Clinical trial NCT04839991: Study of CB307 in Patients With Advanced and/or Metastatic PSMA-positive Tumours.
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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
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®
Lead sponsor: Crescendo Biologics Ltd.
Sponsor class: INDUSTRY
First posted: 2021-04-09
Enrollment: 70
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Intervention model description: Initial dose escalation cohorts followed by dose expansion cohorts consisting of 2 arms, monotherapy and combination therapy cohorts .
Primary purpose: TREATMENT

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

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.

Eligibility criteria: 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

Primary outcomes:
measure: Number of participants with treatment-related adverse events as assessed by CTCAE v5.0
timeFrame: The nature and frequency of any DLTs during the DLT-monitoring period assessed based on NCI CTCAE v5.0. up to 20 months duration.
measure: Number of participants with treatment-related adverse events with CB307 in combination with pembrolizumab as assessed by CTCAE v5.0
timeFrame: 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:
measure: To evaluate clinical efficacy measured as progression-free survival according to RECIST v.1.1 or PCWG3
timeFrame: 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
measure: To evaluate clinical efficacy and duration of response by radiographic progression free survival (rPFS)
timeFrame: radiographic progression free survival up to 20 months duration;
measure: To evaluate anti-tumor response according to RECIST v.1.1 or PCWG3
timeFrame: anti-tumor response according to RECIST v1.1 or PCWG3 up to 20 months duration;
measure: To measure how the body processes CB307 in the body over time
timeFrame: PK parameters of CB307: data collected at time point 0 at each dosing period up to 20 months duration.
measure: Pharmacokinetic of CB307 T1/2
timeFrame: Data collected up to 20 months duration.
measure: Pharmacokinetic of CB307 Tmax
timeFrame: Data collected up to 20 months duration.
measure: To measure Tumour Immune response
timeFrame: Tumor response per RECIST ver 1.1 up to 20 months duration
measure: Relationship of CB307 to anti tumour response
timeFrame: PSA response defined as a >50% decrease in PSA up to 20 months duration
Other outcomes:
Locations:
city: Seattle
country: United States
facility: University of Washington
state: Washington
city: Amsterdam
country: Netherlands
facility: Antoni van Leeuwenhoek
state: Noord-Holland
city: Amsterdam
country: Netherlands
facility: VUMC Research B.V
state: Noord-Holland
city: Groningen
country: Netherlands
facility: University Medical Center Groningen,
city: Rotterdam
country: Netherlands
facility: Erasmus University Medical Center Rotterdam
city: Utrecht
country: Netherlands
facility: UMC Utrecht Cancer Center
city: Pamplona
country: Spain
facility: Clinica Universidad de Navarra
state: Navarra
city: Barcelona
country: Spain
facility: hospital clinic de Barcelona
city: Barcelona
country: Spain
facility: hospital de la Sanat Creu i Sant Pau
city: Madrid
country: Spain
facility: Clinica Universidad de Navarra
city: Madrid
country: Spain
facility: HU Fundacion Jimenez Diaz
city: Madrid
country: Spain
facility: Hospital Universitario 12 de Octubre
city: Madrid
country: Spain
facility: Hospital Universitario HM Sanchinarro
city: Madrid
country: Spain
facility: NEXT Oncology Hospital Quironsalud Madrid
city: Murcia
country: Spain
facility: HU Virgen de la Arrixaca
city: Sevilla
country: Spain
facility: HU Virgen del Rocio - PPDS
city: Manchester
country: United Kingdom
facility: The Christie NHS Foundation Trust
state: Greater Manchester
city: London
country: United Kingdom
facility: Royal Marsden Hospital
state: Surrey
city: London
country: United Kingdom
facility: University College London Hospitals NHS Foundation Trust
city: London
country: United Kingdom
facility: Sarah Cannon Research Institute, UK
Study officials:
affiliation: Crescendo Biologics
name: K Hashimoto
role: STUDY_DIRECTOR
References: