An Extension Protocol for the Extended Use of Talimogene Laherparepvec for Eligible Patients Who Participated in Study 002/03 (NCT00289016)

Phase 2 Extension Protocol for Extended Use of OncoVEX^GM-CSF for Eligible Patients Participating in Study 002/03: Study of the Efficacy, Safety and Immunogenicity of OncoVEX^GM-CSF in Patients With Stage IIIc and Stage IV Malignant Melanoma

The primary objective of this extension study was to further assess the safety and tolerability of talimogene laherparepvec. Secondary objectives were to assess objective tumor response rate and survival.

This was an extension study to the multicenter, open-label, phase 2 Study 002/03 (NCT00289016). Participants who had received the maximum 24 treatments under Study 002/03 and met the inclusion and exclusion criteria were eligible to enroll.

Participants continued to receive talimogene laherparepvec until discontinuation criteria were met. The discontinuation criteria were complete response, clinically significant progressive disease that rendered further dosing futile, receipt of 24 treatments or 12 months on treatment (whichever was longer), occurrence of an unacceptable toxicity, death, investigator determination that other treatment was warranted, or another criterion for withdrawal from treatment (participant request, noncompliance with study procedures, or sponsor request).

Inclusion Criteria:

1. Previously participated in Study 002/03 and met 1 of the following:

   1. Received the maximum 24 treatment injections in Study 002/03 and had not yet achieved a complete response (CR) and whose response to OncoVEX^GM-CSF indicated that treatment beyond 12 months was warranted, or
   2. Did achieve a CR in Study 002/03 and developed disease progression within 12 months of achieving a CR, or
   3. Terminated treatment in Study 002/03 to allow for treatment of brain metastases. Treatment for brain metastases was no longer ongoing and the patient was able to return to OncoVEX^GM-CSF injections within 3 months of completing treatment for brain metastases.

2. Eastern Cooperative Oncology Group (ECOG) Performance status of 0 or 1.

Exclusion Criteria:

1. Prior Common Toxicity Criteria for Adverse Events (CTCAE) Grade 3 or 4 toxicity related to OncoVEX^GM-CSF of any organ system (with the exception of injection site reactions, fever and vomiting);
2. History of Grade 3 fatigue lasting > 1 week while on OncoVEX^GM-CSF treatment;
3. History of Grade 3 arthralgia/myalgias while on OncoVEX^GM-CSF treatment;
4. History of ≥ Grade 2 autoimmune reactions, allergic reactions or urticaria or other OncoVEX^GM-CSF-related non-hematological toxicities while on OncoVEX^GM-CSF treatment that required a dose delay or discontinuation of OncoVEX^GM-CSF therapy;
5. Symptomatic malignant disease progression that required alternative melanoma treatment;
6. Primary malignancy disease progression despite treatment with OncoVEX^GM-CSF;
7. Patient requested to be withdrawn from or was unable to comply with the demands of Study 002/03.
8. Patient was withdrawn from Study 002/03 at the discretion of the Investigator.