Patient case: 86-year-old female with melanoma; genetic feature: high tumor mutational burden

Clinical trial: Study to Evaluate the Safety/ Efficacy of T-VEC in Japanese Subjects With Unresectable Stage IIIB-IV Malignant Melanoma

Summary: No formal statistical hypothesis will be tested for safety endpoints in this trial. Based on the well tolerated safety profile from a global phase 3 study, it is hypothesized that talimogene laherparepvec will be safe and well tolerated in Japanese subjects with unresectable Stage IIIB-IVM1c melanoma. A DRR is hypothesized to be consistent with results from the global phase 3 study


Eligibility: Inclusion Criteria:
  -  Histologically confirmed diagnosis of melanoma
  -  Subject with stage IIIB to IVM1c melanoma that is not surgically resectable
  -  Subject who is treatment naive and is determined by the physician to be not suitable or eligible for the approved systemic anticancer drug therapy in Japan. Subject may also have received prior systemic anticancer treatment consisting of chemotherapy, immunotherapy, or targeted therapy. 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, where appropriate) defined as one or more of the following:
  -  at least 1 injectable cutaneous, subcutaneous, or nodal melanoma lesion greater or equal to 10 mm in longest diameter, OR
  -  multiple injectable melanoma lesions that in aggregate have a longest diameter of greater or equal to 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 greater or equal to 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 greater or equal to10 mm longest diameter superficial cutaneous or subcutaneous melanoma lesion as measured by calipers
  -  multiple superficial melanoma lesions which in aggregate have a total diameter of greater or equal to 10 mm
  -  Serum lactate dehydrogenase (LDH) levels less than or equal to 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
  -  Other Inclusion Criteria May Apply.
  Exclusion Criteria:
  -  Clinically active cerebral metastases. Subjects with up to 3 cerebral metastases may be enrolled, provided that all lesions have been adequately treated with stereotactic radiation therapy (including Gamma Knife) or craniotomy, with no evidence of progression and have not required steroids for at least 2 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 less than or equal to 3 visceral metastases, no lesion greater than 3 cm in longest dimension 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 disease (eg, pneumonitis, glomerulonephritis, vasculitis, or other), or history of autoimmune disease that required systemic treatment (ie, use of corticosteroids, immunosuppressive drugs or biological agents used for treatment of autoimmune diseases) in past 2 months prior to enrollment.
  -  Active herpetic skin lesions or prior complications of herpetic 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
  -  Other investigational procedures while participating in this study are excluded.
  -  Known to have acute or chronic active hepatitis B infection, acute or chronic active hepatitis C infection or human immunodeficiency virus (HIV) infection
  -  Subject has known sensitivity to bovine- or porcine derived components or to any of the products or components to be administered during dosing.
  -  History of other malignancy within the past 3 years
  -  Other Exclusion Criteria May Apply

Relevance to patient case: not relevant