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

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)

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+.

Study Overview

• Status: Active, not recruiting
• Conditions: Advanced and/or Metastatic Solid Tumours
• Intervention / Treatment: Drug: Radiolabelled CB307; Drug: CB307

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.

• Study Type: Interventional
• Enrollment (Actual): 5
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: MD MD; Phone Number: +44 (0)1223 497140; Email: Clinicaltrials@crescendobiologics.com
• Study Contact Backup: Name: Julia Tilson; Phone Number: 07725 844778; Email: jtilson@crescendobiologics.com

Study Locations

• Netherlands
  • Groningen, Netherlands, P.O. Box 30 001
    • University Medical Center Groningen,

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Part A - Optimisation Phase; 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; CB307 radiolabelled with 89-Zirconium (89Zr CB307): drug product is formulated at a concentration of 1 mg/mL (37 MBq); Other Names: 89Zr-CB307; Drug: CB307; Trispecific Humabody® targeting CD137, prostate specific membrane antigen and human serum albumin
Experimental: Part B - Expansion phase; 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; CB307 radiolabelled with 89-Zirconium (89Zr CB307): drug product is formulated at a concentration of 1 mg/mL (37 MBq); Other Names: 89Zr-CB307; Drug: CB307; Trispecific Humabody® targeting CD137, prostate specific membrane antigen and human serum albumin

What is the study measuring?

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.

Collaborators and Investigators

• Sponsor: Crescendo Biologics Ltd.
• Collaborators: University Medical Center Groningen
• Investigators: Study Director: Julia Tilson, Crescendo Biologics Limited

Study record dates

Study Major Dates

• Study Start (Actual): December 20, 2022
• Primary Completion (Actual): January 31, 2024
• Study Completion (Estimated): October 31, 2024

Study Registration Dates

• First Submitted: March 7, 2023
• First Submitted That Met QC Criteria: April 28, 2023
• First Posted (Actual): May 1, 2023

Study Record Updates

• Last Update Posted (Estimated): February 28, 2024
• Last Update Submitted That Met QC Criteria: February 26, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Keywords: Biodistribution; Prostate Specific Membrane Antigen (PSMA); Solid Tumours; Castration-resistant prostate cancer (CRPC); Phase 1 Study; CD137; Crescendo Biologics; CB307; HSA; Humabody®; Radiolabelled CB307; 89-Zirconium
• Additional Relevant MeSH Terms: Neoplasms
• Other Study ID Numbers: CBT307-1-RL; 2021-006256-13 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No