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Talimogene Laherparepvec With Pembrolizumab in Melanoma Following Progression on Prior Anti-PD-1 Based Therapy (MASTERKEY-115)

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ClinicalTrials.gov Identifier: NCT04068181
Recruitment Status : Recruiting
First Posted : August 28, 2019
Last Update Posted : August 6, 2020
Sponsor:
Collaborator:
Merck Sharp & Dohme Corp.
Information provided by (Responsible Party):
Amgen

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.

Condition or disease Intervention/treatment Phase
Melanoma Drug: Talimogene laherparepvec Drug: Pembrolizumab Phase 2

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 100 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official 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
Actual Study Start Date : January 22, 2020
Estimated Primary Completion Date : May 23, 2021
Estimated Study Completion Date : November 23, 2023


Arm Intervention/treatment
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.
Drug: 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.


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




Primary Outcome Measures :
  1. Overall response (Complete Response [CR] plus partial response [PR] by investigator assessment using modified Response Evaluation Criteria in Solid Tumor [RECIST v1.1]) [ Time Frame: Up to 4 years ]
    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.


Secondary Outcome Measures :
  1. 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). [ Time Frame: Up to 4 years ]
    To evaluate the efficacy of talimogene laherparepvec in combination with pembrolizumab, as assessed by Complete Response Rate.

  2. 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). [ Time Frame: Up to 4 years ]
    To evaluate the efficacy of talimogene laherparepvec in combination with pembrolizumab, as assessed by Best Overall Response.

  3. 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). [ Time Frame: Up to 4 years ]
    To evaluate the efficacy of talimogene laherparepvec in combination with pembrolizumab, as assessed by Durable Response Rate.

  4. 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). [ Time Frame: Up to 4 years ]
    To evaluate the efficacy of talimogene laherparepvec in combination with pembrolizumab, as assessed by Duration Of Response.

  5. 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). [ Time Frame: Up to 4 years ]
    To evaluate the efficacy of talimogene laherparepvec in combination with pembrolizumab, as assessed by Disease Control Rate.

  6. Overall Response by investigator assessment using modified immune-related Response Criteria simulating Response Evaluation Criteria in Solid Tumors (irRC-RECIST). [ Time Frame: Up to 4 years ]
    To evaluate the efficacy of talimogene laherparepvec in combination with pembrolizumab, as assessed by Objective Response Rate using modified irRC-RECIST.

  7. 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). [ Time Frame: Up to 4 years ]
    To evaluate the efficacy of talimogene laherparepvec in combination with pembrolizumab, as assessed by Progression Free Survival.

  8. Overall Survival (OS) [ Time Frame: Up to 4 years ]
    To evaluate the efficacy of talimogene laherparepvec in combination with pembrolizumab, as assessed by Overall Survival.

  9. Incidence of treatment-emergent adverse events. [ Time Frame: Up to 4 years ]
    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.

  10. Incidence of treatment related adverse events. [ Time Frame: Up to 4 years ]
    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.

  11. Incidence of abnormal laboratory tests. [ Time Frame: Up to 4 years ]
    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.

  12. Time to subsequent anti-cancer therapy. [ Time Frame: Up to 4 years ]
    To evaluate time to subsequent anti-cancer therapy.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 99 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Key Inclusion Criteria:

  • 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 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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04068181


Contacts
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Contact: Amgen Call Center 866-572-6436 medinfo@amgen.com

Locations
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United States, California
Research Site Recruiting
Santa Barbara, California, United States, 93105
United States, Delaware
Research Site Recruiting
Newark, Delaware, United States, 19713
United States, Florida
Research Site Recruiting
Orlando, Florida, United States, 32806
United States, Kentucky
Research Site Recruiting
Louisville, Kentucky, United States, 40202
United States, Minnesota
Research Site Recruiting
Fridley, Minnesota, United States, 55432
United States, Ohio
Research Site Recruiting
Cleveland, Ohio, United States, 44195
United States, Texas
Research Site Recruiting
Austin, Texas, United States, 78731
Research Site Recruiting
Dallas, Texas, United States, 75246
Research Site Recruiting
The Woodlands, Texas, United States, 77380
Australia, Queensland
Research Site Recruiting
Southport, Queensland, Australia, 4215
Australia, South Australia
Research Site Recruiting
Woodville South, South Australia, Australia, 5011
Australia, Victoria
Research Site Recruiting
Melbourne, Victoria, Australia, 3000
Research Site Recruiting
Melbourne, Victoria, Australia, 3004
France
Research Site Recruiting
Grenoble Cedex 9, France, 38043
Research Site Recruiting
Nantes Cedex 1, France, 44093
Research Site Recruiting
Paris, France, 75010
Research Site Recruiting
Pierre Benite Cedex, France, 69495
Research Site Recruiting
Villejuif, France, 94805
Germany
Research Site Recruiting
Dresden, Germany, 01307
Research Site Recruiting
Hannover, Germany, 30625
Research Site Recruiting
Regensburg, Germany, 93053
Greece
Research Site Recruiting
Athens, Greece, 11527
Research Site Recruiting
Ioannina, Greece, 45500
Research Site Recruiting
Thessaloniki, Greece, 546 22
Italy
Research Site Recruiting
Meldola FC, Italy, 47014
Research Site Recruiting
Milano, Italy, 20141
Netherlands
Research Site Recruiting
Amsterdam, Netherlands, 1066 CX
Poland
Research Site Recruiting
Gdansk, Poland, 80-214
Research Site Recruiting
Warszawa, Poland, 02-781
Spain
Research Site Recruiting
Madrid, Spain, 28046
Research Site Recruiting
Madrid, Spain, 28050
Sponsors and Collaborators
Amgen
Merck Sharp & Dohme Corp.
Investigators
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Study Director: MD Amgen
Additional Information:
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Responsible Party: Amgen
ClinicalTrials.gov Identifier: NCT04068181    
Other Study ID Numbers: 20180115
2019-001906-61 ( EudraCT Number )
First Posted: August 28, 2019    Key Record Dates
Last Update Posted: August 6, 2020
Last Verified: August 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: De-identified individual patient data for variables necessary to address the specific research question in an approved data sharing request
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Informed Consent Form (ICF)
Clinical Study Report (CSR)
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 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.
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. 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.
URL: http://www.amgen.com/datasharing

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Amgen:
Melanoma
Talimogene Laherparepvec
Pembrolizumab
Oncolytic immunotherapy
Anti-PD-1
Checkpoint inhibitor
MASTERKEY-115
Additional relevant MeSH terms:
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Melanoma
Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Nerve Tissue
Nevi and Melanomas
Pembrolizumab
Talimogene laherparepvec
Antineoplastic Agents, Immunological
Antineoplastic Agents