A Phase II Study of Pembrolizumab in Subjects with Gastric Cancer

  • Research type

    Research Study

  • Full title

    A Phase II Clinical Trial of Pembrolizumab as Monotherapy and in Combination with Cisplatin+5-Fluorouracil in Subjects with Recurrent or Metastatic Gastric or Gastroesophageal Junction Adenocarcinoma.

  • IRAS ID

    178245

  • Contact name

    Prof. Daniel Hochhauser

  • Contact email

    d.hochhauser@ucl.ac.uk

  • Sponsor organisation

    Merck Sharp & Dohme LLC

  • Eudract number

    2014-003574-16

  • Duration of Study in the UK

    2 years, 11 months, 19 days

  • Research summary

    Summary of Research
    Cancer is one of the most common fatal disease globally and solid tumours constitute an important part of these cancers. Pembrolizumab (MK-3475) has shown promising results in clinical trial subjects with gastric cancer where it has generally been well tolerated.

    Programmed cell death 1 (PD1) is a protein present on the surface of immune cells which fight cancer. When immune cells encounter cancer cells PD1 becomes activated by programmed cell death ligand 1 (PDL1) and PDL2 which are proteins on the surface of cancer cells. The activated immune cells become exhausted or die thus stopping them from attacking the cancer. The study drug pembrolizumab (MK-3475) has been developed to block PD1/PDL1 interaction, thereby increasing the immune attack on cancers.

    The purpose of this study is to determine the safety, tolerability and effectiveness of pembrolizumab (MK3475) administered at 200 mg dosing every 3 weeks alone or in combination with cisplatin and 5-fluorouracil in subjects with gastric cancer. This study either will recruit males and females who are at least 18 years of age and have advanced gastric or gastroesophageal junction adenocarcinoma

    The study will last 36 months. The patients will be divided into three groups. The study will begin by enrolling subjects in groups 1 and 2 concurrently. Group 1 will enroll subjects receiving pembrolizumab as a third line monotherapy (about 180 subjects) whose disease has progressed after taking two previous anti-cancer treatments. They will receive pembrolizumab (MK3475) every 3 weeks regardless of PD-L1 status until the first 40 subjects are allocated.

    The second group will enroll approximately 40 subjects which will receive pembrolizumab (MK3475) as first line therapy in combination with Cisplatin plus 5-Fluorouracil if they have not received any previous anti-cancer treatment regardless of PD-L1 status.
    Enrollment into group 3 will commence once enrollment of group 2 is complete. Approximately 50 subjects with PD-L1 positive expression who had not received any previous anticancer treatment will be enrolled into the group and will receive pembrolizumab (MK3475).

    Subjects will be monitored regularly for safety and clinical and/or radiographic evidence of disease progression. Subjects with both positive and non-detectable PD-L1 expressions on solid tumours will be recruited.

    Approximately 270 subjects of at least 18 years of age will be enrolled in the study which will take place at 1 centre in the UK.

    The study is funded by Merck Sharp & Dohme Limited.

    Summary of Results
    https://eur03.safelinks.protection.outlook.com/?url=https%3A%2F%2Fu2790089.ct.sendgrid.net%2Fls%2Fclick%3Fupn%3DXv3JSvJ-2B3M71ppf7N9agbRehJ-2Fi4xyo44sEgJVCl5Bdj8o1FpylFwbn362DUDJ-2FzfCAHSkSTFrjTQ3ThyXgf7QN43YIPF0gOTI8JP9z-2F8wubqdtL-2Fsu6RfDJV0eXVfKl_ipY_E1aO2-2BZlVOSJJV-2FajQqskegTd6IRomHYTi-2Fbt8SH3YKP9ofayHGnVfJ6iO9eI-2FB3ZIwEXPRlGmQVAEbp8u7TnrtGxwnNst1Rp4A-2Bo7JDvOho1VZx0Odhqwm53Zl3sdjmyyeJLDeEI-2F9Rzvqs7Yz8JGGImHsV4HAfo1mKC0fywM-2BlnhW-2FYvWGQPw6tfHmokMg1vBAbTUGRMA9jQyHiX2GKA-3D-3D&data=05%7C01%7Capprovals%40hra.nhs.uk%7C92d5577a5cf24c539f3208da9731206b%7C8e1f0acad87d4f20939e36243d574267%7C0%7C0%7C637988534522732134%7CUnknown%7CTWFpbGZsb3d8eyJWIjoiMC4wLjAwMDAiLCJQIjoiV2luMzIiLCJBTiI6Ik1haWwiLCJXVCI6Mn0%3D%7C3000%7C%7C%7C&sdata=tXM49xQ1K%2Fy2LdevjUEgpJ884%2BgBkBAIzlitkK6KHHE%3D&reserved=0

  • REC name

    East of England - Cambridgeshire and Hertfordshire Research Ethics Committee

  • REC reference

    15/EE/0234

  • Date of REC Opinion

    8 Oct 2015

  • REC opinion

    Further Information Favourable Opinion