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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT04068181




Registration number
NCT04068181
Ethics application status
Date submitted
22/08/2019
Date registered
28/08/2019

Titles & IDs
Public title
Talimogene Laherparepvec With Pembrolizumab in Melanoma Following Progression on Prior Anti-PD-1 Based Therapy (MASTERKEY-115) (Mk-3475-A07/KEYNOTE-A07).
Scientific title
Phase 2 Study of Talimogene Laherparepvec in Combination With Pembrolizumab in Subjects With Unresectable/Metastatic Stage IIIB-IVM1d Melanoma Who Have Progressed on Prior Anti PD-1 Based Therapy
Secondary ID [1] 0 0
2019-001906-61
Secondary ID [2] 0 0
20180115
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

Experimental: Cohort 1 - Locally Recurrent/Metastatic - Primary Resistance - Includes participants who received anti-PD1 therapy in the locally recurrent/metastatic setting and experienced a best overall response of disease progression or stable disease prior to confirmed disease progression.

Participants will receive talimogene laherparepvec at an initial dose of up to 4.0 mL of 10\^6 plaque-forming units (PFU)/mL on Day 1. Subsequent doses of up to 4.0 mL of 10\^8 PFU/mL will be administered every 3 weeks for up to 35 cycles in total. Participants will also receive pembrolizumab at a dose of 200 mg every 3 weeks for up to 35 cycles.

Experimental: Cohort 2 - Locally Recurrent/Metastatic - Acquired Resistance - Includes participants who received anti-PD-1 therapy in the locally recurrent/metastatic setting and experienced confirmed disease progression following a complete or partial response on anti-PD-1 therapy.

Participants will receive talimogene laherparepvec at an initial dose of up to 4.0 mL of 10\^6 plaque-forming units (PFU)/mL on Day 1. Subsequent doses of up to 4.0 mL of 10\^8 PFU/mL will be administered every 3 weeks for up to 35 cycles in total. Participants will also receive pembrolizumab at a dose of 200 mg every 3 weeks for up to 35 cycles.

Experimental: Cohort 3 - Adjuvant Setting -Disease Free Interval < 6 months - Includes participants who received anti-PD-1 therapy in the adjuvant setting and experienced confirmed disease progression following a disease-free interval of \< 6 months after starting the adjuvant anti-PD-1 therapy.

Participants will receive talimogene laherparepvec at an initial dose of up to 4.0 mL of 10\^6 plaque-forming units (PFU)/mL on Day 1. Subsequent doses of up to 4.0 mL of 10\^8 PFU/mL will be administered every 3 weeks for up to 35 cycles in total. Participants will also receive pembrolizumab at a dose of 200 mg every 3 weeks for up to 35 cycles.

Experimental: Cohort 4 - Adjuvant Setting -Disease Free Interval = 6 months - Includes participants who received anti PD-1 therapy in the adjuvant setting and experienced confirmed disease progression following a disease-free interval of = 6 months after starting the adjuvant PD-1 inhibitor.

Participants will receive talimogene laherparepvec at an initial dose of up to 4.0 mL of 10\^6 plaque-forming units (PFU)/mL on Day 1. Subsequent doses of up to 4.0 mL of 10\^8 PFU/mL will be administered every 3 weeks for up to 35 cycles in total. Participants will also receive pembrolizumab at a dose of 200 mg every 3 weeks for up to 35 cycles.


Treatment: Drugs: Talimogene laherparepvec
Intralesional injection into injectable cutaneous, subcutaneous and nodal legions.

Treatment: Drugs: Pembrolizumab
Intravenous (IV) infusion.
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Objective Response Rate (ORR) Per Modified RECIST v1.1
Timepoint [1] 0 0
Every 12 weeks. Maximum overall time on-study (treatment + follow up) at data cut off was 17.48 months.
Secondary outcome [1] 0 0
Complete Response Rate (CRR) Per Modified RECIST v1.1
Timepoint [1] 0 0
Every 12 weeks. Maximum overall time on-study (treatment + follow up) at data cut off was 17.48 months.
Secondary outcome [2] 0 0
Complete Response Rate (iCRR) Per Modified Immune-related Response Criteria (irRC) RECIST v1.1
Timepoint [2] 0 0
Every 12 weeks. Maximum overall time on-study (treatment + follow up) at data cut off was 17.48 months.
Secondary outcome [3] 0 0
BOR Per Modified RECIST v1.1
Timepoint [3] 0 0
Every 12 weeks. Maximum overall time on-study (treatment + follow up) at data cut off was 17.48 months.
Secondary outcome [4] 0 0
Best Overall Response (iBOR) Per Modified irRC-RECIST
Timepoint [4] 0 0
Every 12 weeks. Maximum overall time on-study (treatment + follow up) at data cut off was 17.48 months.
Secondary outcome [5] 0 0
Durable Response Rate (DRR) Per Modified RECIST v1.1
Timepoint [5] 0 0
Every 12 weeks. Maximum overall time on-study (treatment + follow up) at data cut off was 17.48 months.
Secondary outcome [6] 0 0
Durable Response Rate (iDRR) Per Modified irRC-RECIST
Timepoint [6] 0 0
Every 12 weeks. Maximum overall time on-study (treatment + follow up) at data cut off was 17.48 months.
Secondary outcome [7] 0 0
DOR Per Modified RECIST v1.1
Timepoint [7] 0 0
Every 12 weeks. Maximum overall time on-study (treatment + follow up) at data cut off was 17.48 months.
Secondary outcome [8] 0 0
iDOR Per Modified irRC-RECIST
Timepoint [8] 0 0
Every 12 weeks. Maximum overall time on-study (treatment + follow up) at data cut off was 17.48 months.
Secondary outcome [9] 0 0
Disease Control Rate (DCR) Per Modified RECIST v1.1
Timepoint [9] 0 0
Every 12 weeks. Maximum overall time on-study (treatment + follow up) at data cut off was 17.48 months.
Secondary outcome [10] 0 0
Disease Control Rate (iDCR) Per Modified irRC-RECIST
Timepoint [10] 0 0
Every 12 weeks. Maximum overall time on-study (treatment + follow up) at data cut off was 17.48 months.
Secondary outcome [11] 0 0
Objective Response Rate (iORR) Per Modified irRC-RECIST
Timepoint [11] 0 0
Every 12 weeks. Maximum overall time on-study (treatment + follow up) at data cut off was 17.48 months.
Secondary outcome [12] 0 0
Progression Free Survival (PFS) Per Modified RECIST v1.1
Timepoint [12] 0 0
Every 12 weeks. Maximum overall time on-study (treatment + follow up) at data cut off was 17.48 months.
Secondary outcome [13] 0 0
Progression Free Survival (iPFS) Per Modified irRC-RECIST
Timepoint [13] 0 0
Every 12 weeks. Maximum overall time on-study (treatment + follow up) at data cut off was 17.48 months.
Secondary outcome [14] 0 0
Overall Survival (OS)
Timepoint [14] 0 0
Every 12 weeks. Maximum overall time on-study (treatment + follow up) at data cut off was 17.48 months.
Secondary outcome [15] 0 0
Number of Participants Who Experienced a Treatment-emergent Adverse Event (TEAE)
Timepoint [15] 0 0
Day 1 to up to 90 days post-last dose of treatment. The maximum duration of talimogene laherparepvec treatment at data cut off was 74.7 weeks and pembrolizumab treatment at data cut off was 75.9 weeks.
Secondary outcome [16] 0 0
Time to First Subsequent Anti-cancer Therapy
Timepoint [16] 0 0
Every 12 weeks. Maximum overall time on-study (treatment + follow up) at data cut off was 17.48 months.
Secondary outcome [17] 0 0
DOR Per Modified RECIST v1.1
Timepoint [17] 0 0
Every 12 weeks up to 4 years
Secondary outcome [18] 0 0
iDOR Per Modified irRC-RECIST
Timepoint [18] 0 0
Every 12 weeks up to 4 years
Secondary outcome [19] 0 0
Progression Free Survival (PFS) Per Modified RECIST v1.1
Timepoint [19] 0 0
Every 12 weeks up to 4 years
Secondary outcome [20] 0 0
Progression Free Survival (iPFS) Per Modified irRC-RECIST
Timepoint [20] 0 0
Every 12 weeks up to 4 years
Secondary outcome [21] 0 0
Overall Survival (OS)
Timepoint [21] 0 0
Every 12 weeks up to 4 years
Secondary outcome [22] 0 0
Time to First Subsequent Anti-cancer Therapy
Timepoint [22] 0 0
Every 12 weeks up to 4 years

Eligibility
Key inclusion criteria
Key

* Age = 18 years with histologically confirmed diagnosis of stage IIIB to IVM1d melanoma and for whom surgery is not recommended. Subjects with stage IVM1d disease may be enrolled with up to 3 cerebral metastases, provided that all lesions have been adequately treated with stereotactic radiation therapy, craniotomy, or gamma knife therapy, with no evidence of progression and not requiring steroids for at least 2 months prior to enrollment.
* Subjects must have measurable disease and be a candidate for intralesional therapy administration into cutaneous, subcutaneous, or nodal lesions.
* Subjects must have had prior treatment (for at least 2 to 3 consecutive cycles within an 8 week period) with a PD-1 inhibitor and have confirmed disease progression (as defined by RECIST v1.1 criteria). The anti-PD-1 therapy must be the immediate prior line of therapy before enrollment and subjects with disease progression on more than 1 line of anti-PD-1 therapy are not eligible.
* ECOG performance status of 0 or 1.
* Adequate hematologic, renal, hepatic, and coagulation function.

Key
Minimum age
18 Years
Maximum age
99 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
* Subjects considered by the investigator to have rapid clinical progression due to melanoma
* Subjects with prior treatment and disease progression on more than 1 line of anti-PD-1 therapy
* Stage IVM1d subjects must not have greater than 3 cerebral melanoma metastases, or clinically active cerebral melanoma metastases requiring therapy, and/or carcinomatous meningitis regardless of clinical stability.
* 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 must not have history or evidence of symptomatic autoimmune glomerulonephritis, vasculitis, or other symptomatic autoimmune disease, or active 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 may not have been previously treated with talimogene laherparepvec or any other oncolytic virus.
* 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
Non-randomised 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
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
22/01/2020
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
26/02/2024
Sample size
Target
Accrual to date
Final
72
Recruitment in Australia
Recruitment state(s)
NSW,QLD,SA,VIC
Recruitment hospital [1] 0 0
Melanoma Institute Australia - North Sydney
Recruitment hospital [2] 0 0
Tasman Oncology Research - Southport
Recruitment hospital [3] 0 0
The Queen Elizabeth Hospital - Woodville South
Recruitment hospital [4] 0 0
Peter MacCallum Cancer Centre - Melbourne
Recruitment hospital [5] 0 0
The Alfred Hospital - Melbourne
Recruitment postcode(s) [1] 0 0
2060 - North Sydney
Recruitment postcode(s) [2] 0 0
4215 - Southport
Recruitment postcode(s) [3] 0 0
5011 - Woodville South
Recruitment postcode(s) [4] 0 0
3000 - Melbourne
Recruitment postcode(s) [5] 0 0
3004 - Melbourne
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
Delaware
Country [3] 0 0
United States of America
State/province [3] 0 0
Florida
Country [4] 0 0
United States of America
State/province [4] 0 0
Kentucky
Country [5] 0 0
United States of America
State/province [5] 0 0
Minnesota
Country [6] 0 0
United States of America
State/province [6] 0 0
New York
Country [7] 0 0
United States of America
State/province [7] 0 0
Ohio
Country [8] 0 0
United States of America
State/province [8] 0 0
Texas
Country [9] 0 0
Canada
State/province [9] 0 0
Ontario
Country [10] 0 0
Canada
State/province [10] 0 0
Quebec
Country [11] 0 0
France
State/province [11] 0 0
Bordeaux
Country [12] 0 0
France
State/province [12] 0 0
Grenoble Cedex 9
Country [13] 0 0
France
State/province [13] 0 0
Nantes Cedex 1
Country [14] 0 0
France
State/province [14] 0 0
Paris
Country [15] 0 0
France
State/province [15] 0 0
Pierre Benite Cedex
Country [16] 0 0
France
State/province [16] 0 0
Villejuif
Country [17] 0 0
Germany
State/province [17] 0 0
Dresden
Country [18] 0 0
Germany
State/province [18] 0 0
Hannover
Country [19] 0 0
Germany
State/province [19] 0 0
Regensburg
Country [20] 0 0
Germany
State/province [20] 0 0
Tübingen
Country [21] 0 0
Greece
State/province [21] 0 0
Athens
Country [22] 0 0
Greece
State/province [22] 0 0
Ioannina
Country [23] 0 0
Greece
State/province [23] 0 0
Thessaloniki
Country [24] 0 0
Italy
State/province [24] 0 0
Bergamo
Country [25] 0 0
Italy
State/province [25] 0 0
Meldola FC
Country [26] 0 0
Italy
State/province [26] 0 0
Milano
Country [27] 0 0
Netherlands
State/province [27] 0 0
Amsterdam
Country [28] 0 0
Netherlands
State/province [28] 0 0
Rotterdam
Country [29] 0 0
Poland
State/province [29] 0 0
Gdansk
Country [30] 0 0
Poland
State/province [30] 0 0
Poznan
Country [31] 0 0
Poland
State/province [31] 0 0
Warszawa
Country [32] 0 0
Spain
State/province [32] 0 0
AndalucÃ-a
Country [33] 0 0
Spain
State/province [33] 0 0
PaÃ-s Vasco
Country [34] 0 0
Spain
State/province [34] 0 0
Barcelona
Country [35] 0 0
Spain
State/province [35] 0 0
Madrid
Country [36] 0 0
United Kingdom
State/province [36] 0 0
London

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 LLC
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
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

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
De-identified individual patient data for variables necessary to address the specific research question in an approved data sharing request

Supporting document/s available: Study protocol, Statistical analysis plan (SAP), Informed consent form (ICF), Clinical study report (CSR)
When will data be available (start and end dates)?
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 have been granted marketing authorizationin 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.
Available to whom?
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. If not approved, a Data Sharing Independent Review Panel will arbitrate and make the final decision. 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.
Available for what types of analyses?
How or where can data be obtained?
IPD available at link: http://www.amgen.com/datasharing


What supporting documents are/will be available?




Results publications and other study-related documents

No documents have been uploaded by study researchers.


Results are available at https://clinicaltrials.gov/study/NCT04068181