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NSCLCPhase 2/3IMPRINTNCT06218069

Immuno-pet IMaging ResPonses AdministeRed Immune CheckpoiNt InhibiTor

A Phase 2/3 study testing Sasanlimab, non-ablative radiotherapy and [89Zr]Zr-crefmirlimab berdoxam in people with NSCLC, run by Radboud University Medical Center at 2 sites in 2 countries.

Not yet recruiting

Opening soon. The study is approved but enrolment has not started yet. Sites may already take enquiries.

Sites and contacts
Official record
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Trial 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. Read more about this study

Who is it for?
Ages 50 years and older
Conditions the study is for
NSCLC
What is being tested?
Sasanlimab, non-ablative radiotherapy and [89Zr]Zr-crefmirlimab berdoxam
Could I receive a placebo?
No, everyone receives an active treatment
How many people
20 participants
Where
2 sitesin 2 countries
Study dates
Feb 2025to Mar 2027
Phase
Phase 2/3
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 50 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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).

Who cannot join

  • 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
Show all 9Show fewer
  • Prior radiation therapy to the chest
  • Splenectomy
  • Enrolled in a current investigational drug trial

Trial locations and contacts

2 sites in 2 countries. Contact the study team or a site near you to ask about taking part.

Erik HJ Aarntzen, Dr. contact

+31629669360

Erik.Aarntzen@radboudumc.nl

Evelien AJ van Genugten, MSc contact

+31681216281

Evelien.vanGenugten@radboudumc.nl

2 sites in 2 countries

Germany1 site

  • Eberhard Karls Universitaet Tuebingen (EKUT)

    Tübingen, 72074

    Dominik Sonanini, Dr., Dominik.Sonanini@med.uni-tuebingen.de

Other trials in Germany

Netherlands1 site

  • Radboud University Medical Center (Radboudumc)

    Nijmegen, Gelderland, 6525 GA

    Erik HJ Aarntzen, Dr., +31629669360, Erik.Aarntzen@radboudumc.nl

    Evelien AJ van Genugten, MSc, +31681216281, Evelien.vanGenugten@radboudumc.nl

Other trials in Netherlands

About this study

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

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.

Read the 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.

Conditions
NSCLC
Being tested
Sasanlimab, non-ablative radiotherapy, [89Zr]Zr-crefmirlimab berdoxam
Keywords
neo-adjuvant, immune therapy, in vivo imaging, PETscan, anti-PD1

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • SasanlimabDrug

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

    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 radiotherapyRadiation

    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 berdoxamDrug

    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.

Study groups in NCT06218069
Study groupRoleWhat they receive
Site EKUT (Tuebingen)Active comparatorPatients 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.
Receives: Drug: Sasanlimab; Drug: [89Zr]Zr-crefmirlimab berdoxam
Site Radboudumc (Nijmegen)Active comparatorPatients 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.
Receives: Drug: Sasanlimab; Radiation: non-ablative radiotherapy; Drug: [89Zr]Zr-crefmirlimab berdoxam

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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.

    Measured: 2 years

  2. 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.

    Measured: 2 years

  3. 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).

    Measured: 2 years

Secondary outcomes (4)

  1. Demonstrate induction of CD8+ T-cells

    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.

    Measured: 2 years

  2. Framework for PETscan interpretation

    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.

    Measured: 2 years

  3. Identify immune signatures

    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.

    Measured: 2 years

  4. Explore pathological response rate

    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.

    Measured: 2 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted23 Jan 2024
  2. Study startFeb 2025 (estimated)
  3. Primary completionDec 2025 (estimated)
  4. Study completionMar 2027 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2/3
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Parallel groups
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.
Masking
None (open label)
Enrolment
20 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT06218069
Sponsor's protocol ID
IMAGIO-IMPRINT
Acronym
IMPRINT
Status last verified
Nov 2024
First submitted
19 Dec 2023
Last updated
29 Nov 2024
Results posted
No
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No: Raw and/or processed data will be made available for researchers upon reasonable request.

Publications

  • Rosner S, Reuss JE, Zahurak M, Zhang J, Zeng Z, Taube J, Anagnostou V, Smith KN, Riemer J, Illei PB, Broderick SR, Jones DR, Topalian SL, Pardoll DM, Brahmer JR, Chaft JE, Forde PM. Five-Year Clinical Outcomes after Neoadjuvant Nivolumab in Resectable Non-Small Cell Lung Cancer. Clin Cancer Res. 2023 Feb 16;29(4):705-710. doi: 10.1158/1078-0432.CCR-22-2994.

    PubMed 36794455

  • Reuss JE, Anagnostou V, Cottrell TR, Smith KN, Verde F, Zahurak M, Lanis M, Murray JC, Chan HY, McCarthy C, Wang D, White JR, Yang S, Battafarano R, Broderick S, Bush E, Brock M, Ha J, Jones D, Merghoub T, Taube J, Velculescu VE, Rosner G, Illei P, Pardoll DM, Topalian S, Naidoo J, Levy B, Hellmann M, Brahmer JR, Chaft JE, Forde PM. Neoadjuvant nivolumab plus ipilimumab in resectable non-small cell lung cancer. J Immunother Cancer. 2020 Sep;8(2):e001282. doi: 10.1136/jitc-2020-001282.

    PubMed 32929052

  • Forde PM, Spicer J, Lu S, Provencio M, Mitsudomi T, Awad MM, Felip E, Broderick SR, Brahmer JR, Swanson SJ, Kerr K, Wang C, Ciuleanu TE, Saylors GB, Tanaka F, Ito H, Chen KN, Liberman M, Vokes EE, Taube JM, Dorange C, Cai J, Fiore J, Jarkowski A, Balli D, Sausen M, Pandya D, Calvet CY, Girard N; CheckMate 816 Investigators. Neoadjuvant Nivolumab plus Chemotherapy in Resectable Lung Cancer. N Engl J Med. 2022 May 26;386(21):1973-1985. doi: 10.1056/NEJMoa2202170. Epub 2022 Apr 11.

    PubMed 35403841

  • Forde PM, Chaft JE, Smith KN, Anagnostou V, Cottrell TR, Hellmann MD, Zahurak M, Yang SC, Jones DR, Broderick S, Battafarano RJ, Velez MJ, Rekhtman N, Olah Z, Naidoo J, Marrone KA, Verde F, Guo H, Zhang J, Caushi JX, Chan HY, Sidhom JW, Scharpf RB, White J, Gabrielson E, Wang H, Rosner GL, Rusch V, Wolchok JD, Merghoub T, Taube JM, Velculescu VE, Topalian SL, Brahmer JR, Pardoll DM. Neoadjuvant PD-1 Blockade in Resectable Lung Cancer. N Engl J Med. 2018 May 24;378(21):1976-1986. doi: 10.1056/NEJMoa1716078. Epub 2018 Apr 16.

    PubMed 29658848

  • 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.

    PubMed 37272513

  • 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.

    PubMed 33603241

  • Altorki NK, McGraw TE, Borczuk AC, Saxena A, Port JL, Stiles BM, Lee BE, Sanfilippo NJ, Scheff RJ, Pua BB, Gruden JF, Christos PJ, Spinelli C, Gakuria J, Uppal M, Binder B, Elemento O, Ballman KV, Formenti SC. Neoadjuvant durvalumab with or without stereotactic body radiotherapy in patients with early-stage non-small-cell lung cancer: a single-centre, randomised phase 2 trial. Lancet Oncol. 2021 Jun;22(6):824-835. doi: 10.1016/S1470-2045(21)00149-2. Epub 2021 May 18.

    PubMed 34015311

  • Cytlak UM, Dyer DP, Honeychurch J, Williams KJ, Travis MA, Illidge TM. Immunomodulation by radiotherapy in tumour control and normal tissue toxicity. Nat Rev Immunol. 2022 Feb;22(2):124-138. doi: 10.1038/s41577-021-00568-1. Epub 2021 Jul 1.

    PubMed 34211187

  • Rodriguez-Ruiz ME, Vanpouille-Box C, Melero I, Formenti SC, Demaria S. Immunological Mechanisms Responsible for Radiation-Induced Abscopal Effect. Trends Immunol. 2018 Aug;39(8):644-655. doi: 10.1016/j.it.2018.06.001. Epub 2018 Jul 11.

    PubMed 30001871

  • Hu-Lieskovan S, Braiteh F, Grilley-Olson JE, Wang X, Forgie A, Bonato V, Jacobs IA, Chou J, Johnson ML. Association of Tumor Mutational Burden and Immune Gene Expression with Response to PD-1 Blockade by Sasanlimab Across Tumor Types and Routes of Administration. Target Oncol. 2021 Nov;16(6):773-787. doi: 10.1007/s11523-021-00833-2. Epub 2021 Oct 25.

    PubMed 34694529

  • Al-Khami AA, Youssef S, Abdiche Y, Nguyen H, Chou J, Kimberlin CR, Chin SM, Kamperschroer C, Jessen B, Kern B, Budimir N, Dillon CP, Xu A, Clark JD, Chou J, Kraynov E, Rajpal A, Lin JC, Salek-Ardakani S. Pharmacologic Properties and Preclinical Activity of Sasanlimab, A High-affinity Engineered Anti-Human PD-1 Antibody. Mol Cancer Ther. 2020 Oct;19(10):2105-2116. doi: 10.1158/1535-7163.MCT-20-0093. Epub 2020 Aug 26.

    PubMed 32847983

Questions about this trial

What is this clinical trial studying?

A Phase 2/3 study testing Sasanlimab, non-ablative radiotherapy and [89Zr]Zr-crefmirlimab berdoxam in people with NSCLC, run by Radboud University Medical Center at 2 sites in 2 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 6 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: opening soon, as of the sponsor's last update on 29 Nov 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites in Germany, Netherlands. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact Erik HJ Aarntzen, Dr. (+31629669360, Erik.Aarntzen@radboudumc.nl), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

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). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT06218069, which also lists 11 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 29 Nov 2024.

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