Phase 1 study of SYD985 + niraparib in patients with solid tumours

  • Research type

    Research Study

  • Full title

    A two-part phase I study with the antibody-drug conjugate SYD985 in combination with niraparib to evaluate safety, pharmacokinetics and efficacy in patients with HER2-expressing locally advanced or metastatic solid tumours

  • IRAS ID

    276977

  • Contact name

    Udai Banerji

  • Contact email

    udai.Banerji@icr.ac.uk

  • Sponsor organisation

    Byondis B.V.

  • Eudract number

    2019-002937-12

  • Clinicaltrials.gov Identifier

    NCT04235101

  • Duration of Study in the UK

    2 years, 8 months, 19 days

  • Research summary

    Research Summary

    This study aims to assess the activity of an experimental medicinal drug, SYD985, in combination with the approved drug, niraparib, in adult patients with advanced or metastatic solid cancers, who have progressed on standard therapy or for whom no standard therapy exists, and whose cancer expresses the HER2 protein.

    SYD985 is an antibody-drug conjugate. It consists of a toxin linked to an antibody and is designed to bind to a protein (HER2 protein) that exists in certain types of cancer, and release the toxin into the cancer cell.

    Niraparib works by stopping a particular protein (PARP) from repairing cancer cell DNA, which results in tumour cell death.

    This study is split into two parts, a dose escalation part (around 30 patients) followed by a dose expansion part (up to approximately 90 patients). The aim of the dose escalation part is to find a safe dose, by determining the Maximum Tolerated Dose, and establish the recommended combined SYD985/niraparib regimen for the next part of the study. The dose expansion part of the study aims to evaluate the anti-tumour activity and to further confirm the safety of SYD985/niraparib.

    This study and is planned to run in approximately 25 hospitals across Europe, including 3 study hospitals in the UK. All participants will receive a combined SYD985/niraparib regimen in the form of a SYD985 infusion once every three weeks and a niraparib tablet taken orally once daily for either 1, 2 or 3 weeks as instructed by the study doctor. Each three week treatment period will be called a "cycle".

    The study consists of a screening period of up to 28 days, a treatment period lasting until disease progression or unacceptable toxicity occurs and a follow-up period lasting until the end of the study or until patient death, loss to follow-up or consent withdrawal.

    This study is being sponsored by Synthon Biopharmaceuticals BV.

    Summary of Results

    The primary purpose of the study was to assess the safety and activity of a new medicinal drug called SYD985 in combination with an approved drug called niraparib (Zejula®). Niraparib has been approved by the regulatory authority in the UK, the Medicines and Healthcare Products Regulatory Agency (MHRA), to treat certain types of cancer. This study investigated different dose levels and evaluated the safety of the SYD985/niraparib combination in patients with cancer. A total of 32 patients, including 9 from the United Kingdom, have been treated in this study. In total, up to 8 different combination dose levels have been tested in the study. Most patients (68%) discontinued the study because of progression of their cancer, four (13%) because of adverse effects. The overall safety profile was similar to what was previously known for individual treatments combined in this study. Although the combination treatment was effective in about one third of the treated patients, no added value was observed with combination treatment compared to what was known and expected for each of the 2 individual treatments. Therefore, the study was prematurely stopped and did not proceed to the planned second part in which larger groups of patients with specific cancer types were to be treated.

  • REC name

    East of Scotland Research Ethics Service REC 2

  • REC reference

    20/ES/0034

  • Date of REC Opinion

    17 Apr 2020

  • REC opinion

    Further Information Favourable Opinion