An Extended Use Study of Safety and Efficacy of Talimogene Laherparepvec in Melanoma

Study Overview
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Brief Summary
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The purpose of this study is to learn about the safety and the risks of using talimogene laherparepvec in patients who already received treatment with talimogene laherparepvec in study 005/05 (NCT00769704), and to see if extended treatment with talimogene laherparepvec can destroy melanoma tumors.

Official Title
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An Extension Protocol to Evaluate the Efficacy and Safety of Extended Use Treatment With OncoVEX^GM-CSF for Eligible Melanoma Patients Participating in Study 005/05

Conditions
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Melanoma

Intervention / Treatment
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* Biological: Talimogene Laherparepvec
* Drug: Granulocyte Macrophage Colony-Stimulating Factor (GM-CSF)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Previously participated in protocol 005/05 (NCT00769704) and: received the maximum number of talimogene laherparepvec treatment injections or cycles of GM-CSF allowable for that patient on study 005/05, or new injectable lesion(s) appeared after previous resolution of all injectable disease while on study 005/05. New injectable lesions must have appeared within ≤ 12 months from the End of Treatment visit on the 005/05 study. In the opinion of the investigator and the sponsor's medical monitor further treatment is warranted [e.g., those patients who do not have clinically relevant progressive disease (PDr)]. Performance status (Eastern Cooperative Oncology Group, ECOG) 0 or 1. For patients randomized to talimogene laherparepvec only: Injectable disease (i.e. suitable for direct injection or through the use of ultrasound guidance) defined as at least 1 injectable cutaneous, subcutaneous or nodal melanoma lesion. There is no minimum size for injection. Exclusion Criteria: Prior Common Terminology Criteria for Adverse Events (CTCAE) grade 3 or 4 toxicity related to talimogene laherparepvec of any organ system (with the exception of injection site reactions, fever and vomiting). History of Grade 3 fatigue lasting > 1 week while on talimogene laherparepvec treatment. History of Grade 3 arthralgia/myalgias while on talimogene laherparepvec treatment. History of ≥ Grade 2 autoimmune reactions, allergic reactions or urticaria or other talimogene laherparepvec related non-hematological toxicities while on talimogene laherparepvec treatment that required a dose delay or discontinuation of talimogene laherparepvec therapy. PDr while participating in study 005/05 Patient requested to be withdrawn from study 005/05 or was unable to comply with the demands of the 005/05 trial. At the discretion of the investigator, patient was withdrawn from the 005/05 trial.

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
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: GM-CSF<br>Granulocyte macrophage colony-stimulating factor (GM-CSF) was administered at a dose of 125 μg/m²/day subcutaneously for 14 consecutive days followed by 14 days of rest, in 28-day treatment cycles for up to 12 months or until a complete response, occurrence of an unacceptable toxicity, death or another criterion for withdrawal from treatment was met. Participants who demonstrated a partial response after being on treatment for 12 months could continue to be treated until disease progression or another treatment discontinuation criterion was met. | Drug: Granulocyte Macrophage Colony-Stimulating Factor (GM-CSF)<br>* 125 µg/m² subcutaneous injection<br>|
| Experimental: Talimogene Laherparepvec<br>Talimogene laherparepvec was administered at a concentration of 10⁸ plaque forming units (PFU)/mL injected into 1 or more skin or subcutaneous tumors on Days 1 and 15 of each 28-day cycle for up to 12 months or until a complete response, occurrence of an unacceptable toxicity, death or another criterion for withdrawal from treatment was met. Participants who demonstrated a partial response after being on treatment for 12 months could continue to be treated until disease progression or another treatment discontinuation criterion was met. | Biological: Talimogene Laherparepvec<br>* Up to 4 mL of 10⁸ pfu/mL/per 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 Treatment-emergent Adverse Events (AEs) | AEs were graded according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE), version 3.0 based on the following guideline: Grade 1: Mild AE; Grade 2: Moderate AE; Grade 3: Severe AE; Grade 4: Life-threatening or disabling AE; Grade 5: Death related to AE. Treatment-related AE refers to AEs that have possible or probable relation to study treatment as determined by the investigator. A serious AE is one that meets one or more of the following criteria/outcomes: Results in death. Is life-threatening. Requires inpatient hospitalization or prolongation of existing hospitalization. Results in persistent or significant disability/incapacity. Is a congenital anomaly/birth defect. Is an important medical event. | From first administration of study drug in the extension period until 30 days after last dose. Median duration of treatment was 50 weeks in the GM-CSF group and 36 weeks in the talimogene laherparepvec group. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective Response Rate | Objective response rate was defined as the percentage of participants with a best overall response of complete response (CR) or partial response (PR) assessed by the investigator. Best overall response for a patient is the best overall response observed across all time points and is cumulative (ie, includes responses during the parent study 005/05 and during Study 005/05-E). Disease assessments were performed at the beginning of each treatment cycle and assessed in accordance with modified World Health Organization criteria. CR: Disappearance of all clinical evidence of tumor (both measurable and non-measurable but evaluable disease); PR: ≥ 50% reduction in the sum of the products of the perpendicular diameters of all measurable tumors at the time of assessment as compared to baseline. | From randomization in study 005/05 until the data-cut-off date for the extension period of 08 August 2014; median treatment duration for 005/05 and 005/05-E studies combined was 88 weeks for talimogene laherparepvec and 100 weeks for GM-CSF. | 
| Durable Response Rate | Durable response rate is defined as the percentage of participants with a complete response (CR) or partial response (PR) assessed by the investigator, initiating at any time while receiving talimogene laherparepvec or GM-CSF therapy on the 005/05 or the 005/05-E study and maintained continuously for at least 6 months from response initiation. This reflects all new sites of disease as well as disease sites identified at baseline. Disease assessments were performed at the beginning of each treatment cycle in accordance with modified World Health Organization criteria. CR: Disappearance of all clinical evidence of tumor (both measurable and non-measurable but evaluable disease); PR: ≥ 50% reduction in the sum of the products of the perpendicular diameters of all measurable tumors at the time of assessment as compared to baseline. | From randomization in study 005/05 until the data-cut-off date for the extension period of 08 August 2014; median treatment duration for 005/05 and 005/05-E studies combined was 88 weeks for talimogene laherparepvec and 100 weeks for GM-CSF. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Melanoma, Stage IIIb, IIIc and IV Disease, oncolytic, OncoVex, OncoVEX^GM-CSF