Advanced and/or Metastatic Solid TumoursPhase 1POTENTIANCT04839991
Study of CB307 in Patients With Advanced and/or Metastatic PSMA-positive Tumours.
A Phase 1 study testing CB307 in people with Advanced and/or Metastatic Solid Tumours, run by Crescendo Biologics Ltd. at 20 sites in 4 countries.
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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Advanced and/or Metastatic Solid Tumours
- What is being tested?
- CB307
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 70 participants
- Where
- 20 sitesin 4 countries
- Study dates
- 8 Jun 2021to 25 Sep 2024
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Trial locations and contacts
20 sites in 4 countries.
20 sites in 4 countries
Spain10 sites, 10 recruiting
- Recruiting
hospital clinic de Barcelona
Barcelona, 08036
Oscar Reig, oreig@clinic.cat
- Recruiting
hospital de la Sanat Creu i Sant Pau
Barcelona, 08041
Georgia Anguera Palacios, ganguera@santpau.cat
- Recruiting
Clinica Universidad de Navarra
Madrid, 28027
Ignacio Melero, imelero@unav.es
Ignacio Melero
- Recruiting
HU Fundacion Jimenez Diaz
Madrid, 28040
Bernard Doger de Speville Uribe, bernard.doger@startmadrid.com
Bernard Doger de Speville Uribe
- Recruiting
Hospital Universitario 12 de Octubre
Madrid, 28041
Daniel Castellano, cdanicas@hotmail.com
Daniel Castellano
- Recruiting
Hospital Universitario HM Sanchinarro
Madrid, 28050
Irene Moreno, irene.moreno@startmadrid.com
Irene Moreno
- Recruiting
NEXT Oncology Hospital Quironsalud Madrid
Madrid, 28050
Valentina Boni, vboni@nextoncology.eu
- Recruiting
HU Virgen de la Arrixaca
Murcia, 30120
Jose Luis Alonso Romero, josel.alonso2@carm.es
- Recruiting
Clinica Universidad de Navarra
Pamplona, Navarre, 31008
Ignacio Melero, imelero@unav.es
Ignacio Melero
- Recruiting
HU Virgen del Rocio - PPDS
Seville, 41013
Alejandro Falcon, afalconglez@gmail.com
Netherlands5 sites, 4 recruiting
- Recruiting
Antoni van Leeuwenhoek
Amsterdam, North Holland, 1066 CX
MD, f.opdam@nki.nl
- Withdrawn
VUMC Research B.V
Amsterdam, North Holland, 1081 HV
- Recruiting
University Medical Center Groningen,
Groningen, P.O. Box 30 001
MD, e.g.e.de.vries@umcg.nl
Elisabeth De Vries
- Recruiting
Erasmus University Medical Center Rotterdam
Rotterdam
MD, m.lolkema@erasmusmc.nl
- Recruiting
UMC Utrecht Cancer Center
Utrecht, 3584 CX
Eelke Gort, MD, E.H.Gort-2@umcutrecht.nl
United Kingdom4 sites, 4 recruiting
- Recruiting
Royal Marsden Hospital
London, Surrey, SM2 5PT
MD, Johann.DeBono@icr.ac.uk
Johann De Bono
- Recruiting
University College London Hospitals NHS Foundation Trust
London, NW1 2BU
Anuradha Jayaram, anuradha.jayaram@nhs.net
Anuradha Jayaram
- Recruiting
Sarah Cannon Research Institute, UK
London, W1G 6AD
Anya Williams, anya.williams@hcahealthcare.co.uk
Anya Williams
- Recruiting
The Christie NHS Foundation Trust
Manchester, Greater Manchester, M20 4BX
MD, fiona.thistlethwaite@christie.nhs.uk
Fiona Thistlethwaite
United States1 site, 1 recruiting
- Recruiting
University of Washington
Seattle, Washington, 98109-5311
Jessica Hawley, jehawley@uw.edu
About this study
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
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
Read the 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 (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.
- Conditions
- Advanced and/or Metastatic Solid Tumours
- Being tested
- CB307
- 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®
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CB307Drug
Tri-specific Humabody® targeting CD137, prostate specific membrane antigen and human serum albumin
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: Drug: CB307 |
What is being measured
The primary outcome is the main question the study is designed to answer.
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)
Measured: 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
Measured: 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
To measure how well the treatment succeeds in producing the desired effect.
Measured: 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)
To measure how well the treatment succeeds in producing the desired effect.
Measured: radiographic progression free survival up to 20 months duration;
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.
Measured: 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
To evaluate the pharmacokinetic trough levels before administration of CB307
Measured: PK parameters of CB307: data collected at time point 0 at each dosing period up to 20 months duration.
Pharmacokinetic of CB307 T1/2
To evaluate the pharmacokinetic T1/2 after 3rd dose via IV for multiple dose levels of CB307
Measured: Data collected up to 20 months duration.
Pharmacokinetic of CB307 Tmax
To evaluate the pharmacokinetic Tmax after 3rd dose via IV for multiple dose levels of CB307
Measured: Data collected up to 20 months duration.
To measure Tumour Immune response
To determine the potential of CB307 to produce an immune response and assess the relationship with other outcome measures
Measured: Tumor response per RECIST ver 1.1 up to 20 months duration
Relationship of CB307 to anti tumour response
To evaluate the preliminary CB307 dose in relationship to activity of changes in tumour
Measured: PSA response defined as a >50% decrease in PSA up to 20 months duration
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Apr 2021
- Study start8 Jun 2021
- Primary completion25 Jul 2024 (estimated)
- Study completion25 Sep 2024 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Advanced and/or Metastatic Solid TumoursStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Model description
- Initial dose escalation cohorts followed by dose expansion cohorts consisting of 2 arms, monotherapy and combination therapy cohorts .
- Masking
- None (open label)
- Enrolment
- 70 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Crescendo Biologics Ltd.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- K Hashimoto, Study director, Crescendo Biologics
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04839991
- Sponsor's protocol ID
- CBT307-1
- Other IDs
- 2019-004584-46, 2019
- Acronym
- POTENTIA
- Status last verified
- Nov 2023
- First submitted
- 29 Mar 2021
- Last updated
- 18 Nov 2023
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
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.
PubMed 38957926
Study at a glance
From the registry record, last updated by the sponsor on 18 Nov 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT04839991
- Acronym / sponsor ID
- POTENTIA / CBT307-1
- 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
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 70 participants (estimated)
- Lead sponsor
- Crescendo Biologics Ltd.Industry (pharma, biotech, devices)
- Study start
- 8 Jun 2021 (actual)
- Primary completion
- 25 Jul 2024 (estimated)
- Study completion
- 25 Sep 2024 (estimated)
- First posted
- 9 Apr 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
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 (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.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- Initial dose escalation cohorts followed by dose expansion cohorts consisting of 2 arms, monotherapy and combination therapy cohorts .
| Arm | Type | Receives |
|---|---|---|
| Multi center open label Dose Escalation followed by Cohort Expansion: Part 2A | Experimental | Drug: CB307Patients 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. |
| Multi center open label Dose Escalation followed by Combination Cohort Expansion : Part 2B | Experimental | Drug: CB307Patients 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- 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
Key exclusion criteria (6 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| CB307Tri-specific Humabody® targeting CD137, prostate specific membrane antigen and human serum albumin | Drug | 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 |
Primary outcome
Number of participants with treatment-related adverse events as assessed by CTCAE v5.0
Time frame: 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)
Number of participants with treatment-related adverse events with CB307 in combination with pembrolizumab as assessed by CTCAE v5.0
Time frame: 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.
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
8 secondary outcomes
To evaluate clinical efficacy measured as progression-free survival according to RECIST v.1.1 or PCWG3
Time frame: 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)
Time frame: radiographic progression free survival up to 20 months duration;
To evaluate anti-tumor response according to RECIST v.1.1 or PCWG3
Time frame: 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
Time frame: PK parameters of CB307: data collected at time point 0 at each dosing period up to 20 months duration.
Pharmacokinetic of CB307 T1/2
Time frame: Data collected up to 20 months duration.
Pharmacokinetic of CB307 Tmax
Time frame: Data collected up to 20 months duration.
To measure Tumour Immune response
Time frame: Tumor response per RECIST ver 1.1 up to 20 months duration
Relationship of CB307 to anti tumour response
Time frame: PSA response defined as a >50% decrease in PSA up to 20 months duration
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Nov 2023.
- Derived from this study: PubMed 38957926Wilford 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
K Hashimoto study director
Crescendo Biologics
20 sites in 4 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing CB307 in people with Advanced and/or Metastatic Solid Tumours, run by Crescendo Biologics Ltd. at 20 sites in 4 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 18 Nov 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 20 sites in Spain, Netherlands, United Kingdom, United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact MD (01223497140, Clinicaltrials@crescendobiologics.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of participants with treatment-related adverse events as assessed by CTCAE v5.0 (time frame: 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 study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04839991, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Nov 2023.