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

NCT03256344 | Completed Phase 1 Results FDA Drug

• 1 other identifier: 20140299
• Study Type: interventional
• Target: 36
• Locations: 6 countries
• Sites: 17

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.

Conditions

Metastatic Triple Negative Breast Cancer; Metastatic Colorectal Cancer

Keywords

Liver Metastases

Outcome Measures

Primary Outcomes (1)

• Number of Participants Who Experienced a Dose-Limiting Toxicity (DLT)

  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.

  From Day 1 up to the start of Cycle 3 (each cycle is 21 days)

Secondary Outcomes (9)

• Objective Response Rate (ORR)

  Every 12 weeks (± 28 days) up to approximately 3.5 years.

• Best Overall Response (BOR)

  Every 12 weeks (± 28 days) up to approximately 3.5 years.

• Duration of Response (DOR)

  Every 12 weeks (± 28 days) up to approximately 3.5 years.

• Lesion Level Response in Injected Tumor Lesions

  Every 12 weeks (± 28 days) up to approximately 3.5 years.

• Lesion Level Response in Uninjected Tumor Lesions

  Every 12 weeks (± 28 days) up to approximately 3.5 years.

Study Arms (2)

Talimogene Laherparepvec with Atezolizumab: Triple Negative Breast Cancer (TNBC)

EXPERIMENTAL

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; Biological: Atezolizumab

Talimogene Laherparepvec with Atezolizumab: Colorectal Cancer (CRC)

EXPERIMENTAL

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; Biological: Atezolizumab

Interventions

Talimogene Laherparepvec BIOLOGICAL

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

Also known as: IMLYGIC

Talimogene Laherparepvec with Atezolizumab: Colorectal Cancer (CRC); Talimogene Laherparepvec with Atezolizumab: Triple Negative Breast Cancer (TNBC)

Atezolizumab BIOLOGICAL

A monoclonal antibody given by intravenous injection.

Also known as: MPDL3280A

Talimogene Laherparepvec with Atezolizumab: Colorectal Cancer (CRC); Talimogene Laherparepvec with Atezolizumab: Triple Negative Breast Cancer (TNBC)

Eligibility Criteria

• Age: 18 Years - 99 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Amgen: lead
• Roche-Genentech: collaborator

Study Sites (17)

University of California Los Angeles

Los Angeles, California, 90095, United States

Location

Columbia University Medical Center

New York, New York, 10032, United States

Location

Stony Brook University

Stony Brook, New York, 11794-9446, United States

Location

Liverpool Hospital

Liverpool, New South Wales, 2170, Australia

Location

Monash Medical Centre

Clayton, Victoria, 3168, Australia

Location

Fiona Stanley Hospital

Murdoch, Western Australia, 6150, Australia

Location

Breast Cancer Research Centre - WA

Nedlands, Western Australia, 6009, Australia

Location

Universite Catholique de Louvain Cliniques Universitaires Saint Luc

Brussels, 1200, Belgium

Location

Universitair Ziekenhuis Gent

Ghent, 9000, Belgium

Location

Charite Universitätsmedizin Berlin, Charité Campus Virchow-Klinikum

Berlin, 13353, Germany

Location

Universitätsklinikum Bonn

Bonn, 53105, Germany

Location

Universitätsklinik Tübingen

Tübingen, 72076, Germany

Location

Hospital del Mar

Barcelona, Cataluña, 08003, Spain

Location

Hospital General Universitario Gregorio Marañon

Madrid, 28007, Spain

Location

Hospital Universitario Ramon y Cajal

Madrid, 28034, Spain

Location

Inselspital Bern

Bern, 3010, Switzerland

Location

Hopitaux Universitaires de Geneve

Geneva, 1211, Switzerland

Location

Related Publications (1)

• 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.

  PMID: 36863095 BACKGROUND

Related Links

• AmgenTrials clinical trials website

MeSH Terms

Conditions

Triple Negative Breast Neoplasms; Colorectal Neoplasms

Interventions

talimogene laherparepvec; atezolizumab

Condition Hierarchy (Ancestors)

Breast Neoplasms; Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases

Results Point of Contact

• Title: Study Director
• Organization: Amgen Inc.

medinfo@amgen.com

866-572-6436

Study Officials

• MD

  Amgen

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: OTHER
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 8, 2017
• First Posted: August 22, 2017
• Study Start: March 19, 2018
• Primary Completion: May 26, 2020
• Study Completion: December 3, 2021
• Last Updated: May 14, 2024
• Results First Posted: June 9, 2021

Record last verified: 2024-05

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, 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.

Locations

AU (4); ES (3); CH (2); DE (3); BE (2); US (3)