First in Human study for the evaluation of SAR43459 with cemiplimab
Research type
Research Study
Full title
A Phase 1/1b First-in-human Dose Escalation and Expansion Study for the Evaluation of Safety, Pharmacokinetics, Pharmacodynamics, and Anti-tumor Activity of SAR439459 Administered Intravenously as Monotherapy and in Combination with Cemiplimab in Adult Patients with Advanced Solid Tumors
IRAS ID
253029
Contact name
Jeff Evans
Contact email
Sponsor organisation
Sanofi-aventis recherche & développement
Eudract number
2018-001113-32
Duration of Study in the UK
2 years, 7 months, 11 days
Research summary
Summary of Research
The TCD14678 study in the UK is looking at the treatment of patients with either of the following solid tumors: Advanced unresectable or metastatic melanoma who failed after one prior therapy based on anti-PD-1 or anti-PD-L1 or colorectal adenocarcinoma with mesenchymal molecular subtype. The protocol includes a urothelial cancer arm, but the UK will not recruit to this arm.
The TCD14678 study will last around 2 years and is planned to include approximately 225 study participants, about 8 of whom will be from the UK. The UK will take part in Part 2B of the study. Patients will receive SAR439459 in combination with cemiplimab.
SAR439459, is an experimental drug (not approved yet by health authority) being tested for the first time in humans to treat adult patients with advanced solid tumours. SAR439459 is a monoclonal antibody called anti- TGFβ designed to bind and to block the effects of a molecule called “transforming growth factor beta (TGFβ)”. TGFβ has many effects in the body and is often over-produced in cancers: Research has shown that TGFβ could help tumours grow, spread, and avoid being attacked by the immune system. SAR439459 may help treat cancer by blocking TGFβ's cancer growth promoting effects.
Cemiplimab has recently been approved in the United States for the treatment of cutaneous squamous cell carcinoma. It is a human monoclonal anti-PD-1 antibody that works with the body’s immune system to treat cancer.
The purpose of this study is to assess if the combination of both drugs may enhance antitumoral activity by improving the immune responses.
The study is planned to take place in 2 NHS centres in Scotland and Wales. Patients who meet the inclusion/exclusion criteria will attend the hospital research site and will receive study treatment in 3 weekly cycles, until their cancer worsens or until unacceptable side effects occur.Summary of Results
The study was discontinued due to lack of clear efficacy in relatively homogenous independent population cohorts, and in the context of bleeding risk leading to some fatal outcomes, particularly in patients to the HCC (hepatocellular carcinoma) cohort.REC name
West of Scotland REC 1
REC reference
19/WS/0085
Date of REC Opinion
27 Aug 2019
REC opinion
Further Information Favourable Opinion