Immuno-pet IMaging ResPonses AdministeRed Immune CheckpoiNt InhibiTor

NCT ID: NCT06218069

Last Updated: 2024-11-29

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

NOT_YET_RECRUITING

Clinical Phase

PHASE2/PHASE3

Total Enrollment

20 participants

Study Classification

INTERVENTIONAL

Study Start Date

2025-02-28

Study Completion Date

2027-03-31

Brief Summary

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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

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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.

Conditions

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NSCLC

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

PARALLEL

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 Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Site EKUT (Tuebingen)

Patients will receive a single subcutaneous administration of the immunotherapy sasanlimab in a fixed dose of 300 mg in a neo-adjuvant setting, followed by curative-intended surgery.

Patients will also receive 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.

Group Type ACTIVE_COMPARATOR

Sasanlimab

Intervention Type 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.

[89Zr]Zr-crefmirlimab berdoxam

Intervention Type 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.

Site Radboudumc (Nijmegen)

Patients will receive a single subcutaneous administration of the immunotherapy sasanlimab in a fixed dose of 300 mg in a neo-adjuvant setting, and 3 days of non-ablative dose radiation therapy starting with sasanlimab injection. This is followed by curative-intended surgery.

Patients will also receive 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.

Group Type ACTIVE_COMPARATOR

Sasanlimab

Intervention Type 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.

non-ablative radiotherapy

Intervention Type 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

Intervention Type 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.

Interventions

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Sasanlimab

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.

Intervention Type DRUG

non-ablative radiotherapy

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.

Intervention Type RADIATION

[89Zr]Zr-crefmirlimab berdoxam

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.

Intervention Type DRUG

Other Intervention Names

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humanized hinge region-stabilized IgG4 monoclonal anti-PD1 antibody PF-06801591

Eligibility Criteria

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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
Minimum Eligible Age

50 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Pfizer

INDUSTRY

Sponsor Role collaborator

ImaginAb, Inc.

INDUSTRY

Sponsor Role collaborator

University Hospital Tuebingen

OTHER

Sponsor Role collaborator

Radboud University Medical Center

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Michel M van den Heuvel, Prof.dr.

Role: PRINCIPAL_INVESTIGATOR

Radboud University Medical Center (Radboudumc)

Dominik Sonanini, Dr.

Role: PRINCIPAL_INVESTIGATOR

Eberhard Karls Universitaet Tuebingen (EKUT)

Locations

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Eberhard Karls Universitaet Tuebingen (EKUT)

Tübingen, , Germany

Site Status

Radboud University Medical Center (Radboudumc)

Nijmegen, Gelderland, Netherlands

Site Status

Countries

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Germany Netherlands

Central Contacts

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Erik HJ Aarntzen, Dr.

Role: CONTACT

+31629669360

Evelien AJ van Genugten, MSc

Role: CONTACT

+31681216281

Facility Contacts

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Dominik Sonanini, Dr.

Role: primary

Erik HJ Aarntzen, Dr.

Role: primary

+31629669360

Evelien AJ van Genugten, MSc

Role: backup

+31681216281

References

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Other Identifiers

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IMAGIO-IMPRINT

Identifier Type: -

Identifier Source: org_study_id