Low-dose Interleukin-2 and Pembrolizumab in Melanoma and Renal Cell Cancer

Study Overview
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Brief Summary
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This study will evaluate the safety and disease control rate of the combination of pembrolizumab plus low-dose interleukin-2 in patients who have either advanced melanoma or renal cell cancer.

Official Title
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Low-dose Interleukin-2 and Pembrolizumab Among Patients With Metastatic Melanoma and Renal Cell Carcinoma

Conditions
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Carcinoma, Renal Cell, Melanoma

Intervention / Treatment
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* Drug: Pembrolizumab
* Drug: Interleukin-2


Participation Criteria
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Eligibility Criteria
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Main Inclusion Criteria Stage IV or unresectable stage III malignant melanoma or renal cell carcinoma. Melanoma Patients must have failed anti-PD-1/PD-L1 antibody therapy. Patients must have failed ipilimumab or be intolerant of ipilimumab and therefore unable to receive ipilimumab. Patients may, but are not obligated, to have failed high- dose IL2. BRAF status must be known or unable to be performed. If the melanoma expresses a BRAF mutation of V600E, V600K, or V600R patient must have received and progressed through a BRAF inhibitor or have failed that therapy due to toxicity. Renal Cell Carcinoma Patients must have failed anti-PD-1/PD-L1 antibody therapy. Patients must have failed a VEGF pathway inhibitor and a second tyrosine kinase inhibitor. Patients may, but are not obligated, to have failed high- dose IL2. Measurable disease based upon RECIST 1.1. Subjects with brain metastases will be eligible if the following are true: Subjects with ≤ 3 brain metastases All metastases are ≤ 3 cm All metastases have been treated and are asymptomatic Steroids are not required for management of the brain metastases All metastases have been stable for 1 month following treatment Subjects with > 3 brain metastases All metastases are ≤ 3 cm All metastases have been treated and are asymptomatic Steroids are not required for management of the brain metastases All metastases have been stable for 6 months following treatment Performance status: ECOG 0-1. Adequate organ function. Ability to provide informed consent. Main Exclusion Criteria: Pregnancy Currently participating and receiving study therapy or has participated in a study of an investigational agent and received study therapy or used an investigational device within 4 weeks of the first dose of treatment. Has a diagnosis of primary or secondary immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 3 weeks prior to the first dose of trial treatment. Replacement doses of steroids are permitted. Known history of active TB (Bacillus Tuberculosis) Hypersensitivity to pembrolizumab or any of its excipients. Known additional malignancies (exceptions DCIS or LCIS, basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or in situ cervical cancer that has undergone potentially curative therapy). Prior anti-cancer monoclonal antibody (mAb) within 3 weeks prior to study Day 1 or who has not recovered (i.e., ≤ Grade 1 or at baseline) from adverse events due to agents administered more than 3 weeks earlier. 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. Known carcinomatous meningitis. Active autoimmune disease that has required systemic treatment in the past 2 years. Patients may be eligible if they have the following autoimmune diseases: thyroiditis or hypothyroidism, mild arthritis, diabetes, resolved hypophysitis, ulcerative colitis after total abdominal colectomy. Active infection requiring systemic therapy. Known psychiatric or substance abuse disorders. Known history of Human Immunodeficiency Virus (HIV). Known active Hepatitis B virus (HBV) or Hepatitis C virus (HCV). Has received a live vaccine within 30 days of planned start of study therapy. Severe chronic pulmonary disease. Congestive heart failure, angina, or symptomatic cardiac arrhythmia or is classified according to the New York Heart Association classification as having Class III or IV heart disease. History of (non-infectious) pneumonitis that required steroids or current pneumonitis.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Level 1<br>Pembrolizumab (200 mg) administered intravenously (day 2 of cycle 1; day 1 of cycles 2 and beyond); Low dose-interleukin 2 (LD-IL2) 12 MIU/m2 administered subcutaneously (days 1-5 and 8-12 of each cycle); each cycle is 21 days. | Drug: Pembrolizumab<br>* Pembrolizumab solution<br>* Other names: KEYTRUDA;Drug: Interleukin-2<br>* Interleukin-2 solution<br>* Other names: IL-2;|
| Experimental: Level -1<br>Pembrolizumab (200 mg) administered intravenously (day 2 of cycle 1; day 1 of cycles 2 and beyond); Low dose-interleukin 2 (LD-IL2) 5 MIU/m2 administered subcutaneously (days 1-5 and 8-12 of each cycle); each cycle is 21 days. | Drug: Pembrolizumab<br>* Pembrolizumab solution<br>* Other names: KEYTRUDA;Drug: Interleukin-2<br>* Interleukin-2 solution<br>* Other names: IL-2;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety: adverse event profile | Obtain preliminary data on the safety of LD-IL2 with pembrolizumab | up to 90 days post-treatment | 
| Disease control rate: melanoma | Estimate the disease control rate (CR+PR+SD by RECIST 1.1) among candidate patients with metastatic melanoma treated with pembrolizumab and LD-IL2 and to determine whether disease control is significantly improved. SD for 6 months or more will be considered SD for the purpose of this assessment. | baseline and every 9 weeks (up to week 104) | 
| Disease control rate: renal cell cancer | Estimate the disease control rate (CR+PR+SD by RECIST 1.1) among patients with metastatic renal cell cancer treated with pembrolizumab and LD-IL2 and to determine whether disease control is significantly improved. SD for 6 months or more will be considered SD for the purpose of this assessment. | baseline and every 9 weeks (up to week 104) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression free survival: metastatic melanoma | Estimate progression-free survival defined as the duration of time from first response (SD/PR/CR) to time of recurrence/progression or death from any cause, whichever occurs first | From first response (SD/PR/CR) to time of recurrence/progression or death from any cause, whichever occurs first, assessed for an estimated total of 120 months. | 
| Progression free survival: renal cell cancer | Estimate progression-free survival defined as the duration of time from first response (SD/PR/CR) to time of recurrence/progression or death from any cause, whichever occurs first | From first response (SD/PR/CR) to time of recurrence/progression or death from any cause, whichever occurs first, assessed for an estimated total of 120 months. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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pembrolizumab, IL-2, interleukin-2, MK-3475