DK222 PET imaging at Johns Hopkins

An Open-label, Single-center Clinical Trial of [18F]DK222 PET/CT for Imaging of Patients With Non-Small-Cell Lung Cancer (NSCLC) and Urothelial Cancer Who Are Eligible for Treatment With Anti-PD(L)-1

This Phase 1 trial will test a PET imaging agent called [18F]DK222 in adults with non-small cell lung cancer or urothelial cancer who are eligible for PD-1/PD-L1 therapy to see if it is safe and how it distributes and how much radiation it gives off.

Quick facts

• Phase: Phase 1
• Study type: Interventional
• Enrollment: 6 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins (Academic / other)
• Drugs / interventions: radiation
• Locations: 1 site (Baltimore, Maryland)
• Trial ID: NCT07140315 on ClinicalTrials.gov

What this trial studies

[18F]DK222 is a first-in-human PET radiotracer designed to bind PD-L1 on tumors and immune cells. In this Phase 1 protocol at Johns Hopkins, adults with histologically confirmed non-small cell lung cancer or urothelial cancer will receive a single injection of [18F]DK222 followed by serial PET imaging and blood sampling to characterize biodistribution, pharmacokinetics, and radiation dosimetry. Safety and preliminary toxicity will be monitored with clinical exams and laboratory testing. Imaging results will be compared with available PD-L1 immunohistochemistry to explore correlations between tracer uptake and tissue PD-L1.

Who should consider this trial

Good fit: Adults (≥18) with histologically confirmed non-small cell lung cancer or urothelial cancer who are eligible for anti-PD-1/PD-L1 therapy, have ECOG performance status 0–2, adequate organ function, and available PD-L1 testing or tissue are ideal candidates.

Not a fit: Patients with other cancer types, ECOG >2, inadequate organ function, or those unable to travel to Johns Hopkins for imaging are unlikely to benefit from participation.

Why it matters

Potential benefit: If successful, [18F]DK222 could provide a noninvasive PET scan to map PD-L1 in tumors and help guide immunotherapy decisions.

How similar studies have performed: Other early-phase PD-L1–targeted PET tracers have shown feasibility and tumor uptake in small studies, but [18F]DK222 is a first-in-human agent with unproven clinical utility.

Eligibility criteria

Inclusion Criteria:

* Subjects must sign informed consent prior to inclusion in this trial.
* Subjects must be ≥18 years of age and competent to give informed consent.
* Subjects must be diagnosed with histologically confirmed NSCLC or UC and eligible for anti-PD(L)-1 therapy.
* PD-L1 immunohistochemistry result using a Clinical Laboratory Improvement Amendments (CLIA) assay must be available or if not available then sufficient tissue must be available to perform PD-L1 testing.
* Subjects must score at least 0 to 2 on the Eastern Cooperative Oncology Group (ECOG) Performance Status.
* Subjects must have adequate organ function as defined by the following laboratory values (determined within 28 days prior to randomization/registration) or as deemed not clinically significant by physician on record:

  * White blood cells (WBC) ≥ 2000 /μL
  * Absolute neutrophil count (ANC) ≥ 1500 /μL
  * Platelets ≥ 100 x103 /μL
  * Hemoglobin ≥ 9 g/dL or ≥ 5.6 mmol/L
  * Serum creatinine ≤ 1.5 times upper limit of normal (ULN) or creatinine clearance greater than or equal to 60 ml/min (using the Cockcroft-Gault formula)
  * Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 3 times ULN
  * Bilirubin ≤ 1.5 times ULN (Except patients with the Gilbert Syndrome, for whom a maximum of ≤ 3.0 mg/dL is acceptable)
* Women of childbearing potential (WOCBP) should have a negative serum pregnancy test within 24 hours prior to receiving the first administration \[18F\]DK222. Women with non-childbearing potential may be included if either surgically sterile or have been postmenopausal for ≥ 1 year.
* WOCBP and men who are sexually active with WOCBP must agree to use appropriate method(s) of contraception.

Exclusion Criteria:

* Prior treatment, in either de novo disease or during this recurrence, with an anti-PD-L1 or anti-PD-L2 antibody. A minimum of 4 month washout period is required for patients treated with anti-PD-L1 or anti-PD-L2 therapy. Patients with disease that was previously treated with anti-PD-1, anti-PD-L1, anti-PD-L2 antibody, or any other antibody or drug specifically targeting T-cell co-stimulation or immune checkpoint pathways, but now have a new recurrence, would be eligible.
* Subjects who have not recovered to Common Terminology Criteria for Adverse Events (CTCAE) v5.0 Grade 1 or better from the adverse events due to previous cancer therapy.
* Treatment with corticosteroids in an increasing dosage in the 7 days prior to the first administration of anti-PD1. (A stable or decreasing dosage of ≤ 10 mg dexamethasone or equivalent is allowed. In addition, inhaled or topical steroids and adrenal replacement doses are permitted in the absence of active autoimmune disease.)
* A severe hypersensitivity reaction to prior treatment with a monoclonal antibody, or known hypersensitivity to study drugs components.
* Any serious or uncontrolled medical disorder or active infection that, in the opinion of the investigator, may increase the risk associated with study participation, study drug administration, or would impair the ability of the patients to receive protocol therapy.
* Women of childbearing potential with a positive serum or urine pregnancy test (minimum sensitivity 10 IU/L or equivalent units of HCG) within 24 hours prior to the start of imaging.
* Breastfeeding women.
* Inability to comply with other requirements of the protocol.

Where this trial is running

Baltimore, Maryland

• Johns Hopkins Hospital — Baltimore, Maryland, United States (Recruiting)

Study contacts

• Principal investigator: Seyed Ali Mosallaie, MD — Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
• Study coordinator: Mehreen Nabi

Conditions Non-Small Cell Lung Cancer; Urothelial Cancer; PD-L1; PD-1; PET; Imaging; MSCLC; UC