Clinical trial NCT04068181: Talimogene Laherparepvec With Pembrolizumab in Melanoma Following Progression on Prior Anti-PD-1 Based Therapy (MASTERKEY-115) (Mk-3475-A07/KEYNOTE-A07).
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Melanoma
Keywords: Melanoma
Talimogene Laherparepvec
Pembrolizumab
Oncolytic immunotherapy
Anti-PD-1
Checkpoint inhibitor
MASTERKEY-115
Lead sponsor: Amgen
Sponsor class: INDUSTRY
Collaborators: name: Merck Sharp & Dohme LLC
First posted: 2019-08-28
Enrollment: 72
Sex: ALL
Minimum age (years): 18
Maximum age (years): 99
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


Eligibility 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.

Primary outcomes:
measure: Objective Response Rate (ORR) Per Modified RECIST v1.1
timeFrame: Every 12 weeks. Maximum overall time on-study (treatment + follow up) was 46.23 months
Secondary outcomes:
measure: Complete Response Rate (CRR) Per Modified RECIST v1.1
timeFrame: Every 12 weeks. Maximum overall time on-study (treatment + follow up) was 46.23 months
measure: Complete Response Rate (iCRR) Per Modified Immune-related Response Criteria (irRC) RECIST v1.1
timeFrame: Every 12 weeks. Maximum overall time on-study (treatment + follow up) was 46.23 months
measure: BOR Per Modified RECIST v1.1
timeFrame: Every 12 weeks. Maximum overall time on-study (treatment + follow up) was 46.23 months
measure: Best Overall Response (iBOR) Per Modified irRC-RECIST
timeFrame: Every 12 weeks. Maximum overall time on-study (treatment + follow up) was 46.23 months
measure: Durable Response Rate (DRR) Per Modified RECIST v1.1
timeFrame: Every 12 weeks. Maximum overall time on-study (treatment + follow up) was 46.23 months
measure: Durable Response Rate (iDRR) Per Modified irRC-RECIST
timeFrame: Every 12 weeks. Maximum overall time on-study (treatment + follow up) was 46.23 months
measure: DOR Per Modified RECIST v1.1
timeFrame: Every 12 weeks. Maximum overall time on-study (treatment + follow up) was 46.23 months
measure: iDOR Per Modified irRC-RECIST
timeFrame: Every 12 weeks. Maximum overall time on-study (treatment + follow up) was 46.23 months
measure: Disease Control Rate (DCR) Per Modified RECIST v1.1
timeFrame: Every 12 weeks. Maximum overall time on-study (treatment + follow up) was 46.23 months
measure: Disease Control Rate (iDCR) Per Modified irRC-RECIST
timeFrame: Every 12 weeks. Maximum overall time on-study (treatment + follow up) was 46.23 months
measure: Objective Response Rate (iORR) Per Modified irRC-RECIST
timeFrame: Every 12 weeks. Maximum overall time on-study (treatment + follow up) was 46.23 months
measure: Progression Free Survival (PFS) Per Modified RECIST v1.1
timeFrame: Every 12 weeks. Maximum overall time on-study (treatment + follow up) was 46.23 months
measure: Progression Free Survival (iPFS) Per Modified irRC-RECIST
timeFrame: Every 12 weeks. Maximum overall time on-study (treatment + follow up) was 46.23 months
measure: Overall Survival (OS)
timeFrame: Every 12 weeks. Maximum overall time on-study (treatment + follow up) was 46.23 months
measure: Number of Participants Who Experienced a Treatment-emergent Adverse Event (TEAE)
timeFrame: Serious TEAEs were collected up to 90 days post-last dose of treatment. Non-serious TEAEs were collected up to 30 days post-last dose of treatment. The maximum duration of treatment exposure was 105.9 weeks.
measure: Time to First Subsequent Anti-cancer Therapy
timeFrame: Every 12 weeks. Maximum overall time on-study (treatment + follow up) was 46.23 months
Other outcomes:
Locations:
city: Santa Barbara
country: United States
facility: Sansum Clinic
state: California
city: Newark
country: United States
facility: Medical Oncology Hematology Consultants Helen F Graham Cancer Center
state: Delaware
city: Orlando
country: United States
facility: University of Florida Health Cancer Center at Orlando Health
state: Florida
city: Louisville
country: United States
facility: University of Louisville James Graham Brown Cancer Center
state: Kentucky
city: Fridley
country: United States
facility: Allina Health Systems dba Virginia Piper Cancer Institute
state: Minnesota
city: Albany
country: United States
facility: New York Oncology Hematology, PC
state: New York
city: Cleveland
country: United States
facility: Cleveland Clinic
state: Ohio
city: Austin
country: United States
facility: Texas Oncology Austin Central
state: Texas
city: Dallas
country: United States
facility: Baylor Scott and White Research Institute
state: Texas
city: The Woodlands
country: United States
facility: United States Oncology Regulatory Affairs Corporate Office
state: Texas
city: North Sydney
country: Australia
facility: Melanoma Institute Australia
state: New South Wales
city: Southport
country: Australia
facility: Tasman Oncology Research
state: Queensland
city: Woodville South
country: Australia
facility: The Queen Elizabeth Hospital
state: South Australia
city: Melbourne
country: Australia
facility: Peter MacCallum Cancer Centre
state: Victoria
city: Melbourne
country: Australia
facility: The Alfred Hospital
state: Victoria
city: Toronto
country: Canada
facility: Princess Margaret Cancer Centre
state: Ontario
city: Montreal
country: Canada
facility: Jewish General Hospital
state: Quebec
city: Quebec
country: Canada
facility: CHU de Quebec-Universite Laval
city: Bordeaux
country: France
facility: Centre Hospitalier Universitaire de Bordeaux - HÃ´pital Saint AndrÃ©
city: Grenoble Cedex 9
country: France
facility: Centre Hospitalier Universitaire de Grenoble - Hopital Nord Michallon
city: Nantes Cedex 1
country: France
facility: Centre Hospitalier Universitaire de Nantes, HÃ´pital HÃ´tel Dieu
city: Paris
country: France
facility: Hopital Saint Louis
city: Pierre Benite Cedex
country: France
facility: Centre Hospitalier Lyon Sud
city: Villejuif
country: France
facility: Gustave Roussy
city: Dresden
country: Germany
facility: UniversitÃ¤tsklinikum Carl Gustav Carus der Technischen UniversitÃ¤t Dresden
city: Hannover
country: Germany
facility: Medizinische Hochschule Hannover
city: Regensburg
country: Germany
facility: UniversitÃ¤tsklinikum Regensburg
city: TÃ¼bingen
country: Germany
facility: UniversitÃ¤tsklinikum TÃ¼bingen
city: Athens
country: Greece
facility: General Hospital of Athens Laiko
city: Ioannina
country: Greece
facility: University Hospital of Ioannina
city: Thessaloniki
country: Greece
facility: Bioclinic of Thessaloniki
city: Bergamo
country: Italy
facility: Azienda Socio Sanitaria Territoriale Papa Giovanni XXIII
city: Meldola FC
country: Italy
facility: IRCCS - Istituto Romagnolo per lo Studio dei Tumori (IRST) "Dino Amadori"
city: Milano
country: Italy
facility: IRCCS Istituto Europeo di Oncologia
city: Amsterdam
country: Netherlands
facility: Nederlands Kanker Instituut, Antoni van Leeuwenhoekziekenhuis
city: Rotterdam
country: Netherlands
facility: Erasmus Medisch Centrum
city: Gdansk
country: Poland
facility: Uniwersyteckie Centrum Kliniczne Centrum Medycyny Nieinwazyjnej
city: Poznan
country: Poland
facility: Szpital Kliniczny im Heliodora Swiecickiego Uniwersytetu Medycznego im Karola Marcinkowskiego w Pozn
city: Warszawa
country: Poland
facility: Narodowy Instytut Onkologii im Marii Sklodowskiej-Curie â€" Panstwowy Instytut Badawczy
city: Malaga
country: Spain
facility: Hospital Clinico Universitario Virgen de la Victoria
state: AndalucÃ-a
city: San Sebastian
country: Spain
facility: Onkologikoa
state: PaÃ-s Vasco
city: Barcelona
country: Spain
facility: Hospital Universitari Vall d Hebron
city: Madrid
country: Spain
facility: Hospital Universitario La Paz
city: Madrid
country: Spain
facility: Hospital Universitario Madrid Sanchinarro
city: London
country: United Kingdom
facility: Guys Hospital
city: London
country: United Kingdom
facility: Royal Marsden Hospital
Study officials:
affiliation: Amgen
name: MD
role: STUDY_DIRECTOR
References:
citation: 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.