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

Sponsor

Crescendo Biologics Ltd. (Industry)

Overall Status

Recruiting

CT.gov ID

NCT04839991

Collaborator

(none)

Enrollment

Locations

Arms

27.6

Anticipated Duration (Months)

Patients Per Site

0.3

Patients Per Site Per Month

Study Details

Study Description

Brief 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 RP2D.

Condition or Disease	Intervention/Treatment	Phase
Advanced and/or Metastatic Solid Tumours	Drug: CB307	Phase 1

Detailed 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. The study will consist of a dose escalation phase (Part 1) and a cohort expansion phase (Part 2) which will consist of 2 arms. Approximately 70 patients will participate in total. Patients will receive CB307 IV, 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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

70 participants

Allocation:

Non-Randomized

Intervention Model:

Single Group Assignment

Intervention Model Description:

Initial dose escalation cohorts followed by a single dose expansion cohort. The cohort expansion phase will consist of 2 arms.Initial dose escalation cohorts followed by a single dose expansion cohort. The cohort expansion phase will consist of 2 arms.

Masking:

None (Open Label)

Masking Description:

Open Label multi center non randomised study.

Primary Purpose:

Treatment

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

Actual Study Start Date :

Jun 8, 2021

Anticipated Primary Completion Date :

Jul 25, 2023

Anticipated Study Completion Date :

Sep 25, 2023

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Multi center open label Dose Escalation followed by Cohort Expansion: Part 2A Patients will receive CB307 IV infused every 7 days. Duration of treatment cycle is 21 days. Once the Dose Escalation phase (Part 1) is completed Cohort Expansion phase (Part 2) will begin. Part 2A arm will enrol patients with PSMA+ solid tumours. Treatment will continue until loss of clinical benefit, intolerable toxicity, withdrawal of consent or the study is stopped. Estimated study duration is 20 months.	Drug: CB307 Tri-specific Humabody targeting CD137, prostate specific membrane antigen and human serum albumin
Experimental: Multi center open label Dose Escalation followed by Cohort Expansion: Part 2B Patients will receive CB307 IV infused every 7 days. Duration of treatment cycle is 21 days. Once the Dose Escalation phase (Part 1) is completed Cohort Expansion phase (Part 2) will begin. Part 2B arm will enrol patients with PSMA+ metastatic, castration resistant prostate cancer patients with mutations of sponsor interest. Treatment will continue until loss of clinical benefit, intolerable toxicity, withdrawal of consent or the study is stopped. Estimated study duration is 20 months.	Drug: CB307 Tri-specific Humabody targeting CD137, prostate specific membrane antigen and human serum albumin

Arm

Intervention/Treatment

Experimental: Multi center open label Dose Escalation followed by Cohort Expansion: Part 2A

Patients will receive CB307 IV infused every 7 days. Duration of treatment cycle is 21 days. Once the Dose Escalation phase (Part 1) is completed Cohort Expansion phase (Part 2) will begin. Part 2A arm will enrol patients with PSMA+ solid tumours. Treatment will continue until loss of clinical benefit, intolerable toxicity, withdrawal of consent or the study is stopped. Estimated study duration is 20 months.

Drug: CB307

Tri-specific Humabody targeting CD137, prostate specific membrane antigen and human serum albumin

Experimental: Multi center open label Dose Escalation followed by Cohort Expansion: Part 2B

Patients will receive CB307 IV infused every 7 days. Duration of treatment cycle is 21 days. Once the Dose Escalation phase (Part 1) is completed Cohort Expansion phase (Part 2) will begin. Part 2B arm will enrol patients with PSMA+ metastatic, castration resistant prostate cancer patients with mutations of sponsor interest. Treatment will continue until loss of clinical benefit, intolerable toxicity, withdrawal of consent or the study is stopped. Estimated study duration is 20 months.

Drug: CB307

Tri-specific Humabody targeting CD137, prostate specific membrane antigen and human serum albumin

Outcome Measures

Primary Outcome Measures

Number of participants with treatment-related adverse events as assessed by CTCAE v5.0 [The nature and frequency of any DLTs during the DLT-monitoring period assessed based on NCI CTCAE v5.0. up to 20 months duration.]
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)

Secondary Outcome Measures

To evaluate clinical efficacy measured as progression-free survival according to RECIST v.1.1 or PCWG3 [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]
To measure how well the treatment succeeds in producing the desired effect.
To measure how the body processes CB307 in the body over time [PK parameters of CB307: data collected at time point 0 at each dosing period up to 20 months duration.]
To evaluate the pharmacokinetic trough levels before administration of CB307
Pharmacokinetic of CB307 T1/2 [Data collected up to 20 months duration.]
To evaluate the pharmacokinetic T1/2 after 3rd dose via IV for multiple dose levels of CB307
Pharmacokinetic of CB307 Tmax [Data collected up to 20 months duration.]
To evaluate the pharmacokinetic Tmax after 3rd dose via IV for multiple dose levels of CB307
To measure Tumour Immune response [Tumor response per RECIST ver 1.1 up to 20 months duration]
To determine the potential of CB307 to produce an immune response and assess the relationship with other outcome measures
Relationship of CB307 to anti tumour response [PSA response defined as a >50% decrease in PSA up to 20 months duration]
To evaluate the preliminary CB307 dose in relationship to activity of changes in tumour

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Capable of understanding the written informed consent
Aged at least 18 years
Not amenable to standard of care
ECOG PS 0-1
Has 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 metastasis
Adequate organ function
Cohort Expansion phase - Part 2B arm patients only: Has known mutations of sponsor interest

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Antoni van Leeuwenhoek	Amsterdam	Noord-Holland	Netherlands	1066 CX
2	VUMC Research B.V	Amsterdam	Noord-Holland	Netherlands	1081 HV
3	University Medical Center Groningen,	Groningen		Netherlands	P.O. Box 30 001
4	Erasmus University Medical Center Rotterdam	Rotterdam		Netherlands
5	UMC Utrecht Cancer Center	Utrecht		Netherlands	3584 CX
6	The Christie NHS Foundation Trust	Manchester	Greater Manchester	United Kingdom	M20 4BX
7	The Clatterbridge Cancer Centre NHS Foundation Trust	Bebington	Merseyside	United Kingdom	CH63 4JY
8	Royal Marsden Hospital	London	Surrey	United Kingdom	SM2 5PT
9	University College London Hospitals NHS Foundation Trust	London		United Kingdom	NW1 2BU
10	Sarah Cannon Research Institute, UK	London		United Kingdom	W1G 6AD