Study of CB307 in Patients With Advanced and/or Metastatic PSMA-positive Tumours.

Advanced and/or Metastatic Solid Tumours Clinical Trial

— POTENTIA  

Official title:

A Phase 1 Open-Label, Dose Escalation and Expansion Trial to Investigate the Safety, Pharmacokinetics and Pharmacodynamics of CB307, a Trispecific Humabody® T-cell Enhancer, in Patients With PSMA+ Advanced and/or Metastatic Solid Tumours

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04839991
• Other study ID #: CBT307-1
• Secondary ID: 2019-004584-46
• Status: Recruiting
• Phase: Phase 1
• Start date: June 8, 2021
• Est. completion date: September 25, 2024

Study information

• Verified date: November 2023
• Source: Crescendo Biologics Ltd.
• Contact: MD
• Phone: 01223497140
• Email: Clinicaltrials[@]crescendobiologics.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

FIH, Phase 1, open-label, multi centre study of CB307, a trispecific Humabody® T-cell enhancer, in patients with advanced and/or metastatic PSMA+ solid tumours to assess safety and tolerability to determine MTD and preliminary RP2D.In addition this study will assess the safety and efficacy of CB307 when given in combination with pembrolizumab (KEYTRUDA®) in patients with metastatic PSMA+ castration-resistant cancer

Description:

FIH, Phase 1, open-label, multi centre, non randomised study of CB307, a trispecific Humabody® T-cell enhancer, in patients with advanced and/or metastatic PSMA+ solid tumours (Part 1 & 2A) and patients with metastatic PSMA+ castration-resistant cancer (Part 2B) . The study will consist of a dose escalation phase (Part 1) and a cohort expansion phase (Part 2) which will consist of 2 arms . Part 2 will evaluate safety and preliminary efficacy of CB307 (both as monotherapy and in combination with pembrolizumab) at the MTD or preliminary RP2D as determined in Part 1. Approximately 70 patients will participate in total. Patients will receive either CB307 alone or CB307 with pembrolizumab IV (Part 2B), until loss of clinical benefit, unacceptable toxicity, withdrawal of consent or end of study. The dose escalation may be adapted by the SRC based on clinical experience and safety review.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 70
• Est. completion date: September 25, 2024
• Est. primary completion date: July 25, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. Capable of understanding the written informed consent

2. Aged at least 18 years

3. Not amenable to standard of care

4. ECOG PS <=2

5. Has documented histologically confirmed diagnosis of PSMA+ advanced or metastatic solid tumours

6. Has radiologically measurable disease per RECIST v1.1 or elevated serum PSA for castration resistant prostate cancer patients with only bone metastasis

7. Adequate organ function

Exclusion Criteria:

1. Subjects with autoimmune disease or regular immunosuppressants

2. Has discontinued from anti-CTLA 4, anti-PD1 or anti-PD(L)1 antibody because of intolerable toxicity

3. Has brain metastasis including leptomeningeal metastasis or primary brain tumour

4. Has current or history of CNS disease

5. Has known active infection

6. Part 2B only - has prior treatment with anti PD(L)1 or anti CTLA4

Related Conditions & MeSH terms

• Advanced and/or Metastatic Solid Tumours
• Neoplasms

Intervention

Drug:
• CB307
Tri-specific Humabody® targeting CD137, prostate specific membrane antigen and human serum albumin

Locations

Country	Name	City	State
Netherlands	Antoni van Leeuwenhoek	Amsterdam	Noord-Holland
Netherlands	VUMC Research B.V	Amsterdam	Noord-Holland
Netherlands	University Medical Center Groningen,	Groningen
Netherlands	Erasmus University Medical Center Rotterdam	Rotterdam
Netherlands	UMC Utrecht Cancer Center	Utrecht
Spain	hospital clinic de Barcelona	Barcelona
Spain	hospital de la Sanat Creu i Sant Pau	Barcelona
Spain	Clinica Universidad de Navarra	Madrid
Spain	Hospital Universitario 12 de Octubre	Madrid
Spain	Hospital Universitario HM Sanchinarro	Madrid
Spain	HU Fundacion Jimenez Diaz	Madrid
Spain	NEXT Oncology Hospital Quironsalud Madrid	Madrid
Spain	HU Virgen de la Arrixaca	Murcia
Spain	Clinica Universidad de Navarra	Pamplona	Navarra
Spain	HU Virgen del Rocio - PPDS	Sevilla
United Kingdom	Royal Marsden Hospital	London	Surrey
United Kingdom	Sarah Cannon Research Institute, UK	London
United Kingdom	University College London Hospitals NHS Foundation Trust	London
United Kingdom	The Christie NHS Foundation Trust	Manchester	Greater Manchester
United States	University of Washington	Seattle	Washington

Sponsors (1)

Lead Sponsor	Collaborator
Crescendo Biologics Ltd.

Countries where clinical trial is conducted

United States,  Netherlands,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of participants with treatment-related adverse events as assessed by CTCAE v5.0	The objective of the study is to assess the safety and tolerability of the study drug CB307 and to determine the MTD (maximum tolerated dose)	The nature and frequency of any DLTs during the DLT-monitoring period assessed based on NCI CTCAE v5.0. up to 20 months duration.
Primary	Number of participants with treatment-related adverse events with CB307 in combination with pembrolizumab as assessed by CTCAE v5.0	The objective of the study is to assess the safety and tolerability of the study drug CB307 in combination with pembrolizumab to assess safety and tolerability of the combined treatment regimen	The nature and frequency of any DLTs during the DLT-monitoring period for participants with combination therapy, assessed based on NCI CTCAE v5.0. up to 20 months duration.
Secondary	To evaluate clinical efficacy measured as progression-free survival according to RECIST v.1.1 or PCWG3	To measure how well the treatment succeeds in producing the desired effect.	Progression-free survival according to RECIST v1.1 or PCWG3 up to 20 months duration; and change from baseline in anti-drug (CB307) antibodies (ADA up to 20 months duration
Secondary	To evaluate clinical efficacy and duration of response by radiographic progression free survival (rPFS)	To measure how well the treatment succeeds in producing the desired effect.	radiographic progression free survival up to 20 months duration;
Secondary	To evaluate anti-tumor response according to RECIST v.1.1 or PCWG3	To measure how well the treatment succeeds in producing the desired effect.	anti-tumor response according to RECIST v1.1 or PCWG3 up to 20 months duration;
Secondary	To measure how the body processes CB307 in the body over time	To evaluate the pharmacokinetic trough levels before administration of CB307	PK parameters of CB307: data collected at time point 0 at each dosing period up to 20 months duration.
Secondary	Pharmacokinetic of CB307 T1/2	To evaluate the pharmacokinetic T1/2 after 3rd dose via IV for multiple dose levels of CB307	Data collected up to 20 months duration.
Secondary	Pharmacokinetic of CB307 Tmax	To evaluate the pharmacokinetic Tmax after 3rd dose via IV for multiple dose levels of CB307	Data collected up to 20 months duration.
Secondary	To measure Tumour Immune response	To determine the potential of CB307 to produce an immune response and assess the relationship with other outcome measures	Tumor response per RECIST ver 1.1 up to 20 months duration
Secondary	Relationship of CB307 to anti tumour response	To evaluate the preliminary CB307 dose in relationship to activity of changes in tumour	PSA response defined as a >50% decrease in PSA up to 20 months duration