Advanced and/or Metastatic Solid Tumours
Conditions
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®
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.
Interventions
DRUGCB307
Tri-specific Humabody® targeting CD137, prostate specific membrane antigen and human serum albumin
Sponsors
Crescendo Biologics Ltd.
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Masking description
Open Label multi center non randomised study.
Intervention model description
Initial dose escalation cohorts followed by dose expansion cohorts consisting of 2 arms, monotherapy and combination therapy cohorts .
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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) |
| Number of participants with treatment-related adverse events with CB307 in combination with pembrolizumab as assessed by CTCAE v5.0 | 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 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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 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 |
| 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 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 |
| 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 evaluate clinical efficacy and duration of response by radiographic progression free survival (rPFS) | radiographic progression free survival up to 20 months duration; | To measure how well the treatment succeeds in producing the desired effect. |
Countries
Netherlands, Spain, United Kingdom, United States
Contacts
Primary ContactMD
Backup ContactMD
Outcome results
None listed