Immuno-pet IMaging ResPonses AdministeRed Immune CheckpoiNt InhibiTor

Официальное название

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

Обзор

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.

Подробное описание

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.

Вмешательства

• Препарат 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 investigat
• Лучевая терапия 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.
• Препарат [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.

Первичные конечные точки

• Number of participants with successful completion of curative surgery within 42 days after start of subcutaneous sasanlimab as neo-adjuvant treatment. [Срок оценки: 2 years]
• The number of CTC grade ≥3 toxicity related to subcutaneous sasanlimab as neo-adjuvant treatment. [Срок оценки: 2 years]
• Detection of treatment induced immune related responses after subcutaneous sasanlimab as neo-adjuvant treatment. [Срок оценки: 2 years]

Вторичные конечные точки (4)

• Demonstrate induction of CD8+ T-cells [Срок оценки: 2 years]
• Framework for PETscan interpretation [Срок оценки: 2 years]
• Identify immune signatures [Срок оценки: 2 years]
• Explore pathological response rate [Срок оценки: 2 years]

Критерии участия

Критерии включения

• 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).

Критерии исключения

• 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

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Нерандомизированное

Модель

Параллельные группы

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Германия · 1 центр

• Eberhard Karls Universitaet Tuebingen (EKUT) — Tübingen

Нидерланды · 1 центр

• Radboud University Medical Center (Radboudumc) — Nijmegen

Публикации

• 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. PMID 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 cel PMID 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 PMID 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 PMID 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. PMID 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 PMID 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 J PMID 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. PMID 34211187

Идентификаторы

NCT: NCT06218069 · IMAGIO-IMPRINT

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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