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NCT Number: NCT06218069

Immuno-pet IMaging ResPonses AdministeRed Immune CheckpoiNt InhibiTor

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.

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Key information

Conditions

NSCLC

Age range

50 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2 / Phase 3

Primary location

Eberhard Karls Universitaet Tuebingen (EKUT), Tübingen, Germany

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About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

Sasanlimab

Drug

6 mL of the study drug will be administered subcutaneous injection in the abdominal fat fold. If SC injections in the abdominal location are not possible, SC injections can be administered in a distributed manner in the thighs. SC injections in the upper extremities (eg, deltoid, upper and lower arm) are not permitted. Any observed abnormality at the injection site (e.g. erythema, induration, ecchymosis, injection site pain, injection site pruritus) will be monitored and judged by the investigator to determine whether a corresponding AE should be reported.

Other names: humanized hinge region-stabilized IgG4 monoclonal anti-PD1 antibody, PF-06801591

non-ablative radiotherapy

Radiation

Patients will receive a total dose of 24Gy irradiation to the tumor, fractionated in 3 doses of 8Gy, on three consecutive days and starting on the day of first sasanlimab administration.

[89Zr]Zr-crefmirlimab berdoxam

Drug

Prior to sasanlimab injection and prior to surgery, [89Zr]Zr-crefmirlimab berdoxam (1.5 mg protein dose labelled with activity dose 37 MBq Zirconium-89) will be administered via an intravenous catheter. After 21-27 hours after injection patient will undergo a whole-body PETscan te detect CD8+ T-cell infiltration.

Primary outcomes

  1. Number of participants with successful completion of curative surgery within 42 days after start of subcutaneous sasanlimab as neo-adjuvant treatment.

    Time frame: 2 years

    Feasibility will be determined on all patients who have entered the treatment phase of the study, i.e. received at least one course of neo-adjuvant sasanlimab. Feasibility is defined as successful completion of curative surgery within 42 days after start of neo-adjuvant treatment (= day 1). No delays will be allowed. Results will be reported in a descriptive fashion, including percentages, mean and standard deviation, median and range for the time-related measures.

  2. The number of CTC grade ≥3 toxicity related to subcutaneous sasanlimab as neo-adjuvant treatment.

    Time frame: 2 years

    Safety will be defined as the number of CTC grade ≥3 toxicity related to neo-adjuvant sasanlimab. Results will be reported in a descriptive fashion.

  3. Detection of treatment induced immune related responses after subcutaneous sasanlimab as neo-adjuvant treatment.

    Time frame: 2 years

    Efficacy will be defined as the detection of treatment induced immune related responses in >15% of the patients. Results will be reported in a descriptive fashion, for both cohorts of each n=10 patients (sasanlimab with and without radiotherapy).

Secondary outcomes

  1. Demonstrate induction of CD8+ T-cells

    Time frame: 2 years

    Determine changes from baseline in immune profiles, including maturation stages, activation markers, chemokine receptors and functional markers on different lymphocyte (sub-)populations assessed by multipanel flowcytometry on samples obtained at 3 weeks and expressed in percentages and absolute numbers per mL.

  2. Framework for PETscan interpretation

    Time frame: 2 years

    Determine the (changes in) relative distributions of tracer uptake (e.g., CD8+ T-cell distributions) across tumor, tumor-draining lymph node(s), spleen, bone marrow, blood pool and distant lymph nodes computed from [89Zr]Zr-crefmirlimab berdoxam PET images.

    Correlative analyses of CD8+ T-cell profiles will be done in peripheral blood at the time point of scanning and resected tumor sections.

  3. Identify immune signatures

    Time frame: 2 years

    The absolute number, mean and maximum density of CD8+ T-cells/mm^2 tumor tissue will be determined and correlated with conventional pathological response assessment and clinical endpoint of 1- and 2-year recurrence free survival.

    The absolute number, mean and maximum density of other immune cell (sub-)populations will be determined by multipanel immunohistochemistry and immunofluorescence analyses on the resected tumor tissue and correlated to pathological and clinical response, as above.

  4. Explore pathological response rate

    Time frame: 2 years

    The conventional pathological response assessment will be compared for both study arms and reported as absolute number and percentage of total subjects who received sasanlimab prior to surgery in that study arm.

    Comparative and descriptive analyses of immune cell signatures in peripheral blood, [89Zr]Zr-crefmirlimab berdoxam and resected tumor specimen with respect to both study arms will be performed to explore potential effect of radiotherapy on immune responses.

Study contacts

Contact information is provided by the study sponsor or research team.

Erik HJ Aarntzen, Dr.

CONTACT

[email protected]

+31629669360

Evelien AJ van Genugten, MSc

CONTACT

[email protected]

+31681216281

Sponsors and collaborators

Lead sponsor

Radboud University Medical Center

Other

Collaborators

  • ImaginAb, Inc.
  • Pfizer
  • University Hospital Tuebingen

Registry information

Official study title

Immuno-pet IMaging ResPonses AdministeRed Immune CheckpoiNt InhibiTor (IMPRINT)

Acronym: IMPRINT

Important dates

Study start
2025
Primary completion
2025
Study completion
2027
First posted
Jan 23, 2024
Registry last updated
Nov 29, 2024

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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