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

Study Overview
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Brief Summary
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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.

Detailed Description
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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).

Official Title
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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

Conditions
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Melanoma

Intervention / Treatment
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* Biological: Talimogene Laherparepvec


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Previously participated in Study 002/03 and met 1 of the following: 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 Did achieve a CR in Study 002/03 and developed disease progression within 12 months of achieving a CR, or 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. Eastern Cooperative Oncology Group (ECOG) Performance status of 0 or 1. Exclusion Criteria: 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); History of Grade 3 fatigue lasting > 1 week while on OncoVEX^GM-CSF treatment; History of Grade 3 arthralgia/myalgias while on OncoVEX^GM-CSF treatment; 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; Symptomatic malignant disease progression that required alternative melanoma treatment; Primary malignancy disease progression despite treatment with OncoVEX^GM-CSF; Patient requested to be withdrawn from or was unable to comply with the demands of Study 002/03. Patient was withdrawn from Study 002/03 at the discretion of the Investigator.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Talimogene Laherparepvec<br>Participants received talimogene laherparepvec 10⁸ plaque forming units (PFU)/mL (up to 4 mL depending on tumor size) administered intratumorally every 2 weeks, on Day 1 and Day 15 of 28-day cycles until discontinuation criteria were met. | Biological: Talimogene Laherparepvec<br>* Administered by intratumoral injection.<br>* Other names: IMLYGIC;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Adverse Events | The severity of an adverse event (AE) was graded according to Common Toxicity Criteria for Adverse Events (CTCAE) Version 3 (1 = mild, 2 = moderate, 3 = severe, 4 = life-threatening, 5 = death). Serious adverse events include death, life-threatening events, events requiring or prolonging hospitalization, result in persistent or significant disability/incapacity, or a congenital anomaly/birth defect, or otherwise important medical events that may jeopardise the patient or require intervention to prevent one of the above outcomes. | From the first dose of talimogene laherparepvec in Study 002-03-E and within 30 days of the last dose; median duration of treatment was 267 days. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With an Objective Response | Objective response is defined as participants with an overall best response of complete response or partial response. The objective response to treatment was assessed by computed tomography (CT) scanning or other clinical measurement using modified Response Evaluation Criteria In Solid Tumors (RECIST). Responses must have been confirmed two visits not less than 4 weeks apart. Tumor burden for a visit was calculated as the sum of the longest diameters of all tumors identified and measured up to that visit. Tumor response at each visit was derived from tumor burden, as follows: Complete response (CR): zero tumor burden Partial response (PR): a 30% or greater decrease in tumor burden Progressive disease (PD): a 20% or greater increase in tumor burden Stable disease (SD): none of the above (a < 30% decrease and < 20% increase in tumor burden) | Every 12 weeks from the start of therapy in this extension protocol, or 12 weeks from the last assessment in the 002/03 protocol (whichever date is later) through 30 days after administration of the last dose; median duration of treatment was 267 days. | 
| Number of Participants Alive at the Time of Study Discontinuation or Completion |  | At end of study, median duration of treatment was 267 days |