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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03256344
Recruitment Status : Completed
First Posted : August 22, 2017
Results First Posted : June 9, 2021
Last Update Posted : January 21, 2022
Sponsor:
Collaborator:
Roche-Genentech
Information provided by (Responsible Party):
Amgen

Brief 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.


Condition or disease Intervention/treatment Phase
Metastatic Triple Negative Breast Cancer Metastatic Colorectal Cancer Biological: Talimogene Laherparepvec Biological: Atezolizumab Phase 1

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 36 participants
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Other
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
Actual Study Start Date : March 19, 2018
Actual Primary Completion Date : May 26, 2020
Actual Study Completion Date : December 3, 2021

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Breast Cancer

Arm Intervention/treatment
Experimental: Talimogene Laherparepvec with Atezolizumab: Triple Negative Breast Cancer (TNBC)
Participants with TNBC with liver metastases administered intrahepatic injection of talimogene laherparepvec into liver metastases via guided injection (either ultrasound or computerized tomography) on Day 1 of each cycle for a maximum of 12 cycles, where each cycle is 21 days. Participants administered 10^6 plaque-forming units/milliliter (PFU/mL) on Day 1 of Cycle 1 and 10^8 PFU/mL on Day 1 of each cycle thereafter. Participants also administered 1200 mg atezolizumab via intravenous injection on Day 1 of each cycle.
Biological: Talimogene Laherparepvec
Virally based anti-cancer immunotherapy given by direct injection into tumors.
Other Name: IMLYGIC

Biological: Atezolizumab
A monoclonal antibody given by intravenous injection.
Other Name: MPDL3280A

Experimental: Talimogene Laherparepvec with Atezolizumab: Colorectal Cancer (CRC)
Participants with CRC with liver metastases administered intrahepatic injection of talimogene laherparepvec into liver metastases via guided injection (either ultrasound or computerized tomography) on Day 1 of each cycle for a maximum of 12 cycles, where each cycle is 21 days. Participants administered 10^6 PFU/mL on Day 1 of Cycle 1 and 10^8 PFU/mL on Day 1 of each cycle thereafter. Participants also administered 1200 mg atezolizumab via intravenous injection on Day 1 of each cycle.
Biological: Talimogene Laherparepvec
Virally based anti-cancer immunotherapy given by direct injection into tumors.
Other Name: IMLYGIC

Biological: Atezolizumab
A monoclonal antibody given by intravenous injection.
Other Name: MPDL3280A




Primary Outcome Measures :
  1. Number of Participants Who Experienced a Dose-Limiting Toxicity (DLT) [ Time Frame: From Day 1 up to the start of Cycle 3 (each cycle is 21 days) ]

    Toxicities were graded using the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. A DLT was considered as any of the below, if judged by the investigator to be related to either treatment:

    • Grade ≥ 4 neutropenia (absolute neutrophil count [ANC] < 500/μl) lasting ≥ 7 days
    • Grade ≥ 3 febrile neutropenia
    • Grade ≥ 4 thrombocytopenia
    • Grade ≥ 4 anemia
    • Grade ≥ 4 rash
    • Serious herpetic events
    • Grade ≥ 3 symptomatic hepatic toxicities that do not resolve to Grade ≤ 2 within 48 hours or Grade ≥ 3 asymptomatic hepatic toxicities that do not resolve to Grade ≤ 1 within 3 weeks of onset
    • Grade ≥ 3 non-hematologic, non-hepatic organ toxicity
    • Grade 5 toxicity (ie, death)
    • Any other intolerable toxicity leading to permanent discontinuation of treatment

    DLTs were to occur within the DLT evaluation period, defined as the period between the initial 10^6 PFU/mL dose and 3 weeks following the initial 10^8 PFU/mL dose or the start of Cycle 3, whichever occurred first.



Secondary Outcome Measures :
  1. Objective Response Rate (ORR) [ Time Frame: Every 12 weeks (± 28 days). Maximum overall time on-study (treatment + follow up) at data cut off was 32 months (TNBC cohort) and 19 months (CRC cohort). ]
    ORR was defined as the incidence rate of either a complete response (CR) or partial response (PR) based on modified immune-related response criteria simulating Response Evaluation Criteria in Solid Tumors(irRC-RECIST) criteria. A CR was a complete disappearance of all lesions and a PR was a decrease in tumor burden 30% or more relative to baseline.

  2. Best Overall Response (BOR) [ Time Frame: Every 12 weeks (± 28 days). Maximum overall time on-study (treatment + follow up) at data cut off was 32 months (TNBC cohort) and 19 months (CRC cohort). ]

    BOR was defined as the best visit response based on modified irRC-RECIST criteria:

    • CR: a complete disappearance of all lesions
    • PR: a decrease in tumor burden 30% or more relative to baseline
    • Stable disease (SD): neither sufficient shrinkage to qualify for CR or PR nor sufficient increase to qualify for progressive disease (PD)
    • PD: an increase in tumor burden of 20% or more and at least 5 mm absolute increase relative to nadir (minimum recorded tumor burden)
    • Unevaluable (UE): any lesion present at baseline which was not assessed or was unable to be evaluated leading to an inability to determine the status of that particular tumor

  3. Duration of Response (DOR) [ Time Frame: Every 12 weeks (± 28 days). Maximum overall time on-study (treatment + follow up) at data cut off was 32 months (TNBC cohort) and 19 months (CRC cohort). ]
    DOR was defined as the time from the date of an initial response that is subsequently confirmed to the earlier of PD per modified irRC RECIST or death. Participants who have not ended their response at the time of analysis were censored at the last evaluable tumor assessment.

  4. Lesion Level Response in Injected Tumor Lesions [ Time Frame: Every 12 weeks (± 28 days). Maximum overall time on-study (treatment + follow up) at data cut off was 32 months (TNBC cohort) and 19 months (CRC cohort). ]

    Responses for individual tumor lesions for hepatic and non-hepatic tumors injected wtih treatment were assessed for the following responses:

    • Lesion complete response rate (L-CRR): Disappearance of lesion
    • Lesion partial response rate (L-PRR): Decrease in tumor burden 30% or more relative to baseline
    • Lesion objective response rate (L-ORR): Either a L-CRR or L-PRR based on modified irRC-RECIST criteria

  5. Lesion Level Response in Uninjected Tumor Lesions [ Time Frame: Every 12 weeks (± 28 days). Maximum overall time on-study (treatment + follow up) at data cut off was 32 months (TNBC cohort) and 19 months (CRC cohort). ]

    Responses for individual tumor lesions for hepatic and non-hepatic tumors that were not injected with treatment were assessed for the following responses:

    • L-CRR: Disappearance of lesion
    • L-PRR: Decrease in tumor burden 30% or more relative to baseline
    • L-ORR: Either a L-CRR or L-PRR based on modified irRC-RECIST criteria

  6. Durable Response Rate (DRR) [ Time Frame: Every 12 weeks (± 28 days). Maximum overall time on-study (treatment + follow up) at data cut off was 32 months (TNBC cohort) and 19 months (CRC cohort). ]
    DRR was defined as the percentage of participants with an objective response with a DOR of at least 6 months.

  7. Disease Control Rate (DCR) [ Time Frame: Every 12 weeks (± 28 days). Maximum overall time on-study (treatment + follow up) at data cut off was 32 months (TNBC cohort) and 19 months (CRC cohort). ]
    DCR was defined as the percentage of participants that have a best overall response in one of the following categories: CR/PR/SD.

  8. Progression-free Survival (PFS) [ Time Frame: Every 12 weeks (± 28 days). Maximum overall time on-study (treatment + follow up) at data cut off was 32 months (TNBC cohort) and 19 months (CRC cohort). ]
    PFS was defined as time from first dose to the date of first of confirmed disease progression per modified irRC-RECIST criteria, or death. Results were estimated using the Kaplan-Meier method.

  9. Overall Survival (OS) [ Time Frame: Every 12 weeks (± 28 days). Maximum overall time on-study (treatment + follow up) at data cut off was 32 months (TNBC cohort) and 19 months (CRC cohort). ]
    OS was defined as the time from the date of first dose to the date of death from any cause. Results were estimated using the Kaplan-Meier method.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years to 99 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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, Subjects with triple negative breast cancer with liver metastases, or subjects with colorectal cancer with liver metastases are eligible if they have had disease progression during or after one or more prior standard of care systemic anti-cancer therapy (eg,chemotherapy, targeted therapy) for metastatic disease or if they progress during or within 6 months of receiving adjuvant therapy. If subjects, in the opinion of the investigator, are deemed not appropriate candidates for systemic anti-cancer therapy for metastatic disease or if they refuse systemic anti-cancer therapy for metastatic disease, they may be eligible after investigator discussion with Sponsor medical monitor for approval.
  • 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 weeks 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 magnetic resonance imagine (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.
  • Criteria 7, Other Medical Conditions as noted in the protocol.
  • Criteria 8, Other Exclusion Criteria May Apply.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03256344


Locations
Show Show 17 study locations
Sponsors and Collaborators
Amgen
Roche-Genentech
Investigators
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Study Director: MD Amgen
  Study Documents (Full-Text)

Documents provided by Amgen:
Study Protocol  [PDF] July 8, 2019
Statistical Analysis Plan  [PDF] November 25, 2019

Additional Information:
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Responsible Party: Amgen
ClinicalTrials.gov Identifier: NCT03256344    
Other Study ID Numbers: 20140299
First Posted: August 22, 2017    Key Record Dates
Results First Posted: June 9, 2021
Last Update Posted: January 21, 2022
Last Verified: January 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: De-identified individual patient data for variables necessary to address the specific research question in an approved data sharing request
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Informed Consent Form (ICF)
Clinical Study Report (CSR)
Time Frame: Data sharing requests relating to this study will be considered beginning 18 months after the study has ended and either 1) the product and indication have been granted marketing authorization in both the US and Europe or 2) clinical development for the product and/or indication discontinues and the data will not be submitted to regulatory authorities. There is no end date for eligibility to submit a data sharing request for this study.
Access Criteria: Qualified researchers may submit a request containing the research objectives, the Amgen product(s) and Amgen study/studies in scope, endpoints/outcomes of interest, statistical analysis plan, data requirements, publication plan, and qualifications of the researcher(s). In general, Amgen does not grant external requests for individual patient data for the purpose of re-evaluating safety and efficacy issues already addressed in the product labelling. Requests are reviewed by a committee of internal advisors. If not approved, a Data Sharing Independent Review Panel will arbitrate and make the final decision. Upon approval, information necessary to address the research question will be provided under the terms of a data sharing agreement. This may include anonymized individual patient data and/or available supporting documents, containing fragments of analysis code where provided in analysis specifications. Further details are available at the URL below.
URL: https://www.amgen.com/datasharing

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Amgen:
Liver Metastases
Additional relevant MeSH terms:
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Breast Neoplasms
Colorectal Neoplasms
Neoplasm Metastasis
Triple Negative Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Colonic Diseases
Intestinal Diseases
Rectal Diseases
Neoplastic Processes
Pathologic Processes
Atezolizumab
Talimogene laherparepvec
Antineoplastic Agents
Antineoplastic Agents, Immunological