Low-dose Interleukin-2 and Pembrolizumab in Melanoma and Renal Cell Cancer (UVA-AM-002)

William Grosh, MD

Status and phase: Withdrawn; Phase 2; Phase 1

Conditions: Carcinoma, Renal Cell; Melanoma

Treatments: Drug: Interleukin-2; Drug: Pembrolizumab

Study type: Interventional

Funder types: Other

Identifiers

NCT03111901

18537

Details and patient eligibility

About

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.

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

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.

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

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0 participants in 2 patient groups

Level 1

Experimental group

Description:

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.

Treatment:

Drug: Pembrolizumab

Drug: Interleukin-2

Level -1

Experimental group

Description:

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.

Treatment:

Drug: Pembrolizumab

Drug: Interleukin-2