Pembrolizumab+lenvatinib,2nd-line+intervention for select solid tumors

• Research type

  Research Study

• Full title

  A Multicenter, Open-label Phase 2 Study of Lenvatinib (E7080/MK-7902) Plus Pembrolizumab (MK-3475) in Previously Treated Subjects with Selected Solid Tumors (LEAP-005)

• IRAS ID

  256948

• Contact name

  Donna Graham

• Contact email

  donna.graham8@nhs.net

• Sponsor organisation

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

• Eudract number

  2018-003747-37

• Duration of Study in the UK

  5 years, 5 months, 0 days

• Research summary

  The purpose of this study is to determine the safety and effectiveness of combining two study drugs, pembrolizumab and lenvatinib, in previously treated participants with triple negative breast, ovarian, gastric, colorectal, glioblastoma or biliary tract cancer.

  This study was designed as a proof-of-concept in single treatment group disease cohorts whose lines-of-treatment have no defined standard of care.

  Pembrolizumab has been developed to block PD1/PDL1 interaction, thereby increasing the immune attack on cancers. 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.

  Lenvatinib works by blocking proteins called Vascular Endothelial Growth Factors which cancer cells can use to help themselves grow. Studies have shown that lenvatinib can also help increase the immune attack on cancers.

  Early studies show that the combination of lenvatinib and pembrolizumab can help increase the immune response against cancers cells and may provide a new treatment option for patients.

  This phase II study will last approximately 5 years and will recruit approximately 180 male/female participants aged 18 years or over (female only for ovarian cancer). They will be grouped by their cancer type and will receive lenvatinib 20 mg orally once a day, plus pembrolizumab 200 mg intravenously every 3 weeks, for up to 2 years. Participants may continue lenvatinib treatment only, beyond 2 years, if they experience clinical benefit.

  The study is sponsored by Merck Sharp & Dohme Limited (MSD), and co-funded by MSD and Eisai. It will take place at 5 study centres in UK.

  Lay summary of study results: https://gbr01.safelinks.protection.outlook.com/?url=https%3A%2F%2Ftrack.pstmrk.it%2F3ts%2Fclinicaltrials.gov%252Fstudy%252FNCT03797326%253Fterm%253D7902-005%2526rank%253D1%2FNBTI%2FpdPAAQ%2FAQ%2F6787c948-a4b4-4a2c-a4ee-c30d009d9edb%2F1%2FFX1vz6kk0z&data=05%7C02%7Csurreyborders.rec%40hra.nhs.uk%7Ca9f65ccb9ef749edcabd08de0fe50405%7C8e1f0acad87d4f20939e36243d574267%7C0%7C0%7C638965673451682802%7CUnknown%7CTWFpbGZsb3d8eyJFbXB0eU1hcGkiOnRydWUsIlYiOiIwLjAuMDAwMCIsIlAiOiJXaW4zMiIsIkFOIjoiTWFpbCIsIldUIjoyfQ%3D%3D%7C0%7C%7C%7C&sdata=m%2FdDNV4L9wsRMaS0QlsHRrIjOkoDThKObvJjkFPrPOw%3D&reserved=0

  Has the registry been updated to include summary results?: Yes
  If yes - please enter the URL to summary results: https://gbr01.safelinks.protection.outlook.com/?url=https%3A%2F%2Ftrack.pstmrk.it%2F3ts%2Fclinicaltrials.gov%252Fstudy%252FNCT03797326%253Fterm%253D7902-005%2526rank%253D1%2526tab%253Dresults%2FNBTI%2FpdPAAQ%2FAQ%2F6787c948-a4b4-4a2c-a4ee-c30d009d9edb%2F2%2FvQ_Tub5hUH&data=05%7C02%7Csurreyborders.rec%40hra.nhs.uk%7Ca9f65ccb9ef749edcabd08de0fe50405%7C8e1f0acad87d4f20939e36243d574267%7C0%7C0%7C638965673451705436%7CUnknown%7CTWFpbGZsb3d8eyJFbXB0eU1hcGkiOnRydWUsIlYiOiIwLjAuMDAwMCIsIlAiOiJXaW4zMiIsIkFOIjoiTWFpbCIsIldUIjoyfQ%3D%3D%7C0%7C%7C%7C&sdata=sdQJL%2BG1ycJcZIqdrPgcRCFSTkUg4ZAb8W102LYEZxY%3D&reserved=0
  If no – why not?:
  Did you follow your dissemination plan submitted in the IRAS application form (Q A51)?: Yes
  If yes, describe or provide URLs to disseminated materials: PRESENTED AT:
  - IGCS LEAP-005 Ovarian
  - ASCO GI LEAP-005 Biliary
  - ASCO GI LEAP-005 Gastric
  - ASCO GI LEAP-005 CRC
  - ESGO LEAP-005 Ovarian enc
  - SABCS LEAP005 Breast
  - ASCO LEAP-005 Gastric enc
  - ASCO LEAP-005 Biliary enc
  - ASCO LEAP-005 CRC encore
  - WCGC LEAP-005 Pancr TiP
  - JSCO LEAP-005 Pan TiP enc
  - DGHO LEAP-005 Biliary enc
  - APPLE LEAP-005 Panc TiP e
  - APPLE LEAP-005 Biliary en

  PUBLICATION(S):
  - LEAP Program Study Design
  - SITC 005 LenvatinibTiP
  - ESMO LEAP005 AllCohort LB
  - IGCS LEAP-005 Ovarian
  - SABCS LEAP005 Breast
  - ASCO GI LEAP-005 Biliary
  - ASCO GI LEAP-005 Gastric
  - ASCO GI LEAP-005 CRC
  - ESGO LEAP-005 Ovarian enc
  - ASCO LEAP-005 Gastric enc
  - ASCO LEAP-005 Biliary enc
  - ASCO LEAP-005 CRC encore
  - WCGC LEAP-005 Pancr TiP
  - DGHO LEAP-005 Biliary enc
  - LEAP-005 Breast (IA5)
  - LEAP-005 Ovarian (IA5)
  - LEAP-005 GBM Cohort E (IA5) manuscript
  - LEAP-005 IA5 CRC (Cohort D) manuscript
  - LEAP-005 Gast, BTC, Panc (Cohorts C, F, G) mnscrpt
  - LEAP-005 GBM Cohort E (IA5) manuscript
  If pending, date when dissemination is expected:
  If no, explain why you didn't follow it:
  Have participants been informed of the results of the study?: Yes
  If yes, describe and/or provide URLs to materials shared and how they were shared: The Sponsor has shared the study results with the Investigators and the Investigators have been asked to share the results with the trial participants, as appropriate.
  The main Participant Information Sheet directs participants to the website: https://gbr01.safelinks.protection.outlook.com/?url=https%3A%2F%2Ftrack.pstmrk.it%2F3ts%2Fwww.ClinicalTrials.gov%2FNBTI%2FpdPAAQ%2FAQ%2F6787c948-a4b4-4a2c-a4ee-c30d009d9edb%2F3%2FfoKV2dNPMG&data=05%7C02%7Csurreyborders.rec%40hra.nhs.uk%7Ca9f65ccb9ef749edcabd08de0fe50405%7C8e1f0acad87d4f20939e36243d574267%7C0%7C0%7C638965673451722357%7CUnknown%7CTWFpbGZsb3d8eyJFbXB0eU1hcGkiOnRydWUsIlYiOiIwLjAuMDAwMCIsIlAiOiJXaW4zMiIsIkFOIjoiTWFpbCIsIldUIjoyfQ%3D%3D%7C0%7C%7C%7C&sdata=Zk8eYn424rnQ%2BQHw8MtHvJEyAYvI%2BuQf4wA4oKhBzqI%3D&reserved=0 where a summary of results for the study can be located.

  If pending, date when feedback is expected:
  If no, explain why they haven't:
  Have you enabled sharing of study data with others?: Yes
  If yes, describe or provide URLs to how it has been shared: MSD’s data sharing policy is publicly available at EngageZone: Data Sharing https://gbr01.safelinks.protection.outlook.com/?url=https%3A%2F%2Ftrack.pstmrk.it%2F3ts%2Fengagezone.msd.com%252Fds_documentation.php%2FNBTI%2FpdPAAQ%2FAQ%2F6787c948-a4b4-4a2c-a4ee-c30d009d9edb%2F4%2Fx0oTcp4vAx&data=05%7C02%7Csurreyborders.rec%40hra.nhs.uk%7Ca9f65ccb9ef749edcabd08de0fe50405%7C8e1f0acad87d4f20939e36243d574267%7C0%7C0%7C638965673451737400%7CUnknown%7CTWFpbGZsb3d8eyJFbXB0eU1hcGkiOnRydWUsIlYiOiIwLjAuMDAwMCIsIlAiOiJXaW4zMiIsIkFOIjoiTWFpbCIsIldUIjoyfQ%3D%3D%7C0%7C%7C%7C&sdata=jBf2zs3HALqM2P9r0SSjQWJS0SSA5NVEfpUQiPyhrKM%3D&reserved=0 (also referenced on the ClinicalTrials.gov page).
  If no, explain why sharing hasn't been enabled:
  Have you enabled sharing of tissue samples and associated data with others?: No
  If yes, describe or provide a URL:
  If no, explain why: At this time, the Sponsor has no specific plans to share the genomic data with anyone or on any public genomic databases. However, the Sponsor may share data as scientific journals are increasingly calling for transparency when publishing genomic results and this sometimes may include sharing anonymised genomic data on public genomic databases.

  Specimens will not be sold for commercial purposes; however, they may be used by the Sponsor or our collaborators to develop new drugs or diagnostics. While the Sponsor will not sell the samples, the Sponsor may need to share them with other parties who are working for or with the Sponsor.

  Only Sponsor designated researchers will have access to the samples.
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• REC name

  London - Surrey Borders Research Ethics Committee

• REC reference

  19/LO/0285

• Date of REC Opinion

  2 May 2019

• REC opinion

  Further Information Favourable Opinion