Study of CB307 in patients with advanced and/or growing cancer
Research type
Research Study
Full 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 (POTENTIA).
IRAS ID
279624
Contact name
Johann de Bono
Contact email
Sponsor organisation
Crescendo Biologics Limited
Eudract number
2019-004584-46
Duration of Study in the UK
3 years, 0 months, 0 days
Research summary
Summary of Research
Cancer is the leading cause of death worldwide despite several new agents providing survival benefits to patients. Many cancer indications have a poor prognosis, and the management of most advanced solid tumours remains challenging because of the high rate of tumour recurrence or the development of distant secondary growths.CB307 is an investigational product being developed by Crescendo Biologics Ltd. for the treatment of solid tumours with expression of a protein called prostate specific membrane antigen (PSMA).
This is a Phase I, First in Human study. Up to 50 participants, men and woman over the age of 18 with PSMA+ solid tumours that are not responsive to standard of care will take part at approximately 10 study sites in the United Kingdom and Europe.
All participants that qualify for the study will receive CB307 for the entire duration of the study treatment period and will continue the treatment period until loss of clinical benefit, intolerable toxicity is observed, withdrawal of consent or the study is stopped, whichever comes first.The study Treatment Period consists of 2 parts; Dose Escalation Phase (Part 1) and Cohort Expansion Phase (Part 2).
Part 1 will assess escalating doses of CB307 in approximately 30 participants in order to find the most effective dose of the study drug.
Part 2 will assess the safety and how well the most effective dose of CB307 (as determined by Part 1) works in approximately 6-30 participants
The overall purpose of this study is to assess the safety, tolerability and most effective dose of the study drug CB307 when it is administered over 60 minutes once per week intravenously (through the vein).
Summary of Results
Results – overall safety of patients on study
• Safety results of the study showed that CB307, the investigational study drug, was well tolerated when administered to patients either on its own or in combination with another marketed drug, pembrolizumab.
• No serious or high-level Adverse Events (AE’s - Grade 4) were seen or AEs which lead to the death of a patient were reported in the study.
• After the drug was given to patients there were no clear dose-dependent toxicities observed in the study.
• Only 2 patients had low grade dose toxicities (DLT) events of unusually higher levels of transaminase in the blood (hypertransaminasemia) which were quickly resolved to normal
• Administering both drugs together showed no new AEs when compared with giving CB307 alone.
Results – Drug interactions on the body (Pharmacokinetics-PK) PK Part 1 – CB307 Following administration of CB307 the patients blood serum concentration showed a rapid absorption of CB307 into serum followed by a reduction, clearing the drug from the body quickly. This was seen at all dose levels given up to a maximum CB307 drug dose of 800 mg with a trend for increasing half-life with increasing dose level. These PK characteristics of CB307 dosing were the same when multiple doses of CB307 were given to the same patient every seven days.
PK Part 2 – CB307 & Pembrolizumab
When patients were given CB307 and pembrolizumab at the same time (30 minutes between each administration to the patient) the PK profile was similar in patients who received 800 mg CB307 alone. The PK characteristics were generally similar to those observed in Part 1.
Results - Efficacy
The best overall clinical response in patients (anti-tumour efficacy) was seen when CB307 (800mg) was given to patients. A partial response was seen in 2 patients. Additionally, stable disease, or no decline in clinical benefit was also seen in 7 patients. The clinical benefit rate of administering CB307 was observed in at total of 9 patients.
However, there was no real enhancement seen in anti-tumour response observed when CB307 was administered with pembrolizumab compared with CB307 on its own.REC name
London - Chelsea Research Ethics Committee
REC reference
20/LO/1287
Date of REC Opinion
26 Jan 2021
REC opinion
Further Information Favourable Opinion