MelanomaPhase 2NCT04068181
Talimogene Laherparepvec With Pembrolizumab in Melanoma Following Progression on Prior Anti-PD-1 Based Therapy (MASTERKEY-115) (Mk-3475-A07/KEYNOTE-A07).
A Phase 2 study testing Talimogene laherparepvec and Pembrolizumab in people with Melanoma, run by Amgen at 46 sites in 11 countries.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 to 99 years
- Conditions the study is for
- Melanoma
- What is being tested?
- Talimogene laherparepvec and Pembrolizumab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 72 participants
- Where
- 46 sitesin 11 countries
- Study dates
- 22 Jan 2020to 26 Feb 2024
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 99 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
Trial locations and contacts
46 sites in 11 countries.
46 sites in 11 countries
United States10 sites
New York Oncology Hematology, PC
Albany, New York, 12208
Texas Oncology Austin Central
Austin, Texas, 78731
Cleveland Clinic
Cleveland, Ohio, 44195
Baylor Scott and White Research Institute
Dallas, Texas, 75246
Allina Health Systems dba Virginia Piper Cancer Institute
Fridley, Minnesota, 55432
University of Louisville James Graham Brown Cancer Center
Louisville, Kentucky, 40202
Medical Oncology Hematology Consultants Helen F Graham Cancer Center
Newark, Delaware, 19713
University of Florida Health Cancer Center at Orlando Health
Orlando, Florida, 32806
Sansum Clinic
Santa Barbara, California, 93105
United States Oncology Regulatory Affairs Corporate Office
The Woodlands, Texas, 77380
France6 sites
Centre Hospitalier Universitaire de Bordeaux - Hôpital Saint André
Bordeaux, 33075
Centre Hospitalier Universitaire de Grenoble - Hopital Nord Michallon
Grenoble, 38043
Centre Hospitalier Universitaire de Nantes, Hôpital Hôtel Dieu
Nantes, 44093
Hopital Saint Louis
Paris, 75010
Centre Hospitalier Lyon Sud
Pierre-Bénite, 69495
Gustave Roussy
Villejuif, 94805
Australia5 sites
Peter MacCallum Cancer Centre
Melbourne, Victoria, 3000
The Alfred Hospital
Melbourne, Victoria, 3004
Melanoma Institute Australia
North Sydney, New South Wales, 2060
Tasman Oncology Research
Southport, Queensland, 4215
The Queen Elizabeth Hospital
Woodville South, South Australia, 5011
Spain5 sites
Hospital Universitari Vall d Hebron
Barcelona, 08035
Onkologikoa
Donostia / San Sebastian, PaÃ-s Vasco, 20014
Hospital Universitario La Paz
Madrid, 28046
Hospital Universitario Madrid Sanchinarro
Madrid, 28050
Hospital Clinico Universitario Virgen de la Victoria
Málaga, AndalucÃ-a, 29010
Germany4 sites
Universitätsklinikum Carl Gustav Carus der Technischen Universität Dresden
Dresden, 01307
Medizinische Hochschule Hannover
Hanover, 30625
Universitätsklinikum Regensburg
Regensburg, 93053
Universitätsklinikum Tübingen
Tübingen, 72076
Canada3 sites
Jewish General Hospital
Montreal, Quebec, H3T 1E2
CHU de Quebec-Universite Laval
Québec, Quebec, G1R 2J6
Princess Margaret Cancer Centre
Toronto, Ontario, M5G 2M9
Greece3 sites
General Hospital of Athens Laiko
Athens, 11527
University Hospital of Ioannina
Ioannina, 45500
Bioclinic of Thessaloniki
Thessaloniki, 546 22
Italy3 sites
Azienda Socio Sanitaria Territoriale Papa Giovanni XXIII
Bergamo, 24127
IRCCS - Istituto Romagnolo per lo Studio dei Tumori (IRST) "Dino Amadori"
Meldola FC, 47014
IRCCS Istituto Europeo di Oncologia
Milan, 20141
Poland3 sites
Uniwersyteckie Centrum Kliniczne Centrum Medycyny Nieinwazyjnej
Gdansk, 80-214
Szpital Kliniczny im Heliodora Swiecickiego Uniwersytetu Medycznego im Karola Marcinkowskiego w Pozn
Poznan, 60-780
Narodowy Instytut Onkologii im Marii Sklodowskiej-Curie â€" Panstwowy Instytut Badawczy
Warsaw, 02-781
Netherlands2 sites
Nederlands Kanker Instituut, Antoni van Leeuwenhoekziekenhuis
Amsterdam, 1066 CX
Erasmus Medisch Centrum
Rotterdam, 3015 GD
United Kingdom2 sites
Guys Hospital
London, SE1 9RT
Royal Marsden Hospital
London, SW3 6JJ
About this study
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
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
- Being tested
- Talimogene laherparepvec, Pembrolizumab
- Keywords
- Melanoma, Talimogene Laherparepvec, Pembrolizumab, Oncolytic immunotherapy, Anti-PD-1, Checkpoint inhibitor, MASTERKEY-115
- Medical subject headings
- Melanoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Talimogene laherparepvecDrug
Intralesional injection into injectable cutaneous, subcutaneous and nodal legions.
PembrolizumabDrug
Intravenous (IV) infusion.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: 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. Receives: 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. Receives: Drug: Talimogene laherparepvec; Drug: Pembrolizumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
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).
Measured: 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
CRR was defined as the incidence of a BOR of CR 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).
Confirmation of CR was not required per modified RECIST v1.1.
Measured: 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
iCRR was defined as the incidence of a best overall response (iBOR) of a complete response (iCR) per modified irRC-RECIST:
- iCR: Disappearance of all lesions (whether measurable or not and whether baseline or new). Any pathological lymph nodes (whether target or nontarget) must have had a reduction in short axis to < 10 mm.
Confirmation of iCR was required per modified irRC-RECIST.
Measured: Every 12 weeks. Maximum overall time on-study (treatment + follow up) was 46.23 months
BOR Per Modified RECIST v1.1
BOR was the best overall visit response up to \& including the first overall visit response of PD:
- CR: Disappearance of all target \& non-target lesions. Any pathological lymph nodes must have had a reduction in short axis to <10 mm. All lymph nodes must have been non-pathological in size.
- PR: ≥30% decrease in the sum of diameters of target lesions.
- Stable disease (SD): Neither sufficient shrinkage to qualify for PR/CR nor sufficient increase to qualify for PD.
- PD: ≥20% increase in the sum of diameters of target lesions and an increase of ≥5mm. Progression of existing non-target lesions.
- Unable to evaluate (UE): Any lesion present at baseline which was not assessed or unable to be evaluated leading to an inability to determine the status of that particular tumor.
- Non-CR/Non-PD: Persistence of 1+ non-target lesion(s). Non-CR/non-PD was relevant to participants who did not have measurable disease at baseline.
Confirmation of CR, PR \& PD were not required per modified RECIST 1.1.
Measured: Every 12 weeks. Maximum overall time on-study (treatment + follow up) was 46.23 months
Best Overall Response (iBOR) Per Modified irRC-RECIST
iBOR was defined as the best overall visit response up to and including the first overall visit response of progressive disease (iPD) per modified irRC-RECIST:
- iCR: Disappearance of all lesions (whether measurable or not and whether baseline or new). Any pathological lymph nodes (whether target or nontarget) must have a reduction in short axis to < 10 mm.
- Partial response (iPR): Decrease in tumor burden ≥ 30% relative to baseline.
- Stable disease (iSD): Neither sufficient shrinkage to qualify for iPR or iCR nor sufficient increase to qualify for iPD.
- iPD: Increase in tumor burden ≥ 20% and at least 5 mm absolute increase.
- Unable to evaluate (iUE): Any lesion present at baseline or a new measurable lesion which was not assessed or was unable to be evaluated leading to an inability to determine the status of that particular tumor for that time point.
Confirmation of iCR, iPR and iPD was required per modified irRC-RECIST.
Measured: Every 12 weeks. Maximum overall time on-study (treatment + follow up) was 46.23 months
Durable Response Rate (DRR) Per Modified RECIST v1.1
DRR was defined as the percentage of participants with a CR or PR per modified RECIST v1.1 with a duration of response (DOR) ≥ 6 months. One month was calculated based on 365.25 days per year.
- 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.
Confirmation of CR and PR were not required per modified RECIST v1.1.
Measured: Every 12 weeks. Maximum overall time on-study (treatment + follow up) was 46.23 months
Durable Response Rate (iDRR) Per Modified irRC-RECIST
iDRR was defined as the percentage of participants with an iCR or iPR per modified irRC-RECIST with a duration of response (iDOR) ≥ 6 months. One month was calculated based on 365.25 days per year.
- iCR: Disappearance of all lesions (whether measurable or not and whether baseline or new). Any pathological lymph nodes (whether target or nontarget) must have a reduction in short axis to < 10 mm.
- iPR: Decrease in tumor burden ≥ 30% relative to baseline.
Confirmation of iCR and iPR were required per modified irRC-RECIST.
Measured: Every 12 weeks. Maximum overall time on-study (treatment + follow up) was 46.23 months
DOR Per Modified RECIST v1.1
DOR was defined as the time from the date of an initial response of CR or PR to the earlier of PD/death. Participants who had not ended their response at the time of analysis were censored at their last evaluable tumor assessment date before start of first subsequent anticancer therapy. One month was calculated based on 365.25 days per year.
- CR:Disappearance of all target \& non-target lesions. All lymph nodes must have a reduction in short axis to <10 mm. Any pathological lymph nodes 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.
- PD:At least a 20% increase in the sum of diameters of target lesions. The sum must also demonstrate an increase of at least 5mm. Unequivocal progression of existing non-target lesions.
Confirmation of CR, PR and PD were not required per modified RECIST v1.1.
Measured: Every 12 weeks. Maximum overall time on-study (treatment + follow up) was 46.23 months
iDOR Per Modified irRC-RECIST
iDOR was defined as the time from the date of an initial response that is subsequently confirmed to the earlier of iPD per modified irRC-RECIST.
Participants who had not ended their response at the time of analysis were censored at their last evaluable tumor assessment date before start of first subsequent anticancer therapy. One month was calculated based on 365.25 days per year.
- iCR: Disappearance of all target and non-target lesions. All lymph nodes must have a reduction in short axis to < 10 mm.
- iPR: At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.
- iPD: At least a 20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5mm. Unequivocal progression of existing non-target lesions.
Measured: Every 12 weeks. Maximum overall time on-study (treatment + follow up) was 46.23 months
Disease Control Rate (DCR) Per Modified RECIST v1.1
DCR per modified RECIST v1.1 was defined as the incidence of a BOR of CR, PR or SD.
- 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.
- SD: Neither sufficient shrinkage to qualify for PR or CR nor sufficient increase to qualify for PD.
Confirmation of CR and PR were not required per modified RECIST v1.1.
Measured: Every 12 weeks. Maximum overall time on-study (treatment + follow up) was 46.23 months
Disease Control Rate (iDCR) Per Modified irRC-RECIST
iDCR per modified irRC-RECIST was defined as the incidence of an iBOR of iCR, iPR or iSD.
- iCR: Disappearance of all target and non-target lesions. All lymph nodes must have a reduction in short axis to < 10 mm.
- iPR: At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.
- iSD: Neither sufficient shrinkage to qualify for iPR or iCR nor sufficient increase to qualify for iPD.
Confirmation of iCR and iPR were required per modified irRC-RECIST.
Measured: Every 12 weeks. Maximum overall time on-study (treatment + follow up) was 46.23 months
Objective Response Rate (iORR) Per Modified irRC-RECIST
iORR was defined as the incidence of an iBOR of iCR or iPR per modified irRC-RECIST
- iCR: Disappearance of all lesions (whether measurable or not and whether baseline or new). Any pathological lymph nodes (whether target or nontarget) must have a reduction in short axis to < 10 mm.
- iPR: Decrease in tumor burden ≥ 30% relative to baseline.
Confirmation of iCR and iPR were required per modified irRC-RECIST.
Measured: Every 12 weeks. Maximum overall time on-study (treatment + follow up) was 46.23 months
Progression Free Survival (PFS) Per Modified RECIST v1.1
PFS per modified RECIST 1.1 was defined as the interval from first dose to the earlier event of PD or death from any cause. Participants without an event were censored at their last evaluable post-baseline tumor assessment if available, otherwise were censored on study Day 1. One month was calculated based on 365.25 days per year.
- PD: At least a 20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5mm. Unequivocal progression of existing non-target lesions.
Measured: Every 12 weeks. Maximum overall time on-study (treatment + follow up) was 46.23 months
Progression Free Survival (iPFS) Per Modified irRC-RECIST
iPFS per modified irRC-RECIST was defined as the interval from first dose to the earlier event of iPD or death from any cause. Participants without an event were censored at their last evaluable post-baseline tumor assessment if available, otherwise were censored on study Day 1. One month was calculated based on 365.25 days per year.
- iPD: Increase in tumor burden ≥ 20% and at least 5 mm absolute increase.
Measured: Every 12 weeks. Maximum overall time on-study (treatment + follow up) was 46.23 months
Overall Survival (OS)
OS was defined as the interval from first dose to death from any cause. Participants without an event were censored at the last date known to be alive. One month was calculated based on 365.25 days per year.
Measured: Every 12 weeks. Maximum overall time on-study (treatment + follow up) was 46.23 months
Number of Participants Who Experienced a Treatment-emergent Adverse Event (TEAE)
Evaluation of TEAEs included the number of participants with at least 1:
- TEAE
- Treatment-related TEAE
- Common Terminology Criteria for Adverse Events (CTCAE) grade ≥ 3 TEAE
- Treatment-related CTCAE grade ≥ 3 TEAE
- Serious TEAE
- Serious treatment-related TEAE
- Fatal TEAE
- Fatal treatment-related TEAE
- TEAE of interest
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.
A CTCAE grade ≥ 3 was determined using the CTCAE grading systems based on CTCAE version 5.0 per the below definitions:
- Grade 3: Severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self care activities of daily living.
- Grade 4: Life-threatening consequences; urgent intervention indicated.
- Grade 5: Death related to TEAE.
Abnormal laboratory tests were also recorded as TEAEs.
Measured: 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.
Time to First Subsequent Anti-cancer Therapy
Time to first subsequent anti-cancer therapy was defined as the time from enrollment to the start of subsequent anticancer therapy. Participants who did not start subsequent anticancer therapy were censored as the last known to be alive date. One month was calculated based on 365.25 days per year.
Measured: Every 12 weeks. Maximum overall time on-study (treatment + follow up) was 46.23 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Aug 2019
- Study start22 Jan 2020
- Primary completion19 Aug 2021
- Study completion26 Feb 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for MelanomaStudies of the same condition, open and under way.
- More trials run by AmgenThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 72 participants (actual)
Sponsor and investigators
- Lead sponsor
- Amgen
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Merck Sharp & Dohme LLC
- Responsible party
- Sponsor
- Investigators
- MD, Study director, Amgen
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04068181
- Sponsor's protocol ID
- 20180115
- Other IDs
- 2019-001906-61, 2019
- Status last verified
- Nov 2024
- First submitted
- 22 Aug 2019
- Last updated
- 7 Jan 2025
- Results posted
- Yes, on ClinicalTrials.gov
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: De-identified individual patient data for variables necessary to address the specific research question in an approved data sharing request
Publications
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.
PubMed 38870745
Study at a glance
From the registry record, last updated by the sponsor on 7 Jan 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT04068181
- Acronym / sponsor ID
- 20180115
- Conditions
- Melanoma
- Keywords
- Melanoma, Talimogene Laherparepvec, Pembrolizumab, Oncolytic immunotherapy, Anti-PD-1, Checkpoint inhibitor, MASTERKEY-115
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 72 participants (actual)
- Lead sponsor
- AmgenIndustry (pharma, biotech, devices)
- Collaborators
- Merck Sharp & Dohme LLC
- Study start
- 22 Jan 2020 (actual)
- Primary completion
- 19 Aug 2021 (actual)
- Study completion
- 26 Feb 2024 (actual)
- First posted
- 28 Aug 2019 (actual)
- Results
- Posted 9 Sep 2022
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Cohort 1 - Locally Recurrent/Metastatic - Primary Resistance | Experimental | Drug: Talimogene laherparepvec, Drug: PembrolizumabIncludes 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. |
| Cohort 2 - Locally Recurrent/Metastatic - Acquired Resistance | Experimental | Drug: Talimogene laherparepvec, Drug: PembrolizumabIncludes 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. |
| Cohort 3 - Adjuvant Setting -Disease Free Interval < 6 months | Experimental | Drug: Talimogene laherparepvec, Drug: PembrolizumabIncludes 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. |
| Cohort 4 - Adjuvant Setting -Disease Free Interval ≥ 6 months | Experimental | Drug: Talimogene laherparepvec, Drug: PembrolizumabIncludes 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. |
Who may qualify
- Ages
- 18 to 99 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 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 (7 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Talimogene laherparepvecIntralesional injection into injectable cutaneous, subcutaneous and nodal legions. | Drug | 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 |
| PembrolizumabIntravenous (IV) infusion. | Drug | 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 |
Primary outcome
Objective Response Rate (ORR) Per Modified RECIST v1.1
Time frame: Every 12 weeks. Maximum overall time on-study (treatment + follow up) was 46.23 months
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).
16 secondary outcomes
Complete Response Rate (CRR) Per Modified RECIST v1.1
Time frame: 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
Time frame: Every 12 weeks. Maximum overall time on-study (treatment + follow up) was 46.23 months
BOR Per Modified RECIST v1.1
Time frame: Every 12 weeks. Maximum overall time on-study (treatment + follow up) was 46.23 months
Best Overall Response (iBOR) Per Modified irRC-RECIST
Time frame: Every 12 weeks. Maximum overall time on-study (treatment + follow up) was 46.23 months
Durable Response Rate (DRR) Per Modified RECIST v1.1
Time frame: Every 12 weeks. Maximum overall time on-study (treatment + follow up) was 46.23 months
Durable Response Rate (iDRR) Per Modified irRC-RECIST
Time frame: Every 12 weeks. Maximum overall time on-study (treatment + follow up) was 46.23 months
DOR Per Modified RECIST v1.1
Time frame: Every 12 weeks. Maximum overall time on-study (treatment + follow up) was 46.23 months
iDOR Per Modified irRC-RECIST
Time frame: Every 12 weeks. Maximum overall time on-study (treatment + follow up) was 46.23 months
Disease Control Rate (DCR) Per Modified RECIST v1.1
Time frame: Every 12 weeks. Maximum overall time on-study (treatment + follow up) was 46.23 months
Disease Control Rate (iDCR) Per Modified irRC-RECIST
Time frame: Every 12 weeks. Maximum overall time on-study (treatment + follow up) was 46.23 months
Objective Response Rate (iORR) Per Modified irRC-RECIST
Time frame: Every 12 weeks. Maximum overall time on-study (treatment + follow up) was 46.23 months
Progression Free Survival (PFS) Per Modified RECIST v1.1
Time frame: Every 12 weeks. Maximum overall time on-study (treatment + follow up) was 46.23 months
Progression Free Survival (iPFS) Per Modified irRC-RECIST
Time frame: Every 12 weeks. Maximum overall time on-study (treatment + follow up) was 46.23 months
Overall Survival (OS)
Time frame: Every 12 weeks. Maximum overall time on-study (treatment + follow up) was 46.23 months
Number of Participants Who Experienced a Treatment-emergent Adverse Event (TEAE)
Time frame: 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.
Time to First Subsequent Anti-cancer Therapy
Time frame: Every 12 weeks. Maximum overall time on-study (treatment + follow up) was 46.23 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 Jan 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 38870745Robert 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.
- AmgenTrials clinical trials websiteLink provided by the sponsor.
- Individual participant dataSharing planned: Yes. De-identified individual patient data for variables necessary to address the specific research question in an approved data sharing request
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
MD study director
Amgen
46 sites in 11 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Talimogene laherparepvec and Pembrolizumab in people with Melanoma, run by Amgen at 46 sites in 11 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 7 Jan 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 46 sites in United States, France, Australia, Spain, Germany and 6 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 9 Sep 2022). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Objective Response Rate (ORR) Per Modified RECIST v1.1 (time frame: Every 12 weeks. Maximum overall time on-study (treatment + follow up) was 46.23 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04068181, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 7 Jan 2025.