A Phase I Study to Assess PSMA+ and PSMA- Tumour Lesions

Study Overview
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Brief Summary
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CB307 is a trispecific Humabody® targeting CD137; PSMA; and human serum albumin (HSA) undergoing Phase 1 assessment in patients with PSMA+ solid tumours. This sub study will assess the biodistribution of radiolabelled CB307 in patients with advanced and/or metastatic solid tumours that are PSMA+.

Detailed Description
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Phase 1, Open-label, single centre, non-randomised study during which, enrolled patients will undergo a number of PET scans following administration of 89Zr-CB307, in order to assess the uptake of the radiolabelled drug. A post-treatment tumour biopsy for the assessment of PSMA expression will also be taken, if medically feasible, after the last PET scan. The sub-study consists of 2 parts: an Optimisation Phase (Part A) and an Expansion Phase (Part B). In Part A, both 89Zr-CB307 and CB307 will be administered to patients. The timing of the scans, post-dose tumour biopsy and CB307 dose will be optimised as determined by the Optimisation Review Committee (ORC). In Part B (Expansion Phase), 89Zr-CB307 PET scanning will be performed based on the optimal dosing and timing determined in Part A. The sub-study will continue for 7 days after the tracer injection. Patients will then be enrolled into the main study and will receive Cycle 1 Day 1 (C1D1) CB307 treatment according to the main study protocol.

Official Title
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A Phase I Study to Assess Biodistribution of 89Zr-CB307 in PSMA+ and PSMA- Tumour Lesions (A Sub-study of CBT307-1 Study - EUDRACT 2019-004584-46)

Conditions
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Advanced and/or Metastatic Solid Tumours

Intervention / Treatment
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* Drug: Radiolabelled CB307
* Drug: CB307


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Capable of understanding the written informed consent. Aged at least 18 years. Not amenable to standard of care. ECOG PS of 0 or 1. Documented histologically confirmed diagnosis of PSMA+ advanced or metastatic solid tumours. Has radiologically measurable disease per RECIST v1.1 or elevated serum PSA for castration resistant prostate cancer patients with only bone metastases. Adequate organ function. Willing to have a biopsy sample taken immediately after the last PET scan before initiation of the main study. Exclusion Criteria: Subjects with autoimmune disease or regular immunosuppressants. Has discontinued from anti-CTLA 4, anti-PD1 or anti-PD-L1 antibody because of intolerable toxicity. Has brain metastasis including leptomeningeal metastasis or primary brain tumour. Has current or history of CNS disease. Has known active infection. Biopsy cannot be safely obtained after the last PET scan, and not provided their consent.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Interventional Model Description: Following administration of 89Zr-CB307, enrolled patients will undergo a number of PET scans where uptake of the radiolabelled drug will be assessed
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Part A - Optimisation Phase<br>Following administration of 89Zr-CB307, patients will undergo PET scans The timing of the scans and CB307 dose administration will be determined by the Optimisation Review Committee (ORC) | Drug: Radiolabelled CB307<br>* CB307 radiolabelled with 89-Zirconium (89Zr CB307): drug product is formulated at a concentration of 1 mg/mL (37 MBq)<br>* Other names: 89Zr-CB307;Drug: CB307<br>* Trispecific Humabody® targeting CD137, prostate specific membrane antigen and human serum albumin<br>|
| Experimental: Part B - Expansion phase<br>89Zr-CB307 PET scanning will be performed based on the optimal dosing and timing determined in Part A by the Optimisation Review Committee (ORC) | Drug: Radiolabelled CB307<br>* CB307 radiolabelled with 89-Zirconium (89Zr CB307): drug product is formulated at a concentration of 1 mg/mL (37 MBq)<br>* Other names: 89Zr-CB307;Drug: CB307<br>* Trispecific Humabody® targeting CD137, prostate specific membrane antigen and human serum albumin<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Assessment of the safety of 89Zr-CB307 by assessing incidence of adverse events following administration of 89Zr-CB307. | Incidence (frequency and severity) of adverse events following administration of 89Zr-CB307 assessed by CTCAE version 5.0 | Throughout study completion, up to 8 months from first patient recruited. | 
| Assessment of 89Zr-CB307 uptake by PET scan by measuring maximum standardized uptake value in the tumour lesions. | SUVpeak - maximum standardized uptake value. | Throughout study completion, up to 8 months from first patient recruited. | 
| Assessment of 89Zr-CB307 uptake by PET scan by measuring mean standardized uptake value in the tumour lesions. | SUVmean - mean standardized uptake value. | Throughout study completion, up to 8 months from first patient recruited. | 
| Assessment of 89Zr-CB307 uptake by PET scan by measuring percentage of injected dose per gram of tissue in the tumour lesions. | %ID/g - percentage of injected dose per gram. | Throughout study completion, up to 8 months from first patient recruited. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Phase 1 Study, Solid Tumours, Castration-resistant prostate cancer (CRPC), Prostate Specific Membrane Antigen (PSMA), Crescendo Biologics, CB307, Humabody®, Radiolabelled CB307, 89-Zirconium, Biodistribution, HSA, CD137