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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT02263508




Registration number
NCT02263508
Ethics application status
Date submitted
26/09/2014
Date registered
13/10/2014
Date last updated
28/10/2019

Titles & IDs
Public title
Pembrolizumab With or Without Talimogene Laherparepvec or Talimogene Laherparepvec Placebo in Unresected Melanoma (KEYNOTE-034)
Scientific title
A Phase 1b/3, Multicenter, Trial of Talimogene Laherparepvec in Combination With Pembrolizumab (MK-3475) for Treatment of Unresectable Stage IIIB to IVM1c Melanoma (MASTERKEY-265/KEYNOTE-034)
Secondary ID [1] 0 0
2014-000185-22
Secondary ID [2] 0 0
20110265
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Melanoma 0 0
Condition category
Condition code
Cancer 0 0 0 0
Malignant melanoma

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - talimogene laherparepvec
Treatment: Drugs - pembrolizumab (MK-3475)
Treatment: Drugs - placebo

Experimental: Phase 1b; - Phase 1b: talimogene laherparepvec and pembrolizumab (MK-3475)

Experimental: Phase 3 Arm 1; - Phase 3 Arm 1: talimogene laherparepvec and pembrolizumab (MK-3475)

Experimental: Phase 3 Arm 2; - Phase 3 Arm 2: placebo and pembrolizumab (MK-3475)


Treatment: Drugs: talimogene laherparepvec
Phase 1b: talimogene laherparepvec will be administered by intralesional injection at Day 1, Week -5; then every 2 weeks starting at Day 1, Week -2; Phase 3, Arm 1 talimogene laherparepvec will be administered by intralesional injection at Day 1 Week 0, 3, 5, 7 then every 3 weeks starting at Day 1 Week 9.

Treatment: Drugs: pembrolizumab (MK-3475)
Phase 1b: pembrolizumab will be administered intravenously every 2 weeks starting at Day 1 Week 0; Phase 3, Arm 1 and Arm 2 pembrolizumab will be administered intravenously on Day 1 Week 0, then every 3 weeks starting at Day 1 Week 3.

Treatment: Drugs: placebo
Phase 3, Arm 2 placebo will be administered by intralesional injection at Day 1 Week 0, 3, 5, 7 then every 3 weeks starting at Day 1 Week 9.

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Incidence of dose limiting toxicities (DLT) - Phase 1b: To evaluate the safety, as assessed by incidence of dose limiting toxicity (DLT), of talimogene laherparepvec in combination with pembrolizumab (MK-3475)
Timepoint [1] 0 0
Start of treatment until 6 weeks from the initial administration of pembrolizumab (MK-3475)
Primary outcome [2] 0 0
Progression Free Survival (PFS) (response evaluation by blinded central review assessed modified RECIST 1.1) - Phase 3: 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 1.1 [RECIST]).
Timepoint [2] 0 0
up to 44 months
Primary outcome [3] 0 0
Overall Survival - Phase 3: To evaluate the efficacy of talimogene laherparepvec with pembrolizumab versus placebo with pembrolizumab, as assessed by overall survival (OS).
Timepoint [3] 0 0
up to 62 months
Secondary outcome [1] 0 0
Incidence of adverse events (AEs) - Incidence of treatment-emergent and treatment-related adverse events and abnormal laboratory tests (all AEs, grade = 3 AEs, serious adverse events, fatal AEs, and AEs defined as events of interest)
Timepoint [1] 0 0
Start of treatment to 30 (+7) days after end of treatment
Secondary outcome [2] 0 0
Objective Response Rate (ORR) - To evaluate the efficacy, as assessed by ORR of treatment with talimogene laherparepvec in combination with pembrolizumab in Phase 1b and talimogene laherparepvec in combination with pembrolizumab verses placebo in Phase 3.
Timepoint [2] 0 0
Start of treatment and every 12 weeks until confirmed disease progression, assessed up to 60 months
Secondary outcome [3] 0 0
Best overall response (BOR) - To be assessed for Phase 3
Timepoint [3] 0 0
Start of treatment and every 12 weeks until confirmed disease progression, assessed up to 60 months
Secondary outcome [4] 0 0
Durable response rate (DRR) defined as rate of objective responses for a duration of 6 months or longer - To be assessed for Phase 1b, Phase 3
Timepoint [4] 0 0
Start of treatment and every 12 weeks until confirmed disease progression, assessed up to 60 months
Secondary outcome [5] 0 0
Duration of response (DOR) - To be assessed for Phase 1b, Phase 3
Timepoint [5] 0 0
Start of treatment and every 12 weeks until confirmed disease progression, assessed up to 60 months
Secondary outcome [6] 0 0
Disease Control Rate (DCR) - To be assessed for Phase 1b, Phase 3
Timepoint [6] 0 0
Start of treatment and every 12 weeks until confirmed disease progression, assessed up to 60 months
Secondary outcome [7] 0 0
Overall survival (OS) - To be assessed for Phase 1b, Phase 3
Timepoint [7] 0 0
Start of treatment and every 12 weeks during long term follow up until 60 months after last subject enrolled. Calculated from date of Randomization to date of death.
Secondary outcome [8] 0 0
As assessed by the QLQ-C30 subject questionnaires - Phase 3: To evaluate patient reported outcomes (PRO)
Timepoint [8] 0 0
weeks 0, then every 3, 6, 9, 12 weeks then every 6 weeks until the end of the study and at safety follow up, assessed up to 60 months
Secondary outcome [9] 0 0
Complete response rate (CRR) - by blinded independent central assessed modified immune-related response criteria simulating response evaluation criteria in solid tumors for Phase 3
Timepoint [9] 0 0
Start of treatment and every 12 weeks until confirmed disease progression, assessed up to 60 months

Eligibility
Key inclusion criteria
Key

- Age = 18 years with histologically confirmed diagnosis of melanoma and stage IIIB to
IVM1c for whom surgery is not recommended.

- Subjects must have measurable disease and be a candidate for intralesional therapy
administration into cutaneous, subcutaneous, or nodal lesions.

- ECOG performance status of 0 or 1.

- Adequate hematologic, hepatic, renal, and coagulation function.

- Subjects with 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 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.

Key
Minimum age
18 Years
Maximum age
95 Years
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
- Subjects must not have clinically active cerebral metastases.

- 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.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s


The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Active, not recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,QLD,SA,VIC,WA
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Research Site - North Sydney
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Research Site - Woodville South
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Research Site - Geelong
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Research Site - Heidelberg
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Research Site - Melbourne
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Research Site - Prahran
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Research Site - Murdoch
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2060 - North Sydney
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2298 - Waratah
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2500 - Wollongong
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4215 - Southport
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4102 - Woolloongabba
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5011 - Woodville South
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3220 - Geelong
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3084 - Heidelberg
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3000 - Melbourne
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3181 - Prahran
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6150 - Murdoch
Recruitment outside Australia
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Southampton

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Amgen
Address
Country
Other collaborator category [1] 0 0
Commercial sector/Industry
Name [1] 0 0
Merck Sharp & Dohme Corp.
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
Phase 1b Subjects will be treated with talimogene laherparepvec until all injectable tumors
have disappeared, disease progression per modified Immune-Related Response Criteria (irRC),
or intolerance of study treatment, up to a maximum of 24 months of study treatment. Subjects
will be treated with MK-3475 (pembrolizumab) until complete response (CR) disease progression
per irRC, or intolerance of study treatment, up to a maximum of 24 months of study treatment.
In Phase 3, Subjects will be treated with talimogene laherparepvec plus pembrolizumab(arm 1)
or placebo plus pembrolizumab (arm 2) until 24 months from the date of the first dose of
pembrolizumab or end of treatment due to disappearance of injectable lesions, complete
response, disease progression per irRC-RECIST or intolerance of study treatment.
Trial website
https://clinicaltrials.gov/show/NCT02263508
Trial related presentations / publications
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. Erratum in: Cell. 2018 Aug 9;174(4):1031-1032.
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. Review.
Public notes

Contacts
Principal investigator
Name 0 0
MD
Address 0 0
Amgen
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Summary results
Other publications