Working...
ClinicalTrials.gov
ClinicalTrials.gov Menu
Trial record 1 of 2 for:    20140318
Previous Study | Return to List | Next Study

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT02509507
Recruitment Status : Recruiting
First Posted : July 28, 2015
Last Update Posted : August 2, 2019
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

Layout table for study information
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 : July 4, 2022
Estimated Study Completion Date : December 13, 2023

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Liver Cancer

Arm Intervention/treatment
Experimental: Phase Ib/II 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 Ib/II 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 up to 35 cycles.




Primary Outcome Measures :
  1. Subject incidence DLTs separately in Group A and B observed in monotherapy and combination cohorts and in each tumor type seperately in Part 2 [ Time Frame: 3 year ]
  2. To evaluate in Part 2 ORR per modified 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

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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

Summary of Subject Eligibility Criteria:

Key Inclusion Criteria:

Subjects must be age ≥ 18 years at the time of informed consent. They must have histologically or cytologically confirmed BC, CRC, GEC, melanoma, NSCLC, or RCC with liver metastases or HCC.

Part 2 Group B is restricted to HCC (fibrolamellar and mixed hepatocellular/cholangiocarcinoma subtypes are not eligible). Non-HCC 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 and lesions that are suitable for injection.

Eastern Cooperative Oncology Group (ECOG) 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.

Liver function tests may be mildly abnormal but within the parameters. Child Pugh score must be A to B7.

Key Exclusion Criteria:

Subjects must not be candidates for hepatic surgery or locoregional therapy of liver tumors with curative intent or planned immediate 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 active 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 oral or intravenous systemic 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
Layout table for location contacts
Contact: Amgen Call Center 866-572-6436 medinfo@amgen.com

Locations
Layout table for location information
United States, California
Research Site Recruiting
Los Angeles, California, United States, 90095
United States, District of Columbia
Research Site Recruiting
Washington, District of Columbia, United States, 20007
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
United States, New York
Research Site Recruiting
New York, New York, United States, 10065
United States, Texas
Research Site Recruiting
Houston, Texas, United States, 77030
Belgium
Research Site Recruiting
Edegem, Belgium, 2650
Research Site Recruiting
Gent, Belgium, 9000
Germany
Research Site Recruiting
Berlin, Germany, 13353
Research Site Recruiting
Tübingen, Germany, 72076
Korea, Republic of
Research Site Recruiting
Seongnam-si, Gyeonggi-do, Korea, Republic of, 463-712
Research Site Recruiting
Seoul, Korea, Republic of, 03080
Research Site Recruiting
Seoul, Korea, Republic of, 120-752
Spain
Research Site Recruiting
Barcelona, Cataluña, Spain, 08035
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
Research Site Recruiting
Zurich, Switzerland, 8091
Sponsors and Collaborators
Amgen
Merck Sharp & Dohme Corp.
Investigators
Layout table for investigator information
Study Director: MD Amgen

Additional Information:
Layout table for additonal 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: August 2, 2019
Last Verified: July 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: De-identified individual patient data for variables necessary to address the specific research question in an approved data sharing request
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Informed Consent Form (ICF)
Clinical Study Report (CSR)
Time Frame: Data sharing requests relating to this study will be considered beginning 18 months after the study has ended and either 1) the product and indication (or other new use) have been granted marketing authorization in both the US and Europe or 2) clinical development for the product and/or indication discontinues and the data will not be submitted to regulatory authorities. There is no end date for eligibility to submit a data sharing request for this study.
Access Criteria: Qualified researchers may submit a request containing the research objectives, the Amgen product(s) and Amgen study/studies in scope, endpoints/outcomes of interest, statistical analysis plan, data requirements, publication plan, and qualifications of the researcher(s). In general, Amgen does not grant external requests for individual patient data for the purpose of re-evaluating safety and efficacy issues already addressed in the product labelling. Requests are reviewed by a committee of internal advisors, and if not approved, may be further arbitrated by a Data Sharing Independent Review Panel. Upon approval, information necessary to address the research question will be provided under the terms of a data sharing agreement. This may include anonymized individual patient data and/or available supporting documents, containing fragments of analysis code where provided in analysis specifications. Further details are available at the link below.
URL: https://www.amgen.com/datasharing

Keywords provided by Amgen:
Liver tumours

Additional relevant MeSH terms:
Layout table for 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
Talimogene laherparepvec
Antineoplastic Agents, Immunological
Antineoplastic Agents