Study of Talimogene Laherparepvec With Atezolizumab for Triple Negative Breast Cancer and Colorectal Cancer With Liver Metastases
Condition: Metastatic Triple Negative Breast Cancer; Metastatic Colorectal Cancer
MeSH terms: Breast Neoplasms; Colorectal Neoplasms; Neoplasm Metastasis; Triple Negative Breast Neoplasms
Study type: Interventional
Phase: Phase 1

Summary: 
      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.
    

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.
    

Intervention name(s): Talimogene Laherparepvec; Atezolizumab
Intervention type(s): Biological; Biological
Intervention description(s): Virally based anti-cancer immunotherapy given by direct injection into tumors.; A monoclonal antibody given by intravenous injection.
Other intervention name(s): IMLYGIC; MPDL3280A
Intervention MeSH terms: Atezolizumab; Talimogene laherparepvec
Allocation: Non-Randomized
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Other
Keywords: Liver Metastases