Efficacy and Safety Study of Talimogene Laherparepvec Compared to Granulocyte Macrophage Colony Stimulating Factor (GM-CSF) in Melanoma

BioVex

Status and phase: Completed; Phase 3

Conditions: Melanoma

Treatments: Biological: Talimogene laherparepvec; Biological: GM-CSF

Study type: Interventional

Funder types: Industry

Identifiers

NCT00769704

005/05

20110263 (Other Identifier)

2008-006140-20 (EudraCT Number)

Details and patient eligibility

About

The objective of this study is to evaluate the efficacy and safety of treatment with talimogene laherparepvec compared to subcutaneously administered GM-CSF in patients with unresectable Stage IIIb, IIIc and Stage IV melanoma. The efficacy endpoints of the study aim to demonstrate overall clinical benefit for patients treated with talimogene laherparepvec as compared to GM-CSF.

Enrollment: 437 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Males or females age ≥ 18 years
• Stage IIIb, IIIc or stage IV disease that is not surgically resectable
• Injectable disease (i.e. suitable for direct injection or through the use of ultrasound guidance)
• At least 1 injectable cutaneous, subcutaneous or nodal melanoma lesion >= 10 mm in longest diameter or, multiple injectable melanoma lesions which in aggregate have a longest diameter of >= 10 mm
• Serum lactate dehydrogenase (LDH) levels less than 1.5 x upper limit of normal (ULN)
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
• Prolongation in International Normalized Ratio (INR), Prothrombin Time (PT), and Partial Thromboplastin Time (PTT) when the result is from therapeutic anticoagulation treatment are permitted for patients whose injectable lesions are cutaneous and/or subcutaneous such that direct pressure could be applied in the event of excessive bleeding

Exclusion criteria

• Clinically active cerebral or any bone metastases. Patients with up to 3 (neurological performance status of 0) cerebral metastases may be enrolled, provided that all lesions have been adequately treated with stereotactic radiation therapy, craniotomy, gammaknife therapy, with no evidence of progression, and have not required steroids, for at least two (2) months prior to randomization
• Greater than 3 visceral metastases (this does not include lung metastases or nodal metastases associated with visceral organs). For patients with < 3 visceral metastases, no lesion > 3 cm, and liver lesions must meet Response Evaluation Criteria In Solid Tumors (RECIST) criteria for stable disease for at least 1 month prior to randomization

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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437 participants in 2 patient groups

GM-CSF

Active Comparator group

Description:

Granulocyte macrophage colony-stimulating factor (GM-CSF) was administered at a dose of 125 μg/m²/day subcutaneously for 14 days, followed by a 14-day rest period for 24 weeks. Participants could continue treatment until clinically relevant disease progression, intolerability, withdrawal of consent, complete remission, or lack of response by 12 months, for a maximum of 18 months.

Treatment:

Biological: GM-CSF

Talimogene Laherparepvec

Experimental group

Description:

Participants received talimogene laherparepvec on Days 1 and 15 of each 28-day cycle for 24 weeks. The initial dose of talimogene laherparepvec was at a concentration of 10⁶ plaque forming units (PFU)/mL, injected into 1 or more skin, subcutaneous or nodal tumors. Subsequent doses began at least 3 weeks after the first dose and consisted of talimogene laherparepvec at a concentration of 10⁸ PFU/mL. Participants could continue treatment until clinically relevant disease progression, intolerability, withdrawal of consent, complete remission, lack of response by 12 months, or disappearance of all injectable lesions, for a maximum of 18 months.

Treatment:

Biological: Talimogene laherparepvec