Advanced and/or Metastatic Solid Tumours
Conditions
Keywords
Phase 1 Study, Solid Tumours, Castration-resistant prostate cancer (CRPC), Prostate Specific Membrane Antigen (PSMA), Crescendo Biologics, CD137, CB307, Humabody®, Radiolabelled CB307, 89-Zirconium, Biodistribution, HSA
Brief summary
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
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.
Interventions
DRUGRadiolabelled CB307
CB307 radiolabelled with 89-Zirconium (89Zr CB307): drug product is formulated at a concentration of 1 mg/mL (37 MBq)
DRUGCB307
Trispecific Humabody® targeting CD137, prostate specific membrane antigen and human serum albumin
Sponsors
University Medical Center Groningen
Crescendo Biologics Ltd.
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Masking description
Open-label single center non-randomised study
Intervention 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
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Assessment of the safety of 89Zr-CB307 by assessing incidence of adverse events following administration of 89Zr-CB307. | Throughout study completion, up to 8 months from first patient recruited. | Incidence (frequency and severity) of adverse events following administration of 89Zr-CB307 assessed by CTCAE version 5.0 |
| Assessment of 89Zr-CB307 uptake by PET scan by measuring maximum standardized uptake value in the tumour lesions. | Throughout study completion, up to 8 months from first patient recruited. | SUVpeak - maximum standardized uptake value. |
| Assessment of 89Zr-CB307 uptake by PET scan by measuring mean standardized uptake value in the tumour lesions. | Throughout study completion, up to 8 months from first patient recruited. | SUVmean - mean standardized uptake value. |
| Assessment of 89Zr-CB307 uptake by PET scan by measuring percentage of injected dose per gram of tissue in the tumour lesions. | Throughout study completion, up to 8 months from first patient recruited. | %ID/g - percentage of injected dose per gram. |
Countries
Netherlands
Outcome results
None listed