Trial to Evaluate the Safety of Talimogene Laherparepvec Injected Into Tumors Alone and in Combination With Systemic Pembrolizumab MK-3475-611/Keynote-611 (MASTERKEY-318)

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)

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.

Study Overview

• Status: Completed
• Conditions: Hepatocellular Carcinoma; Liver Metastases; Liver Tumors; Cutaneous or Subcutaneous Lymph Node
• Intervention / Treatment: Drug: Talimogene Laherparepvec; Drug: Pembrolizumab

• Study Type: Interventional
• Enrollment (Actual): 127
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • Liverpool, New South Wales, Australia, 2170
      • Liverpool Hospital
    • North Sydney, New South Wales, Australia, 2060
      • Melanoma Institute Australia
  • Queensland
    • Southport, Queensland, Australia, 4215
      • Tasman Oncology Research
• Austria
  • Salzburg, Austria, 5020
    • Landeskrankenhaus Salzburg
• Belgium
  • Bruxelles, Belgium, 1200
    • Universite Catholique de Louvain Cliniques Universitaires Saint Luc
  • Edegem, Belgium, 2650
    • Universitair Ziekenhuis Antwerpen
  • Gent, Belgium, 9000
    • Universitair Ziekenhuis Gent
• Germany
  • Berlin, Germany, 13353
    • Charite Universitätsmedizin Berlin, Charité Campus Virchow-Klinikum
  • Bonn, Germany, 53127
    • Universitatsklinikum Bonn
  • Reutlingen, Germany, 72764
    • Kreiskliniken Reutlingen - Klinikum am Steinenberg
  • Tübingen, Germany, 72076
    • Universitatsklinikum Tubingen
• Korea, Republic of
  • Seongnam-si, Gyeonggi-do, Korea, Republic of, 463-712
    • CHA Bundang Medical Center, CHA University
  • Seoul, Korea, Republic of, 03080
    • Seoul National University Hospital
  • Seoul, Korea, Republic of, 120-752
    • Severance Hospital Yonsei University Health System
• Poland
  • Gdansk, Poland, 80-214
    • Uniwersyteckie Centrum Kliniczne
• Spain
  • Madrid, Spain, 28050
    • Hospital Universitario Madrid Sanchinarro
  • Madrid, Spain, 28009
    • Hospital General Universitario Gregorio Marañon
  • Cataluña
    • Barcelona, Cataluña, Spain, 08035
      • Hospital Universitari Vall D Hebron
    • Barcelona, Cataluña, Spain, 08036
      • Hospital Clinic i Provincial de Barcelona
• Switzerland
  • Geneva 14, Switzerland, 1211
    • Hôpitaux Universitaires de Genève
  • Lausanne, Switzerland, 1011
    • Centre Hospitalier Universitaire Vaudois
  • Winterthur, Switzerland, 8401
    • Kantonsspital Winterthur
  • Zurich, Switzerland, 8091
    • UniversitaetsSpital Zuerich
• United States
  • Arizona
    • Scottsdale, Arizona, United States, 85258
      • HonorHealth Research Institute
  • California
    • Santa Monica, California, United States, 90404
      • University of California Los Angeles
  • District of Columbia
    • Washington, District of Columbia, United States, 20007
      • Georgetown-Howard University Center for Clinical Translational Science
  • Kentucky
    • Louisville, Kentucky, United States, 40202
      • University of Louisville James Graham Brown Cancer Center
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Washington University School of Medicine, Center for Advanced Medicine
  • New Jersey
    • New Brunswick, New Jersey, United States, 08903
      • Rutgers Cancer Institute of New Jersey
  • New York
    • New York, New York, United States, 10065
      • Memorial Sloan Kettering Cancer Center
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15213
      • University of Pittsburgh
  • Texas
    • Houston, Texas, United States, 77030
      • University of Texas MD Anderson Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Summary of Subject Eligibility Criteria:

Key Inclusion Criteria:

Subjects must be age ≥ 18 years at the time of informed consent. Subjects must have histologically or cytologically confirmed disease.

Part 1 is restricted to BC, CRC, GEC, melanoma, NSCLC, or RCC with liver metastases or HCC.

Part 2 Group A is restricted to advanced hormone receptor positive BC, CRC, TNBC, CSCC, and BCC with or without liver metastases.

• Part 2 Hormone receptor positive Breast Cancer Arm only: Histologically and/or cytologically confirmed diagnosis of estrogen receptor (ER) positive and/or progesterone receptor (PrR) positive breast cancer.
• Triple negative breast cancer: Histologically and/or cytologically confirmed diagnosis of ER negative, PrR negative, human epidermal growth factor receptor 2 (HER2)-Neu negative.

Part 2 Group B is restricted to HCC (fibrolamellar and mixed hepatocellular/cholangiocarcinoma subtypes are not eligible).

For HCC subjects with a diagnosis of hepatitis B, they must be on antiviral therapy for at least 4 weeks prior to enrollment and hepatitis B virus (HBV) viral load by real-time polymerase chain reaction (qPCR) must be < 100 IU/mL. HCC subjects with past or ongoing hepatitis C infection must have completed treatment for hepatitis C at least 1 month prior to study enrollment and hepatitis C viral load must be undetectable; subjects with hepatitis B and C must fulfill the eligibility criteria for hepatitis B and hepatitis C. Subjects with unresectable locally recurrent TNBC are 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 melanoma CSCC or NSCLC do not need to have received prior therapy. In Part 1, subjects must have measurable liver tumors and liver tumors that are suitable for injection. In Part 2, subjects must have measurable disease and cutaneous, subcutaneous, lymph node, or liver tumors suitable for injection. 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, enrollment for this study has stopped. 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.

Key Exclusion Criteria:

Subjects must not be candidates for surgery or locoregional therapy 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 or major 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 (1) have no central nervous system (CNS) metastasis, or carcinomatous meningitis, or (2) if CNS metastasis is present, must have stable treated cerebral metastases. Subjects must not have symptomatic auto-immune disease or be symptomatically 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 qPCR must be undetectable, and they must not have had recent treatment within 12 weeks for HBV or HCV with certain antiviral medications in Part 1 Group B cohorts 1-5 and 6a, and Part 2 Group B HCC without viral hepatitis. For all patients in Part 1 and for patients in Part 2 where intrahepatic liver injection is planned (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, enrollment for this study has stopped), 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, oncolytic viruses, or tumor vaccine. 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / 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 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.
Experimental: Phase Ib/II Talimogene Laherparepvec + Pembrolizumab; Combination treatment of Talimogene Laherparepvec and Pembrolizumab	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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants Who Experienced a Dose Limiting Toxicity (DLT)	All toxicities were graded using the Common Terminology Criteria for Adverse Events (CTCAE) version 4.03: Grade 1: Mild; Grade 2: Moderate; Grade 3: Severe or medically significant but not immediately life threatening; Grade 4: Life threatening consequences; Grade 5: Death related to adverse event (AE) The occurrence of specific pre-defined toxicities during the DLT evaluation period were considered a DLT if judged by the investigator to be related to talimogene laherparepvec and/or pembrolizumab. All Grade 5 toxicities, intolerable toxicities that lead to permanent discontinuation of talimogene laherparepvec and/or pembrolizumab and Grade 3 or higher AEs related to talimogene laherparepvec and/or pembrolizumab that resulted in a study treatment delay by > 2 weeks were considered DLTs.	Cycle 1 and Cycle 2: Day 1 to Day 21
Part 2 Only: Objective Response Rate (ORR) Per Modified Immune-related Response Criteria Simulating Response Evaluation Criteria in Solid Tumors (irRC-RECIST).	ORR was defined as the percentage of participants with a best overall response of complete response (CR) or partial response (PR) per modified irRC-RECIST.; CR: Disappearance of all lesions (whether measurable or not and whether baseline or new) and confirmation by a repeat, consecutive assessment no less than 4 weeks (28 days) from the date first documented. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to < 10 mm.; PR: Decrease in tumor burden ≥ 30% relative to baseline confirmed by a consecutive assessment at least 4 weeks (28 days) after first documentation.	Up to 154 weeks
Part 2 Only: Number of Participants Who Experienced a Treatment-emergent Adverse Event (TEAE)	A TEAE was defined as an event that emerged during treatment, having been absent pretreatment, or worsened relative to the pretreatment state. A treatment-related TEAE was defined as a TEAE that was suspected to be related to the study treatment.	Day 1 to 30 days post-last dose of talimogene laherparepvec or pembrolizumab, whichever is later. The maximum duration of talimogene laherparepvec treatment was 102.4 weeks and pembrolizumab treatment was 109.3 weeks in Part 2.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Part 1 Only: ORR Per Modified irRC-RECIST	ORR was defined as the percentage of participants with a best overall response of CR or PR per modified irRC-RECIST.; CR: Disappearance of all lesions (whether measurable or not and whether baseline or new) and confirmation by a repeat, consecutive assessment no less than 4 weeks (28 days) from the date first documented. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to < 10 mm.; PR: Decrease in tumor burden ≥ 30% relative to baseline confirmed by a consecutive assessment at least 4 weeks (28 days) after first documentation.	Up to 297 weeks
Best Overall Response (BOR) Per Modified irRC-RECIST	BOR was defined as the number of participants with a best visit response in the following order: CR, PR, stable disease (SD), progressive disease (PD), or unevaluable (UE) as per modified irRC-RECIST.; CR: Disappearance of all lesions and confirmation by assessment no less than 4 weeks (28 days) from the date first documented. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to < 10 mm.; PR: Decrease in tumor burden ≥ 30% relative to baseline confirmed by a consecutive assessment at least 4 weeks (28 days) after first documentation.; SD: Neither sufficient shrinkage to qualify for CR or PR nor sufficient increase to qualify for PD.; PD: Increase in tumor burden ≥ 20 % and at least 5 mm absolute increase relative to nadir confirmation by a repeat, consecutive assessment no less than 4 weeks (28 days) from the date first documented PD.; UE: Any lesion present at baseline which was not assessed or was unable to be evaluated.	Up to 297 weeks
Durable Response Rate (DRR) Per Modified irRC-RECIST	DRR per modified irRC-RECIST was defined as the percentage of participants with an objective response (CR/PR) with a duration of response of at least 6 months.; CR: Disappearance of all lesions and confirmation by assessment no less than 4 weeks (28 days) from the date first documented. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to < 10 mm.; PR: Decrease in tumor burden ≥ 30% relative to baseline confirmed by a consecutive assessment at least 4 weeks (28 days) after first documentation.	Up to 297 weeks
Duration of Response (DOR) Per Modified irRC-RECIST	DOR per modified irRC-RECIST was defined as the time from the date of an initial response (CR/PR) that was subsequently confirmed to the earlier of PD or death. DOR was estimated using the Kaplan-Meier method.; CR: Disappearance of all lesions and confirmation by assessment no less than 4 weeks (28 days) from the date first documented. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to < 10 mm.; PR: Decrease in tumor burden ≥ 30% relative to baseline confirmed by a consecutive assessment at least 4 weeks (28 days) after first documentation.; PD: Increase in tumor burden ≥ 20 % and at least 5 mm absolute increase relative to nadir confirmation by a repeat, consecutive assessment no less than 4 weeks (28 days) from the date first documented PD.	Up to 297 weeks
Disease Control Rate (DCR) Per Modified irRC-RECIST	DCR per modified irRC-RECIST was defined as percentage of participants that had a BOR in 1 of the following: CR, PR or SD.; CR: Disappearance of all lesions and confirmation by assessment no less than 4 weeks (28 days) from the date first documented. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to < 10 mm.; PR: Decrease in tumor burden ≥ 30% relative to baseline confirmed by a consecutive assessment at least 4 weeks (28 days) after first documentation.; SD: Neither sufficient shrinkage to qualify for CR or PR nor sufficient increase to qualify for PD.	Up to 297 weeks
Progression Free Survival (PFS) Per Modified irRC-RECIST	PFS was defined as the time from first dose to the date of first of PD per modified irRC-RECIST criteria, or death, whichever occurs first. PFS was estimated using the Kaplan-Meier method. Participants that did not have an event of death or disease progression were censored at the latter of their last evaluable tumor assessment date or first dose date.; PD: Increase in tumor burden ≥ 20 % and at least 5 mm absolute increase relative to nadir confirmation by a repeat, consecutive assessment no less than 4 weeks (28 days) from the date first documented PD.	Up to 297 weeks
Overall Survival (OS)	OS was defined as the time from the date of first dose date to the date of death from any cause. OS time was censored at the last date the participant was known to be alive when the confirmation of death was absent or unknown, or at the date 24 months after the last participant enrolled if the last known to be alive/death date was beyond it. One month = 365.25/12 days. OS was estimated using the Kaplan-Meier method.	Up to 297 weeks
Part 1 Only: Number of Participants Who Experienced a TEAE	A TEAE was defined as an event that emerged during treatment, having been absent pretreatment, or worsened relative to the pretreatment state. A treatment-related TEAE was defined as a TEAE that was suspected to be related to the study treatment.	Day 1 to 30 days post-last dose of talimogene laherparepvec or pembrolizumab, whichever is later. The maximum duration of talimogene laherparepvec treatment was 34.1 weeks and pembrolizumab treatment was 98.3 weeks in Part 1.
Percentage of Participants With Detectable Talimogene Laherparepvec Deoxyribonucleic Acid (DNA) in Blood	Blood samples were tested using real-time polymerase chain reaction (qPCR). Detectable DNA was defined as a positive result by qPCR analysis.	Week 1 to Week 10
Percentage of Participants With Detectable Talimogene Laherparepvec DNA in Urine	Urine samples were tested using qPCR. Detectable DNA was defined as a positive result by qPCR analysis.	Week 1 to Week 10
Percentage of Participants With Clearance of Talimogene Laherparepvec in Blood	Blood samples were tested using qPCR. A participant was defined as having cleared talimogene laherparepvec if a negative qPCR in a sample was obtained following a prior positive test and if there were no subsequent positive test results in the same cycle.	Cycles 2, 3 and 4: Day 1 pre-dose. Each cycle was 21 days.
Percentage of Participants With Clearance of Talimogene Laherparepvec in Urine	Urine samples were tested using qPCR. A participant was defined as having cleared talimogene laherparepvec if a negative qPCR in a sample was obtained following a prior positive test and if there were no subsequent positive test results in the same cycle.	Cycles 2, 3 and 4: Day 1 pre-dose. Each cycle was 21 days.
Percentage of Participants With Detectable Talimogene Laherparepvec DNA at the Surface of Injection Site	The number of participants with positive qPCR and subsequent positive plaque assays were evaluated from swabs of skin surface of injections. Detectable DNA was defined as a positive result by qPCR analysis.	Week 1 to Week 10
Percentage of Participants With Detectable Talimogene Laherparepvec Virus at the Surface of Injection Site	The percentage of participants with detectable virus were evaluated from swabs of skin surface of injections. Detectable virus was defined as a positive result by TCID50.	Week 1 to Week 10
Percentage of Participants With Detectable Talimogene Laherparepvec DNA at the Exterior of the Occlusive Dressing	The percentage of participants with positive qPCR and subsequent positive plaque assays were evaluated from swabs of the exterior of the occlusive dressing. Detectable DNA was defined as a positive result by qPCR analysis.	Week 1 to Week 7
Percentage of Participants With Detectable Talimogene Laherparepvec Virus at the Exterior of the Occlusive Dressing	The percentage of participants with detectable virus were evaluated from swabs of the exterior of the occlusive dressings. Detectable virus was defined as a positive result by TCID50.	Week 1 to Week 7
Percentage of Participants With Detectable Talimogene Laherparepvec DNA at the Oral Mucosa	The percentage of participants with positive qPCR and subsequent positive plaque assays were evaluated from swabs of the oral mucosa. Detectable DNA was defined as a positive result by qPCR analysis.	Part 1: Week 1 to Week 37. Part 2: Week 1 to Week 43
Percentage of Participants With Detectable Talimogene Laherparepvec Virus at the Oral Mucosa	The percentage of participants with detectable virus were evaluated from swabs of the oral mucosa. Detectable virus was defined as a positive result by TCID50.	Week 1 to Week 7
Percentage of Participants With Detectable Talimogene Laherparepvec DNA in Lesions Suspected to be Herpetic in Origin	The percentage of participants with positive qPCR were evaluated in any swab of a lesion suspected to be herpetic in origin. Detectable DNA was defined as a positive result by qPCR analysis. Participants returned to the clinic within 3 days of the occurrence of reportable lesion suspected to be herpetic in origin such as cold sores or vesicles. The lesion was evaluated by the Investigator and swabbed if herpes simplex virus infection was suspected.	Day 1 to 30 days post-last dose of talimogene laherparepvec. The maximum duration of talimogene laherparepvec treatment was 102.4 weeks and pembrolizumab treatment was 109.3 weeks.

Collaborators and Investigators

• Sponsor: Amgen
• Collaborators: Merck Sharp & Dohme LLC
• Investigators: Study Director: MD, Amgen

Publications and helpful links

Helpful Links

• AmgenTrials clinical trials website

Study record dates

Study Major Dates

• Study Start (Actual): February 5, 2016
• Primary Completion (Actual): February 14, 2022
• Study Completion (Actual): July 11, 2023

Study Registration Dates

• First Submitted: July 10, 2015
• First Submitted That Met QC Criteria: July 24, 2015
• First Posted (Estimated): July 28, 2015

Study Record Updates

• Last Update Posted (Actual): August 6, 2024
• Last Update Submitted That Met QC Criteria: July 10, 2024
• Last Verified: July 1, 2024

More Information

Terms related to this study

• Keywords: Liver tumours
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Digestive System Neoplasms; Liver Diseases; Liver Neoplasms; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Antineoplastic Agents, Immunological; Immune Checkpoint Inhibitors; Pembrolizumab; Talimogene laherparepvec
• Other Study ID Numbers: 20140318; 2014-005386-67 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: De-identified individual patient data for variables necessary to address the specific research question in an approved data sharing request
• IPD Sharing 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.
• IPD Sharing 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.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; CSR