A Study of Talimogene Laherparepvec in Stage IIIc and Stage IV Malignant Melanoma

A Phase II 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 the study was to assess the clinical efficacy of talimogene laherparepvec in terms of tumor response rates.

Inclusion Criteria:

1. Patients with histologically proven stage IIIc (including two or more palpable lymph nodes, extracapsular or in-transit metastases) or stage IV melanoma that is not eligible for curative surgery and who have one or more tumors that are accessible for direct injection.
2. Tumors 0.5 to 10 cm in the longest diameter that are suitable for injection (i.e. not bleeding or weeping).
3. Serum lactate dehydrogenase (LDH) levels ≤ 2.0 times the upper limit of normal.
4. Aged 18 years or more.
5. Eastern Cooperative Oncology Group (ECOG) Performance status 0 or 1.
6. Clinically immunocompetent.
7. Recovered from prior therapy with at least 4 weeks since the last exposure to chemotherapy or radiotherapy.
8. Total white cell count ≥ 3.0 x 10^9/L, platelet count ≥ 80 x 10^9/L.
9. Serum creatinine ≤ 0.2 mmol/L.
10. Bilirubin ≤ 1.5 times the upper limit of the normal range, aspartate aminotransferase (AST)/alanine aminotransferase (ALT) equal to or less than twice the upper limit of the normal range and alkaline phosphatase equal to or less than twice the upper limit of the normal range.

Exclusion Criteria:

1. Participation in any previous melanoma immunotherapy trial within one month prior to entry to this trial or any trial of any other investigational agent within the last month prior to entry to this trial.
2. Tumors to be injected lying in mucosal regions or close to an airway, major blood vessel or spinal cord that, in the opinion of the Investigators, could cause occlusion or compression in the case of tumor swelling or erosion into a major vessel in the case of necrosis.
3. Pregnancy, lactation or lack of effective contraception in women of child-bearing potential; lack of effective contraception in men if the partner is of child-bearing potential; women must have been practising an effective contraceptive method for at least three months prior to entry in to the trial (hormonal contraception or intrauterine device in conjunction with a barrier method OR surgically sterilised). Men must use a condom or be surgically sterilised.
4. Major surgery within the 14 days prior to entry to the trial.
5. Intercurrent serious infections within the 28 days prior to entry to the trial.
6. Life-threatening illness unrelated to cancer.
7. Treatment with antiviral agents within the 14 days prior to entry to the trial.
8. Uncontrolled congestive cardiac failure.
9. Clinically active autoimmune disease.
10. Dermatoses involving or near to the tumors to be injected. Limb tumors may not be injected if active dermatoses are present on the same limb. Trunk and head and neck tumors must not be injected if dermatoses are present within 50 cm of the tumor.
11. Known to test positive for human immunodeficiency virus (HIV), hepatitis B or C or syphilis.
12. Patient only has injectable tumors that are not potentially resectable in the case of tumor necrosis or swelling.
13. Previous history of malignancies of other types that have occurred or recurred within the previous 5 years with the exception of cone biopsied carcinoma of the cervix.
14. Corticosteroid use.