab given every 3 weeks (200 mg) by IV infusion.
Other Name: Keytruda
Ipilimumab given every 3 weeks (200 mg) by IV infusion for total of 4 doses.
Other Name: Yervoy
- Overall Response Rate (OR) Per irRECIST [ Time Frame: 16 weeks ]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
- Progression Free Survival Using the Kaplan Meier Method [ Time Frame: 24 months ]Time to disease progression or death. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.
- Number of Participants With Adverse Events [ Time Frame: 30 days after the end of treatment ]Any treatment-related adverse event
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|Ages Eligible for Study:||18 Years and older (Adult, Older Adult)|
|Sexes Eligible for Study:||All|
|Accepts Healthy Volunteers:||No|
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.
The subject must be excluded from participating in the trial if the subject:
- Has received study therapy (including investigational device) as part of a clinical trial within 4 weeks of the first dose of treatment, with the exclusion of an anti-PD1/L1 antibody given as either a single agent or non-CTLA-4 antibody containing combination.
- 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.
- Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
- Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting with the pre-screening or screening visit through 120 days after the last dose of trial treatment.
- Has received prior therapy with an anti-CTLA4 agent.
- Has a known history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies).
- Has known active Hepatitis B (e.g., HBsAg reactive) or Hepatitis C (e.g., HCV RNA [qualitative] is detected).
- Has received a live vaccine within 30 days of planned start of study therapy.
Note: Seasonal influenza vaccines for injection are generally inactivated flu vaccines and are allowed; however intranasal influenza vaccines are live attenuated vaccines, and are not allowed.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02743819
|United States, Alabama|
|University of South Alabama|
|Mobile, Alabama, United States, 36604|
|United States, Florida|
|Mount Sinai Medical Center of Florida|
|Miami Beach, Florida, United States, 33140|
|H. Lee Moffitt Cancer Center and Research Institute|
|Tampa, Florida, United States, 33612|
|United States, Illinois|
|University of Chicago|
|Chicago, Illinois, United States, 60637|
|Decatur Memorial Hospital|
|Decatur, Illinois, United States, 62526|
|NorthShore University HealthSystem|
|Evanston, Illinois, United States, 60201|
|Oncology Specialists S.C.|
|Park Ridge, Illinois, United States, 60068|
|Illinois Cancer Care|
|Peoria, Illinois, United States, 61615|
|United States, Indiana|
|Fort Wayne Medical Oncology and Hematology, Inc.|
|Fort Wayne, Indiana, United States, 46804|
|United States, Virginia|
|Virginia Commonwealth University/ Massey Cancer Center|
|Richmond, Virginia, United States, 23298|
|Principal Investigator:||Thomas Gajewski, M.D.||University of Chicago|
Documents provided by University of Chicago:
|Responsible Party:||University of Chicago|
|Other Study ID Numbers:||
IRB15-1788 ( Other Identifier: University of Chicago )
|First Posted:||April 19, 2016 Key Record Dates|
|Results First Posted:||April 21, 2022|
|Last Update Posted:||March 6, 2023|
|Last Verified:||March 2023|
|Studies a U.S. FDA-regulated Drug Product:||Yes|
|Studies a U.S. FDA-regulated Device Product:||No|
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms, Nerve Tissue
Nevi and Melanomas
Antineoplastic Agents, Immunological
Immune Checkpoint Inhibitors
Molecular Mechanisms of Pharmacological Action