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

Study Overview
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Brief Summary
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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
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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.

Official Title
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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

Conditions
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Advanced and/or Metastatic Solid Tumours

Intervention / Treatment
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* Drug: CB307


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 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 Exclusion Criteria: 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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Interventional Model Description: Initial dose escalation cohorts followed by dose expansion cohorts consisting of 2 arms, monotherapy and combination therapy cohorts .
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Multi center open label Dose Escalation followed by Cohort Expansion: Part 2A<br>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<br>* Tri-specific Humabody® targeting CD137, prostate specific membrane antigen and human serum albumin<br>|
| Experimental: Multi center open label Dose Escalation followed by Combination Cohort Expansion : Part 2B<br>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<br>* Tri-specific Humabody® targeting CD137, prostate specific membrane antigen and human serum albumin<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | 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. | 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. | 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 | 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 | 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 | 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 | 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 | PSA response defined as a >50% decrease in PSA up to 20 months duration | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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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®