1) Unresected stage IIIB to IVM1c melanoma
Conditions
Interventions
Patients will receive several doses of Talimogene laherparepvec. The initial
dose is up to 4.0 mL of 10^6 PFU/mL. Subsequent doses of are up to 4.0 mL of
10^8 PFU/mL. The second dose up to 4.0 mL of
Biomarker
Talimogene Laherparepvec
Unresected Stage IIIB to IVM1c Melanoma
Sponsors
Amgen
Eligibility
Age
18 Years to 64 Years
Inclusion criteria
Inclusion criteria: - Subject has provided informed consent prior to initiation of any study-specific activities/procedures ;- Male or female age * 18 years at the time of informed consent;- Histologically confirmed diagnosis of melanoma;- Subject with stage IIIB to IVM1c melanoma for whom surgery is not recommended;- Subject who is treatment naïve or had received prior treatment for melanoma. Any systemic treatment for melanoma must have been completed at least 28 days prior to enrollment;- Candidate for intralesional therapy (ie, disease is appropriate for direct injection or through the use of ultrasound guidance) defined as one of the following:;-at least 1 injectable cutaneous, subcutaneous, or nodal melanoma lesion * 10 mm in longest diameter, or;- multiple injectable melanoma lesions that in aggregate have a longest diameter of * 10 mm;- Measurable disease defined as one or more of the following:;- at least 1 melanoma lesion that can be accurately and serially measured in at least 2 dimensions and for which the greatest diameter is * 10 mm as measured by contrast-enhanced or spiral computed tomography (CT) scan, magnetic resonance imaging (MRI), or ultrasound for nodal/soft tissue disease (including lymph nodes);- at least 1 * 10 mm superficial cutaneous or subcutaneous melanoma lesion as measured by calipers;- multiple superficial melanoma lesions which in aggregate have a total diameter of * 10 mm;- Serum lactate dehydrogenase (LDH) levels * 1.5 X upper limit of normal (ULN) within 28 days prior to enrollment ;- Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 (see Appendix E);- Adequate organ function determined within 28 days prior to enrollment, defined as follows:;- absolute neutrophil count * 1500/mm3;- platelet count * 75,000/mm3;- hemoglobin * 8 g/dL without need for hematopoietic growth factor or transfusion support;- serum creatinine * 1.5 x ULN ;- serum bilirubin * 1.5 x ULN;- aspartate amino transferase (AST) * 2.5 x ULN;- alanine amino transferase (ALT) * 2.5 x ULN;- alkaline phosphatase * 2.5 x ULN;- serum albumin * 2.5 g/dL;- prothrombin time (PT) * 1.5 x ULN (or international normalization ratio [INR] * 1.3)*;- partial thromboplastin time (PTT) * 1.5 x ULN
Exclusion criteria
Exclusion criteria: - Clinically active cerebral metastases. Subjects 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 (including Gamma Knife) or resection, with no evidence of progression and have not required steroids for at least two months prior to enrollment.;- Greater than 3 visceral metastases (this does not include lung metastases or nodal metastases associated with visceral organs). For subjects with 3 visceral metastases, no lesion > 3 cm and liver lesions must be stable for at least 1 month prior to enrollment.;- Bone metastases;- Primary ocular or mucosal melanoma;- History or evidence of symptomatic autoimmune pneumonitis, glomerulonephritis, vasculitis, or other symptomatic autoimmune disease;- Evidence of clinically significant immunosuppression such as the following:;* primary immunodeficiency state such as Severe Combined Immunodeficiency Disease;*concurrent opportunistic infection;*receiving systemic immunosuppressive therapy (> 2 weeks), including oral steroid doses > 10 mg/day of prednisone or equivalent during the 2 monthsprior to enrollment;- Active herpetic skin lesions or prior complications of HSV-1 infection (eg, herpetic keratitis or encephalitis);- Requires intermittent or chronic systemic (intravenous or oral) treatment with an antiherpetic drug (eg, acyclovir), other than intermittent topical use;- Previous treatment with talimogene laherparepvec;- Currently receiving treatment with another investigational device or drug study, or less than 28 days since ending treatment with another investigational device or drug study(s);- Other investigational procedures while participating in this study are excluded;- Known to have acute or chronic active hepatitis B infection;- Known to have acute or chronic active hepatitis C infection;- Known to have human immunodeficiency virus infection;- History of other malignancy within the past 3 years with the following exceptions:;* malignancy treated with curative intent and with no known active disease present for * 3 years before enrollment and felt to be at low risk for recurrence by the treating physician * adequately treated non-melanoma skin cancer without evidence of disease * adequately treated cervical carcinoma in situ without evidence of disease * adequately treated breast ductal carcinoma in situ without evidence of disease *prostatic intraepithelial neoplasia without evidence of prostate cancer *adequately treated urothelial papillary noninvasive carcinoma or carcinoma in situ;- Subject has known sensitivity to any of the products or components to be administered during dosing;- Subject likely to not be available to complete all protocol required study visits or procedures, and/or to comply with all required study procedures to the best of the subject*s and investigator*s knowledge;- History or evidence of any other clinically significant disorder, condition or disease (with the exception of those outlined above) that, in the opinion of the investigator or Amgen medical monitor, if consulted, would pose a risk to subject safety or interfere with the study evaluation, procedures, or completion;- Subject previously has entered this study;- Female subject is pregnant or breast-feeding, or planning to become pregnant during study treatment and through 3 months after the last dose of talimogene laherparepvec;- Female subject of chil
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| To explore the correlation between baseline intratumoral CD8+ cell density and objective response rate (ORR) in subjects with unresected stage IIIB to IVM1c melanoma treated with talimogene laherparepvec | — |
Secondary
| Measure | Time frame |
|---|---|
| - to explore the correlation between baseline intratumoral CD8+ cell density and durable response rate (DRR), duration of response (DOR), and changes in tumor burden - to explore the correlation between changes in intratumoral CD8+ cell density during treatment and ORR, DRR, DOR, and changes in tumor burden - to evaluate ORR, DOR, time to treatment failure (TTF), DRR, OS, and change in tumor burden during treatment - to evaluate the safety and tolerability of talimogene laherparepvec | — |
Countries
Austria, Belgium, France, Germany, Greece, Hungary, Italy, Netherlands, Poland, Russian Federation, Spain, United Kingdom, United States of America
Outcome results
None listed