Immuno-pet IMaging ResPonses AdministeRed Immune CheckpoiNt InhibiTor

NCT06218069 | Not Yet Recruiting Phase 2 FDA Drug

• 1 other identifier: IMAGIO-IMPRINT
• Study Type: interventional
• Target: 20
• Locations: 2 countries
• Sites: 2

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.

Conditions

NSCLC

Keywords

neo-adjuvant; immune therapy; in vivo imaging; PETscan; anti-PD1

Outcome Measures

Primary Outcomes (3)

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

  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 years

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

  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.

  2 years

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

  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).

  2 years

Secondary Outcomes (4)

• Demonstrate induction of CD8+ T-cells

  2 years

• Framework for PETscan interpretation

  2 years

• Identify immune signatures

  2 years

• Explore pathological response rate

  2 years

Study Arms (2)

Site EKUT (Tuebingen)

ACTIVE COMPARATOR

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.

Drug: Sasanlimab; Drug: [89Zr]Zr-crefmirlimab berdoxam

Site Radboudumc (Nijmegen)

ACTIVE COMPARATOR

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.

Drug: Sasanlimab; Radiation: non-ablative radiotherapy; Drug: [89Zr]Zr-crefmirlimab berdoxam

Interventions

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.

Also known as: humanized hinge region-stabilized IgG4 monoclonal anti-PD1 antibody, PF-06801591

Site EKUT (Tuebingen); Site Radboudumc (Nijmegen)

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.

Site Radboudumc (Nijmegen)

[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.

Site EKUT (Tuebingen); Site Radboudumc (Nijmegen)

Eligibility Criteria

• Age: 50 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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).

You may not qualify if:

• 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

Sponsors & Collaborators

• Radboud University Medical Center: lead
• Pfizer: collaborator
• ImaginAb, Inc.: collaborator
• University Hospital Tuebingen: collaborator

Study Sites (2)

Eberhard Karls Universitaet Tuebingen (EKUT)

Tübingen, 72074, Germany

Location

Radboud University Medical Center (Radboudumc)

Nijmegen, Gelderland, 6525 GA, Netherlands

Location

Related Publications (11)

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• Wakelee H, Liberman M, Kato T, Tsuboi M, Lee SH, Gao S, Chen KN, Dooms C, Majem M, Eigendorff E, Martinengo GL, Bylicki O, Rodriguez-Abreu D, Chaft JE, Novello S, Yang J, Keller SM, Samkari A, Spicer JD; KEYNOTE-671 Investigators. Perioperative Pembrolizumab for Early-Stage Non-Small-Cell Lung Cancer. N Engl J Med. 2023 Aug 10;389(6):491-503. doi: 10.1056/NEJMoa2302983. Epub 2023 Jun 3.

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• Cascone T, William WN Jr, Weissferdt A, Leung CH, Lin HY, Pataer A, Godoy MCB, Carter BW, Federico L, Reuben A, Khan MAW, Dejima H, Francisco-Cruz A, Parra ER, Solis LM, Fujimoto J, Tran HT, Kalhor N, Fossella FV, Mott FE, Tsao AS, Blumenschein G Jr, Le X, Zhang J, Skoulidis F, Kurie JM, Altan M, Lu C, Glisson BS, Byers LA, Elamin YY, Mehran RJ, Rice DC, Walsh GL, Hofstetter WL, Roth JA, Antonoff MB, Kadara H, Haymaker C, Bernatchez C, Ajami NJ, Jenq RR, Sharma P, Allison JP, Futreal A, Wargo JA, Wistuba II, Swisher SG, Lee JJ, Gibbons DL, Vaporciyan AA, Heymach JV, Sepesi B. Neoadjuvant nivolumab or nivolumab plus ipilimumab in operable non-small cell lung cancer: the phase 2 randomized NEOSTAR trial. Nat Med. 2021 Mar;27(3):504-514. doi: 10.1038/s41591-020-01224-2. Epub 2021 Feb 18.

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  PMID: 32847983 BACKGROUND

Study Officials

• Michel M van den Heuvel, Prof.dr.

  Radboud University Medical Center (Radboudumc)

  PRINCIPAL INVESTIGATOR

• Dominik Sonanini, Dr.

  Eberhard Karls Universitaet Tuebingen (EKUT)

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Erik HJ Aarntzen, Dr.

CONTACT

+31629669360; Erik.Aarntzen@radboudumc.nl

Evelien AJ van Genugten, MSc

CONTACT

+31681216281; Evelien.vanGenugten@radboudumc.nl

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: December 19, 2023
• First Posted: January 23, 2024
• Study Start: February 1, 2025
• Primary Completion: December 1, 2025
• Study Completion (Estimated): March 1, 2027
• Last Updated: November 29, 2024

Record last verified: 2024-11

Data Sharing

• IPD Sharing: Will not share

Locations

DE (1); NL (1)