Clinical Trials /

Trial to Evaluate the Safety of Talimogene Laherparepvec Injected Into Tumors Alone and in Combination With Systemic Pembrolizumab MK-3475-611/Keynote-611

NCT02509507

Description:

This is a phase 1b/2, multicenter, open-label, basket trial to evaluate the safety of talimogene laherparepvec injected intrahepatically into liver tumors alone and in combination with systemic IV administration of pembrolizumab, in subjects with non-HCC liver metastases from BC, CRC, gastroesophageal cancer (GEC), melanoma, NSCLC, RCC in Part 1 Group A, and subjects with HCC with and without viral hepatitis in Part 1 Group B (viral hepatitis is only applicable in combination setting), and to evaluate the efficacy and safety of intratumoral talimogene laherparepvec in combination with systemic pembrolizumab in subjects with advanced TNBC, hormone receptor positive breast cancer, CRC, CSCC, and BCC in Part 2 Group A and subjects with HCC with and without viral hepatitis in Part 2 Group B. 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 five 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.

Related Conditions:
  • Adenocarcinoma of the Gastroesophageal Junction
  • Breast Carcinoma
  • Colorectal Carcinoma
  • Esophagogastric Carcinoma
  • Hepatocellular Carcinoma
  • Melanoma
  • Non-Small Cell Lung Carcinoma
  • Renal Cell Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Trial to Evaluate the Safety ofTalimogene Laherparepvec Injected Into Liver Tumors Alone and in Combination With Systemic Pembrolizumab
  • Official Title: 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 (MASTERKEY-318)

Clinical Trial IDs

  • ORG STUDY ID: 20140318
  • SECONDARY ID: 2014-005386-67
  • NCT ID: NCT02509507

Conditions

  • Hepatocellular Carcinoma
  • Liver Metastases

Interventions

DrugSynonymsArms
Talimogene LaherparepvecPhase Ib/II Talimogene Laherparepvec
PembrolizumabPhase Ib/II Talimogene Laherparepvec + Pembrolizumab

Purpose

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.

Trial Arms

NameTypeDescriptionInterventions
Phase Ib/II Talimogene LaherparepvecExperimentalTalimogene Laherparepvec
  • Talimogene Laherparepvec
Phase Ib/II Talimogene Laherparepvec + PembrolizumabExperimentalCombination treatment of Talimogene Laherparepvec and Pembrolizumab
  • Pembrolizumab

Eligibility 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.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Subject incidence DLTs separately in Group A and B observed in monotherapy and combination cohorts and in each tumor type seperately in Part 2
Time Frame:3 year
Safety Issue:
Description:

Secondary Outcome Measures

Measure:Safety: Subject incidence of treatment-related and treatment-emergent adverse events in monotherapy and combination of Part 1 and each separate tumour type in Part 2
Time Frame:5 years
Safety Issue:
Description:
Measure:Safety: To estimate the incidence of detectable talimogene laherparepvec DNA in blood and urine
Time Frame:5 years
Safety Issue:
Description:
Measure:Safety: To estimate the incidence of clearance of talimogene laherparepvec DNA from blood and urine
Time Frame:5 years
Safety Issue:
Description:
Measure:Safety: To estimate the rate of detection and incidence of talimogene laherparepvec DNA and virus at the surface of talimogene laherparepvec injection site, the exterior of the occlusive dressing, and the oral mucosa
Time Frame:5 years
Safety Issue:
Description:
Measure:Safety: To estimate the incidence of talimogene laherparepvec DNA detection in lesions suspected to be herpetic in origin
Time Frame:5 years
Safety Issue:
Description:
Measure:Efficacy: Objective response rate (ORR)
Time Frame:5 years
Safety Issue:
Description:To evaluate the efficacy of intrahepatic injection of talimogene laherparepvec in the overall population and by tumor type (non-hepatocellular carcinoma and hepatocellular carcinoma)
Measure:Efficacy: Best overall response (BOR)
Time Frame:5 years
Safety Issue:
Description:To evaluate the efficacy of intrahepatic injection of talimogene laherparepvec in the overall population and by tumor type (non-hepatocellular carcinoma and hepatocellular carcinoma)
Measure:Efficacy: Durable response rate (DRR)
Time Frame:5 years
Safety Issue:
Description:To evaluate the efficacy of intrahepatic injection of talimogene laherparepvec in the overall population and by tumor type (non-hepatocellular carcinoma and hepatocellular carcinoma)
Measure:Efficacy: Duration of response (DOR)
Time Frame:5 years
Safety Issue:
Description:To evaluate the efficacy of intrahepatic injection of talimogene laherparepvec in the overall population and by tumor type (non-hepatocellular carcinoma and hepatocellular carcinoma)
Measure:Efficacy: Response in injected and uninjected lesions
Time Frame:5 years
Safety Issue:
Description:To evaluate the efficacy of intrahepatic injection of talimogene laherparepvec in the overall population and by tumor type (non-hepatocellular carcinoma and hepatocellular carcinoma)
Measure:Efficacy: Disease control rate (DCR)
Time Frame:5 years
Safety Issue:
Description:To evaluate the efficacy of intrahepatic injection of talimogene laherparepvec in the overall population and by tumor type (non-hepatocellular carcinoma and hepatocellular carcinoma)
Measure:Efficacy Progression-free survival (PFS)
Time Frame:5 years
Safety Issue:
Description:To evaluate the efficacy of intrahepatic injection of talimogene laherparepvec in the overall population and by tumor type (non-hepatocellular carcinoma and hepatocellular carcinoma)
Measure:Efficacy: Overall survival (OS)
Time Frame:5 years
Safety Issue:
Description:To evaluate the efficacy of intrahepatic injection of talimogene laherparepvec in the overall population and by tumor type (non-hepatocellular carcinoma and hepatocellular carcinoma)

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Amgen

Trial Keywords

  • Liver tumours

Last Updated

December 4, 2019