SHARP

Key Outcome parameters

Primary endpoints:

• To assess the relative change in uptake of [18F]F-AraG in tumor lesions on anti-PD-1 treatment:
  • To define tracer uptake in all tumor lesions and lymphoid organs (lymph nodes, spleen) per [18F]F-AraG PET scan
  • To assess the changes in uptake between baseline and after 2 and 6 weeks on-treatment
• To associate baseline, on-treatment [18F]F-AraG uptake and tumor response to anti-PD-1 therapy:
  • To associate baseline tumor [18F]F-AraG uptake and objective response rate (ORR, defined as complete response (CR) and partial response (PR)) at 6 and 12 weeks
  • To associate change in tumor [18F]F-AraG uptake as measured between baseline and 2 weeks and 6 weeks on-treatment, respectively, and objective response rate (ORR, defined as complete response (CR) and partial response (PR)) at 6 and 12 weeks

Secondary endpoints:

• To assess the relationship between baseline tumor uptake of [18F]F-AraG, T cell infiltration and activation state at baseline:
  • to assess viable tumor cells
  • to assess T-cell infiltration in tumor and stroma
  • to quantify T cell infiltration using multiplex IHC (VECTRA) analysis panels for T-cell subsets, for monocytes and metabolic milieu, and panels directed at resistance as well as RNA sequencing to assess tumor microenvironment

Exploratory endpoints:

• To explore the relationship between change of tumor uptake of [18F]F-AraG and changes in PBMC subsets
• To visually correlate the [18F]F-AraG autoradiogram with IHC read outs for tumor cells and T-cells

Intervention

All patients will undergo 3 [18F]F-AraG PET scanning procedures according to the institutional protocols

Key inclusion criteria

Inclusion criteria

• Histologically confirmed NSCLC, a histological biopsy is mandatory, negative for EGFR and ALK mutations
• Be willing to provide either archival biopsy or fresh biopsy at screening.
• Stage IIIB-IV patients that are planned to be treated with anti-PD-1 monotherapy
• High PD-L-1 expression (≥50% TPS)
• No prior systemic therapy for the trearment of cancer
• Be willing and able to provide written informed consent for the trial.
• Have a performance status of 0-2 on the ECOG Performance Scale
• Be above 18 years of age on day of signing informed consent

Key exclusion criteria

Exclusion criteria

• Subjects with a condition requiring systemic treatment with either corticosteroids (> 10 mg daily prednisone equivalent) or other immunosuppressive medications within 14 days of day 0. Inhaled or topical steroids, and adrenal replacement steroid >10 mg daily prednisone equivalent, are permitted in the absence of active autoimmune disease
• Untreated or symptomatic brain metastases
• Additional malignancy that is progressing or requires active treatment. Exceptions include basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or in situ cervical cancer that has undergone potentially curative therapy.
• Evidence of interstitial lung disease or active, non-infectious pneumonitis
• Active infection requiring systemic therapy
• A history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies)
• Active Hepatitis B or C
• Psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial
• Patient is pregnant or breastfeeding or expecting to conceive within the projected duration of the trial, starting with the screening visit through 12 weeks after the last administration of [18F]F-AraG