Register a trial

The ANZCTR website will be unavailable from 1pm until 3pm (AEDT) on Wednesday the 30th of October for website maintenance. Please be sure to log out of the system in order to avoid any loss of data.

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this information for consumers
Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT02626000




Registration number
NCT02626000
Ethics application status
Date submitted
18/11/2015
Date registered
10/12/2015

Titles & IDs
Public title
Talimogene Laherparepvec With Pembrolizumab for Recurrent Metastatic Squamous Cell Carcinoma of the Head and Neck (MASTERKEY232 / KEYNOTE-137)
Scientific title
A Phase 1b/3 Multicenter, Randomized, Trial of Talimogene Laherparepvec in Combination With Pembrolizumab for the Treatment of Subjects With Recurrent or Metastatic Squamous Cell Carcinoma of the Head and Neck
Secondary ID [1] 0 0
20130232 / KEYNOTE-137
Secondary ID [2] 0 0
20130232
Universal Trial Number (UTN)
Trial acronym
MASTERKEY232
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Carcinoma of the Head and Neck 0 0
Condition category
Condition code
Cancer 0 0 0 0
Non melanoma skin cancer
Cancer 0 0 0 0
Kidney
Cancer 0 0 0 0
Head and neck

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Talimogene Laherparepvec
Treatment: Other - Pembrolizumab

Experimental: Talimogene Laherparepvec + Pembrolizumab - Talimogene laherparepvec is administered by intralesional injection into injectable cutaneous, subcutaneous, and nodal lesions at an initial dose of 106 plaque-forming units (PFU) per mL on day 1 followed by a dose of 108 PFU/mL 3 weeks after the initial dose and every 3 weeks (Q3W) thereafter. Pembrolizumab is administered by intravenous infusion at a dose of 200 mg Q3W after the initial dose. Participants are treated until complete response, no injectable lesions, confirmed disease progression, intolerance of study treatment, 24 months from the date of the first dose of talimogene laherparepvec, or end of study, whichever occurred first.


Treatment: Drugs: Talimogene Laherparepvec
The initial dose of talimogene laherparepvec is up to 8.0 mL of 106 PFU/mL. Subsequent doses of talimogene laherparepvec are up to 8.0 mL of 108 PFU/mL.

Treatment: Other: Pembrolizumab
Administered as a 30-minute intravenous infusion at a dose of 200 mg Q3W
Intervention code [1] 0 0
Treatment: Drugs
Intervention code [2] 0 0
Treatment: Other
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Number of Participants With a Dose Limiting Toxicity (DLT)
Timepoint [1] 0 0
First 6 weeks after the initial administration of talimogene laherparepvec and pembrolizumab in combination
Secondary outcome [1] 0 0
Objective Response Rate
Timepoint [1] 0 0
Up to the primary analysis data cutoff date of 02 November 2017; median (minimum, maximum) time on follow-up was 14.36 (1.4, 67.0) weeks.
Secondary outcome [2] 0 0
Complete Response Rate
Timepoint [2] 0 0
Up to the primary analysis data cutoff date of 02 November 2017; median (minimum, maximum) time on follow-up was 14.36 (1.4, 67.0) weeks.
Secondary outcome [3] 0 0
Best Overall Confirmed Response
Timepoint [3] 0 0
Up to the primary analysis data cutoff date of 02 November 2017; median (minimum, maximum) time on follow-up was 14.36 (1.4, 67.0) weeks.
Secondary outcome [4] 0 0
Duration of Confirmed Response
Timepoint [4] 0 0
Up to the primary analysis data cutoff date of 02 November 2017; median (minimum, maximum) time on follow-up was 14.36 (1.4, 67.0) weeks.
Secondary outcome [5] 0 0
Disease Control Rate
Timepoint [5] 0 0
Up to the primary analysis data cutoff date of 02 November 2017; median (minimum, maximum) time on follow-up was 14.36 (1.4, 67.0) weeks.
Secondary outcome [6] 0 0
Progression Free Survival
Timepoint [6] 0 0
Up to the primary analysis data cutoff date of 02 November 2017; median (minimum, maximum) time on follow-up was 14.36 (1.4, 67.0) weeks.
Secondary outcome [7] 0 0
Overall Survival
Timepoint [7] 0 0
Up to the primary analysis data cutoff date of 02 November 2017; median (minimum, maximum) time on follow-up was 14.36 (1.4, 67.0) weeks.
Secondary outcome [8] 0 0
Number of Participants With Adverse Events
Timepoint [8] 0 0
From first dose of study drug to 30 days after last dose; the median (range) duration of treatment was 5.6 (0.1 to 75.3) weeks for talimogene laherparepvec and 6.1 (0.1, 105.3) weeks for pembrolizumab.

Eligibility
Key inclusion criteria
Inclusion Criteria

* Male or female age = 18 years at the time of informed consent
* Histologically confirmed diagnosis of metastatic or recurrent SCCHN of the oral cavity, oropharynx, hypopharynx, or larynx. Disease must be unsuitable for curative surgical resection and must not be amenable to curative radiotherapy.
* Disease must have progressed after treatment with a platinum-containing regimen and should be defined as one of the following:

i. disease progression or recurrence between 3 to 6 months of prior curatively intended multimodal therapy (which includes platinum therapy) for locoregionally advanced SCCHN.

ii. disease progression or recurrence after prior platinum therapy in the recurrent or metastatic setting Note: This criterion is only applicable for subjects who have not had treatment in the recurrent/metastatic setting

* Subject must be candidate for intralesional therapy administration defined as one or more of the following:

i. at least 1 injectable cutaneous, subcutaneous, or nodal SCCHN tumor = 10 mm in longest diameter ii. multiple injectable cutaneous, subcutaneous, or nodal SCCHN tumors that in aggregate have a longest diameter of = 10 mm Note: Mucosal surfaces of tumor lesions and visceral metastases should not be injected.
* Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
* Adequate organ function determined within 14 days prior to enrollment
* Female subject of childbearing potential must have a negative pregnancy test within 72 hours prior to enrollment.
* Other Inclusion Criteria May Apply
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Exclusion Criteria

* Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis.
* Primary nasopharyngeal carcinoma.
* Subject at risk of airway compromise in the event of postinjection tumor swelling/inflammation based on investigator judgment.
* Phase 3: Previous treatment with 3 or more systemic regimens given for recurrent and/or metastatic disease
* History of other malignancy within the past 3 years
* History of interstitial lung disease (ILD).
* Prior therapy with talimogene laherparepvec, pembrolizumab, other anti-PD-1, any other antibody or drug specifically targeting T-cell co-stimulation or immune check point pathway.
* History or evidence of active autoimmune disease that has required systemic treatment in the past 2 years (ie, with use of disease modifying agents, corticosteroids or immunosuppressive drugs).
* Evidence of clinically significant immunosuppression
* Active herpetic skin lesions or prior complications of herpetic infection (eg, herpetic keratitis or encephalitis).
* Requires intermittent or chronic treatment with an antiherpetic drug (eg, acyclovir), other than intermittent topical use.
* Prior chemotherapy, radiotherapy, biological cancer therapy, targeted therapy, or major surgery within 28 days prior to enrollment or has not recovered to Common Terminology Criteria for Adverse Events (CTCAE) grade 1 or better from adverse event due to cancer therapy administered more than 28 days prior to enrollment.
* Expected to require other cancer therapy while on study with the exception of local palliative radiation treatment to the site of bone and other metastasis.
* Known human immunodeficiency virus (HIV) disease.
* Has acute or chronic active hepatitis B virus or hepatitis C virus infection or received treatment with nucleotide analogs such as those used in the treatment of hepatitis B virus (eg, lamivudine, adefovir, tenofovir, telbivudine, entecavir), ribavirin, or interferon alpha within 12 weeks of initiation of study treatment.
* Received live vaccine within 28 days prior to enrollment.
* Subject is pregnant or breast-feeding, or expecting to conceive or father children within the duration of the trial
* Female subject of childbearing potential or male subject of reproductive potential who is unwilling to use acceptable method(s) of effective contraception during study treatment and through 3 months after the last dose of talimogene laherparepvec/placebo or 4 months after the last dose of pembrolizumab, whichever is later.
* Sexually active subjects or their partners unwilling to use male or female latex condom to avoid potential viral transmission during sexual contact while on treatment and within 30 days after treatment with talimogene laherparepvec/placebo.
* Subject who is unwilling to minimize exposure with his/her blood or other body fluids to individuals who are at higher risks for herpes simplex virus type 1 (HSV-1)-induced complications (eg, immunosuppressed individuals, HIV-positive individuals, pregnant women, or children under the age of 1 year) during talimogene laherparepvec treatment and through 30 days after the last dose of talimogene laherparepvec
* Has history of (non-infectious) pneumonitis that required steriods or current pneumonitis
* Subjects with tumor that directly contacts or encases a major blood vessel AND there is ulceration and/or fungation onto the skin surface
* History of re-irradiation to a field which includes the carotid arteries
* Other Exclusion Criteria May Apply

Study design
Purpose of the study
Treatment
Allocation to intervention
NA
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Phase 1
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
6/04/2016
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
28/08/2020
Sample size
Target
Accrual to date
Final
36
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 0 0
Research Site - Geelong
Recruitment hospital [2] 0 0
Research Site - Melbourne
Recruitment postcode(s) [1] 0 0
3220 - Geelong
Recruitment postcode(s) [2] 0 0
3000 - Melbourne
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Delaware
Country [2] 0 0
United States of America
State/province [2] 0 0
Illinois
Country [3] 0 0
United States of America
State/province [3] 0 0
Kentucky
Country [4] 0 0
United States of America
State/province [4] 0 0
Montana
Country [5] 0 0
United States of America
State/province [5] 0 0
New York
Country [6] 0 0
United States of America
State/province [6] 0 0
Ohio
Country [7] 0 0
Austria
State/province [7] 0 0
Salzburg
Country [8] 0 0
Belgium
State/province [8] 0 0
Bruxelles
Country [9] 0 0
Belgium
State/province [9] 0 0
Wilrijk
Country [10] 0 0
Canada
State/province [10] 0 0
Ontario
Country [11] 0 0
France
State/province [11] 0 0
Bordeaux
Country [12] 0 0
France
State/province [12] 0 0
Pierre-Benite
Country [13] 0 0
France
State/province [13] 0 0
Toulouse cedex 9
Country [14] 0 0
Greece
State/province [14] 0 0
Athens
Country [15] 0 0
Greece
State/province [15] 0 0
Ioannina
Country [16] 0 0
Italy
State/province [16] 0 0
Milano
Country [17] 0 0
Spain
State/province [17] 0 0
Andalucía
Country [18] 0 0
Spain
State/province [18] 0 0
Cataluña
Country [19] 0 0
Spain
State/province [19] 0 0
Madrid
Country [20] 0 0
Switzerland
State/province [20] 0 0
Bellinzona
Country [21] 0 0
Switzerland
State/province [21] 0 0
Geneva 14
Country [22] 0 0
Switzerland
State/province [22] 0 0
Zurich
Country [23] 0 0
United Kingdom
State/province [23] 0 0
Birmingham
Country [24] 0 0
United Kingdom
State/province [24] 0 0
London
Country [25] 0 0
United Kingdom
State/province [25] 0 0
Oxford
Country [26] 0 0
United Kingdom
State/province [26] 0 0
Sutton
Country [27] 0 0
United Kingdom
State/province [27] 0 0
Wirral

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Amgen
Address
Country
Other collaborator category [1] 0 0
Commercial sector/industry
Name [1] 0 0
Merck Sharp & Dohme LLC
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
MD
Address 0 0
Amgen
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
De-identified individual patient data for variables necessary to address the specific research question in an approved data sharing request

Supporting document/s available: Study protocol, Statistical analysis plan (SAP), Informed consent form (ICF), Clinical study report (CSR)
When will data be available (start and end dates)?
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 (or other new use) 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.
Available to whom?
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, and if not approved, may be further arbitrated by a Data Sharing Independent Review Panel. 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.
Available for what types of analyses?
How or where can data be obtained?
IPD available at link: https://www.amgen.com/datasharing


What supporting documents are/will be available?




Results publications and other study-related documents

No documents have been uploaded by study researchers.


Results are available at https://clinicaltrials.gov/study/NCT02626000