Immuno-pet iMaging resPonses administeRed Immune checkpoiNt inhibiTor

NSCLC Clinical Trial

— IMPRINT  

Official title:

Immuno-pet iMaging resPonses administeRed Immune checkpoiNt inhibiTor (IMPRINT)

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06218069
• Other study ID #: IMAGIO-IMPRINT
• Status: Not yet recruiting
• Phase: Phase 2/Phase 3
• Start date: August 2024
• Est. completion date: March 2027

Study information

• Verified date: November 2023
• Source: Radboud University Medical Center
• Contact: Erik HJ Aarntzen, Dr.
• Phone: +31629669360
• Email: Erik.Aarntzen[@]radboudumc.nl
• Is FDA regulated: No
• Study type: Interventional

Clinical 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.

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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 20
• Est. completion date: March 2027
• Est. primary completion date: May 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 50 Years and older

Eligibility

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

Related Conditions & MeSH terms

• NSCLC

Intervention

Drug:
• 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.

Radiation:
• 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.

Drug:
• [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.

Locations

Country	Name	City	State
Germany	Eberhard Karls Universitaet Tuebingen (EKUT)	Tuebingen
Netherlands	Radboud University Medical Center (Radboudumc)	Nijmegen	Gelderland

Sponsors (4)

Lead Sponsor	Collaborator
Radboud University Medical Center	ImaginAb, Inc., Pfizer, University Hospital Tuebingen

Countries where clinical trial is conducted

Germany,  Netherlands, 

References & Publications (11)

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. Erratum In: N Engl J Med. 2018 Nov 29;379(22):2185. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

* Note: There are 11 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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
Primary	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	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.	2 years
Secondary	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.	2 years
Secondary	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.	2 years
Secondary	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.	2 years