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Trial details imported from ClinicalTrials.gov

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




Registration number
NCT04068181
Ethics application status
Date submitted
22/08/2019
Date registered
28/08/2019
Date last updated
5/11/2020

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: Talimogene Laherparepvec and Pembrolizumab - To evaluate the efficacy and safety of talimogene laherparepvec in combination with pembrolizumab following disease progression on prior anti-PD-1 therapy in unresectable/metastatic melanoma (stage IIIB-IVM1d) or prior anti-PD-1 therapy in the adjuvant setting.


Treatment: Drugs: Talimogene laherparepvec
On day 1 the first dose of talimogene laherparepvec will be up to 4.0 mL of 10^6 PFU/mL by intralesional injection into injectable cutaneous, subcutaneous, and nodal lesions with or without image ultrasound guidance. The second dose of up to 4.0 mL of 10^8 PFU/mL talimogene laherparepvec will be administered 21 days after the initial dose.
Subsequent doses of up to 4.0 mL of 10^8 PFU/mL talimogene laherparepvec will be given every 3 weeks.

Treatment: Drugs: Pembrolizumab
Pembrolizumab will be administered intravenously at a fixed dose of 200 mg every 3 weeks.

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

Outcomes
Primary outcome [1] 0 0
Overall response (Complete Response [CR] plus partial response [PR] by investigator assessment using modified Response Evaluation Criteria in Solid Tumor [RECIST v1.1]) - To evaluate the efficacy of talimogene laherparepvec in combination with pembrolizumab as assessed by Objective Response Rate (ORR) in subjects with unresectable/metastatic stage IIIB-IVM1d melanoma who have progressed on prior anti-PD-1 therapy.
Timepoint [1] 0 0
Up to 4 years
Secondary outcome [1] 0 0
Complete Response by investigator assessment using modified Response Evaluation Criteria in Solid Tumor (RECIST v1.1) and modified immune-related Response Criteria simulating Response Evaluation Criteria in Solid Tumors (irRC-RECIST). - To evaluate the efficacy of talimogene laherparepvec in combination with pembrolizumab, as assessed by Complete Response Rate.
Timepoint [1] 0 0
Up to 4 years
Secondary outcome [2] 0 0
Best Overall Response (BOR) by investigator assessment using modified Response Evaluation Criteria in Solid Tumor (RECIST v1.1) and modified immune-related Response Criteria simulating Response Evaluation Criteria in Solid Tumors (irRC-RECIST). - To evaluate the efficacy of talimogene laherparepvec in combination with pembrolizumab, as assessed by Best Overall Response.
Timepoint [2] 0 0
Up to 4 years
Secondary outcome [3] 0 0
Durable Response by investigator assessment using modified Response Evaluation Criteria in Solid Tumor (RECIST v1.1) and modified immune-related Response Criteria simulating Response Evaluation Criteria in Solid Tumors (irRC-RECIST). - To evaluate the efficacy of talimogene laherparepvec in combination with pembrolizumab, as assessed by Durable Response Rate.
Timepoint [3] 0 0
Up to 4 years
Secondary outcome [4] 0 0
Duration Of Response (DOR) by investigator assessment using modified Response Evaluation Criteria in Solid Tumor (RECIST v1.1) and modified immune-related Response Criteria simulating Response Evaluation Criteria in Solid Tumors (irRC-RECIST). - To evaluate the efficacy of talimogene laherparepvec in combination with pembrolizumab, as assessed by Duration Of Response.
Timepoint [4] 0 0
Up to 4 years
Secondary outcome [5] 0 0
Disease Control by investigator assessment using modified Response Evaluation Criteria in Solid Tumor (RECIST v1.1) and modified immune-related Response Criteria simulating Response Evaluation Criteria in Solid Tumors (irRC-RECIST). - To evaluate the efficacy of talimogene laherparepvec in combination with pembrolizumab, as assessed by Disease Control Rate.
Timepoint [5] 0 0
Up to 4 years
Secondary outcome [6] 0 0
Overall Response by investigator assessment using modified immune-related Response Criteria simulating Response Evaluation Criteria in Solid Tumors (irRC-RECIST). - To evaluate the efficacy of talimogene laherparepvec in combination with pembrolizumab, as assessed by Objective Response Rate using modified irRC-RECIST.
Timepoint [6] 0 0
Up to 4 years
Secondary outcome [7] 0 0
Progression Free Survival (PFS) by investigator assessment using modified Response Evaluation Criteria in Solid Tumor (RECIST) v1.1 and modified immune-related Response Criteria simulating Response evaluation criteria in Solid Tumors (irRC-RECIST). - To evaluate the efficacy of talimogene laherparepvec in combination with pembrolizumab, as assessed by Progression Free Survival.
Timepoint [7] 0 0
Up to 4 years
Secondary outcome [8] 0 0
Overall Survival (OS) - To evaluate the efficacy of talimogene laherparepvec in combination with pembrolizumab, as assessed by Overall Survival.
Timepoint [8] 0 0
Up to 4 years
Secondary outcome [9] 0 0
Incidence of treatment-emergent adverse events. - To evaluate the safety of talimogene laherparepvec in combination with pembrolizumab as assessed by incidence of treatment emergent adverse events in patients who have progressed on prior anti-PD-1 therapy.
Timepoint [9] 0 0
Up to 4 years
Secondary outcome [10] 0 0
Incidence of treatment related adverse events. - To evaluate the safety of talimogene laherparepvec in combination with pembrolizumab as assessed by incidence of treatment-related adverse events in patients who have progressed on prior anti-PD-1 therapy.
Timepoint [10] 0 0
Up to 4 years
Secondary outcome [11] 0 0
Incidence of abnormal laboratory tests. - To evaluate the safety of talimogene laherparepvec in combination with pembrolizumab as assessed by abnormal laboratory tests in patients who have progressed on prior anti-PD-1 therapy.
Timepoint [11] 0 0
Up to 4 years
Secondary outcome [12] 0 0
Time to subsequent anti-cancer therapy. - To evaluate time to subsequent anti-cancer therapy.
Timepoint [12] 0 0
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
Gender
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
N/A
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
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
Recruitment hospital [1] 0 0
Research Site - North Sydney
Recruitment hospital [2] 0 0
Research Site - Southport
Recruitment hospital [3] 0 0
Research Site - Woodville South
Recruitment hospital [4] 0 0
Research Site - 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
Warszawa
Country [31] 0 0
Spain
State/province [31] 0 0
Andalucía
Country [32] 0 0
Spain
State/province [32] 0 0
País Vasco
Country [33] 0 0
Spain
State/province [33] 0 0
Barcelona
Country [34] 0 0
Spain
State/province [34] 0 0
Madrid
Country [35] 0 0
United Kingdom
State/province [35] 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 Corp.
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
This is a phase 2, open-label, single-arm, multicenter clinical trial designed to evaluate
the efficacy and safety of talimogene laherparepvec in combination with pembrolizumab
following disease progression on prior anti-PD-1 therapy in unresectable/metastatic melanoma
(stage IIIB-IVM1d) or prior anti-PD-1 therapy in the adjuvant setting. Subjects will be
treated with talimogene laherparepvec and pembrolizumab until confirmed complete response,
disappearance of all injectable lesions, documented confirmed disease progression per
modified immune-related Response Criteria simulating Response Evaluation Criteria in Solid
Tumors (irRC-RECIST), intolerance of study treatment, or 102 weeks from the first dose of
talimogene laherparepvec and/or pembrolizumab, whichever occurs first.
Trial website
https://clinicaltrials.gov/show/NCT04068181
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
Amgen Call Center
Address 0 0
Country 0 0
Phone 0 0
866-572-6436
Fax 0 0
Email 0 0
medinfo@amgen.com
Contact person for scientific queries

Summary results
For IPD and results data, please see https://clinicaltrials.gov/show/NCT04068181