Phase II Study of Pembrolizumab and Ipilimumab Following Initial Anti-PD1/L1 Antibody
Overview
- Phase
- Phase 2
- Intervention
- Pembrolizumab
- Conditions
- Melanoma
- Sponsor
- University of Chicago
- Enrollment
- 70
- Locations
- 10
- Primary Endpoint
- Overall Response Rate (OR) Per irRECIST
- Status
- Active, not recruiting
- Last Updated
- 10 months ago
Overview
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.
Detailed Description
Primary Objective: 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. Secondary Objective 1. To summarize the progression-free survival (RECIST v1.1 and irRC) of the combination following prior treatment with anti-PD1/L1 antibody. 2. To assess the safety of the combination following prior treatment with anti-PD1/L1 antibody. Exploratory Objective: To evaluate changes in the tumor microenvironment and other biospecimens before and after adding ipilimumab to pembrolizumab.
Investigators
Eligibility Criteria
Inclusion Criteria
- •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.
- •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
Exclusion Criteria
- •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.
Arms & Interventions
Treatment
Treatment with the combination of pembrolizumab and ipilimumab.
Intervention: Pembrolizumab
Treatment
Treatment with the combination of pembrolizumab and ipilimumab.
Intervention: Ipilimumab
Outcomes
Primary Outcomes
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
Secondary Outcomes
- Progression Free Survival Using the Kaplan Meier Method(24 months)
- Number of Participants With Adverse Events(30 days after the end of treatment)