68Ga-grazytracer PET/CT of Tumor Responses to Immunotherapy

68Ga-grazytracer PET/CT of Tumor Responses to Immunotherapy in Subjects with Solid Tumor or Lymphoma

This is an open-label positron emission tomography/computed tomography (PET/CT) study to investigate the safety and clinical predictive value of 68Ga-grazytracer in subjects with solid tumor or lymphoma receiving immunotherapy.

Study Overview

• Status: Completed
• Conditions: Cancer
• Intervention / Treatment: Drug: 68Ga-grazytracer

Detailed Description

The investigators recently developed a granzyme B-specific radiotracer named 68Ga-grazytracer. This clinical trial aims to investigate whether granzyme B PET imaging using 68Ga-grazytracer could early identify tumor responses to immune checkpoint inhibitory therapy or CAR-T therapy in subjects with solid tumor and lymphoma. PET/CT imaging of 68Ga-grazytracer will be performed in subjects after immunotherapy.

• Study Type: Interventional
• Enrollment (Actual): 24
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China, 100142
      • Beijing Cancer Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Study Population

Patients at Being Cancer Hospital who are confirmed non-small cell lung cancer or melanoma and will receive immunotherapy.

Description

Inclusion Criteria:

1. Participants who were diagnosed with malignant tumors;
2. Patients who were scheduled to receive immunotherapy based on a decision made by a multidisciplinary team;
3. participants who had no prior immunotherapy;
4. participants who had no regional therapy within 3 months;
5. Participants aged ≥18 years.

Exclusion Criteria:

1. participants with a concurrent disease that would impede the treatment regimen;
2. Participants who were unable or unwilling to provide written informed consent.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: N/A
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Feasibility and safety of 68Ga-grazytracer; The purpose of the study is to evaluate the safety and early predictive performance of 68Ga-grazytracer for immunotherapy.	Drug: 68Ga-grazytracer; 68Ga-grazytracer PET/CT: after intravenous injection of 2.96-3.7 MBq/kg body weight of quality-controlled 68Ga-grazytracer, a Biograph mCT Flow 64 scanner or Total-body PET/CT uEXPLORER scanner will be applied, and the scan range will be from the top of the head to 1/3 of the upper thigh.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Biodistribution of 68Ga-grazytracer	The distribution of 68Ga-grazytracer in tumors and healthy tissues will be examined through total-body dynamic PET/CT imaging.	3 year
Analyzing the in vivo granzyme B-specificity of 68Ga-grazytracer	The specificity of 68Ga-grazytracer will be validated by correlating the immunohistochemistry results of granzyme B in either surgical or biopsy tissue samples with the standardized uptake values (SUV) of 68Ga-grazytracer in the tumors.	3 year
Assessing the early predictive value of 68Ga-grazytracer for immunotherapy response	Participants will be categorized into groups with high or low 68Ga-grazytracer uptake in tumor lesions. The progression-free survival and treatment response, as assessed by RECIST 1.1 criteria, will be compared across these groups.	3 year
Incidence of 68Ga-grazytracer-emergent Adverse Events	Any adverse events following the administration of the radiotracer will be monitored.	3 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Correlation analysis of 68Ga-grazytracer uptake and tumor immune phenotype	Participants' tumors will be classified as either "desert" or "non-desert" based on immunohistochemistry staining of CD8 from tumor samples. Subsequently, the relationship between 68Ga-grazytracer uptake and the tumors' immune phenotype will be compared.	3 year

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Granzyme B expression analysis of tumor tissues	Tumor tissues obtained from biopsy or surgery will be stained for granzyme B	1 year
Correlation analysis of 68Ga-grazytracer uptake and lesion size changes	The SUVs of 68Ga-grazytracer in individual lesions will be compared to the changes in lesion sizes	1 year

Collaborators and Investigators

• Sponsor: Peking University Cancer Hospital & Institute
• Collaborators: Peking University Health Science Center
• Investigators: Study Director: Nan Li, M.D., Peking University Cancer Hospital & Institute; Study Director: Zhaofei Liu, Ph.D., Peking University; Study Director: Zhi Yang, Ph.D., Peking University Cancer Hospital & Institute

Publications and helpful links

General Publications

• Zhou H, Wang Y, Xu H, Shen X, Zhang T, Zhou X, Zeng Y, Li K, Zhang L, Zhu H, Yang X, Li N, Yang Z, Liu Z. Noninvasive interrogation of CD8+ T cell effector function for monitoring early tumor responses to immunotherapy. J Clin Invest. 2022 Aug 15;132(16):e161065. doi: 10.1172/JCI161065.

Study record dates

Study Major Dates

• Study Start (Actual): September 22, 2021
• Primary Completion (Actual): May 25, 2024
• Study Completion (Actual): May 31, 2024

Study Registration Dates

• First Submitted: July 27, 2021
• First Submitted That Met QC Criteria: August 3, 2021
• First Posted (Actual): August 11, 2021

Study Record Updates

• Last Update Posted (Actual): December 4, 2024
• Last Update Submitted That Met QC Criteria: December 2, 2024
• Last Verified: December 1, 2024

More Information

Terms related to this study

• Keywords: PET/CT; Immunotherapy; Immune checkpoint inhibition; Granzyme B; 68Ga labeling
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms by Histologic Type; Neoplasms; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Lung Neoplasms; Neuroendocrine Tumors; Nevi and Melanomas; Carcinoma, Non-Small-Cell Lung; Melanoma
• Other Study ID Numbers: 2021KT86

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No