Patient case: 56-year-old female with basal cell carcinoma; genetic feature: PTCH1

Clinical trial: Safety Study of Talimogene Laheraprepvec Injected Into Hepatocellular Carcinoma and Metastatic Liver Tumors

Summary: This is a phase 1, multicenter, open-label trial to evaluate the safety of talimogene laherparepvec, injected intrahepatically, into liver tumors with known progression in subjects with Hepatocellular carcinoma and subjects with liver metastases from breast adenocarcinoma, colorectal adenocarcinoma, gastroesophageal cancer (adenocarcinoma or squamous cell carcinoma), melanoma, non-small cell lung cancer, or clear cell renal cell carcinoma. The study consists of 2 parts and 2 groups. Part 1 is a 3+3 dose escalation consisting of 3 sequential dose cohorts each administering talimogene laherparepvec in increasing dose concentrations and dose volumes. In Part 1, the Maximum Tolerated Dose determination of non-hepatocellular carcinoma liver metastases (Group A) will be evaluated separately from hepatocellular carcinoma (Group B), and each dose cohort will need to be deemed safe for non-hepatocellular carcinoma subjects before it will be administered in hepatocellular carcinoma subjects. Part 2 consists of expansion cohorts administering the Maximum Tolerated Dose of talimogene laherparepvec determined from Part 1 for Groups A (non-hepatocellular carcinoma) and B (hepatocellular carcinoma) to approximately 10 subjects for each tumor type.


Eligibility: Inclusion Criteria:
  -  Subjects must have histologically confirmed breast adenocarcinoma, colorectal adenocarcinoma, gastroesophageal cancer (adenocarcinoma or squamous cell carcinoma), melanoma, non-small cell lung cancer, or clear cell renal cell carcinoma with liver metastases or hepatocellular carcinoma with known disease progression.
  -  Non-hepatocellular carcinoma subjects must have received at least 1 prior standard of care systemic anti-cancer therapy for their metastatic disease.
  -  Subjects must have measurable liver tumors that are suitable for injection.
  -  Eastern Cooperative Oncology Group performance status must be 0 or 1, and life expectancy should be approximately 5 months or more.
  -  Adequate hematological, renal, hepatic and coagulation function is required.
  -  Child-Pugh score must be A to B7.
  Exclusion Criteria:
  -  Subjects must not be candidates for hepatic surgery or locoregional therapy of liver tumors with curative intent or planned systemic anti-cancer therapy.
  -  Liver tumors must not be estimated to invade approximately more than one-third of the liver.
  -  Liver tumor-directed therapy, hepatic surgery, antibody-based therapy, or immunotherapy must not have been performed < 28 days, chemotherapy < 21 days, and targeted small molecule therapy or hormonal therapy < 14 days prior to enrollment.
  -  Subjects must have either no central nervous system metastasis or irradiated, stable cerebral metastases from breast adenocarcinoma, non-small cell lung cancer, clear cell renal cell carcinoma, or melanoma.
  -  Subjects must not have history or evidence of symptomatic autoimmune pneumonitis, glomerulonephritis, vasculitis, or other symptomatic autoimmune disease.
  -  Subjects must not have symptomatic auto-immune disease or be immunosuppressed.
  -  Subjects must not have a history of solid organ transplantation.
  -  For non-hepatocellular carcinoma, there must not be acute or chronic hepatitis B virus or hepatitis C virus infection.
  -  For hepatocellular carcinoma,hepatitis B virus and hepatitis C virus viral load must be undetectable, and they must not have had recent treatment with certain antiviral medications.
  -  There should be no macroscopic intravascular invasion of tumors into the main portal vein, hepatic vein, or vena cava.
  -  Subjects must not have active herpetic skin lesions or prior complications of herpetic infection (eg, herpetic keratitis or encephalitis) and must not require treatment with an antiherpetic drug.
  -  Subjects must not require concomitant treatment with warfarin.
  -  Female subjects of childbearing potential who is unwilling to use acceptable method(s) of effective contraception during protocol treatment and through 3 months after the last dose of talimogene laherparepvec.

Relevance to patient case: not relevant