Trial Title:
Low-Dose Interleukin-2 and Pembrolizumab for the Treatment of Stage IV Non-Small Cell Lung Cancer
NCT ID:
NCT05493566
Condition:
Lung Non-Small Cell Carcinoma
Stage IV Lung Cancer AJCC v8
Stage IVA Lung Cancer AJCC v8
Stage IVB Lung Cancer AJCC v8
Conditions: Official terms:
Lung Neoplasms
Carcinoma, Non-Small-Cell Lung
Aldesleukin
Pembrolizumab
Interleukin-2
Study type:
Interventional
Study phase:
Early Phase 1
Overall status:
Recruiting
Study design:
Allocation:
N/A
Intervention model:
Single Group Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Biological
Intervention name:
Aldesleukin
Description:
Given SC
Arm group label:
Treatment (pembrolizumab, aldesleukin)
Other name:
125-L-Serine-2-133-interleukin 2
Other name:
Proleukin
Other name:
r-serHuIL-2
Other name:
Recombinant Human IL-2
Other name:
Recombinant Human Interleukin-2
Intervention type:
Biological
Intervention name:
Pembrolizumab
Description:
Given IV
Arm group label:
Treatment (pembrolizumab, aldesleukin)
Other name:
Keytruda
Other name:
Lambrolizumab
Other name:
MK-3475
Other name:
SCH 900475
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.
Detailed description:
PRIMARY OBJECTIVE:
I. To assess phenotypic, transcriptional, and epigenetic profiles of PD-1+ CD8 T cells
response in patients with stage IV non-small cell lung cancer (NSCLC) treated with the
combination of IL-2 and pembrolizumab.
SECONDARY OBJECTIVE:
I. To evaluate anti-tumor activity of the combination of IL-2 and pembrolizumab by
assessing the objective response rate (ORR) by Response Evaluation Criteria in Solid
Tumors (RECIST 1.1).
II. To evaluate the safety of the combination of IL-2 and pembrolizumab.
OUTLINE:
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.
After completion of the study treatment, patients are followed for up for 6 weeks.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
1. 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.
2. Patients must have measurable disease, as defined by Response Evaluation Criteria in
Solid Tumors (RECIST) 1.1 criteria.
3. No prior therapy for advanced NSCLC.
4. Patients with brain metastasis are eligible if they are asymptomatic or treated and
stable.
5. Age greater than or equal to 18 years.
6. Eastern Cooperative Oncology Group (ECOG) performance status 0-2.
7. Life expectancy of greater than 12 weeks.
8. Patients must have adequate organ and marrow function, including:
1. Absolute neutrophil count (ANC) ≥ 1,500/mcL
2. Platelet count ≥ 100,000/mcL
3. Hemoglobin ≥ 9.0 g/dL (patients may be transfused to meet this)
4. 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)
5. Serum bilirubin l≤ 1.5 x ULN
6. Creatinine Clearance > 60 mL/min
9. 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.
10. For 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.
1. A 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).
2. Examples 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.
11. Ability to understand and the willingness to sign a written informed consent
document.
Exclusion Criteria:
An individual who meets any of the following criteria will be excluded from
participation in this study:
12. Any prior chemotherapy or immunotherapy for advanced lung cancer.
13. Prior treatment with anti-PD-1 or anti-PD-L1 therapies or pathway-targeting agents.
14. Any targetable driver mutation (e.g. ALK, EGFR exon 19 del, etc).
15. Patients with prior allogeneic bone marrow transplantation or prior solid organ
transplantation.
16. Major surgical procedure within 28 days prior to cycle 1, day 1.
17. Evidence of visceral crisis (severe organ dysfunction as assessed by signs,
symptoms, and laboratory values, resulting from rapid progression of neoplastic
disease).
18. Active concomitant malignancy that requires therapy.
19. 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.
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.
2. 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.
20. 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
1. Patients with a history of autoimmune hypothyroidism on a stable dose of
thyroid replacement hormone are eligible.
2. Patients with controlled type 1 diabetes mellitus on a stable insulin regimen
are eligible.
3. 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:
- Rash must cover < 10% of body surface area (BSA)
- Disease 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%)
- No 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)
21. History 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.
22. QTc of >470 msec by EKG.
23. Known clinically significant liver disease, including active viral, alcoholic, or
other hepatitis, cirrhosis, fatty liver, and inherited liver disease.
24. Known HIV infection.
25. Active tuberculosis.
26. Administration of a live, attenuated influenza vaccine (e.g., FluMist) within 4
weeks before Cycle 1, Day 1 or at any time during the study.
27. Severe infections within 4 weeks prior to Cycle 1, Day 1, including but not limited
to hospitalization for complications of infection, bacteremia, or severe pneumonia.
28. Treatment 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).
29. History of severe allergic, anaphylactic, or other hypersensitivity reactions to
chimeric or humanized antibodies or fusion proteins
30. Patients who are pregnant or lactating, or who are intending to become pregnant
during the study.
1. Women of childbearing potential must have a negative serum pregnancy test
result within 14 days prior to initiation of study treatment.
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
Emory University/Winship Cancer Institute
Address:
City:
Atlanta
Zip:
30322
Country:
United States
Status:
Recruiting
Contact:
Last name:
Mashunté Holmes, PhD
Phone:
404-778-1972
Email:
mashunte.holmes@emory.edu
Investigator:
Last name:
Suresh S. Ramalingam
Email:
Principal Investigator
Start date:
November 1, 2022
Completion date:
January 7, 2026
Lead sponsor:
Agency:
Emory University
Agency class:
Other
Collaborator:
Agency:
National Cancer Institute (NCI)
Agency class:
NIH
Source:
Emory University
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05493566