Clinical trial NCT05836623: A Phase I Study to Assess PSMA+ and PSMA- Tumour Lesions
Official title: 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)
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE1
Conditions: Advanced and/or Metastatic Solid Tumours
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
Lead sponsor: Crescendo Biologics Ltd.
Sponsor class: INDUSTRY
Collaborators: name: University Medical Center Groningen
First posted: 2023-05-01
Enrollment: 5
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
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
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Assessment of the safety of 89Zr-CB307 by assessing incidence of adverse events following administration of 89Zr-CB307.
timeFrame: Throughout study completion, up to 8 months from first patient recruited.
measure: Assessment of 89Zr-CB307 uptake by PET scan by measuring maximum standardized uptake value in the tumour lesions.
timeFrame: Throughout study completion, up to 8 months from first patient recruited.
measure: Assessment of 89Zr-CB307 uptake by PET scan by measuring mean standardized uptake value in the tumour lesions.
timeFrame: Throughout study completion, up to 8 months from first patient recruited.
measure: Assessment of 89Zr-CB307 uptake by PET scan by measuring percentage of injected dose per gram of tissue in the tumour lesions.
timeFrame: Throughout study completion, up to 8 months from first patient recruited.
Secondary outcomes:
Other outcomes:
Locations:
city: Groningen
country: Netherlands
facility: University Medical Center Groningen,
Study officials:
affiliation: Crescendo Biologics Limited
name: Julia Tilson
role: STUDY_DIRECTOR
References: