68Ga-grazytracer PET for noninvasive assessment of response to immunotherapy in solid tumors and lymphomas: a phase 1/2 clinical trial

Xiuling Shen, Haoyi Zhou, Xin Zhou, Zongchao Liu, Xiangxi Meng, Linyu Zhang, Yufei Song, Rui Guo, Fei Wang, Kui Li, Wenqing Li, Zhi Yang (), Zhaofei Liu () and Nan Li ()
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Xiuling Shen: Peking University Cancer Hospital & Institute
Haoyi Zhou: Peking University Health Science Center
Xin Zhou: Peking University Cancer Hospital & Institute
Zongchao Liu: Peking University Cancer Hospital & Institute
Xiangxi Meng: Peking University Cancer Hospital & Institute
Linyu Zhang: Peking University Health Science Center
Yufei Song: Peking University Cancer Hospital & Institute
Rui Guo: Peking University Cancer Hospital & Institute
Fei Wang: Peking University Cancer Hospital & Institute
Kui Li: Peking University Health Science Center
Wenqing Li: Peking University Cancer Hospital & Institute
Zhi Yang: Peking University Cancer Hospital & Institute
Zhaofei Liu: Peking University Cancer Hospital & Institute
Nan Li: Peking University Cancer Hospital & Institute

Nature Communications, 2024, vol. 15, issue 1, 1-12

Abstract: Abstract To tackle the clinical challenge of noninvasively assessing immunotherapy efficacy in patients, here we used positron emission tomography (PET) with 68Ga-grazytracer, which targets granzyme B, a crucial effector molecule secreted by activated CD8+ T cells. In this phase 1/2 clinical trial (NCT05000372) involving a diverse cohort of 24 patients with solid tumors and lymphomas who received immunotherapies, including immune checkpoint inhibitors (either alone or with chemotherapies) and chimeric antigen receptor-T cell therapy, we examined the in vivo behaviors of 68Ga-grazytracer. Primary endpoints were safety, biodistribution, granzyme B specificity, and the predictive utility of 68Ga-grazytracer, while secondary endpoint was the relationship between 68Ga-grazytracer uptake and tumor immune phenotype. 68Ga-grazytracer exhibited a safe profile and specifically targeted granzyme B in patients. 68Ga-grazytracer PET showed superior predictive value for short-term prognosis and progression-free survival than those of conventional assessment criteria, including RECIST 1.1 and PERCIST. Moreover, the uptake of 68Ga-grazytracer in tumors was significantly higher in those with a “non-desert” immune phenotype than those with an immune “desert” phenotype, thereby meeting the primary and secondary endpoints of this trial. Collectively, we successfully visualized CD8+ T cell effector function in humans using 68Ga-grazytracer PET, offering insights for enhancing immunotherapy assessment, patient stratification and treatment planning.

Date: 2024
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DOI: 10.1038/s41467-024-53197-2

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