Clinical Trials /

Study of Talimogene Laherparepvec With Atezolizumab for Triple Negative Breast Cancer and Colorectal Cancer With Liver Metastases

NCT03256344

Description:

Approximately 36 DLT-evaluable subjects will be enrolled in this study. The locations of the study will be in the United States, Australia, Europe and Switzerland. The goal of this study is to evaluate the safety of intrahepatic injection (directly into the liver) of talimogene laherparepvec in combination with intravenously administered atezolizumab in subjects with triple negative breast cancer and colorectal cancer with liver metastases.

Related Conditions:
  • Breast Carcinoma
  • Colorectal Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: A Safety Study of Talimogene Laherparepvec Combined With Atezolizumab for Triple Negative Breast Cancer and Colorectal Cancer With Liver Metastases
  • Official Title: A Phase 1b Study of Talimogene Laherparepvec in Combination With Atezolizumab in Subjects With Triple Negative Breast Cancer and Colorectal Cancer With Liver Metastases

Clinical Trial IDs

  • ORG STUDY ID: 20140299
  • NCT ID: NCT03256344

Conditions

  • Metastatic Triple Negative Breast Cancer
  • Metastatic Colorectal Cancer

Interventions

DrugSynonymsArms
Talimogene LaherparepvecIMLYGICTalimogene Laherparepvec with Atezolizumab
AtezolizumabMPDL3280ATalimogene Laherparepvec with Atezolizumab

Purpose

Approximately 36 subjects will be enrolled in this study. The locations of the study will be in the United States, Australia, Europe and Switzerland. The goal of this study is to evaluate the safety of intrahepatic injection (directly into the liver) of talimogene laherparepvec in combination with intravenously administered atezolizumab in subjects with triple negative breast cancer and colorectal cancer with liver metastases.

Detailed Description

      The Screening period is 28 days prior to study enrollment. This study has 2 Cohorts. Cohort
      1: Triple Negative Breast Cancer and Cohort 2: Colorectal Cancer. These cohorts will enroll
      in parallel. There will be a Safety Follow-up period and a Long Term Follow-up period.

      Drug Administration: The participants will receive the study drugs in cycles. If the
      participants are found to be eligible to take part in this study, they will receive
      talimogene laherparepvec as an injection into the hepatic (liver) metastatic sites on Day 1
      of each cycle along with receiving atezolizumab by intravenous infusion on Day 1 of each
      cycle. Each cycle is 21 days for 6 cycles. There is an option for an additional 6 cycles
      after the first 6 intra-hepatic cycles. After the first radiographic assessment at week 10,
      if all injectable liver lesions have been injected but the 4.0 mL maximum volume has not been
      used, injection of clinically assessed non-hepatic cutaneous, subcutaneous, and nodal tumor
      lesions with or without ultrasound guidance will be permitted. Liver lesions should be
      prioritized over cutaneous, subcutaneous and nodal lesions.

      Treatment will continue until a participant experiences a DLT (Dose Limiting Toxicity)
      evaluated in the DLT period (which is 2 cycles from initial dose), has CR (Complete
      Response), has need for an alternative anticancer therapy or experiences a safety concern.

      Study Visits: Cycle 1 to Cycle 12 - The participant will have a physical exam along with
      vital signs and ECOG (Eastern Cooperative Oncology Group) performance level assessment. Blood
      (about 2 Tablespoons) will be drawn for routine tests and to check the immune system. Adverse
      events and medications taken will be reviewed on each cycle.Biomarkers will be taken on
      cycles 1, 2, 3, 6, and safety FU. Tumor Markers (special lab tests associated with the
      cancer, such as particular proteins) will be completed will be take on cycles 1, 4, 7, 10,
      13, every 3 cycles and SFU.

      Central lab tests will be completed on cycles 1, 2, 3, and 6 and safety FU. Cycle 1 Archived
      (prior stored) tumor sample will be obtained. Also, a liver tumor biopsy will be completed at
      Cycles 1, 3 and 6.

      Response Assessments will be completed at Screening and again at Cycles 4, 7, 10, 13 and
      every 3 cycles.

      Throughout the trial a swab for Herpetic tumor will be obtained within 3 days of the event.

      Cycle 1 to 12- The exposure to talimogene laherparepvec by the subject's healthcare provider
      and household member caregiver will be reviewed. Cycles 1, 3, 6-Liver tumor biopsy will be
      completed. Cycles 4, 7, 10, 13 and every 3 cycles -Response assessments will be completed by
      radiographic and clinical tumor assessment.

      Length of Treatment:

      A maximum for 12 cycles of talimogene laherparepvec are allowed during the study. The
      participant may continue taking the study drug for as long as the doctor thinks it is in
      their best interest. The participant will no longer be able to take the study drug if the
      disease gets worse, or if they are unable to follow study directions.

      Safety Follow-up Visit:

      Safety Follow-up visit will be performed about 30 days after the last dose of study
      treatment.

      The participant will have a physical exam, have vital signs taken, assessment of ECOG status
      and have weight measured. Adverse events will be assessed as well as the concominant
      medications. Routine bloodwork and tumor markers will be taken.

      Exposure to talimogene laherparepvec by the healthcare providers of the participant and/or
      close contacts will be assessed.

      Long-Term Follow-up Visits: Participants will be followed for survival every 12 weeks from
      the date of the safety follow-up visit until approximately 24 months after the last subject
      is enrolled. Subsequent cancer treatments will be collected as part of the long-term
      follow-up survival assessment. This is an investigational study. The study doctor can explain
      how the study drugs are designed to work.
    

Trial Arms

NameTypeDescriptionInterventions
Talimogene Laherparepvec with AtezolizumabExperimentalTalimogene laherparepvec given by intralesional injection on Day one and every 21 days per protocol for a maximum on 12 cycles. Atezolizumab given by intravenous injection on Day one and every 21 days per protocol
  • Talimogene Laherparepvec
  • Atezolizumab

Eligibility Criteria

        Inclusion Criteria:

          -  Criteria1, Participant provided informed consent prior to any study-specific
             activities/procedures -Criteria 2, Confirmation of triple negative breast cancer or
             colorectal cancer with liver metastases by laboratory testing

          -  Criteria 3, Participants had disease progression during or after one or more prior
             standard of care systemic anti-cancer therapy (eg chemotherapy, targeted therapy) for
             metastatic disease

          -  Criteria 4, Participants have measurable disease which is equal to one or more
             metastatic liver lesions that can be accurately and serially measured that are greater
             than or equal to 1 cm dimension and for which the longest diameter is greater or equal
             to 1 cm as measured by CT (Computed Tomography) scan or magnetic resonance imaging.
             The metastatic liver lesion(s) must not be in an area that received prior localized
             therapies.

          -  Criteria 5, Metastatic liver lesions for injection must be without necrosis (dead
             tissue )and must be be located where any tumor swelling will not lead to gall bladder
             tract obstruction or lead to bleeding risk

          -  Criteria 6, Eastern Cooperative Oncology Group performance status (ECOG PS) 0 or 1

          -  Criteria 7, Life expectancy greater than or equal to 5 months

          -  Criteria 8, Adequate organ function within 4 wks prior to enrollment. This includes
             hematology, renal, hepatic and blood-clotting functions as defined by protocol.

          -  Criteria 9, Female subjects of childbearing potential should have a negative serum
             pregnancy test within 1 week prior to enrollment

          -  Criteria 10, Other Inclusion Criteria May Apply.

        Exclusion criteria:

          -  Criteria 1, Participant is a candidate for hepatic surgery or local regional therapy
             of liver metastases with curative intent

          -  Criteria 2, More than one third of the liver is estimated to be involved with
             metastases

          -  Criteria 3, There is invasion by cancer into the main blood vessels such as the portal
             vein, hepatic vein or the vena cava

          -  Criteria 4, Participant is currently receiving or has received liver
             metastatic-directed therapy ( eg: radiation, ablation, embolization) less than 4 wks
             prior to enrollment or hepatic surgery

          -  Criteria 5, History of other malignancy within the past 5 years prior to enrollment
             with some exceptions, as outlined in the protocol.

          -  Criteria 6, Active or untreated central nervous system (CNS) metastases per CT or MRI
             evaluation during screening

          -  Participants with a history of CNS metastases are eligible provided they are stable
             and meet the criteria details in the protocol.

          -  Other Medical Conditions as noted in the protocol.

          -  Criteria 7, Other Exclusion Criteria May Apply
      
Maximum Eligible Age:99 Years
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Subject's incidence of dose limiting toxicities (DLTs)
Time Frame:At the end of Cycle 2 (each cycle is 21 days)
Safety Issue:
Description:To evaluate safety of talimogene laherparepvec as assessed by incidence of DLTs

Secondary Outcome Measures

Measure:Objective response rate (ORR)
Time Frame:Every 12 weeks (± 28 days) for approximately 24 months
Safety Issue:
Description:Response evaluation by Investigator using irRC-RECIST
Measure:Best overall response (BOR)
Time Frame:Every 12 weeks (± 28 days) for approximately 24 months
Safety Issue:
Description:Response evaluation by Investigator using irRC-RECIST
Measure:Duration of response (DOR)
Time Frame:Every 12 weeks (± 28 days) for approximately 24 months
Safety Issue:
Description:Response evaluation by Investigator using irRC-RECIST
Measure:Disease control rate (DCR)
Time Frame:Every 12 weeks (± 28 days) for approximately 24 months
Safety Issue:
Description:Response evaluation by Investigator using irRC-RECIST
Measure:Durable response rate (DRR)
Time Frame:Every 12 weeks (± 28 days) for approximately 24 months
Safety Issue:
Description:Response evaluation by Investigator using irRC-RECIST
Measure:Progression-free survival (PFS)
Time Frame:Every 12 weeks (± 28 days) for approximately 24 months
Safety Issue:
Description:Response evaluation by Investigator using irRC-RECIST
Measure:Overall survival (OS)
Time Frame:Every 12 weeks (± 28 days) for approximately 24 months
Safety Issue:
Description:
Measure:Lesion level responses in injected and uninjected tumor lesions
Time Frame:Every 12 weeks (± 28 days) for approximately 24 months
Safety Issue:
Description:

Details

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

Trial Keywords

  • Liver Metastases

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