Phase 2 Study in 1L HNSCC of IT MK-1454 / MK-3475 IV vs MK-3475 IV

  • Research type

    Research Study

  • Full title

    A Phase 2 Study in First Line Metastatic or Unresectable, Recurrent Head and Neck Squamous Cell Carcinoma to Evaluate Intratumoral MK-1454 in Combination with IV Pembrolizumab vs IV Pembrolizumab Monotherapy

  • IRAS ID

    273839

  • Contact name

    Kevin Harrington

  • Contact email

    Kevin.Harrington@icr.ac.uk

  • Sponsor organisation

    Merck Sharp & Dohme Corp., a subsidiary of Merck &Co.,Inc

  • Eudract number

    2019-003060-42

  • Duration of Study in the UK

    3 years, 10 months, 19 days

  • Research summary

    MK-1454 is a stimulator of interferon genes (STING) agonist being studied for the treatment of Head and Neck Squamous Cell Carcinoma (HNSCC). MK-1454 is a cyclic dinucleotide STING agonist with activity across species. Data in animal models show that STING agonists delivered directly into tumours lead to complete tumour regression or significant growth inhibition. They can also induce immune-mediated clearance of non-injected tumours and therefore have potential as cancer therapeutics.

    Programmed cell death 1 (PD1) is a protein present on the surface of immune (attacking) cells which fight cancer. When immune cells meet cancer cells, PD1 becomes activated by programmed cell death ligands 1 and 2 (PDL1 and PDL2) which are proteins on the surface of cancer cells. The activated immune cells die thus stopping them from attacking the cancer. The study drug pembrolizumab has been developed to block PD1/PDL1 interaction, thereby increasing the immune attack on cancers.
    Pembrolizumab monotherapy is approved as first-line treatment of patients with metastatic or with unresectable, recurrent HNSCC for patients whose tumours express PD-L1 or in combination with chemotherapy regardless of PD-L1 expression. Clinical experience with MK-1454 in combination with pembrolizumab thus far indicates that this combination may provide a greater benefit as a cancer therapeutic in the HNSCC patient population.

    This multicentre phase 2 study will recruit approximately 200 male and female (18+) participants. The purpose of this study is to assess the efficacy, safety and tolerability of intratumourally administered MK-1454 in combination with intravenous pembrolizumab versus pembrolizumab monotherapy in HNSCC. Participants will be assigned randomly in 1:1 ratio to one of the two treatment arms.

    The study is funded by Merck Sharp & Dohme Limited and will take place at 6 study centres in the UK.

  • REC name

    London - Hampstead Research Ethics Committee

  • REC reference

    20/LO/0078

  • Date of REC Opinion

    16 Mar 2020

  • REC opinion

    Favourable Opinion