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

NCT ID: NCT04068181

Last Updated: 2025-01-07

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 72 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-01-22
• Study Completion Date: 2024-02-26

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-programmed cell death protein (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.

Conditions

Melanoma

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

Talimogene laherparepvec

Intervention Type: DRUG

Intralesional injection into injectable cutaneous, subcutaneous and nodal legions.

Pembrolizumab

Intervention Type: DRUG

Intravenous (IV) infusion.

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.

Group Type: EXPERIMENTAL

Talimogene laherparepvec

Intervention Type: DRUG

Intralesional injection into injectable cutaneous, subcutaneous and nodal legions.

Pembrolizumab

Intervention Type: DRUG

Intravenous (IV) infusion.

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.

Group Type: EXPERIMENTAL

Talimogene laherparepvec

Intervention Type: DRUG

Intralesional injection into injectable cutaneous, subcutaneous and nodal legions.

Pembrolizumab

Intervention Type: DRUG

Intravenous (IV) infusion.

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.

Group Type: EXPERIMENTAL

Talimogene laherparepvec

Intervention Type: DRUG

Intralesional injection into injectable cutaneous, subcutaneous and nodal legions.

Pembrolizumab

Intervention Type: DRUG

Intravenous (IV) infusion.

Interventions

Talimogene laherparepvec

Intralesional injection into injectable cutaneous, subcutaneous and nodal legions.

Intervention Type: DRUG

Pembrolizumab

Intravenous (IV) infusion.

Intervention Type: DRUG

Eligibility Criteria

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.

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 99 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Merck Sharp & Dohme LLC

INDUSTRY

Sponsor Role: collaborator

Amgen

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

MD

Role: STUDY_DIRECTOR

Amgen

Locations

Sansum Clinic

Santa Barbara, California, United States

Medical Oncology Hematology Consultants Helen F Graham Cancer Center

Newark, Delaware, United States

University of Florida Health Cancer Center at Orlando Health

Orlando, Florida, United States

University of Louisville James Graham Brown Cancer Center

Louisville, Kentucky, United States

Allina Health Systems dba Virginia Piper Cancer Institute

Fridley, Minnesota, United States

New York Oncology Hematology, PC

Albany, New York, United States

Cleveland Clinic

Cleveland, Ohio, United States

Texas Oncology Austin Central

Austin, Texas, United States

Baylor Scott and White Research Institute

Dallas, Texas, United States

United States Oncology Regulatory Affairs Corporate Office

The Woodlands, Texas, United States

Melanoma Institute Australia

North Sydney, New South Wales, Australia

Tasman Oncology Research

Southport, Queensland, Australia

The Queen Elizabeth Hospital

Woodville South, South Australia, Australia

Peter MacCallum Cancer Centre

Melbourne, Victoria, Australia

The Alfred Hospital

Melbourne, Victoria, Australia

Princess Margaret Cancer Centre

Toronto, Ontario, Canada

Jewish General Hospital

Montreal, Quebec, Canada

CHU de Quebec-Universite Laval

Québec, Quebec, Canada

Centre Hospitalier Universitaire de Bordeaux - Hôpital Saint André

Bordeaux, , France

Centre Hospitalier Universitaire de Grenoble - Hopital Nord Michallon

Grenoble, , France

Centre Hospitalier Universitaire de Nantes, Hôpital Hôtel Dieu

Nantes, , France

Hopital Saint Louis

Paris, , France

Centre Hospitalier Lyon Sud

Pierre-Bénite, , France

Gustave Roussy

Villejuif, , France

Universitätsklinikum Carl Gustav Carus der Technischen Universität Dresden

Dresden, , Germany

Medizinische Hochschule Hannover

Hanover, , Germany

Universitätsklinikum Regensburg

Regensburg, , Germany

Universitätsklinikum Tübingen

Tübingen, , Germany

General Hospital of Athens Laiko

Athens, , Greece

University Hospital of Ioannina

Ioannina, , Greece

Bioclinic of Thessaloniki

Thessaloniki, , Greece

Azienda Socio Sanitaria Territoriale Papa Giovanni XXIII

Bergamo, , Italy

IRCCS - Istituto Romagnolo per lo Studio dei Tumori (IRST) "Dino Amadori"

Meldola FC, , Italy

IRCCS Istituto Europeo di Oncologia

Milan, , Italy

Nederlands Kanker Instituut, Antoni van Leeuwenhoekziekenhuis

Amsterdam, , Netherlands

Erasmus Medisch Centrum

Rotterdam, , Netherlands

Uniwersyteckie Centrum Kliniczne Centrum Medycyny Nieinwazyjnej

Gdansk, , Poland

Szpital Kliniczny im Heliodora Swiecickiego Uniwersytetu Medycznego im Karola Marcinkowskiego w Pozn

Poznan, , Poland

Narodowy Instytut Onkologii im Marii Sklodowskiej-Curie â€" Panstwowy Instytut Badawczy

Warsaw, , Poland

Hospital Clinico Universitario Virgen de la Victoria

Málaga, AndalucÃ-a, Spain

Onkologikoa

Donostia / San Sebastian, PaÃ-s Vasco, Spain

Hospital Universitari Vall d Hebron

Barcelona, , Spain

Hospital Universitario La Paz

Madrid, , Spain

Hospital Universitario Madrid Sanchinarro

Madrid, , Spain

Guys Hospital

London, , United Kingdom

Royal Marsden Hospital

London, , United Kingdom

Countries

United States; Australia; Canada; France; Germany; Greece; Italy; Netherlands; Poland; Spain; United Kingdom

References

Robert C, Gastman B, Gogas H, Rutkowski P, Long GV, Chaney MF, Joshi H, Lin YL, Snyder W, Chesney JA. Open-label, phase II study of talimogene laherparepvec plus pembrolizumab for the treatment of advanced melanoma that progressed on prior anti-PD-1 therapy: MASTERKEY-115. Eur J Cancer. 2024 Aug;207:114120. doi: 10.1016/j.ejca.2024.114120. Epub 2024 May 15.

Reference Type: BACKGROUND

PMID: 38870745 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Related Links

http://www.amgentrials.com

AmgenTrials clinical trials website

Other Identifiers

2019-001906-61

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

20180115

Identifier Type: -

Identifier Source: org_study_id