Study of CB307 in Patients With Advanced and/or Metastatic PSMA-positive Tumours.
Status
RECRUITING
Phase
PHASE1
Age
≥ 18 Years
Enrollments
70Conditions
Advanced and/or Metastatic Solid TumoursDrugs
CB307Summary
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.
Locations
1 location Found with status Recruiting
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
Study Plan
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:
CB307Description:
Tri-specific Humabodyu00ae targeting CD137, prostate specific membrane antigen and human serum albumin
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 KEYTRUDAu00ae (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:
CB307Description:
Tri-specific Humabodyu00ae 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
Number of participants with treatment-related adverse events with CB307 in combination with pembrolizumab as assessed by CTCAE v5.0
Secondary Outcome Measures
To evaluate clinical efficacy measured as progression-free survival according to RECIST v.1.1 or PCWG3
To evaluate clinical efficacy and duration of response by radiographic progression free survival (rPFS)
To evaluate anti-tumor response according to RECIST v.1.1 or PCWG3
To measure how the body processes CB307 in the body over time
Pharmacokinetic of CB307 T1/2
Pharmacokinetic of CB307 Tmax
To measure Tumour Immune response
Relationship of CB307 to anti tumour response
Timeline
Last Updated
November 18, 2023Start Date
April 9, 2021Today
January 23, 2025Completion Date ( Estimated )
September 25, 2024
Sponsors of this trial
Lead Sponsor
Crescendo Biologics Ltd.
RECRUITING 
21 - 64 Years