Clinical trial NCT06218069: Immuno-pet IMaging ResPonses AdministeRed Immune CheckpoiNt InhibiTor
Official title: Immuno-pet IMaging ResPonses AdministeRed Immune CheckpoiNt InhibiTor (IMPRINT)
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE2
PHASE3
Conditions: NSCLC
Keywords: neo-adjuvant
immune therapy
in vivo imaging
PETscan
anti-PD1
Lead sponsor: Radboud University Medical Center
Sponsor class: OTHER
Collaborators: name: Pfizer
name: ImaginAb, Inc.
name: University Hospital Tuebingen
First posted: 2024-01-23
Enrollment: 20
Sex: ALL
Minimum age (years): 50
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Arm 1: n=10 patients, who will receive a single subcutaneous injection with sasanlimab at 4-5 weeks prior to surgery.

Arm 2: n=10 patients, who will receive a single subcutaneous injection with sasanlimab at 4-5 weeks prior to surgery, and a single dose radiation therapy in the week following sasanlimab injection.
Primary purpose: TREATMENT

Brief summary: This study investigates whether a single subcutaneous administration of anti-PD-1 antibody can induce CD8+ T-cell tumor-infiltration that can be non-invasively monitored with \[89Zr\]crefmirlimab berdoxam PET imaging as an imaging biomarker.

Detailed description: This is a two-armed open-label feasibility study with exploratory endpoints, where subjects are participating for 2 years after completement of enrollment to determine disease-free survival rates. The therapeutic intervention is a single subcutaneous administration of the humanized hinge region-stabilized IgG4 monoclonal anti-PD1 antibody PF-06801591 (sasanlimab) in a fixed dose of 300 mg in a neo-adjuvant setting, with or without radiation therapy, followed by curative-intended surgery. The diagnostic intervention is a radiolabeled imaging tracer \[89Zr\]Zr-crefmirlimab berdoxam that entails two intravenous administrations of a fixed dose of 1.5 mg protein dose labelled with activity dose 37 MBq Zirconium-89; one at baseline and one at 2 weeks after sasanlimab injection, to visualize CD8+ T-cells in vivo.

Eligibility criteria: Inclusion Criteria:

* Age \>50 years
* Histologically or cytologically proven adenocarcinoma or squamous cell lung cancer
* Primary tumors \>1 cm and \</= 5 cm largest diameter
* Scheduled for curative surgery
* Informed consent
* Adequate bone marrow function (ANC \>/= 1500, platelets \>/=100k, Hgb \> 9), renal function (CLCr \>30 mL/min), liver function (TotalBili \</= 1.5 x ULN; AST and ALT \</=2.5 x ULN).

Exclusion Criteria:

* Inability to undergo SPECT or PET scans
* Pleiomorphic, lepidic, mucinous or large cell neuro-endocrine histological subtypes of non-small cell lung carcinoma
* Histologically confirmed druggable mutation (EGFR, RET, ROS, ALK, BRAF V600, NTRK, NRG1, MET ex14Sk)
* Pregnancy or lactation
* Active infection, auto-immune disease, prior organ-transplantation or haematological condition that requires medication that potentially interferes with immune cell activation.
* Documented medical history of auto-immune disease, organ-transplantation or haematological condition that potentially interferes with immune cell behavior
* Prior radiation therapy to the chest
* Splenectomy
* Enrolled in a current investigational drug trial

Primary outcomes:
measure: Number of participants with successful completion of curative surgery within 42 days after start of subcutaneous sasanlimab as neo-adjuvant treatment.
timeFrame: 2 years
measure: The number of CTC grade ≥3 toxicity related to subcutaneous sasanlimab as neo-adjuvant treatment.
timeFrame: 2 years
measure: Detection of treatment induced immune related responses after subcutaneous sasanlimab as neo-adjuvant treatment.
timeFrame: 2 years
Secondary outcomes:
measure: Demonstrate induction of CD8+ T-cells
timeFrame: 2 years
measure: Framework for PETscan interpretation
timeFrame: 2 years
measure: Identify immune signatures
timeFrame: 2 years
measure: Explore pathological response rate
timeFrame: 2 years
Other outcomes:
Locations:
city: Tuebingen
country: Germany
facility: Eberhard Karls Universitaet Tuebingen (EKUT)
city: Nijmegen
country: Netherlands
facility: Radboud University Medical Center (Radboudumc)
state: Gelderland
Study officials:
affiliation: Radboud University Medical Center (Radboudumc)
name: Michel M van den Heuvel, Prof.dr.
role: PRINCIPAL_INVESTIGATOR
affiliation: Eberhard Karls Universitaet Tuebingen (EKUT)
name: Dominik Sonanini, Dr.
role: PRINCIPAL_INVESTIGATOR
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