High Dose IL-2 in Combination With Anti-PD-1 to Overcome Anti-PD-1 Resistance in Metastatic Melanoma and Renal Cell Carcinoma

NCT03991130 | Terminated Phase 2 DMC FDA Drug

• 1 other identifier: UCSD IIT HD IL-2
• Study Type: interventional
• Target: 6
• Locations: 1 country
• Sites: 1

Brief Summary

The primary objective of this single arm phase 2 trial is to assess the response rate \[complete response (CR) + partial response (PR)\] of combined nivolumab and HD IL-2 in subjects with metastatic melanoma and renal cell carcinoma. Response will be performed after each course of nivolumab and IL-2 using RECIST 1.1. Patients will be treated for one course past best response for a maximum of 3 courses.

Conditions

Melanoma Stage Iv; Renal Cell Carcinoma, Metastatic

Keywords

melanoma; renal cell carcinoma

Outcome Measures

Primary Outcomes (1)

• Overall Response Rate

  The primary endpoint will be the response rate \[complete response (CR) and partial response (PR)\] of combined therapy with nivolumab and HD IL-2 in metastatic melanoma and renal cell carcinoma and will be evaluated using revised RECIST 1.1. Response rate will be computed with associated 95% confidence intervals.

  3 years post treatment

Secondary Outcomes (2)

• Drug Toxicity

  After Initiation of a 35 day study treatment period up to 90 days following the last administration of study treatment

• Progression Free Survival

  1 year +/- 3 months

Study Arms (1)

High Dose IL-2 and Nivolumab

EXPERIMENTAL

Drug: IL-2 and Nivolumab

Interventions

IL-2 and Nivolumab DRUG

Course length will be 35 days. Subjects will receive 480 mg IV of nivolumab on day 1 of the cycle. The patient will be admitted to UCSD Jacobs Medical center for standard HD IL-2 which will be administered every 8 hrs for up to 14 doses days 8-12 per institutional practice. The patient will be readmitted days 22-28 for HD IL-2 every 8 hrs for up to 14 doses. Nivolumab 480 mg IV will be administered day 35. Scans for response will occur 4 weeks after day 35 nivolumab dose and response will be determined by RECIST 1.1 to determine if the patient will receive the next course.

Also known as: High Dose IL-2, Anti-PD-1

High Dose IL-2 and Nivolumab

Eligibility Criteria

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

You may qualify if:

• Patient has the ability to understand and the willingness to sign a written informed consent.
• Age ≥ 18 years at the time of consent.
• At least 6 weeks of prior anti-PD-1 therapy with documented clinical or radiographic progression. Last anti-PD-1 therapy must be within 6 months of enrollment.
• Histologically-confirmed diagnosis of unresectable stage III or metastatic (stage IV) melanoma or renal cell carcinoma
• Measurable disease, defined as at least 1 tumor that fulfills the criteria for a target lesion according to RECIST 1.1, and obtained by imaging within 28 days prior registration for protocol therapy.
• Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 within 28 days prior to registration for protocol therapy.
• Adequate hepatic function within 28 days prior to registration for protocol therapy defined as meeting all of the following criteria:
• total bilirubin ≤ 1.5 × upper limit of normal (ULN) OR direct bilirubin ≤ ULN for subjects with total bilirubin levels \> 1.5 x ULN (except in patients with Gilbert's syndrome who must have a total bilirubin less than 3.0 mg/dl.)
• and aspartate aminotransferase (AST) ≤ 2.5 × ULN or ≤ 5 × ULN for subjects with known hepatic metastases
• and alanine aminotransferase (ALT) ≤ 2.5 × ULN or ≤ 5 × ULN for subjects with known hepatic metastases
• Adequate renal function within 28 days prior to registration for protocol therapy defined by either of the following criteria:
• Serum creatinine ≤ 1.5 mg/dL
• OR if serum creatinine \> 1.5 mg/dL, estimated glomerular filtration rate (GFR) ≥ 50 mL/min
• Adequate hematologic function within 28 days prior to registration for protocol therapy defined as meeting all of the following criteria:
• hemoglobin ≥ 9.0 g/dL

You may not qualify if:

• Active infection requiring systemic therapy
• Women who are pregnant or breastfeeding.
• Second active malignancy within the past 5 years with the exception of localized basal or squamous cell skin cancer, in situ cervical or bladder cancer, or localized prostate cancer under active surveillance.
• Active symptomatic central nervous system (CNS) metastases. Prior treated metastases or asymptomatic metastases are allowed. Patient can receive radiation between treatments if deemed medically necessary.
• Surgery within 4 weeks prior to study treatment except for minor procedures.
• Uncontrolled or poorly-controlled hypertension (\> 160 mmHg systolic or \> 100 mmHg diastolic for \> 4 weeks) despite standard medical management.
• Serious or non-healing wounds, ulcers, or bone fractures within 28 days prior to initiation of study treatment.
• Any arterial thromboembolic events, including but not limited to myocardial infarction, transient ischemic attack, cerebrovascular accident, or unstable angina, within 6 months prior to initiation of study treatment.
• Has any condition that, in the opinion of the investigator, might jeopardize the safety of the patient or interfere with protocol compliance.
• Has any mental or medical condition that prevents the patient from giving informed consent or participating in the trial.
• Known hypersensitivity to nivolumab or IL-2 or any of their components.
• Known history of active tuberculosis.
• Concurrent systemic steroid therapy with doses above physiologic level (more than 10 mg of prednisone daily).
• Active autoimmune disease, including but not limited to myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, vascular thrombosis associated with anti-phospholipid syndrome, granulomatosis with polyangiitis, Sjögren's syndrome, Guillain-Barré syndrome, multiple sclerosis, vasculitis, or glomerulonephritis requiring treatment. Patients cannot be on immunosuppressive medications other than physiologic replacement doses of prednisone (less than 10 mg per day at enrollment) or equivalent steroid. Asymptomatic patients or those stable on non-immunosuppressive medications are eligible.
• Treatment with any investigational agent within 21 days prior to initiation of study treatment and the subject must have recovered from the acute toxic effects of the regimen with the exception of prior anti-PD-1.

Sponsors & Collaborators

• Gregory Daniels: lead

Study Sites (1)

UC San Diego Moores Cancer Center

La Jolla, California, 92093, United States

Location

MeSH Terms

Conditions

Melanoma; Carcinoma, Renal Cell; Neoplasm Metastasis

Interventions

Interleukin-2; Nivolumab; spartalizumab

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Interleukins; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Lymphokines; Proteins; Biological Factors; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Serum Globulins; Globulins

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Clinical Professor

Study Record Dates

• First Submitted: June 16, 2019
• First Posted: June 19, 2019
• Study Start: May 23, 2019
• Primary Completion: January 1, 2025
• Study Completion: January 1, 2025
• Last Updated: February 6, 2025

Record last verified: 2025-02

Locations

US (1)