Study to Evaluate the Safety/ Efficacy of T-VEC in Japanese Subjects With Unresectable Stage IIIB-IV Malignant Melanoma
Condition: Unresectable Stage IIIB-IV Malignant Melanoma
MeSH terms: Melanoma
Study type: Interventional
Phase: Phase 1

Summary: 
      There are 2 fold of purposes for this study. 1 is to evaluate safety and tolerability and the
      other is to study the anti-tumor effects of talimogene laherparepvec in Japanese participants
      with unresectable stage IIIB-IV malignant melanoma.
    

Detailed description: 
      This is a phase 1, multicenter, open-label study of talimogene laherparepvec in Japanese
      participants with unresectable stage IIIB-IVM1c malignant melanoma that are candidates for
      intralesional therapy. The Screening period is 28 days prior to study enrollment. There will
      be a Treatment period, Safety Follow-up period and a Long Term Follow-up period.

      The Screening Period: Informed consent will be obtained prior to screening procedures.
      Screening procedures to determine eligibility include: medical history (including concomitant
      medications, prior therapy for melanoma and BRAF status (if known)), physical exam, vital
      signs, assessment of Eastern Cooperative Oncology Group (ECOG) performance level status,
      electrocardiogram (ECG), laboratory assessments (including hepatitis serology), baseline
      tumor assessments, and adverse events assessment.

      Treatment Period: Initially, 6 Dose Limiting Toxicity (DLT)-evaluable participants will be
      enrolled and treated at 100% dose regimen of talimogene laherparepvec (Up to 4.0 mL of 10_6
      PFU/mL followed by a dose of up to 4.0 mL of 10_8 PFU/mL). Upon demonstration of safety based
      on DLT incidence in the first 6 participants, an additional 12 participants will be enrolled
      and treated at Dose 1 to obtain additional safety data. If dose de-escalation is needed based
      on the DLT evaluation of first 6 participants, then additional 6 participants will be treated
      at lower dose (up to 4.0 mL of 10_6 PFU/mL followed by a dose of up to 4.0 mL of 10_7PFU/mL).
      The duration of treatment will vary for each participants. Participants will be treated until
      the participant has a DLT during the DLT evaluation period, participant has achieved a
      Complete Response, no injectable lesions, clinically relevant (resulting in clinical
      deterioration or requiring change in therapy) disease progression beyond 24-weeks of
      treatment, or safety concern, whichever occurs first. Maximum treatment duration will be 48
      months. The total study duration for an individual participant can be up to 4 years.

      Drug Administration: If the participants are found to be eligible to take part in this study,
      they will receive talimogene laherparepvec by intralesional injection only into injectable
      cutaneous, subcutaneous, and nodal tumors, with or without image ultrasound guidance. The
      first injection of talimogene laherparepvec will take place on day 1 (week 0). The second
      injection should be administered 3 weeks (+ 5 days) after the initial injection. Subsequent
      injections should be given every 2 weeks (± 3 days).

      Study Visits: The participant will have a physical exam along with vital signs and ECOG. At
      any study visit blood may be collected to monitor health and safety, and effects of
      talimogene laherparepvec. Adverse events and medications taken will be reviewed at each study
      visit. The tumor assessment, physical exams, and ECOG performance status will be completed
      after 12 (± 1) weeks on treatment (ie, day 1 of week 11), and then every 12 (± 1) weeks (eg,
      weeks 23, 35, 47 etc.), or more frequently if clinically indicated, until Progressive disease
      beyond 6 months of treatment or until the start of a new anticancer therapy.

      Central Lab tests: Blood for herpes simplex virus type-1 (HSV-1) Antibody Serostatus will
      collected within 3 days prior to dose at day 1 (week 0) and at week 5. Throughout the trial
      any participant developing a lesion of suspected herpetic origin will have a swab of the
      lesion for presence of talimogene laherparepvec DNA obtained within 3 days of the event.

      Exposure to talimogene laherparepvec by the healthcare providers of the participant and/or
      close contacts will be assessed.

      Safety Follow Visit: A safety follow-up visit will be performed 30 (+7) days after the last
      dose. The participant will have a physical exam, have vital signs taken, assessment of ECOG
      status and have weight measured. Adverse events will be assessed as well as the concomitant
      medications. Routine bloodwork and tumor response assessments will be performed.

      Long-Term Follow-up Visits: Follow-up for survival status and, if applicable, commencement of
      any subsequent anticancer melanoma therapy will occur every 12 weeks (± 28 days) by phone or
      clinic visit for all participants who permanently discontinue talimogene laherparepvec for
      any reason other than withdrawal of full consent for up to 24 months after the last
      participant is enrolled in the study. For participants that discontinue talimogene
      laherparepvec for reason other than disease progression, the following additional procedures
      will be conducted during the long-term follow-up: radiographic tumor imaging, clinical tumor
      assessments, ECOG Performance Status assessments, reporting of pregnancy or lactation,
      assessment of swabs of lesions of suspected herpetic origin for presence of talimogene
      laherparepvec DNA, and tumor response assessments until documented disease progression beyond
      24-weeks of treatment, until the start of a new anticancer therapy, or end of study,
      whichever is earliest. If a participant discontinues therapy more than 24 months after the
      last participant was enrolled in the study, when the long-term follow-up period ends, they
      will not enter long-term follow-up.
    

Intervention name(s): Talimogene laherparepvec
Intervention type(s): Drug
Intervention description(s): Talimogene laherparepvec will be administered as an intralesional injection.
Other intervention name(s): Imlygic; T-VEC
Intervention MeSH terms: Talimogene laherparepvec
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Other
Keywords: Unresectable Stage IIIB-IV Malignant Melanoma