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

NCT03111901 | Withdrawn Phase 1 DMC FDA Drug

• 1 other identifier: 18537
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Carcinoma, Renal Cell; Melanoma

Keywords

pembrolizumab; IL-2; interleukin-2; MK-3475

Outcome Measures

Primary Outcomes (3)

• 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 Outcomes (2)

• Progression free survival: metastatic melanoma

  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

  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.

Study Arms (2)

Level 1

EXPERIMENTAL

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; Drug: Interleukin-2

Level -1

EXPERIMENTAL

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; Drug: Interleukin-2

Interventions

Pembrolizumab DRUG

Pembrolizumab solution

Also known as: MK-3475, KEYTRUDA

Level -1; Level 1

Interleukin-2 DRUG

Interleukin-2 solution

Also known as: IL-2

Level -1; Level 1

Eligibility Criteria

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

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• William Grosh, MD: lead

Study Sites (1)

University of Virginia Cancer Center

Charlottesville, Virginia, 22908, United States

Location

MeSH Terms

Conditions

Carcinoma, Renal Cell; Melanoma

Interventions

pembrolizumab; Interleukin-2

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Kidney Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Kidney Diseases; Urologic Diseases; Male Urogenital Diseases; Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Interleukins; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Lymphokines; Proteins; Biological Factors

Study Officials

• William W Grosh, MD

  University of Virginia Health System

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Associate Professor of Medicine

Study Record Dates

• First Submitted: March 23, 2017
• First Posted: April 13, 2017
• Study Start: October 29, 2018
• Primary Completion: October 1, 2023
• Study Completion: October 1, 2023
• Last Updated: July 12, 2019

Record last verified: 2019-07

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)