Low-Dose Interleukin-2 and Pembrolizumab for the Treatment of Stage IV Non-Small Cell Lung Cancer

NCT05493566 | Recruiting Early Phase 1 DMC FDA Drug

• 4 other identifiers: STUDY00003612NCI-2022-00931WINSHIP5477-21P30CA138292
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 1

Brief Summary

This early phase 1 trial will investigate the combination of low-dose interleukin-2 (IL-2) and pembrolizumab in patients with previously untreated stage IV non-small cell lung cancer (NSCLC). Preclinical data demonstrate reinvigoration of exhausted T cells into an effector-like phenotype with improved anti-tumor activity in response to this combination. This study will evaluate T cell function as well as clinical outcomes associated with this combination therapy.

Conditions

Lung Non-Small Cell Carcinoma; Stage IV Lung Cancer AJCC v8; Stage IVA Lung Cancer AJCC v8; Stage IVB Lung Cancer AJCC v8

Outcome Measures

Primary Outcomes (1)

• Immune Response To Combination IL-2 and Pembrolizumab

  Percentage of patients that express a greater than 1.5-fold increase in Ki-67 + PD-L1 + CD8 T cells in peripheral blood by week 3 of combination therapy. A 95% exact confidence interval will be estimated using the Clopper-Pearson method. Descriptive statistical analysis will be utilized to determine frequencies and percentages for categorical measurements.

  Change from Baseline at weeks 1, 2, 3, 6, 12, and 18

Secondary Outcomes (5)

• Objective Response Rate

  Up 6 weeks after study completion

• Progression Free Survival (PFS)

  6 months, 1 year, 3 year, and 5 years

• Overall Survival (OS)

  6 months, 1 year, 3 year, and 5 years

• Dose-limiting Toxicities (DLTs)

  Up 6 weeks after study completion

• Incidence of Adverse Events (AEs)

  Up 6 weeks after study completion

Study Arms (1)

Treatment (pembrolizumab, aldesleukin)

EXPERIMENTAL

Patients will be treated with pembrolizumab 200 mg IV once every 3 weeks in combination with IL-2 given at 5 million IU subcutaneously twice daily for 3 weeks (5 days on, 2 days off each week, first dose in clinic and subsequent doses at home). IL-2 will be given only for the three weeks, after which pembrolizumab will be continued as monotherapy at either 200 mg every 3 weeks or 400 mg every 6 weeks.

Biological: Aldesleukin; Biological: Pembrolizumab

Interventions

Aldesleukin BIOLOGICAL

Given SC

Also known as: 125-L-Serine-2-133-interleukin 2, Proleukin, r-serHuIL-2, Recombinant Human IL-2, Recombinant Human Interleukin-2

Treatment (pembrolizumab, aldesleukin)

Pembrolizumab BIOLOGICAL

Given IV

Also known as: Keytruda, Lambrolizumab, MK-3475, SCH 900475

Treatment (pembrolizumab, aldesleukin)

Eligibility Criteria

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

You may qualify if:

• Patients must have Stage IV non-small cell lung cancer (NSCLC), based on the 8th edition of the American Joint Committee on Cancer (AJCC) NSCLC Staging System. This includes adenocarcinoma and squamous cell carcinoma.
• Patients must have measurable disease, as defined by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria.
• No prior therapy for advanced NSCLC.
• Patients with brain metastasis are eligible if they are asymptomatic or treated and stable.
• Age greater than or equal to 18 years.
• Eastern Cooperative Oncology Group (ECOG) performance status 0-2.
• Life expectancy of greater than 12 weeks.
• Patients must have adequate organ and marrow function, including:
• Absolute neutrophil count (ANC) ≥ 1,500/mcL
• Platelet count ≥ 100,000/mcL
• Hemoglobin ≥ 9.0 g/dL (patients may be transfused to meet this)
• Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase \[SGOT\]) and alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase \[SGPT\]) ≤ 2.5 x institutional upper limit of normal (ULN)
• Serum bilirubin l≤ 1.5 x ULN
• Creatinine Clearance \> 60 mL/min
• Patients must have tumor PD-L1 expression of ≥1% (by 22c3 PD-L1 companion testing); patients whose PD-L1 status could not be determined are also eligible. Patients with known PD-L1 of 0% will be excluded.

You may not qualify if:

• An individual who meets any of the following criteria will be excluded from participation in this study:
• Any prior chemotherapy or immunotherapy for advanced lung cancer.
• Prior treatment with anti-PD-1 or anti-PD-L1 therapies or pathway-targeting agents.
• Any targetable driver mutation (e.g. ALK, EGFR exon 19 del, etc).
• Patients with prior allogeneic bone marrow transplantation or prior solid organ transplantation.
• Major surgical procedure within 28 days prior to cycle 1, day 1.
• Evidence of visceral crisis (severe organ dysfunction as assessed by signs, symptoms, and laboratory values, resulting from rapid progression of neoplastic disease).
• Active concomitant malignancy that requires therapy.
• Treatment with systemic immunosuppressive medications (e.g., prednisone, cyclophosphamide, azathioprine, methotrexate, thalidomide, and anti-tumor necrosis factor \[anti-TNF\] agents) within 2 weeks prior to Cycle 1, Day 1.
• Patients who have received acute, low-dose, systemic immunosuppressant medications (e.g., a one-time dose of dexamethasone for nausea or premedication for contrast dye allergy) are eligible.
• The use of inhaled corticosteroids for chronic obstructive pulmonary disease (COPD) and mineralocorticoids (e.g., fludrocortisone) for patients with orthostatic hypotension or adrenocortical insufficiency is allowed.
• History or risk of autoimmune disease, including but not limited to systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, vascular thrombosis associated with antiphospholipid syndrome, Wegener's granulomatosis, Sjögren's syndrome, Bell's palsy, Guillain-Barré syndrome, multiple sclerosis, autoimmune thyroid disease, vasculitis, or glomerulonephritis
• Patients with a history of autoimmune hypothyroidism on a stable dose of thyroid replacement hormone are eligible.
• Patients with controlled type 1 diabetes mellitus on a stable insulin regimen are eligible.
• Patients with eczema, psoriasis, or lichen simplex chronicus of vitiligo with dermatologic manifestations only (e.g., patients with psoriatic arthritis are excluded) are eligible provided they meet the following conditions:

Sponsors & Collaborators

• Emory University: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

Emory University/Winship Cancer Institute

Atlanta, Georgia, 30322, United States

RECRUITING

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung; Lung Neoplasms

Interventions

aldesleukin; pembrolizumab

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Study Officials

• Suresh S Ramalingam, MD, FACP, FASCO

  Emory University Hospital/Winship Cancer Institute

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Suresh S. Ramalingam, MD, FACP, FASCO

CONTACT

404-778-5378; ssramal@emory.edu

Ralph Millett, MD

CONTACT

rmillet@emory.edu

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: August 2, 2022
• First Posted: August 9, 2022
• Study Start: November 1, 2022
• Primary Completion (Estimated): January 7, 2027
• Study Completion (Estimated): January 7, 2028
• Last Updated: February 12, 2026

Record last verified: 2026-02

Locations

US (1)