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Trial record 1 of 2 for:    Talimogene Laherparepvec head neck
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Talimogene Laherparepvec With Pembrolizumab for Recurrent Metastatic Squamous Cell Carcinoma of the Head and Neck (MASTERKEY232 / KEYNOTE-137) (MASTERKEY232)

This study is currently recruiting participants.
See Contacts and Locations
Verified July 2017 by Amgen
Sponsor:
Collaborator:
Merck Sharp & Dohme Corp.
Information provided by (Responsible Party):
Amgen
ClinicalTrials.gov Identifier:
NCT02626000
First received: November 18, 2015
Last updated: July 19, 2017
Last verified: July 2017
  Purpose
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

Condition Intervention Phase
Carcinoma of the Head and Neck Drug: Talimogene laherparepvec in combination with pembrolizumab Phase 1

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: None (Open Label)
Masking Description:
For Phase 1b there are no 'maskings' as it's open-label. When we start Phase 3 (~Q1'18) however, it will be placebo controlled randomized study, therefore it will be 'masked' i.e. blinded.
Primary Purpose: Other
Official 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

Resource links provided by NLM:


Further study details as provided by Amgen:

Primary Outcome Measures:
  • Incidence of Dose Limiting Toxicity [ Time Frame: At least 6 wks from the initial dosing and 2 doses of treatment ]
    To evaluate the safety, as assessed by incidence of dose limiting toxicity (DLT), of talimogene laherparepvec in combination with pembrolizumab


Secondary Outcome Measures:
  • Incidence of treatment-emergent and treatment-related AEs [ Time Frame: Start of treatment to 30 (+7) days after end of treatme ]
    All adverse events, grade ≥ 3 adverse events, serious adverse events, fatal adverse events, adverse events and serious adverse events leading to discontinuation of treatment, and adverse events defined as events of interest) and clinical laboratory abnormalities.

  • Objective Response Rate [ Time Frame: Up to 24 months of treatment ]
    Response evaluation by investigator using irRECIST

  • Best Overall Response [ Time Frame: Up to 24 months of treatment ]
    Response evaluation by investigator using irRECIST

  • Duration of Response [ Time Frame: Up to 24 months of treatment ]
    Response evaluation by investigator using irRECIST

  • Disease Control Rate [ Time Frame: Up to 24 months of treatment ]
    Response evaluation by investigator using irRECIST

  • Progression Free Survival [ Time Frame: Up to 24 months of treatment ]
    Response evaluation by investigator using irRECIST

  • Overall Survival [ Time Frame: Up to 24 months of treatment ]

Other Outcome Measures:
  • Response rates in injected and uninjected lesions [ Time Frame: Up to 6 months from study discontinuation ]
  • Incidence of detection of talimogene laherparepvec DNA in lesions suspected to be herpetic in origin [ Time Frame: Up to 6 months from study discontinuation ]
  • Subject incidence of anti-pembrolizumab antibodies [ Time Frame: Up to 6 months from study discontinuation ]
  • Serum concentration of pembrolizumab [ Time Frame: Up to 6 months from study discontinuation ]
  • Subject incidence of clearance of talimogene laherparepvec DNA from blood and urine [ Time Frame: Up to 6 months from study discontinuation ]
  • Rate of detection and subject incidence of talimogene laherparepvec DNA and virus from exterior of occlusive dressing, surface of injected lesions, and oral mucosa [ Time Frame: Up to 6 months from study discontinuation ]
  • Potential biomarkers which predict and/or are correlated with clinical outcomes to talimogene laherparepvec and pembrolizumab [ Time Frame: Up to 6 months from study discontinuation ]

Estimated Enrollment: 40
Actual Study Start Date: April 6, 2016
Estimated Study Completion Date: December 4, 2022
Estimated Primary Completion Date: August 23, 2021 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Phase 1b
Talimogene laherparepvec in combination with pembrolizumab
Drug: Talimogene laherparepvec in combination with pembrolizumab
Talimogene laherparepvec will be administered in combination with pembrolizumab starting on day 1. Talimogene laherparepvec: 10^6 PFU/mL followed 3 weeks (+ 3 days) later by 10^8 PFU/mL every 3 weeks (± 3 days). Pembrolizumab: 200 mg will be administered intravenously every 3 weeks (± 3 days). The second dose of pembrolizumab will be administered 3 weeks (+ 3 days) after the initial dose. Subjects will be followed up for serious adverse events until 90 (+ 7) days after the cessation of all study treatment or 30 (+7) days following cessation of treatment if the subject initiates new anticancer therapy (whichever is earlier)

Detailed Description:
This is a phase 1b/3, multicenter, clinical trial. The study will be conducted in 2 parts (phase 1b and phase 3). In phase 1b talimogene laherparepvec will be administered in combination with pembrolizumab to approximately 40 subjects with recurrent or metastatic SCCHN. DLT will be evaluated based on the first 18 DLT-evaluable subjects. An expansion cohort of an additional 22 treated subjects will be enrolled to further evaluate the safety and to estimate the efficacy of the combination of talimogene laherparepvec with pembrolizumab to support a decision to initiate the phase 3 study.
  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

  • 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

Exclusion Criteria

  • Has known active 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 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 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
  • Subject has undergone re-irradiation
  • Other Exclusion Criteria May Apply
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02626000

Contacts
Contact: Amgen Call Center 866-572-6436 medinfo@amgen.com

  Show 32 Study Locations
Sponsors and Collaborators
Amgen
Merck Sharp & Dohme Corp.
Investigators
Study Director: MD Amgen
  More Information

Additional Information:
Responsible Party: Amgen
ClinicalTrials.gov Identifier: NCT02626000     History of Changes
Other Study ID Numbers: 20130232
20130232 / KEYNOTE-137 ( Other Identifier: Merck / Amgen )
Study First Received: November 18, 2015
Last Updated: July 19, 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Amgen:
Recurrent Metastatic Squamous Cell Carcinoma Head and Neck

Additional relevant MeSH terms:
Carcinoma
Carcinoma, Squamous Cell
Head and Neck Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Squamous Cell
Neoplasms by Site
Pembrolizumab
Antineoplastic Agents

ClinicalTrials.gov processed this record on September 21, 2017