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

NCT ID: NCT03256344

Last Updated: 2024-05-14

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 36 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-03-19
• Study Completion Date: 2021-12-03

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.

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.

Conditions

Metastatic Triple Negative Breast Cancer; Metastatic Colorectal Cancer

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: OTHER
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

Talimogene Laherparepvec

Intervention Type: BIOLOGICAL

Virally based anti-cancer immunotherapy given by direct injection into tumors.

Atezolizumab

Intervention Type: BIOLOGICAL

A monoclonal antibody given by intravenous injection.

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.

Group Type: EXPERIMENTAL

Talimogene Laherparepvec

Intervention Type: BIOLOGICAL

Virally based anti-cancer immunotherapy given by direct injection into tumors.

Atezolizumab

Intervention Type: BIOLOGICAL

A monoclonal antibody given by intravenous injection.

Interventions

Talimogene Laherparepvec

Virally based anti-cancer immunotherapy given by direct injection into tumors.

Intervention Type: BIOLOGICAL

Atezolizumab

A monoclonal antibody given by intravenous injection.

Intervention Type: BIOLOGICAL

Other Intervention Names

IMLYGIC; MPDL3280A

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, 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.

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 99 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Roche-Genentech

INDUSTRY

Sponsor Role: collaborator

Amgen

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

MD

Role: STUDY_DIRECTOR

Amgen

Locations

University of California Los Angeles

Los Angeles, California, United States

Columbia University Medical Center

New York, New York, United States

Stony Brook University

Stony Brook, New York, United States

Liverpool Hospital

Liverpool, New South Wales, Australia

Monash Medical Centre

Clayton, Victoria, Australia

Fiona Stanley Hospital

Murdoch, Western Australia, Australia

Breast Cancer Research Centre - WA

Nedlands, Western Australia, Australia

Universite Catholique de Louvain Cliniques Universitaires Saint Luc

Brussels, , Belgium

Universitair Ziekenhuis Gent

Ghent, , Belgium

Charite Universitätsmedizin Berlin, Charité Campus Virchow-Klinikum

Berlin, , Germany

Universitätsklinikum Bonn

Bonn, , Germany

Universitätsklinik Tübingen

Tübingen, , Germany

Hospital del Mar

Barcelona, Cataluña, Spain

Hospital General Universitario Gregorio Marañon

Madrid, , Spain

Hospital Universitario Ramon y Cajal

Madrid, , Spain

Inselspital Bern

Bern, , Switzerland

Hopitaux Universitaires de Geneve

Geneva, , Switzerland

Countries

United States; Australia; Belgium; Germany; Spain; Switzerland

References

Hecht JR, Raman SS, Chan A, Kalinsky K, Baurain JF, Jimenez MM, Garcia MM, Berger MD, Lauer UM, Khattak A, Carrato A, Zhang Y, Liu K, Cha E, Keegan A, Bhatta S, Strassburg CP, Roohullah A. Phase Ib study of talimogene laherparepvec in combination with atezolizumab in patients with triple negative breast cancer and colorectal cancer with liver metastases. ESMO Open. 2023 Apr;8(2):100884. doi: 10.1016/j.esmoop.2023.100884. Epub 2023 Feb 28.

Reference Type: BACKGROUND

PMID: 36863095 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Related Links

http://www.amgentrials.com

AmgenTrials clinical trials website

Other Identifiers

20140299

Identifier Type: -

Identifier Source: org_study_id