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

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

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.

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