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

NCT04068181 | Completed Phase 2 Results FDA Drug

• 2 other identifiers: 201801152019-001906-61
• Study Type: interventional
• Target: 72
• Locations: 11 countries
• Sites: 46

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

Keywords

Melanoma; Talimogene Laherparepvec; Pembrolizumab; Oncolytic immunotherapy; Anti-PD-1; Checkpoint inhibitor; MASTERKEY-115

Outcome Measures

Primary Outcomes (1)

• Objective Response Rate (ORR) Per Modified RECIST v1.1

  ORR was defined as the incidence of a best overall response (BOR) of complete response (CR) or partial response (PR) per modified RECIST v1.1: * CR: Disappearance of all target and non-target lesions. Any pathological lymph nodes (whether target or non-target) must have had a reduction in short axis to \< 10 mm. All lymph nodes must have been non-pathological in size (\< 10mm short axis). * PR: At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. * Non-CR/Non-progressive disease (PD): Persistence of 1 or more non-target lesion(s).

  Every 12 weeks. Maximum overall time on-study (treatment + follow up) was 46.23 months

Secondary Outcomes (16)

• Complete Response Rate (CRR) Per Modified RECIST v1.1

  Every 12 weeks. Maximum overall time on-study (treatment + follow up) was 46.23 months

• Complete Response Rate (iCRR) Per Modified Immune-related Response Criteria (irRC) RECIST v1.1

  Every 12 weeks. Maximum overall time on-study (treatment + follow up) was 46.23 months

• BOR Per Modified RECIST v1.1

  Every 12 weeks. Maximum overall time on-study (treatment + follow up) was 46.23 months

• Best Overall Response (iBOR) Per Modified irRC-RECIST

  Every 12 weeks. Maximum overall time on-study (treatment + follow up) was 46.23 months

• Durable Response Rate (DRR) Per Modified RECIST v1.1

  Every 12 weeks. Maximum overall time on-study (treatment + follow up) was 46.23 months

Study Arms (4)

Cohort 1 - Locally Recurrent/Metastatic - Primary Resistance

EXPERIMENTAL

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.

Drug: Talimogene laherparepvec; Drug: Pembrolizumab

Cohort 2 - Locally Recurrent/Metastatic - Acquired Resistance

EXPERIMENTAL

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.

Drug: Talimogene laherparepvec; Drug: Pembrolizumab

Cohort 3 - Adjuvant Setting -Disease Free Interval < 6 months

EXPERIMENTAL

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.

Drug: Talimogene laherparepvec; Drug: Pembrolizumab

Cohort 4 - Adjuvant Setting -Disease Free Interval ≥ 6 months

EXPERIMENTAL

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.

Drug: Talimogene laherparepvec; Drug: Pembrolizumab

Interventions

Talimogene laherparepvec DRUG

Intralesional injection into injectable cutaneous, subcutaneous and nodal legions.

Cohort 1 - Locally Recurrent/Metastatic - Primary Resistance; Cohort 2 - Locally Recurrent/Metastatic - Acquired Resistance; Cohort 3 - Adjuvant Setting -Disease Free Interval < 6 months; Cohort 4 - Adjuvant Setting -Disease Free Interval ≥ 6 months

Pembrolizumab DRUG

Intravenous (IV) infusion.

Cohort 1 - Locally Recurrent/Metastatic - Primary Resistance; Cohort 2 - Locally Recurrent/Metastatic - Acquired Resistance; Cohort 3 - Adjuvant Setting -Disease Free Interval < 6 months; Cohort 4 - Adjuvant Setting -Disease Free Interval ≥ 6 months

Eligibility Criteria

• Age: 18 Years - 99 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Amgen: lead
• Merck Sharp & Dohme LLC: collaborator

Study Sites (46)

Sansum Clinic

Santa Barbara, California, 93105, United States

Location

Medical Oncology Hematology Consultants Helen F Graham Cancer Center

Newark, Delaware, 19713, United States

Location

University of Florida Health Cancer Center at Orlando Health

Orlando, Florida, 32806, United States

Location

University of Louisville James Graham Brown Cancer Center

Louisville, Kentucky, 40202, United States

Location

Allina Health Systems dba Virginia Piper Cancer Institute

Fridley, Minnesota, 55432, United States

Location

New York Oncology Hematology, PC

Albany, New York, 12208, United States

Location

Cleveland Clinic

Cleveland, Ohio, 44195, United States

Location

Texas Oncology Austin Central

Austin, Texas, 78731, United States

Location

Baylor Scott and White Research Institute

Dallas, Texas, 75246, United States

Location

United States Oncology Regulatory Affairs Corporate Office

The Woodlands, Texas, 77380, United States

Location

Melanoma Institute Australia

North Sydney, New South Wales, 2060, Australia

Location

Tasman Oncology Research

Southport, Queensland, 4215, Australia

Location

The Queen Elizabeth Hospital

Woodville South, South Australia, 5011, Australia

Location

Peter MacCallum Cancer Centre

Melbourne, Victoria, 3000, Australia

Location

The Alfred Hospital

Melbourne, Victoria, 3004, Australia

Location

Princess Margaret Cancer Centre

Toronto, Ontario, M5G 2M9, Canada

Location

Jewish General Hospital

Montreal, Quebec, H3T 1E2, Canada

Location

CHU de Quebec-Universite Laval

Québec, Quebec, G1R 2J6, Canada

Location

Centre Hospitalier Universitaire de Bordeaux - Hôpital Saint André

Bordeaux, 33075, France

Location

Centre Hospitalier Universitaire de Grenoble - Hopital Nord Michallon

Grenoble, 38043, France

Location

Centre Hospitalier Universitaire de Nantes, Hôpital Hôtel Dieu

Nantes, 44093, France

Location

Hopital Saint Louis

Paris, 75010, France

Location

Centre Hospitalier Lyon Sud

Pierre-Bénite, 69495, France

Location

Gustave Roussy

Villejuif, 94805, France

Location

Universitätsklinikum Carl Gustav Carus der Technischen Universität Dresden

Dresden, 01307, Germany

Location

Medizinische Hochschule Hannover

Hanover, 30625, Germany

Location

Universitätsklinikum Regensburg

Regensburg, 93053, Germany

Location

Universitätsklinikum Tübingen

Tübingen, 72076, Germany

Location

General Hospital of Athens Laiko

Athens, 11527, Greece

Location

University Hospital of Ioannina

Ioannina, 45500, Greece

Location

Bioclinic of Thessaloniki

Thessaloniki, 546 22, Greece

Location

Azienda Socio Sanitaria Territoriale Papa Giovanni XXIII

Bergamo, 24127, Italy

Location

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

Meldola FC, 47014, Italy

Location

IRCCS Istituto Europeo di Oncologia

Milan, 20141, Italy

Location

Nederlands Kanker Instituut, Antoni van Leeuwenhoekziekenhuis

Amsterdam, 1066 CX, Netherlands

Location

Erasmus Medisch Centrum

Rotterdam, 3015 GD, Netherlands

Location

Uniwersyteckie Centrum Kliniczne Centrum Medycyny Nieinwazyjnej

Gdansk, 80-214, Poland

Location

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

Poznan, 60-780, Poland

Location

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

Warsaw, 02-781, Poland

Location

Hospital Clinico Universitario Virgen de la Victoria

Málaga, AndalucÃ-a, 29010, Spain

Location

Onkologikoa

Donostia / San Sebastian, PaÃ-s Vasco, 20014, Spain

Location

Hospital Universitari Vall d Hebron

Barcelona, 08035, Spain

Location

Hospital Universitario La Paz

Madrid, 28046, Spain

Location

Hospital Universitario Madrid Sanchinarro

Madrid, 28050, Spain

Location

Guys Hospital

London, SE1 9RT, United Kingdom

Location

Royal Marsden Hospital

London, SW3 6JJ, United Kingdom

Location

Related Publications (1)

• 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.

  PMID: 38870745 BACKGROUND

Related Links

• AmgenTrials clinical trials website

MeSH Terms

Conditions

Melanoma

Interventions

talimogene laherparepvec; pembrolizumab

Condition Hierarchy (Ancestors)

Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Neoplasms by Site; Skin Diseases; Skin and Connective Tissue Diseases

Results Point of Contact

• Title: Study Director
• Organization: Amgen Inc.

medinfo@amgen.com

866-572-6436

Study Officials

• MD

  Amgen

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 22, 2019
• First Posted: August 28, 2019
• Study Start: January 22, 2020
• Primary Completion: August 19, 2021
• Study Completion: February 26, 2024
• Last Updated: January 7, 2025
• Results First Posted: September 9, 2022

Record last verified: 2024-11

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, 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 authorization in 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.

Locations

DE (4); IT (3); US (10); AU (5); FR (6); ES (5); PL (3); CA (3); GB (2); NL (2); GR (3)