Talimogene Laherparepvec With Pembrolizumab for Recurrent Metastatic Squamous Cell Carcinoma of the Head and Neck (MASTERKEY232 / KEYNOTE-137)

NCT02626000 | Completed Phase 1 Results DMC FDA Drug

• 3 other identifiers: 2013023220130232 / KEYNOTE-1372015-003011-38
• Study Type: interventional
• Target: 36
• Locations: 10 countries
• Sites: 31

Brief Summary

The primary objective of this study was to evaluate the safety, as assessed by incidence of dose limiting toxicity (DLT), of talimogene laherparepvec in combination with pembrolizumab in adults with recurrent or metastatic squamous cell carcinoma of the head and neck (SCCHN).

Conditions

Carcinoma of the Head and Neck

Keywords

Recurrent Metastatic Squamous Cell Carcinoma Head and Neck

Outcome Measures

Primary Outcomes (1)

• Number of Participants With a Dose Limiting Toxicity (DLT)

  The following toxicities (graded per the Common Terminology Criteria for Adverse Events v 4.0) were considered DLTs if judged by the investigator to be related to either study drug: * grade 4 non-hematologic (non-laboratory) toxicity * ≥ grade 3 pneumonitis * grade 3 non-hematologic toxicity for \> 3 days with optimal supportive care * grade 3 fatigue was not classified as DLT, regardless of duration * any ≥ grade 3 non-hematologic laboratory value if: * medical intervention was required, * the abnormality led to hospitalization, or * the abnormality persisted at ≥ grade 3 for \> 1 week unless deemed not clinically important by investigator and sponsor * grade 3 or 4 febrile neutropenia * thrombocytopenia \< 25 x 10⁹/L associated with bleeding event requiring intervention * serious herpetic event: herpetic encephalitis, encephalomyelitis, or disseminated herpetic infection * grade 5 toxicity * other intolerable toxicity leading to permanent discontinuation of either study drug.

  First 6 weeks after the initial administration of talimogene laherparepvec and pembrolizumab in combination

Secondary Outcomes (8)

• Objective Response Rate

  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.

• Complete Response Rate

  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.

• Best Overall Confirmed Response

  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.

• Duration of Confirmed Response

  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.

• Disease Control Rate

  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.

Study Arms (1)

Talimogene Laherparepvec + Pembrolizumab

EXPERIMENTAL

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.

Drug: Talimogene Laherparepvec; Biological: Pembrolizumab

Interventions

Talimogene Laherparepvec DRUG

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.

Also known as: IMLYGIC®

Talimogene Laherparepvec + Pembrolizumab

Pembrolizumab BIOLOGICAL

Administered as a 30-minute intravenous infusion at a dose of 200 mg Q3W

Also known as: KEYTRUDA®

Talimogene Laherparepvec + Pembrolizumab

Eligibility Criteria

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

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

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

Study Sites (33)

Research Site

Newark, Delaware, 19713, United States

Location

Research Site

Chicago, Illinois, 60611, United States

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Chicago, Illinois, 60637, United States

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Louisville, Kentucky, 40202, United States

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Billings, Montana, 59101, United States

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New York, New York, 10003, United States

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New York, New York, 10021, United States

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Canton, Ohio, 44718, United States

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Geelong, Victoria, 3220, Australia

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Melbourne, Victoria, 3000, Australia

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Salzburg, 5020, Austria

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Brussels, 1000, Belgium

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Wilrijk, 2610, Belgium

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Toronto, Ontario, M5G 2M9, Canada

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Bordeaux, 33076, France

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Pierre-Bénite, 69495, France

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Toulouse, 31059, France

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Athens, 12462, Greece

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Ioannina, 45500, Greece

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Milan, 20133, Italy

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Seville, Andalusia, 41013, Spain

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L'Hospitalet de Llobregat, Catalonia, 08907, Spain

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Madrid, 28046, Spain

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Madrid, 28050, Spain

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Bellinzona, 6500, Switzerland

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Geneva, 1211, Switzerland

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Zurich, 8091, Switzerland

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Birmingham, B15 2TT, United Kingdom

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London, SE1 7EH, United Kingdom

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London, SW3 6JJ, United Kingdom

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Metropolitan Borough of Wirral, CH63 4JY, United Kingdom

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Oxford, OX3 7LE, United Kingdom

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Sutton, SM2 5PT, United Kingdom

Location

Related Publications (1)

• Harrington KJ, Kong A, Mach N, Chesney JA, Fernandez BC, Rischin D, Cohen EEW, Radcliffe HS, Gumuscu B, Cheng J, Snyder W, Siu LL. Talimogene Laherparepvec and Pembrolizumab in Recurrent or Metastatic Squamous Cell Carcinoma of the Head and Neck (MASTERKEY-232): A Multicenter, Phase 1b Study. Clin Cancer Res. 2020 Oct 1;26(19):5153-5161. doi: 10.1158/1078-0432.CCR-20-1170. Epub 2020 Jul 15.

  PMID: 32669371 DERIVED

Related Links

• AmgenTrials clinical trials website

MeSH Terms

Conditions

Squamous Cell Carcinoma of Head and Neck

Interventions

talimogene laherparepvec; pembrolizumab

Condition Hierarchy (Ancestors)

Carcinoma, Squamous Cell; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Head and Neck Neoplasms; Neoplasms by Site

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 1
• Allocation: NA
• Masking: NONE
• Masking Details: For Phase 1b there are no 'maskings' as it's open-label.
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 18, 2015
• First Posted: December 10, 2015
• Study Start: April 6, 2016
• Primary Completion: November 2, 2017
• Study Completion: August 28, 2020
• Last Updated: September 8, 2021
• Results First Posted: June 10, 2019

Record last verified: 2021-08

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 (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.
• 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, 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.

Locations

FR (3); CA (1); IT (1); AU (1); BE (2); US (8); GR (2); ES (4); CH (3); GB (6)