Talimogene Laherparepvec With Pembrolizumab in Melanoma Following Progression on Prior Anti-PD-1 Based Therapy (MASTERKEY-115) (Mk-3475-A07/KEYNOTE-A07).

• ClinicalTrials.gov Identifier: NCT04068181
• Recruitment Status: Active, not recruiting
• First Posted: August 28, 2019
• Last Update Posted: February 18, 2021
• Sponsor: Amgen
• Collaborator: Merck Sharp & Dohme Corp.
• Information provided by (Responsible Party): Amgen

Study Description

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

Study Design

• 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: January 30, 2022
• Estimated Study Completion Date: July 31, 2024

Arms and Interventions

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.

Outcome Measures

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.

Eligibility Criteria

• 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.

Contacts and Locations

Locations

United States, California

Research Site

Santa Barbara, California, United States, 93105

United States, Delaware

Research Site

Newark, Delaware, United States, 19713

United States, Florida

Research Site

Orlando, Florida, United States, 32806

United States, Kentucky

Research Site

Louisville, Kentucky, United States, 40202

United States, Minnesota

Research Site

Fridley, Minnesota, United States, 55432

United States, New York

Research Site

Albany, New York, United States, 12208

United States, Ohio

Research Site

Cleveland, Ohio, United States, 44195

United States, Texas

Research Site

Austin, Texas, United States, 78731

Research Site

Dallas, Texas, United States, 75246

Research Site

The Woodlands, Texas, United States, 77380

Australia, New South Wales

Research Site

North Sydney, New South Wales, Australia, 2060

Australia, Queensland

Research Site

Southport, Queensland, Australia, 4215

Australia, South Australia

Research Site

Woodville South, South Australia, Australia, 5011

Australia, Victoria

Research Site

Melbourne, Victoria, Australia, 3000

Research Site

Melbourne, Victoria, Australia, 3004

Canada, Ontario

Research Site

Toronto, Ontario, Canada, M5G 2M9

Canada, Quebec

Research Site

Montreal, Quebec, Canada, H3T 1E2

Canada

Research Site

Quebec, Canada, G1R 2J6

France

Research Site

Bordeaux, France, 33075

Research Site

Grenoble Cedex 9, France, 38043

Research Site

Nantes Cedex 1, France, 44093

Research Site

Paris, France, 75010

Research Site

Pierre Benite Cedex, France, 69495

Research Site

Villejuif, France, 94805

Germany

Research Site

Berlin, Germany, 10117

Research Site

Dresden, Germany, 01307

Research Site

Hannover, Germany, 30625

Research Site

Regensburg, Germany, 93053

Research Site

Tübingen, Germany, 72076

Greece

Research Site

Athens, Greece, 11527

Research Site

Ioannina, Greece, 45500

Research Site

Thessaloniki, Greece, 546 22

Italy

Research Site

Bergamo, Italy, 24127

Research Site

Meldola FC, Italy, 47014

Research Site

Milano, Italy, 20141

Netherlands

Research Site

Amsterdam, Netherlands, 1066 CX

Research Site

Rotterdam, Netherlands, 3015 GD

Poland

Research Site

Gdansk, Poland, 80-214

Research Site

Poznan, Poland, 60-780

Research Site

Warszawa, Poland, 02-781

Spain

Research Site

Malaga, Andalucía, Spain, 29010

Research Site

San Sebastian, País Vasco, Spain, 20014

Research Site

Barcelona, Spain, 08035

Research Site

Madrid, Spain, 28046

Research Site

Madrid, Spain, 28050

United Kingdom

Research Site

London, United Kingdom, SE1 9RT

Research Site

London, United Kingdom, SW3 6JJ

Sponsors and Collaborators

Amgen

Merck Sharp & Dohme Corp.

Investigators

• Study Director: MD; Amgen

More Information

Additional Information:

AmgenTrials clinical trials website 

• Responsible Party: Amgen
• ClinicalTrials.gov Identifier: NCT04068181
• Other Study ID Numbers: 20180115; 2019-001906-61 ( EudraCT Number )
• First Posted: August 28, 2019
• Last Update Posted: February 18, 2021
• Last Verified: February 2021

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

• 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:

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