AMGEN 20140318 - T-VEC intrahepatic: A Phase 1b/2, Multicenter, Open-label Trial to Evaluate the Safety of Talimogene Laherparepvec Injected into Liver Tumors Alone and in Combination With Systemic Pembrolizumab
Indication :

Tumeur du foie non opérable (HCC) ou non-HCC


Sponsor :

Amgen


Phase :

I, II


Traitement :

Talimogene Laherparepvec (T-VEC), Pembrolizumab


Spécificités :

BC, GEC, melanoma, NSCLC, RCC with liver metastatis or HCC (PD)
Subjects must not be candidates for hepatic surgery or locoregional therapy of liver tumors
Liver tumors must not be estimated to invade approximately more than one-third of the liver
HCC: monotherapy /TVEC+Pembrolizumab
Non-HCC: TVEC+Pembrolizumab


Site :

CHUV, HUG


Contact(s) :
Prof. Nicolas Mach
Investigateur Principal

HUG - Unité de recherche clinique DFDL
Oncologie

4 rue Gabrielle-Perret-Gentil
Genève
1211

079 553 23 94
Nicolas.Mach@hcuge.ch
Virginie Ancrenaz-Sirot
Coordinatrice

HUG - Unité de recherche clinique DFDL
Oncologie

4 rue Gabrielle-Perret-Gentil
Genève
1211

079 553 23 81
Virginie.Ancrenaz@hcuge.ch
Dr Dorothea Wagner
Investigateur principal

CHUV
Oncologie

Rue de Bugnon 46
Lausanne
1011
Adresser un patient (CHUV): 

Dr Stefan Zimmermann: stefan.zimmermann@chuv.ch
Dr Angela Orcurto: angela.orcurto@chuv.ch

021 314 38 54
do.ion.ref@chuv.ch

Primary objective :

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.


Inclusion criteria :
  • Subjects must have histologically or cytologically confirmed breast 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.
  • Part 2 Group B is restricted to HCC (fibrolamellar and mixed hepatocellular/cholangiocarcinoma subtypes are not eligible).
  • Non-hepatocellular carcinoma 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 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, 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, 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 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 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.