Hepatocellular carcinoma (HCC) and metastatic liver tumors (non-HCC) MedDRA version: 21.0 Level: LLT Classification code 10019828 Term: Hepatocellular carcinoma non-resectable System Organ Class: 100000004864 MedDRA version: 21.0 Level: LLT Classification code 10025628 Term: Malignant liver tumour non-resectable System Organ Class: 100000004864
Conditions
Sponsors
Amgen Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Subjects must be age = 18 years at the time of informed consent. Subjects must have histologically or cytologically confirmed disease. • Part 1 is restricted to BC, CRC, GEC, melanoma, NSCLC, or RCC with liver metastases or HCC. • Part 2 Group A is restricted to advanced hormone receptor positive BC, CRC, TNBC, CSCC, and BCC with or without liver metastases. o Part 2 Hormone receptor positive Breast Cancer Arm only: Histologically and/or cytologically confirmed diagnosis of estrogen receptor (ER) positive and/or progesterone receptor (PrR) positive (ER = 1%, PrR = 1%) breast cancer. o Triple negative breast cancer: Histologically and/or cytologically confirmed diagnosis of ER negative, PR negative, human epidermal growth factor receptor 2 (HER2)-Neu negative (ER =65 years) yes F.1.3.1 Number of subjects for this age range 63
Exclusion criteria
Exclusion criteria: Subjects must not be candidates for surgery or locoregional therapy with curative intent or planned systemic anti-cancer therapy, with the exception of immunotherapy in the combination cohorts (Cohorts 5 and 6 in Part 1 and all subjects in Part 2). Liver tumors must not be estimated to invade approximately more than one-third of the liver. Liver tumor-directed therapy, hepatic surgery or major surgery, antibodybased 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 either (1) have no central nervous system (CNS) metastasis, or carcinomatous meningitis, or (2) if CNS metastasis is present, must have stable treated cerebral metastases from BC, NSCLC, RCC, CRC, GEC, or melanoma. Subjects must not have symptomatic auto-immune disease or be symptomatically immunosuppressed. They must not have a history of solid organ transplantation. For non-HCC, there must not be acute or chronic hepatitis B virus (HBV) or hepatitis C virus (HCV) infection. For HCC with prior hepatitis B and/or C infection, HBV and/or HCV viral load by qPCR must be undetectable, and they must not have had recent treatment within 12 weeks for HBV or HCV with certain antiviral medications in Part 1 Group B cohorts 1-5 and 6a, and Part 2 Group B HCC without viral hepatitis. For all patients in Part 1 and for patients in Part 2 where intrahepatic liver injection is planned, 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); require treatment with an antiherpetic drug; have received live-virus vaccination within 30 days of planned treatment start; have previous therapy with talimogene laherparepvec, oncolytic viruses, or tumor vaccine. They must not require concomitant treatment with warfarin. Subjects in the combination treatment cohort must not have: a history or evidence of psychiatric, substance abuse, or any other clinically significant disorder; toxic effects of the most recent prior chemotherapy not resolved to grade 1 or less (except alopecia); or expected other cancer therapy while on study with the exception of local radiation to the site of bone or other metastasis for palliative treatment. Male subjects of reproductive potential in the combination treatment must be willing to use acceptable methods of effective contraception during treatment and through 4 months after the last dose of pembrolizumab.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Part 1: To evaluate the following, as assessed by the incidence of doselimiting toxicities (DLTs), in subjects with liver metastases (non-hepatocellular) carcinoma [HCC] and subjects with primary HCC in: • Monotherapy Cohorts: the maximum tolerated volume and concentration (MTV and MTC) of intrahepatic injection of talimogene laherparepvec into liver tumors in subjects with non-HCC and subjects with primary HCC without active viral hepatitis • Combination Cohorts: the MTC of intrahepatic injection of talimogene laherparepvec into liver tumors in combination with systemic intravenous (IV) administration of pembrolizumab in subjects with non-HCC, and subjects with primary HCC with or without viral hepatitis Part 2: • To evaluate the efficacy, as assessed by objective response rate (ORR) of intratumoral injection of talimogene laherparepvec in combination with systemic IV administration of pembrolizumab, separately, for each non-HCC tumor type;Secondary Objective: Part 1: To evaluate the efficacy separately by monotherapy versus combination for non-HCC tumors and HCC with and without viral hepatitis when applicable as assessed by: • ORR, best overall response (BOR), durable response rate (DRR), duration of response (DOR), response in injected and uninjected lesions, disease control rate (DCR), progression-free survival (PFS), and overall survival (OS) Part 2: • To evaluate the efficacy in individual tumor types in the non-HCC group and HCC group with and without viral hepatitis as assessed by: o BOR, DRR, DOR, response in injected and uninjected lesions, DCR, PFS, and OS by primary tumor type (TNBC, Hormone receptor positive BC, CRC, CSCC, BCC, and HCC with and without viral hepatitis) SAFETY (Parts 1 and 2) • To evaluate the safety in each monotherapy and combination cohorts in Part 1 and each arm separately in Part 2, as assessed by subject incidence of treatment-emergent and treatment-related adverse events;Primary end point(s): Part 1: Monotherapy c | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Efficacy: Part 1: • ORR, BOR, DRR, DOR, response in injected and uninjected lesions, DCR, PFS, and OS separately for non-HCC and HCC tumors in monotherapy and combination cohorts Part 2: • BOR, DRR, DOR, response in injected and uninjected lesions, DCR, PFS, and OS by primary tumor type arm (TNBC, Hormone receptor positive BC, CRC, CSCC, BCC, and HCC with and without viral hepatitis) Safety: Parts 1 and 2: • Subject incidence of treatment-related and treatment-emergent adverse events (monotherapy and combination cohorts in Part 1, and each tumor type separately in Part 2, and HCC with and without viral hepatitis) • Subject incidence of detectable talimogene laherparepvec DNA in blood and urine • Incidence of clearance of talimogene laherparepvec DNA from blood and urine • Subject incidence (per subject) and rate of detection (per sample) of talimogene laherparepvec DNA and virus at the surface of injection site, the exterior of occlusive dressing, and the oral mucosa • Subject incidence of talimogene laherparepvec DNA detection in lesions suspected to be herpetic in origin;Timepoint(s) of evaluation of this end point: Will be evaluated at Interim and Primary Analysis | — |
Countries
Austria, Belgium, Germany, Poland, Spain, Switzerland
Contacts
Public ContactMedical Information
Amgen GmbH
Outcome results
None listed