CSB-321 Ph 1 in Immunotherapy for the Treatment of Cancer

NCT07057349 | Not Yet Recruiting Phase 1 FDA Drug

• 1 other identifier: CSB-321_101.07
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Metastatic Cancer; Unresectable Solid Tumor

Keywords

cancer immunotherapy; biomarkers, tumor; positron-emission tomography; Granzymes

Outcome Measures

Primary Outcomes (2)

• 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.

  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.

  3-4 hours post injection

Secondary Outcomes (4)

• Descriptive evaluation of [18F]CSB-321 accumulation in tumor foci in participants receiving immunotherapy treatment

  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

  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.

  6 months

• Correlate uptake of [18F]CSB-321 tracer and granzyme B expression as assessed on excisional biopsy or surgical sections when available.

  6 months

Study Arms (1)

[18F]CSB-321 PET Imaging

EXPERIMENTAL

All participants will receive up to 3 doses of \[18F\]CSB-321 with the corresponding PET imaging between 40 and 90 minutes of administration

Drug: [18F]CSB-321

Interventions

[18F]CSB-321 DRUG

\[18F\]CSB-321 is a PET imaging agent that is bound to released granzyme B from T-cells

Also known as: [Al18F]-NODA-CSB-321, CSB-321

[18F]CSB-321 PET Imaging

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Participants 18 years of age and older.
• Participants with either proven metastatic cancer that are going to be treated with one or more checkpoint inhibitors or immunotherapy under the licensed indications for the cancer type. Checkpoint inhibitors include PD-1, PD-L1, CTLA-4 and LAG-3 inhibitors OR Participants with unresectable or metastatic uveal melanoma planned to be treated with tebentafusp-tebn
• Participants must have at least one lesion ≥ 15 mm in diameter or with two lesions both ≥ 15mm in diameter, when an optional biopsy is planned from one of the lesions. Lesion measurements are taken from a diagnostic quality computerized tomography (CT) or Magnetic Resonance Imaging (MRI).
• ECOG performance status ≤ 2 (Karnofsky ≤ 60%).
• Life expectancy of greater than 6 months.
• If female, not of childbearing potential or must have a negative pregnancy test prior to each radiotracer injection.
• Willing and able to undergo all study procedures.
• Need archival lesion tissue ideally available within 90 days of enrollment either from biopsy or surgery without intervening therapy.

You may not qualify if:

• Participants for whom adverse events due to agents administered more than 4 weeks earlier have not resolved to Grade 1 or less, except for immune checkpoint inhibitor related endocrinopathies except for immune checkpoint inhibitor related endocrinopathies or deemed unlikely to be clinically significant by the investigator.
• Participants in cohort 2 (ipilimumab with nivolumab) who have received or are expected to receive an investigational compound within 90 days prior to \[18F\]CSB-321 PET imaging. This includes immunotherapies that are not approved by the US FDA for the indications in this protocol.
• Participants who have received a prior checkpoint inhibitor in the last year except for participants in cohort 3 (Prior checkpoint inhibitors are allowed for this cohort).
• Participants who have received chemotherapy in the prior 6 months or are anticipated to receive chemotherapy in the 6 months following the initial \[18F\]CSB-321 injection for cohorts 2 and 3.
• Any acute or chronic inflammatory disease or medical conditions that in the investigator's opinion may interfere with the study procedures or the interpretation of the study results such as infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia.
• History of allergic reactions to compounds of similar chemical or biologic composition to \[18F\]CSB-321.
• Current treatment with systemic steroids, or immunosuppressive agents. Participants with a condition requiring systemic treatment with either corticosteroids (\< 10 mg daily prednisone equivalent) inhaled or topical steroids, and adrenal replacement steroid doses \> 10 mg daily prednisone equivalent, are permitted in the absence of active autoimmune disease.
• Participants who are unwilling or unable to have a CT scan.
• Males and females unwilling to use adequate contraception prior to study and during study participation.
• If female, nursing.
• Unwilling and/or unable to sign a written informed consent document.
• Laboratory values
• Leukocytes \< 2000/mcL (CTCAE grade 3)
• Absolute neutrophil count \< 1000 mcL (CTCAE grade 3)
• Platelets \< 75,000 mcL (CTCAE grade 2)

Sponsors & Collaborators

• Cytosite Biopharma Inc.: lead

Study Sites (1)

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Related Publications (1)

• Larimer BM, Wehrenberg-Klee E, Dubois F, Mehta A, Kalomeris T, Flaherty K, Boland G, Mahmood U. Granzyme B PET Imaging as a Predictive Biomarker of Immunotherapy Response. Cancer Res. 2017 May 1;77(9):2318-2327. doi: 10.1158/0008-5472.CAN-16-3346.

  PMID: 28461564 BACKGROUND

MeSH Terms

Conditions

Neoplasm Metastasis; Neoplasms

Condition Hierarchy (Ancestors)

Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Ryan Sullivan, MD

  Massachusetts General Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Kimmai T Phan, M.S.

CONTACT

215 6481208; kphan@cytositebio.com

Chanelle Hunter, PhD

CONTACT

2156481208; chunter@cytositebio.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 30, 2025
• First Posted: July 9, 2025
• Study Start: September 1, 2025
• Primary Completion (Estimated): September 1, 2027
• Study Completion (Estimated): February 1, 2029
• Last Updated: July 9, 2025

Record last verified: 2025-06

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)