Metastatic CancerPhase 1NCT07057349
CSB-321 Ph 1 in Immunotherapy for the Treatment of Cancer
A Phase 1 study testing [18F]CSB-321 in people with Metastatic Cancer and Unresectable Solid Tumor, run by Cytosite Biopharma Inc. at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Metastatic Cancer, Unresectable Solid Tumor
- What is being tested?
- [18F]CSB-321
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 40 participants
- Where
- 1 siteUnited States
- Study dates
- 1 Sep 2025to Feb 2029
- Phase
- Phase 1
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
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- 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)
- Total bilirubin > 1.5 x ULN, unless participant has Gilbert' disease.
- AST/ALT > 5 x ULN (CTCAE grade 3)
- Albumin < 2 g/dL
- Alkaline phosphatase > 5 ULN (CTCAE grade 3)
- eGFR < 45 mL/min/1.73 m2 Participants who are stable but have values outside the specified ranges may be included with approval of the study medical monitor.
- Participants with a QTcF of greater than 470 ms as measured by 12-lead ECG.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site
Massachusetts General Hospital
Boston, Massachusetts, 02114
About this study
Official title: Phase 1 Multi-cohort Evaluation of [18F]CSB-321 PET Imaging in Participants Receiving Immunotherapy for the Treatment of Cancer
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.
Read the detailed description
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.
- Conditions
- Metastatic Cancer, Unresectable Solid Tumor
- Being tested
- [18F]CSB-321
- Keywords
- cancer immunotherapy, biomarkers, tumor, positron-emission tomography, Granzymes
- Medical subject headings
- Neoplasm Metastasis, Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
[18F]CSB-321Drug
Also called [Al18F]-NODA-CSB-321, CSB-321
[18F]CSB-321 is a PET imaging agent that is bound to released granzyme B from T-cells
| Study group | Role | What they receive |
|---|---|---|
| [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 Receives: Drug: [18F]CSB-321 |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: 3-4 hours post injection
Secondary outcomes (4)
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
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Jul 2025
- Study start1 Sep 2025 (estimated)
- Primary completionSep 2027 (estimated)
- Study completionFeb 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Metastatic CancerStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Diagnosis
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 40 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Cytosite Biopharma Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Ryan Sullivan, MD, Principal investigator, Massachusetts General Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07057349
- Sponsor's protocol ID
- CSB-321_101.07
- Status last verified
- Jun 2025
- First submitted
- 30 Jun 2025
- Last updated
- 9 Jul 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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.
PubMed 28461564
Study at a glance
From the registry record, last updated by the sponsor on 9 Jul 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase 1 Multi-cohort Evaluation of [18F]CSB-321 PET Imaging in Participants Receiving Immunotherapy for the Treatment of Cancer
- ClinicalTrials.gov ID
- NCT07057349
- Acronym / sponsor ID
- CSB-321_101.07
- Conditions
- Metastatic Cancer, Unresectable Solid Tumor
- Keywords
- cancer immunotherapy, biomarkers, tumor, positron-emission tomography, Granzymes
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 40 participants (estimated)
- Lead sponsor
- Cytosite Biopharma Inc.Industry (pharma, biotech, devices)
- Study start
- 1 Sep 2025 (estimated)
- Primary completion
- Sep 2027 (estimated)
- Study completion
- Feb 2029 (estimated)
- First posted
- 9 Jul 2025 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
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 design
- Primary purpose
- Diagnosis
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| [18F]CSB-321 PET Imaging | Experimental | Drug: [18F]CSB-321All participants will receive up to 3 doses of [18F]CSB-321 with the corresponding PET imaging between 40 and 90 minutes of administration |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- 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.
Key exclusion criteria (21 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| [18F]CSB-321Also: [Al18F]-NODA-CSB-321, CSB-321[18F]CSB-321 is a PET imaging agent that is bound to released granzyme B from T-cells | Drug | [18F]CSB-321 PET Imaging |
Primary outcome
The number of clinically significant changes
Time frame: 3-4 hours post injection
Clinically significant changes from baseline through follow up analysis in physical examination findings, vital signs, and blood chemistry and AEs.
Frequency and grade of adverse events due to [18F]CSB-321
Time frame: 3-4 hours post injection
Number of AE's as assessed by CTCAE 5.0.
4 secondary outcomes
Descriptive evaluation of [18F]CSB-321 accumulation in tumor foci in participants receiving immunotherapy treatment
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
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.
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.
Time frame: 6 months
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Jul 2025.
- Background: PubMed 28461564Larimer 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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Ryan Sullivan, MD principal investigator
Massachusetts General Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing [18F]CSB-321 in people with Metastatic Cancer and Unresectable Solid Tumor, run by Cytosite Biopharma Inc. at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 21 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: opening soon, as of the sponsor's last update on 9 Jul 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Kimmai T Phan, M.S. (215 6481208 ext. 710, kphan@cytositebio.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
The number of clinically significant changes (time frame: 3-4 hours post injection). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT07057349, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Jul 2025.