Single-center with the option to expand to multi-center, international, open label, non-randomized, multiple-dose, multi-cohort study, in participants with metastatic or unresectable cancer. Eligible participants will receive an initial injection of \[18F\]CSB-321 followed by PET imaging prior to administration of the I-O therapy and a second and third injection post treatment each with PET imaging. The images will be analyzed for the distribution of radioactivity. Participants will be followed for adverse events up to 3-4 hours post injection. Available clinical, imaging, and histology data will be collected at follow-up to establish the disease progression for evaluation of \[18F\]CSB-321.
This single site, open label, non-randomized, multiple dose phase 1 study, in participants with metastatic cancer which can be treated with checkpoint inhibitor therapy or bi-specific immunological therapy. The primary safety objective is to test the safety of \[18F\]CSB-321 in participants with cancer. The primary efficacy and secondary objectives are to gain evidence in support of the hypothesis that \[18F\]CSB-321 uptake will correlate with tumoral response to treatment with the I-O therapy. \[18F\]CSB-321 PET imaging will be performed in participants with metastatic cancers that are planned to receive an I-O therapy for cancer treatment. Participants in cohort 1 can receive mono or combination I-O therapies which have FDA approval for the indication of use. They may also receive chemotherapy. Cohort 2 will receive only ipilimumab with nivolumab. Cohort 3 will be treated with tebentafusp-tebn monotherapy or combination I-O therapies. \[18F\]CSB-321 PET imaging will be acquired on one to three separate days: Up to 14 days prior to initial administration of I-O therapy and for cohorts 1 and 2, the next two doses will occur between Day 5 and 42 after initiation of checkpoint inhibitor (cycle 1, which occurs on day 0). For participants treated with tebentafusp-tebn (cohort 3), the second imaging session will take place on 24 hours after the third infusion. The third imaging will be performed 24 hours after the thirteenth Infusion. The available clinical and cross-sectional imaging data will be collected at 6 ± 2- months after initiation of I-O therapy. This follow up period is for collecting data to establish tumor growth and hence I-O therapy treatment efficacy. This will then be used to establish correlations with \[18F\]CSB-321 PET. The 6-month follow-up will be the timepoint used for these correlations. As the participants will be off the investigational treatment, this follow-up period for the 6-month visit is considered differently than the study period and hence AEs will not be collected during this period. See Adverse Event Reporting section 8.2.5 for more details. The optional excisional tumor biopsy will provide the most definitive information regarding the presence of granzyme B in the tumor. These excisional biopsies, when obtained, will be performed following \[18F\]CSB-321 PET imaging, to allow for correlative analysis.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
DIAGNOSTIC
Masking
NONE
Enrollment
40
\[18F\]CSB-321 is a PET imaging agent that is bound to released granzyme B from T-cells
Massachusetts General Hospital
Boston, Massachusetts, United States
The number of clinically significant changes
Clinically significant changes from baseline through follow up analysis in physical examination findings, vital signs, and blood chemistry and AEs.
Time frame: 3-4 hours post injection
Frequency and grade of adverse events due to [18F]CSB-321
Number of AE's as assessed by CTCAE 5.0.
Time frame: 3-4 hours post injection
Descriptive evaluation of [18F]CSB-321 accumulation in tumor foci in participants receiving immunotherapy treatment
Descriptive evaluation of \[18F\]CSB-321 PET images by the central reader and/or the principal investigator and the ability to identify avid lesions
Time frame: Required at 40 and 60 minutes. Optional at 90 and 120 minutes.
Quantified evaluation of [18F]CSB-321 accumulation in tumor foci in participants receiving immunotherapy treatment
Quantification of \[18F\]CSB-321 PET accumulation at tumor site in participants after treatment with an immunotherapy as determined by region(s) of interest analysis.
Time frame: Required at 40 and 60 minutes. Optional at 90 and 120 minutes.
Evaluate correlation of [18F]CSB-321 accumulation in tumor foci to 6-month outcome.
Compare quantified \[18F\]CSB-321 PET uptake to participant treatment response in individual lesions as assessed at 6-month follow-up clinical and/or anatomical imaging (computed tomography (CT) or magnetic resonance imaging (MRI)) assessments and/or 18F-FDG PET images.
Time frame: 6 months
Correlate uptake of [18F]CSB-321 tracer and granzyme B expression as assessed on excisional biopsy or surgical sections when available.
Compare granzyme B protein quantification from biopsied tissue to the \[18F\]CSB-321 PET uptake acquired at the same location.
Time frame: 6 months
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