Trial to Evaluate the Safety ofTalimogene Laherparepvec Injected Into Liver Tumors Alone and in Combination With Systemic Pembrolizumab

Status: Active

Description

This is a phase 1b / 2, multicenter, open-label trial to evaluate the safety of talimogene laherparepvec injected intrahepatically into liver tumors with known progression alone and in combination with systemic IV administration of pembrolizumab, in subjects with non-HCC liver metastases from BC, CRC, GEC, melanoma, NSCLC, RCC, and subjects with HCC. The study consists of 2 parts and 2 groups, and Part 2 includes 2 stages. The objective of Part 1 is to evaluate the safety of intrahepatic injection of talimogene laherparepvec into liver tumors alone and in combination with systemically administered pembrolizumab for the non-HCC (Group A) and HCC (Group B) cohorts separately. Part 2 consists of 2-stage design to evaluate the efficacy and safety of talimogene laherparepvec in combination with systemic pembrolizumab. Efficacy and safety will be evaluated in each of the six non-HCC tumor types from Group A separately. Similarly, the efficacy and safety of the combination treatment will be determined for Group B HCC subjects.

Eligibility Criteria

Inclusion Criteria

  • Summary of Subject Eligibility Criteria: Key Inclusion Criteria: Subjects must be age ≥ 18 years at the time of informed consent. They must have histologically or cytologically confirmed BC, CRC, GEC, melanoma, NSCLC, or RCC with liver metastases or HCC. Part 2 Group B is restricted to HCC (fibrolamellar and mixed hepatocellular/cholangiocarcinoma subtypes are not eligible). Non-HCC subjects must have received at least 1 prior standard of care systemic anti-cancer therapy for their locally advanced or metastatic disease. For the combination cohorts (Cohorts 5 and 6 in Part 1) and Part 2, subjects with metastatic melanoma or NSCLC do not need to have received prior therapy. Subjects must have measurable liver tumors and lesions that are suitable for injection. Eastern Cooperative Oncology Group (ECOG) 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. Liver function tests may be mildly abnormal but within the parameters. Child Pugh score must be A to B7. Key Exclusion Criteria: Subjects must not be candidates for hepatic surgery or locoregional therapy of liver tumors with curative intent or planned immediate 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, 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 either have no central nervous system (CNS) metastasis, or carcinomatous meningitis, or 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 immunosuppressed. They must not have a history of solid organ transplantation. For non-HCC, there must not be acute or chronic active 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 real time polymerase chain reaction (qPCR) must be undetectable, and they must not have had recent treatment within 12 weeks for HBV or HCV 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); require treatment with an oral or intravenous systemic antiherpetic drug; have received live-virus vaccination within 30 days of planned treatment start; have previous therapy with talimogene laherparepvec, oncolyic 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.

Locations & Contacts

California

Los Angeles
UCLA / Jonsson Comprehensive Cancer Center
Status: Active
Name Not Available
San Diego
University of California San Diego
Status: In review
Name Not Available

New York

New York
Memorial Sloan Kettering Cancer Center
Status: Active
Name Not Available

Pennsylvania

Pittsburgh
University of Pittsburgh Cancer Institute (UPCI)
Status: Approved
Name Not Available

Texas

Houston
M D Anderson Cancer Center
Status: Active
Name Not Available

Trial Phase & Type

Trial Phase

Phase I

Trial Type

Treatment

Lead Organization

Lead Organization
Amgen, Inc.

Trial IDs

Primary ID 20140318
Secondary IDs NCI-2015-02069, 2014-005386-67
Clinicaltrials.gov ID NCT02509507