Study to Evaluate the Safety/ Efficacy of T-VEC in Japanese Subjects With Unresectable Stage IIIB-IV Malignant Melanoma

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.