NCT02509507

Trial to Evaluate the Safety of Talimogene Laherparepvec Injected Into Tumors Alone and in Combination With Systemic Pembrolizumab MK-3475-611/Keynote-611

A Phase 1b/2, Multicenter, Open-label, Basket Trial to Evaluate the Safety of Talimogene Laherparepvec Injected Into Liver Tumors Alone and in Combination With Systemic Pembrolizumab in Phase 1b and to Evaluate the Efficacy and Safety of Intratumoral Talimogene Laherparepvec in Combination With Systemic Pembrolizumab to Treat Subjects With Advanced Solid Tumors in Phase 2 (MASTERKEY-318)

• Status: Completed
• Phase: Phase 1 / Phase 2
• Study type: Interventional
• Enrollment: 127 (actual)
• Sponsor: Amgen · Industry
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

This is a phase 1b/2, multicenter, open-label, basket trial to evaluate the safety of talimogene laherparepvec injected intrahepatically into liver tumors alone and in combination with systemic intravenous (IV) administration of pembrolizumab, in subjects with non-hepatocellular carcinoma (HCC) liver metastases from breast adenocarcinoma (BC), colorectal adenocarcinoma (CRC), gastroesophageal cancer (GEC), melanoma, non-small cell lung cancer (NSCLC), clear cell renal cell carcinoma (RCC) in Part 1 Group A, and subjects with HCC with and without viral hepatitis in Part 1 Group B (viral hepatitis is only applicable in combination setting), and to evaluate the efficacy and safety of intratumoral talimogene laherparepvec in combination with systemic pembrolizumab in subjects with advanced triple negative breast cancer (TNBC), hormone receptor positive breast cancer, CRC, cutaneous squamous cell carcinoma (CSCC), and basal cell carcinoma (BCC) in Part 2 Group A and subjects with HCC with and without viral hepatitis in Part 2 Group B. The objective of Part 1 is to evaluate the safety of intrahepatic injection of talimogene laherparepvec into liver tumors alone and in combination with systemically administered pembrolizumab for the non-HCC (Group A) and HCC (Group B) cohorts separately. Part 2 consists of 2-stage design to evaluate the efficacy and safety of talimogene laherparepvec in combination with systemic pembrolizumab. Efficacy and safety will be evaluated in each of the five non-HCC tumor types from Group A separately. Similarly, the efficacy and safety of the combination treatment will be determined for Group B HCC subjects. As of Protocol Amendment 6 (dated 26 October 2021), intrahepatic injections of talimogene laherparepvec and liver biopsies are no longer performed in this study. Enrollment for this study has stopped.

Conditions

• Hepatocellular Carcinoma
• Liver Metastases
• Cutaneous or Subcutaneous Lymph Node
• Liver Tumors

Interventions

Type	Name	Description
DRUG	Talimogene Laherparepvec	Talimogene laherparepvec (T-VEC) administered by intralesional injection into liver tumors, with ultrasound/computed tomography (US/CT) guidance. Part 1: initial dose of T-VEC is 10\^6 plaque forming unit (PFU)/mL up to 4mL in Cohorts 1 \& 2, up to 8mL in Cohorts 3 \& 4 of the Group A \& Group B. The 1st cycle of T-VEC will be 21 (+3) days (from the 1st dose at 10\^6 PFU/mL to the 2nd dose at 10\^7 or 10\^8 PFU/mL). Subsequent cycles of T-VEC will be 21 (±3) days. Max. volume of T-VEC administered at any dose is 4mL (Cohorts 1, 2, 5, and 6) or 8mL (Cohorts 3 \& 4) for any individual lesion or for all lesions combined. Part 2: Initial dose of T-VEC is 10\^6 PFU/mL followed by subsequent T-VEC doses at a concentration of 10\^8 PFU/mL. T-VEC volume is up to 8mL based on the size of the inejected lesions. NOTE: as of Protocol Amendment 6 \[dated 26 October 2021\], intrahepatic injections of talimogene laherparepvec and liver biopsies are no longer performed in this study.
DRUG	Pembrolizumab	Pembrolizumab is a non-Amgen Investigational product that is manufactured by Merck. Pembrolizumab will be labeled, packaged, and distributed by Amgen (or designee) using Amgen (or designee) clinical study drug distribution procedures. Pembrolizumab is supplied as pembrolizumab 100 mg/4 mL vials (25 mg/mL) solution for IV infusion. The trial treatment will consist of a total dose of 200mg administered intravenously every 3 weeks (day 1 of each cycle) for up to 35 cycles.

Timeline

• Start date: 2016-02-05
• Primary completion: 2022-02-14
• Completion: 2023-07-11
• First posted: 2015-07-28
• Last updated: 2024-08-06
• Results posted: 2022-12-30

Locations

32 sites across 9 countries: United States, Australia, Austria, Belgium, Germany, Poland, South Korea, Spain, Switzerland