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

Phase 1
Active, not recruiting
Conditions
Advanced and/or Metastatic Solid Tumours
Interventions
Drug: Radiolabelled CB307
Registration Number
NCT05836623
Lead Sponsor
Crescendo Biologics Ltd.
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.

Recruitment & Eligibility

Status
ACTIVE_NOT_RECRUITING
Sex
All
Target Recruitment
5
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.

Study & Design

Study Type
INTERVENTIONAL
Study Design
SINGLE_GROUP
Arm && Interventions
GroupInterventionDescription
Part B - Expansion phaseRadiolabelled CB30789Zr-CB307 PET scanning will be performed based on the optimal dosing and timing determined in Part A by the Optimisation Review Committee (ORC)
Part A - Optimisation PhaseRadiolabelled CB307Following 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)
Part A - Optimisation PhaseCB307Following 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)
Part B - Expansion phaseCB30789Zr-CB307 PET scanning will be performed based on the optimal dosing and timing determined in Part A by the Optimisation Review Committee (ORC)
Primary Outcome Measures
NameTimeMethod
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.

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.

Secondary Outcome Measures
NameTimeMethod

Trial Locations

Locations (1)

University Medical Center Groningen,

🇳🇱

Groningen, Netherlands

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