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Trial to Evaluate the Safety ofTalimogene Laherparepvec Injected Into Liver Tumors Alone and in Combination With Systemic Pembrolizumab (MASTERKEY-318)

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ClinicalTrials.gov Identifier: NCT02509507
Recruitment Status : Recruiting
First Posted : July 28, 2015
Last Update Posted : April 27, 2018
Sponsor:
Collaborator:
Merck Sharp & Dohme Corp.
Information provided by (Responsible Party):
Amgen

Brief Summary:
This is a phase 1b/2, multicenter, open-label trial to evaluate the safety of talimogene laherparepvec injected intrahepatically into liver tumors with known progression alone and in combination with systemic IV administration of pembrolizumab, in subjects with non-HCC liver metastases from BC, CRC, GEC, melanoma, NSCLC, RCC, and subjects with HCC. The study consists of 2 parts and 2 groups, and Part 2 includes 2 stages. 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 six 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.

Condition or disease Intervention/treatment Phase
Hepatocellular Carcinoma Liver Metastases Drug: Talimogene Laherparepvec Drug: Pembrolizumab Phase 1

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 244 participants
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 1b/2, Multicenter, Open-label Trial to Evaluate the Safety of Talimogene Laherparepvec Injected Into Liver Tumors Alone and in Combination With Systemic Pembrolizumab (MASTERKEY-318)
Actual Study Start Date : February 5, 2016
Estimated Primary Completion Date : October 22, 2021
Estimated Study Completion Date : March 31, 2023

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Liver Cancer

Arm Intervention/treatment
Experimental: Phase 1b Talimogene Laherparepvec
Talimogene Laherparepvec
Drug: Talimogene Laherparepvec
Talimogene laherparepvec (T-VEC) administered by intralesional injection into liver tumors, with US/CT guidance. Part 1: initial dose of T-VEC is 10^6 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: concentration of T-VEC (10^7 or 10^8 PFU/mL) to be administered will be determined on completion of combination treatment, in Part 1. T-VEC will be used at a max. volume of 4 mL (or up to 8mL if determined safe in monotherapy on opening Part 2). If 8ml safety is not established on opening Part 2, only newly enrolled subjects in Part 2 will receive up to a max. of 8mL if safety of administering 8mL in Part 1 is established

Experimental: Phase 1b Talimogene Laherparepvec + Pembrolizumab
Combination treatment of Talimogene Laherparepvec and Pembrolizumab
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 3 cycles.




Primary Outcome Measures :
  1. Subject incidence DLTs separately in Group A and B observed in monotherapy and combination [ Time Frame: 3 year ]
  2. To evaluate in Part 2 ORR per irRC‑RECIST separately by tumor type (BC, CRC, GEC, melanoma, NSCLC, RCC, and HCC) [ Time Frame: 2 years ]

Secondary Outcome Measures :
  1. Safety: Subject incidence of treatment-related and treatment-emergent adverse events in monotherapy and combination of Part 1 and each separate tumour type in Part 2 [ Time Frame: 5 years ]
  2. Safety: To estimate the incidence of detectable talimogene laherparepvec DNA in blood and urine [ Time Frame: 5 years ]
  3. Safety: To estimate the incidence of clearance of talimogene laherparepvec DNA from blood and urine [ Time Frame: 5 years ]
  4. Safety: To estimate the rate of detection and incidence of talimogene laherparepvec DNA and virus at the surface of talimogene laherparepvec injection site, the exterior of the occlusive dressing, and the oral mucosa [ Time Frame: 5 years ]
  5. Safety: To estimate the incidence of talimogene laherparepvec DNA detection in lesions suspected to be herpetic in origin [ Time Frame: 5 years ]

Other Outcome Measures:
  1. Efficacy: Objective response rate (ORR) [ Time Frame: 5 years ]
    To evaluate the efficacy of intrahepatic injection of talimogene laherparepvec in the overall population and by tumor type (non-hepatocellular carcinoma and hepatocellular carcinoma)

  2. Efficacy: Best overall response (BOR) [ Time Frame: 5 years ]
    To evaluate the efficacy of intrahepatic injection of talimogene laherparepvec in the overall population and by tumor type (non-hepatocellular carcinoma and hepatocellular carcinoma)

  3. Efficacy: Durable response rate (DRR) [ Time Frame: 5 years ]
    To evaluate the efficacy of intrahepatic injection of talimogene laherparepvec in the overall population and by tumor type (non-hepatocellular carcinoma and hepatocellular carcinoma)

  4. Efficacy: Duration of response (DOR) [ Time Frame: 5 years ]
    To evaluate the efficacy of intrahepatic injection of talimogene laherparepvec in the overall population and by tumor type (non-hepatocellular carcinoma and hepatocellular carcinoma)

  5. Efficacy: Response in injected and uninjected lesions [ Time Frame: 5 years ]
    To evaluate the efficacy of intrahepatic injection of talimogene laherparepvec in the overall population and by tumor type (non-hepatocellular carcinoma and hepatocellular carcinoma)

  6. Efficacy: Disease control rate (DCR) [ Time Frame: 5 years ]
    To evaluate the efficacy of intrahepatic injection of talimogene laherparepvec in the overall population and by tumor type (non-hepatocellular carcinoma and hepatocellular carcinoma)

  7. Efficacy Progression-free survival (PFS) [ Time Frame: 5 years ]
    To evaluate the efficacy of intrahepatic injection of talimogene laherparepvec in the overall population and by tumor type (non-hepatocellular carcinoma and hepatocellular carcinoma)

  8. Efficacy: Overall survival (OS) [ Time Frame: 5 years ]
    To evaluate the efficacy of intrahepatic injection of talimogene laherparepvec in the overall population and by tumor type (non-hepatocellular carcinoma and hepatocellular carcinoma)

  9. Exploratory: To assess blood and tumor tissue [ Time Frame: 5 years ]
    To evaluate changes in tumor inflammation markers including PD-L1, CD8 and interferon gamma (IFNg) gene expression

  10. Exploratory: Incidence of anti-pembrolizumab antibodies [ Time Frame: 5 years ]
  11. Exploratory: Pharmacokinetics of pembrolizumab [ Time Frame: 5 years ]


Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Subjects must have histologically or cytologically confirmed breast adenocarcinoma, colorectal adenocarcinoma, gastroesophageal cancer (adenocarcinoma or squamous cell carcinoma), melanoma, non-small cell lung cancer, or clear cell renal cell carcinoma with liver metastases or hepatocellular carcinoma with known disease progression.
  • Part 2 Group B is restricted to HCC (fibrolamellar and mixed hepatocellular/cholangiocarcinoma subtypes are not eligible).
  • Non-hepatocellular carcinoma subjects must have received at least 1 prior standard of care systemic anti-cancer therapy for their locally advanced or metastatic disease.
  • For the combination cohorts (cohorts 5 and 6 in Part 1) and Part 2, subjects with metastatic melanoma or NSCLC do not need to have received prior therapy
  • Subjects must have measurable liver tumors that are suitable for injection.
  • Eastern Cooperative Oncology Group performance status must be 0 or 1, and life expectancy should be approximately 5 months or more.
  • Adequate hematological, renal, hepatic and coagulation function is required.
  • Child-Pugh score must be A to B7.

Exclusion Criteria:

  • Subjects must not be candidates for hepatic surgery or locoregional therapy of liver tumors with curative intent or planned systemic anti-cancer therapy, with the exception of immunotherapy in the combination cohorts (Cohorts 5 and 6 in Part 1 and all subjects in Part 2).
  • Liver tumors must not be estimated to invade approximately more than one-third of the liver.
  • Liver tumor-directed therapy, hepatic surgery, antibody-based therapy, or immunotherapy must not have been performed < 28 days, chemotherapy < 21 days, and targeted small molecule therapy or hormonal therapy < 14 days prior to enrollment.
  • Subjects must either have no central nervous system (CNS) metastasis, or carcinomatous meningitis, or if CNS metastasis is present, must have stable treated cerebral metastases from BC, NSCLC, RCC, CRC, GEC, or melanoma. Subjects must not have symptomatic auto-immune disease or be immunosuppressed.
  • They must not have a history of solid organ transplantation.
  • For non-HCC, there must not be acute or chronic hepatitis B virus (HBV) or hepatitis C virus (HCV) infection.
  • For HCC with prior hepatitis B and/or C infection, HBV and/or HCV viral load by real-time polymerase chain reaction (qPCR) must be undetectable, and they must not have had recent treatment within 12 weeks for HBV or HCV with certain antiviral medications.
  • There should be no macroscopic intravascular invasion of tumors into the main portal vein, hepatic vein, or vena cava.
  • Subjects must not: have active herpetic skin lesions or prior complications of herpetic infection (eg, herpetic keratitis or encephalitis); require treatment with an antiherpetic drug; have received live-virus vaccination within 30 days of planned treatment start; have previous therapy with talimogene laherparepvec, oncolyic viruses, or tumor vaccine.
  • They must not require concomitant treatment with warfarin.
  • Subjects in the combination treatment cohort must not have: a history or evidence of psychiatric, substance abuse, or any other clinically significant disorder; toxic effects of the most recent prior chemotherapy not resolved to grade 1 or less (except alopecia); or expected other cancer therapy while on study with the exception of local radiation to the site of bone or other metastasis for palliative treatment.
  • Male subjects of reproductive potential in the combination treatment must be willing to use acceptable methods of effective contraception during treatment and through 4 months after the last dose of pembrolizumab.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02509507


Contacts
Contact: Amgen Call Center 866-572-6436 medinfo@amgen.com

Locations
United States, California
Research Site Recruiting
Los Angeles, California, United States, 90095
United States, Kentucky
Research Site Recruiting
Louisville, Kentucky, United States, 40202
United States, Missouri
Research Site Completed
Saint Louis, Missouri, United States, 63110
United States, New Jersey
Research Site Completed
New Brunswick, New Jersey, United States, 08903
Belgium
Research Site Recruiting
Edegem, Belgium, 2650
Research Site Recruiting
Gent, Belgium, 9000
Spain
Research Site Recruiting
Barcelona, Cataluña, Spain, 08036
Research Site Recruiting
Madrid, Spain, 28009
Research Site Recruiting
Madrid, Spain, 28050
Switzerland
Research Site Recruiting
Geneva 14, Switzerland, 1211
Research Site Recruiting
Lausanne, Switzerland, 1011
Research Site Recruiting
Winterthur, Switzerland, 8401
Sponsors and Collaborators
Amgen
Merck Sharp & Dohme Corp.
Investigators
Study Director: MD Amgen

Additional Information:
Responsible Party: Amgen
ClinicalTrials.gov Identifier: NCT02509507     History of Changes
Other Study ID Numbers: 20140318
2014-005386-67 ( EudraCT Number )
First Posted: July 28, 2015    Key Record Dates
Last Update Posted: April 27, 2018
Last Verified: April 2018

Keywords provided by Amgen:
Liver tumours

Additional relevant MeSH terms:
Carcinoma, Hepatocellular
Liver Neoplasms
Adenocarcinoma
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Digestive System Diseases
Liver Diseases
Pembrolizumab
Antineoplastic Agents