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

NCT04839991 | Unknown Phase 1 DMC FDA Drug

• 2 other identifiers: CBT307-12019-004584-46
• Study Type: interventional
• Target: 70
• Locations: 4 countries
• Sites: 20

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 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

Conditions

Advanced and/or Metastatic Solid Tumours

Keywords

Prostate Specific Membrane Antigen (PSMA); Solid Tumours; Castration-resistant prostate cancer (CRPC); First in Human (FIH); Phase 1 Study; CD137; 4-1BB; Crescendo Biologics; CB307; Humabody®; HSA; Pembrolizumab; KEYTRUDA®

Outcome Measures

Primary Outcomes (2)

• 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.

• 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 Outcomes (8)

• 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 evaluate clinical efficacy and duration of response by radiographic progression free survival (rPFS)

  radiographic progression free survival up to 20 months duration;

• To evaluate anti-tumor response according to RECIST v.1.1 or PCWG3

  anti-tumor response according to RECIST v1.1 or PCWG3 up to 20 months duration;

• 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.

• Pharmacokinetic of CB307 T1/2

  Data collected up to 20 months duration.

Study Arms (2)

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

EXPERIMENTAL

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

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

EXPERIMENTAL

Patients will receive CB307 IV infused every 7 days in combination with KEYTRUDA® (pembrolizumab) IV infused every 21 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. 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

Interventions

CB307 DRUG

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

Multi center open label Dose Escalation followed by Cohort Expansion: Part 2A; Multi center open label Dose Escalation followed by Combination Cohort Expansion : Part 2B

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Capable of understanding the written informed consent
• Aged at least 18 years
• Not amenable to standard of care
• ECOG PS \<=2
• 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

You may not qualify if:

• Subjects with autoimmune disease or regular immunosuppressants
• Has discontinued from anti-CTLA 4, anti-PD1 or anti-PD(L)1 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
• Part 2B only - has prior treatment with anti PD(L)1 or anti CTLA4

Sponsors & Collaborators

• Crescendo Biologics Ltd.: lead

Study Sites (20)

University of Washington

Seattle, Washington, 98109-5311, United States

RECRUITING

Antoni van Leeuwenhoek

Amsterdam, North Holland, 1066 CX, Netherlands

RECRUITING

VUMC Research B.V

Amsterdam, North Holland, 1081 HV, Netherlands

WITHDRAWN

University Medical Center Groningen,

Groningen, P.O. Box 30 001, Netherlands

RECRUITING

Erasmus University Medical Center Rotterdam

Rotterdam, Netherlands

RECRUITING

UMC Utrecht Cancer Center

Utrecht, 3584 CX, Netherlands

RECRUITING

Clinica Universidad de Navarra

Pamplona, Navarre, 31008, Spain

RECRUITING

hospital clinic de Barcelona

Barcelona, 08036, Spain

RECRUITING

hospital de la Sanat Creu i Sant Pau

Barcelona, 08041, Spain

RECRUITING

Clinica Universidad de Navarra

Madrid, 28027, Spain

RECRUITING

HU Fundacion Jimenez Diaz

Madrid, 28040, Spain

RECRUITING

Hospital Universitario 12 de Octubre

Madrid, 28041, Spain

RECRUITING

Hospital Universitario HM Sanchinarro

Madrid, 28050, Spain

RECRUITING

NEXT Oncology Hospital Quironsalud Madrid

Madrid, 28050, Spain

RECRUITING

HU Virgen de la Arrixaca

Murcia, 30120, Spain

RECRUITING

HU Virgen del Rocio - PPDS

Seville, 41013, Spain

RECRUITING

The Christie NHS Foundation Trust

Manchester, Greater Manchester, M20 4BX, United Kingdom

RECRUITING

Royal Marsden Hospital

London, Surrey, SM2 5PT, United Kingdom

RECRUITING

University College London Hospitals NHS Foundation Trust

London, NW1 2BU, United Kingdom

RECRUITING

Sarah Cannon Research Institute, UK

London, W1G 6AD, United Kingdom

RECRUITING

Related Publications (1)

• Wilford T, Bartlett PD, Schlag A, Jasaitis L, Pandha H, Pierce AJ, Hughes R. Solving selectivity issues in LBAs: case study using Gyrolab to quantify CB307, a bispecific Humabody in human serum. Bioanalysis. 2024;16(14):757-769. doi: 10.1080/17576180.2024.2365545. Epub 2024 Jul 3.

  PMID: 38957926 DERIVED

Study Officials

• K Hashimoto

  Crescendo Biologics

  STUDY DIRECTOR

Central Study Contacts

MD

CONTACT

01223497140; Clinicaltrials@crescendobiologics.com

MD

CONTACT

012234947140; info@crescendobiologics.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Masking Details: Open Label multi center non randomised study.
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Initial dose escalation cohorts followed by dose expansion cohorts consisting of 2 arms, monotherapy and combination therapy cohorts .

Study Record Dates

• First Submitted: March 29, 2021
• First Posted: April 9, 2021
• Study Start: June 8, 2021
• Primary Completion: July 25, 2024
• Study Completion: September 25, 2024
• Last Updated: November 18, 2023

Record last verified: 2023-11

Locations

US (1); ES (10); NL (5); GB (4)