REStoring lymphoCytes Using NKTR-255* After chemoradiothErapy in Solid Tumors (RESCUE)
Sponsor: M.D. Anderson Cancer Center
ClinicalTrials ID:NCT05632809
The RESCUE trial evaluates NKTR-255 with durvalumab post-CRT in NSCLC. It aims to restore lymphocytes and assess safety, including radiation pneumonitis. Secondary goals include progression-free and overall survival. Eligibility requires adults with NSCLC, adequate organ function, and ECOG 0-2. NKTR-255 and durvalumab are administered intravenously.
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Program Overview
To learn about the effects of the investigational drug NKTR-255 in combination with the standard drug durvalumab on locally advanced NSCLC when given after CRT.
Description
Primary Objectives:
- Estimate the level of lymphocyte restoration after administration of NKTR-255 concurrently with durvalumab after chemoradiation. Absolute lymphocyte will be obtained along with changes in levels of NK cells, CD4 T cells, CD8 T cells, and B cells from baseline.
- Monitor the safety of NKTR-255, which includes treatment related grade 3+ radiation pneumonitis
Secondary Objectives:
- Estimate the Progression-free survival time distribution
- Estimate the Overall survival time distribution
Exploratory objectives:
- Characterize pharmacokinetics of NKTR-255 and assess immunogenicity of NKTR-255
- Characterize pharmacodynamic effects and changes in activation markers and proliferation of NK and CD8 T cells, and cytokine levels after administration of NKTR-255 in combination with Durvalumab
- Assess the correlation between ctDNA and efficacy measurements
Eligibility Criteria
Inclusion Criteria
- Age 18 years or older
- Histologic diagnosis of non-small cell lung cancer
- Written consent obtained before initiation of any study-related procedures
- Definitive cancer treatment intent
- Absence of current malignancies at other sites, except for adequately treated basal or squamous cell carcinoma of the skin. Cancer survivors who have undergone potentially curative therapy for a prior malignancy who have no evidence of that disease for 5 years and who are deemed at low risk for recurrence are eligible for the study.
- Adequate liver (AST, ALT, Alk Phos, and Tbili <2 fold upper limit) and kidney function (Cr < 2.5 limit of normal and Cr clearance >30)
- ECOG 0-2
Exclusion Criteria
Subjects are to be excluded from the study if any of the following conditions apply:
- HIV infection, cellular immune deficiencies, hypogammaglobulinemia or dysgammaglobulinemia, or hereditary or congenital immunodeficiencies
- Prior diagnosis of hepatitis B or C (unless anti-hepatitis C therapy has produced a sustained virologic response);
- History of clinically significant autoimmune disease, Crohn's disease, ulcerative colitis, or inflammatory disease.
- Serious concomitant disorder, including active systemic infection requiring treatment, as judged by the Investigator.
- Known or suspected hypersensitivity to any component of the investigational product
- Recurrent radiation to the treatment site
- Prior major surgery within 4 weeks of enrollment from which the patient has not recovered
- Other condition or prior therapy that, in the opinion of the Investigator, compromises the subject's welfare or may confound study results
- Previous enrollment in this study
- Pregnancy: a female subject defined as a WOCBP who has a positive urine pregnancy test (e.g. within 72 hours) prior to treatment. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.
- Prior exposure to any anti-PD-1 or anti-PD-L1 antibody.
- Patients must be capable of understanding and providing a written informed consent.
- Patients with leukemias or lymphomas with T cell/histiocyte or NK cell rich component(s) and other variants not otherwise specified that contain high numbers of T or NK cells.
- Evidence of clinically significant interstitial lung disease or active noninfectious pneumonitis during the course of chemoradiation that is unresolved to ≤ grade 1.
- Patients with grade 4 toxicities during chemoradiation not resolved to grade ≤ 1 by the end of chemoradiation.
- Prior exposure to IL-2 or IL-5.
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