TheranosticTrials.org

Clinical Trial · NCT03853187

Imaging Tumor-infiltrating T-cells in Non-small Cell Lung Cancer

Overview

This is an interventional study, to assess feasibility and safety of durvalumab (MEDI4736) in neo-adjuvant setting in patients with resectable NSCLC. Additional analyses of potential imaging biomarkers, e.g. Zr-89 labelled durvalumab (MEDI4736), ex vivo In-111-oxine labelled CD8+ T-cells and high-resolution immune cell imaging, in relation to immunotherapy induced immune responses on quantitative immune histochemical analysis of the resected tumor specimen, will be performed.

Sponsor

Radboud University Medical Center

Phase

Phase 2

Contacts

Erik Aarntzen, MD, PhD (PRINCIPAL_INVESTIGATOR)

Michel van den Heuvel, MD, PhD (PRINCIPAL_INVESTIGATOR)

Jolanda de Vries, MD, PhD (PRINCIPAL_INVESTIGATOR)

ClinicalTrials.gov

NCT03853187

Drug / Compound

durvalumab

Isotope(s):
Target(s):
  • PD-L1
Ligand Class: Antibodies
Chelator: DFO

crefmirlimab

Isotope(s):
Target(s):
  • CD8 Cells
Ligand Class: Small Proteins and Antibody Fragments
Chelator: DFO

Eligibility

Inclusion

  • Haemoglobin ≥9.0 g/dL
  • ECOG performance status of 0 or 1
  • Absolute neutrophil count (ANC) 1.5x (\> 1500 per ml)
  • Measured creatinine clearance (CL) \>40 mL/min or Calculated creatinine CL\>40 mL/min by the Cockcroft-Gault formula (Cockcroft and Gault 1976) or by 24-hour urine collection for determination of creatinine clearance (CCL):
  • Platelet count ≥100 x10\^9/L (\>75,000 per ml)
  • Adequate normal organ and marrow function as defined below:
  • AJCC stage I, II or IIIa as determined by contrast-enhanced CT chest-abdomen and F-18-FDG PET/CT: cT1cN0-1M0, cT2aN0-1M0 en cT3N0-1M0 (T3 separate nodule)
  • Evidence of post-menopausal status or negative urinary or serum pregnancy test for female pre-menopausal patients. Women will be considered post-menopausal if they have been amenorrheic for 12 months or more following cessation of all exogenous hormonal treatments, had radiation-induced menopause with last menses \>1 year ago, had chemotherapy-induced menopause with last menses \>1 year ago, or underwent surgical sterilization (bilateral oophorectomy, bilateral salpingectomy or hysterectomy).
  • Scheduled for resection with curative intent
  • Serum bilirubin ≤1.5x upper limit of normal (ULN). Note: This will not apply to patients with confirmed Gilbert's syndrome (persistent or recurrent hyperbilirubinemia that is predominantly unconjugated in the absence of haemolysis or hepatic pathology), who will be allowed only in consultation with their physician.
  • AST/ALT ≤2.5x upper limit of normal
  • No underlying immune disease (neutro- or lymphopenia, coagulation disorders) that could interfere with T-cell isolation
  • Histopathological proven primary non-small cell lung cancer, with fully evaluable histological biopsies available
  • Solid appearance of the tumor on contrast-enhanced CT

Exclusion

  • Radiotherapy treatment to more than 30% of the bone marrow or with a wide field of radiation within 6 months of the first dose of study drug
  • Adequately treated carcinoma in situ without evidence of disease
  • Malignancy treated with curative intent and with no known active disease ≥5 years before the first dose of IP and of low potential risk for recurrence
  • Any concurrent chemotherapy, IP, biologic, or hormonal therapy for cancer treatment. Concurrent use of hormonal therapy for non-cancer-related conditions (e.g., hormone replacement therapy) is acceptable.
  • Receipt of the last dose of anticancer therapy (chemotherapy, immunotherapy, endocrine therapy, targeted therapy, biologic therapy, tumour embolization, monoclonal antibodies) \<6 months prior to the first dose of study drug
  • History of another primary malignancy except for:
  • Indication for cervical mediastinoscopy according to the local multidisciplinary Thoracic-Oncology meeting