Pembrolizumab With Talimogene Laherparepvec or Placebo in Unresected Melanoma
NCT ID: NCT02263508
Last Updated: 2022-11-14
Study Results
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View full resultsBasic Information
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TERMINATED
PHASE3
713 participants
INTERVENTIONAL
2014-12-08
2021-03-11
Brief Summary
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The primary objective of Phase 3 are to evaluate the efficacy of talimogene laherparepvec with pembrolizumab versus placebo with pembrolizumab, as assessed by progression-free survival (PFS) (response evaluation by blinded independent central review using modified Response Evaluation Criteria in Solid Tumors \[RECIST\] 1.1) and overall survival (OS).
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Detailed Description
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Conditions
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Study Design
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RANDOMIZED
PARALLEL
TREATMENT
DOUBLE
Study Groups
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Phase 1b: Talimogene Laherparepvec + Pembrolizumab
Participants received talimogene laherparepvec at an initial dose of up to 4 mL 10⁶ plaque-forming units (PFU)/mL by intralesional injection. Subsequent doses of talimogene laherparepvec at up to 4 mL of 10⁸ PFU/mL began 3 weeks after the first dose and were administered every 2 weeks until disappearance of injectable lesions, complete response (CR), confirmed disease progression (PD) per modified Immune-related Response Criteria (irRC), intolerance of study treatment, 24 months from the date of the first dose of pembrolizumab, or end of study, whichever occurred first. Participants also received 200 mg pembrolizumab administered intravenously every 2 weeks starting at the time of the third dose of talimogene laherparepvec (week 6) until confirmed PD per modified irRC, treatment intolerance, 24 months from the first dose, or end of study, whichever occurred first.
Talimogene Laherparepvec
Talimogene laherparepvec administered by intratumoral injection
Pembrolizumab
Administered at a dose of 200 mg as an intravenous infusion over approximately 30 minutes.
Phase 3 : Placebo + Pembrolizumab
Participants received up to 4 mL placebo to talimogene laherparepvec by intralesional injection on day 1 of week 0. Subsequent doses of placebo (up to 4 mL) began 3 weeks after the first dose and were administered every 2 weeks until the fifth injection (week 9), and then synchronously with pembrolizumab thereafter every 3 weeks until disappearance of injectable lesions, complete response per modified Immune-related Response Criteria simulating Response Evaluation Criteria in Solid Tumors (irRC-RECIST) (iCR), confirmed iPD per modified irRC-RECIST, intolerance of study treatment, 24 months from the date of the first dose of placebo, or end of study, whichever occurred first. Participants also received 200 mg pembrolizumab administered intravenously every 3 weeks starting on day 1 of week 0, until confirmed iPD per modified irRC-RECIST, treatment intolerance, 24 months from the first dose, or end of study, whichever occurred first.
Pembrolizumab
Administered at a dose of 200 mg as an intravenous infusion over approximately 30 minutes.
Placebo
Administered by intratumoral injection
Phase 3: Talimogene Laherparepvec + Pembrolizumab
Participants received talimogene laherparepvec at an initial dose of up to 4 mL 10⁶ PFU/mL by intralesional injection on day 1. Subsequent doses of talimogene laherparepvec at 10⁸ PFU/mL (up to 4 mL) began 3 weeks after the first dose and were administered every 2 weeks until the fifth injection of talimogene laherparepvec (week 9), and then synchronously with pembrolizumab thereafter every 3 weeks until disappearance of injectable lesions, iCR, confirmed iPD per modified irRC-RECIST, intolerance of study treatment, 24 months from the date of the first dose of talimogene laherparepvec, or end of study, whichever occurred first. Participants also received 200 mg pembrolizumab administered intravenously every 3 weeks starting on day 1 of week 0, until confirmed iPD per modified irRC-RECIST, treatment intolerance, 24 months from the first dose, or end of study, whichever occurred first.
Talimogene Laherparepvec
Talimogene laherparepvec administered by intratumoral injection
Pembrolizumab
Administered at a dose of 200 mg as an intravenous infusion over approximately 30 minutes.
Interventions
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Talimogene Laherparepvec
Talimogene laherparepvec administered by intratumoral injection
Pembrolizumab
Administered at a dose of 200 mg as an intravenous infusion over approximately 30 minutes.
Placebo
Administered by intratumoral injection
Other Intervention Names
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Eligibility Criteria
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Inclusion Criteria
* Subjects must have measurable disease and be a candidate for intralesional therapy administration into cutaneous, subcutaneous, or nodal lesions.
* Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
* Adequate hematologic, hepatic, renal, and coagulation function.
* Subjects with serine/threonine protein kinase B-Raf V600 (BRAFV600) wild-type tumors must not have received any prior systemic anticancer treatment consisting of chemotherapy, immunotherapy, or targeted therapy given in a non-adjuvant setting for unresectable stage IIIB to IVM1c melanoma.
* Subjects with B-Raf V600 (BRAFV600) mutated tumors who have received prior BRAF inhibitor therapy either alone or in combination with mitogen-activated protein kinase kinase (MEK) inhibitor as their only prior systemic therapy are eligible.
* Subjects who received prior adjuvant therapy for melanoma will not be excluded (including, but not limited to, interferon, ipilimumab, limb infusion/perfusion, or use of investigational agents in the adjuvant setting) with the exception that prior adjuvant therapy with inhibitors of programmed cell death-1 (PD-1) or programmed cell death ligand 1 (PD-L1) is not allowed. However, if the subject received adjuvant therapy, the subject must have completed therapy at least 28 days prior to enrollment.
* Subjects must have a tumor sample that is adequate for PD-L1 assessment prior to randomization.
Exclusion Criteria
* Subjects must not have primary uveal or mucosal melanoma, history or evidence of melanoma associated with immunodeficiency states or history of other malignancy within the past 3 years.
* Subjects may not have been previously treated with talimogene laherparepvec, any other oncolytic virus, pembrolizumab, or any other inhibitor of PD-1, PD-L1, or PD-L2.
* Subjects must not have history or evidence of symptomatic autoimmune pneumonitis, glomerulonephritis, vasculitis, other symptomatic autoimmune disease, documented history of autoimmune disease or syndrome requiring systemic treatment in the past 2 years (ie, with use of disease modifying agents, steroids or immunosuppressive agents) except vitiligo or resolved childhood asthma/atopy, or evidence of clinically significant immunosuppression.
* Subjects must not have active herpetic skin lesions or prior complications of herpetic infection and must not require intermittent or chronic treatment with an antiherpetic drug (eg, acyclovir), other than intermittent topical use.
18 Years
95 Years
ALL
No
Sponsors
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Merck Sharp & Dohme LLC
INDUSTRY
Amgen
INDUSTRY
Responsible Party
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Principal Investigators
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MD
Role: STUDY_DIRECTOR
Amgen
Locations
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Research Site
Birmingham, Alabama, United States
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Mobile, Alabama, United States
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Beverly Hills, California, United States
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Duarte, California, United States
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Encinitas, California, United States
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La Jolla, California, United States
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Los Angeles, California, United States
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Los Angeles, California, United States
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Riverside, California, United States
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San Francisco, California, United States
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San Francisco, California, United States
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Santa Monica, California, United States
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Miami, Florida, United States
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Miami Beach, Florida, United States
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Orlando, Florida, United States
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Atlanta, Georgia, United States
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Chicago, Illinois, United States
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Chicago, Illinois, United States
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Louisville, Kentucky, United States
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Baltimore, Maryland, United States
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Boston, Massachusetts, United States
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Detroit, Michigan, United States
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Fridley, Minnesota, United States
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St Louis, Missouri, United States
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Hackensack, New Jersey, United States
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Buffalo, New York, United States
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New York, New York, United States
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New York, New York, United States
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New York, New York, United States
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Cincinnati, Ohio, United States
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Cleveland, Ohio, United States
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Philadelphia, Pennsylvania, United States
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Philadelphia, Pennsylvania, United States
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Pittsburgh, Pennsylvania, United States
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Germantown, Tennessee, United States
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Knoxville, Tennessee, United States
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Nashville, Tennessee, United States
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Dallas, Texas, United States
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Murray, Utah, United States
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Salt Lake City, Utah, United States
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Seattle, Washington, United States
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North Sydney, New South Wales, Australia
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Waratah, New South Wales, Australia
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Wollongong, New South Wales, Australia
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Southport, Queensland, Australia
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Woolloongabba, Queensland, Australia
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Woodville South, South Australia, Australia
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Geelong, Victoria, Australia
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Heidelberg, Victoria, Australia
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Melbourne, Victoria, Australia
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Prahran, Victoria, Australia
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Murdoch, Western Australia, Australia
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Graz, , Austria
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Innsbruck, , Austria
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Salzburg, , Austria
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Vienna, , Austria
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Brussels, , Belgium
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Liège, , Belgium
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Edmonton, Alberta, Canada
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Kingston, Ontario, Canada
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London, Ontario, Canada
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Ottawa, Ontario, Canada
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Toronto, Ontario, Canada
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Montreal, Quebec, Canada
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Québec, Quebec, Canada
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Brno, , Czechia
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Olomouc, , Czechia
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Ostrava-Poruba, , Czechia
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Prague, , Czechia
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Prague, , Czechia
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Prague, , Czechia
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Helsinki, , Finland
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Bordeaux, , France
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Grenoble, , France
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Lille, , France
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Lyon, , France
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Marseille, , France
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Nantes, , France
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Paris, , France
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Pierre-Bénite, , France
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Toulouse, , France
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Vandœuvre-lès-Nancy, , France
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Berlin, , Germany
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Dresden, , Germany
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Erlangen, , Germany
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Essen, , Germany
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Hanover, , Germany
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Heidelberg, , Germany
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Kiel, , Germany
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Leipzig, , Germany
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Mainz, , Germany
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Mannheim, , Germany
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München, , Germany
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Regensburg, , Germany
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Tübingen, , Germany
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Würzburg, , Germany
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Athens, , Greece
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Athens, , Greece
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Heraklion - Crete, , Greece
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Ioannina, , Greece
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Thessaloniki, , Greece
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Budapest, , Hungary
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Pécs, , Hungary
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Szeged, , Hungary
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Bergamo, , Italy
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Brescia, , Italy
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Meldola FC, , Italy
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Milan, , Italy
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Milan, , Italy
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Siena, , Italy
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Amsterdam, , Netherlands
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Amsterdam, , Netherlands
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Groningen, , Netherlands
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Nijmegen, , Netherlands
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Bielsko-Biala, , Poland
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Bydgoszcz, , Poland
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Gdansk, , Poland
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Konin, , Poland
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Krakow, , Poland
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Poznan, , Poland
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Poznan, , Poland
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Szczecin, , Poland
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Warsaw, , Poland
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Wroclaw, , Poland
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Almada, , Portugal
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Lisbon, , Portugal
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Lisbon, , Portugal
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Porto, , Portugal
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Moscow, , Russia
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Saint Petersburg, , Russia
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Groenkloof, Gauteng, South Africa
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Johannesburg, Gauteng, South Africa
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Parktown, Gauteng, South Africa
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Kraaifontein, , South Africa
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Pretoria, , South Africa
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Pretoria, , South Africa
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Seoul, , South Korea
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Seoul, , South Korea
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Donostia / San Sebastian, Basque Country, Spain
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Badalona, Catalonia, Spain
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Barcelona, Catalonia, Spain
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Pamplona, Navarre, Spain
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Valencia, Valencia, Spain
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Madrid, , Spain
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Madrid, , Spain
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Madrid, , Spain
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Bellinzona, , Switzerland
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Bern, , Switzerland
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Geneva, , Switzerland
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Lausanne, , Switzerland
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Zurich, , Switzerland
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Birmingham, , United Kingdom
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Guildford, , United Kingdom
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Leeds, , United Kingdom
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Leicester, , United Kingdom
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London, , United Kingdom
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London, , United Kingdom
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Manchester, , United Kingdom
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Oxford, , United Kingdom
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Preston, , United Kingdom
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Southampton, , United Kingdom
Countries
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References
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Ribas A, Dummer R, Puzanov I, VanderWalde A, Andtbacka RHI, Michielin O, Olszanski AJ, Malvehy J, Cebon J, Fernandez E, Kirkwood JM, Gajewski TF, Chen L, Gorski KS, Anderson AA, Diede SJ, Lassman ME, Gansert J, Hodi FS, Long GV. Oncolytic Virotherapy Promotes Intratumoral T Cell Infiltration and Improves Anti-PD-1 Immunotherapy. Cell. 2017 Sep 7;170(6):1109-1119.e10. doi: 10.1016/j.cell.2017.08.027.
Dummer R, Hoeller C, Gruter IP, Michielin O. Combining talimogene laherparepvec with immunotherapies in melanoma and other solid tumors. Cancer Immunol Immunother. 2017 Jun;66(6):683-695. doi: 10.1007/s00262-017-1967-1. Epub 2017 Feb 25.
Chesney JA, Ribas A, Long GV, Kirkwood JM, Dummer R, Puzanov I, Hoeller C, Gajewski TF, Gutzmer R, Rutkowski P, Demidov L, Arenberger P, Shin SJ, Ferrucci PF, Haydon A, Hyngstrom J, van Thienen JV, Haferkamp S, Guilera JM, Rapoport BL, VanderWalde A, Diede SJ, Anderson JR, Treichel S, Chan EL, Bhatta S, Gansert J, Hodi FS, Gogas H. Randomized, Double-Blind, Placebo-Controlled, Global Phase III Trial of Talimogene Laherparepvec Combined With Pembrolizumab for Advanced Melanoma. J Clin Oncol. 2023 Jan 20;41(3):528-540. doi: 10.1200/JCO.22.00343. Epub 2022 Aug 23.
Watanabe D, Goshima F. Oncolytic Virotherapy by HSV. Adv Exp Med Biol. 2018;1045:63-84. doi: 10.1007/978-981-10-7230-7_4.
Provided Documents
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Document Type: Study Protocol
Document Type: Statistical Analysis Plan
Related Links
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AmgenTrials clinical trials website
Other Identifiers
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2014-000185-22
Identifier Type: EUDRACT_NUMBER
Identifier Source: secondary_id
KEYNOTE-034
Identifier Type: OTHER
Identifier Source: secondary_id
20110265
Identifier Type: -
Identifier Source: org_study_id
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