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Back|NCT05493566Recruiting
Official Title

A Biomarker Study of Low-Dose IL-2 Plus Pembrolizumab in Patients with Stage IV Non-Small Cell Lung Cancer (NSCLC)

Phase
Early Phase 1
Sponsor
Emory University
Enrollment
15
Timeline
Nov 2022 → Jan 2027
About This Study

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.

Eligibility Criteria

Inclusion Criteria

  • 1Patients 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.
  • 2Patients must have measurable disease, as defined by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria.
  • 3No prior therapy for advanced NSCLC.
  • 4Patients with brain metastasis are eligible if they are asymptomatic or treated and stable.
  • 5Age greater than or equal to 18 years.
  • 6Eastern Cooperative Oncology Group (ECOG) performance status 0-2.
  • 7Life expectancy of greater than 12 weeks.
  • 8Patients must have adequate organ and marrow function, including:
  • 9Absolute neutrophil count (ANC) ≥ 1,500/mcL
  • 10Platelet count ≥ 100,000/mcL
  • 11Hemoglobin ≥ 9.0 g/dL (patients may be transfused to meet this)
  • 12Aspartate 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)
  • 13Serum bilirubin l≤ 1.5 x ULN
  • 14Creatinine Clearance \> 60 mL/min
  • 15Patients 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.
  • 16For women of childbearing potential or men with sexual partners of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use a contraceptive method with a failure rate of \< 1% per year during the treatment period and for at least 5 months after the last dose of study treatment.
  • 17A woman is considered to be of childbearing potential if she is postmenarcheal, has not reached a postmenopausal state (≥12 continuous months of amenorrhea with no identified cause other than menopause), and has not undergone surgical sterilization (removal of ovaries and/or uterus).
  • 18Examples of contraceptive methods with a failure rate of \< 1% per year include bilateral tubal ligation, male sterilization, hormonal contraceptives that inhibit ovulation, hormone-releasing intrauterine devices, and copper intrauterine devices. The reliability of sexual abstinence should be evaluated in relation to the duration of the clinical trial and the preferred and usual lifestyle of the patient. Periodic abstinence (e.g., calendar, ovulation, symptothermal, or postovulation methods) and withdrawal are not acceptable methods of contraception.
  • 19Ability to understand and the willingness to sign a written informed consent document.

Exclusion Criteria

  • 1An individual who meets any of the following criteria will be excluded from participation in this study:
  • 2Any prior chemotherapy or immunotherapy for advanced lung cancer.
  • 3Prior treatment with anti-PD-1 or anti-PD-L1 therapies or pathway-targeting agents.
  • 4Any targetable driver mutation (e.g. ALK, EGFR exon 19 del, etc).
  • 5Patients with prior allogeneic bone marrow transplantation or prior solid organ transplantation.
  • 6Major surgical procedure within 28 days prior to cycle 1, day 1.
  • 7Evidence of visceral crisis (severe organ dysfunction as assessed by signs, symptoms, and laboratory values, resulting from rapid progression of neoplastic disease).
  • 8Active concomitant malignancy that requires therapy.
  • 9Treatment 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.
  • 10Patients 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.
  • 11The 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.
  • 12History 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
  • 13Patients with a history of autoimmune hypothyroidism on a stable dose of thyroid replacement hormone are eligible.
  • 14Patients with controlled type 1 diabetes mellitus on a stable insulin regimen are eligible.
  • 15Patients 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:
  • 16Rash must cover \< 10% of body surface area (BSA)
  • 17Disease is well controlled at baseline and only requiring low potency topical steroids (e.g., hydrocortisone 2.5%, hydrocortisone butyrate 0.1%, fluocinolone 0.01%, desonide 0.05%, alclometasone dipropionate 0.05%)
  • 18No acute exacerbations of underlying condition within the last 12 months (requiring psoralen plus ultraviolet A radiation, methotrexate, retinoids, biologic agents, oral calcineurin inhibitors, high potency or oral steroids)
  • 19History of idiopathic pulmonary fibrosis, pneumonitis (including drug induced), organizing pneumonia (i.e., bronchiolitis obliterans, cryptogenic organizing pneumonia, etc.), or evidence of active pneumonitis on screening chest CT scan.
  • 20QTc of \>470 msec by EKG.
  • 21Known clinically significant liver disease, including active viral, alcoholic, or other hepatitis, cirrhosis, fatty liver, and inherited liver disease.
  • 22Known HIV infection.
  • 23Active tuberculosis.
  • 24Administration of a live, attenuated influenza vaccine (e.g., FluMist) within 4 weeks before Cycle 1, Day 1 or at any time during the study.
  • 25Severe infections within 4 weeks prior to Cycle 1, Day 1, including but not limited to hospitalization for complications of infection, bacteremia, or severe pneumonia.
  • 26Treatment with an investigational agent for any condition within 4 weeks prior to Cycle 1, Day 1 (or within five half-lives of the investigational product, whichever is longer).
  • 27History of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric or humanized antibodies or fusion proteins
  • 28Patients who are pregnant or lactating, or who are intending to become pregnant during the study.
  • 29Women of childbearing potential must have a negative serum pregnancy test result within 14 days prior to initiation of study treatment.

Locations

1 site participating in this study

Emory University/Winship Cancer Institute

Atlanta, Georgia 30322

Recruiting

Mashunté Holmes, PhD

mashunte.holmes@emory.edu404-778-1972
Data sourced from ClinicalTrials.govView on ClinicalTrials.gov →