Clinical trial NCT03256344: Study of Talimogene Laherparepvec 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Metastatic Triple Negative Breast Cancer
Metastatic Colorectal Cancer
Keywords: Liver Metastases
Lead sponsor: Amgen
Sponsor class: INDUSTRY
Collaborators: name: Roche-Genentech
First posted: 2017-08-22
Enrollment: 36
Sex: ALL
Minimum age (years): 18
Maximum age (years): 99
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: OTHER

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.

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.
* 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.

Primary outcomes:
measure: Number of Participants Who Experienced a Dose-Limiting Toxicity (DLT)
timeFrame: From Day 1 up to the start of Cycle 3 (each cycle is 21 days)
Secondary outcomes:
measure: Objective Response Rate (ORR)
timeFrame: Every 12 weeks (± 28 days) up to approximately 3.5 years.
measure: Best Overall Response (BOR)
timeFrame: Every 12 weeks (± 28 days) up to approximately 3.5 years.
measure: Duration of Response (DOR)
timeFrame: Every 12 weeks (± 28 days) up to approximately 3.5 years.
measure: Lesion Level Response in Injected Tumor Lesions
timeFrame: Every 12 weeks (± 28 days) up to approximately 3.5 years.
measure: Lesion Level Response in Uninjected Tumor Lesions
timeFrame: Every 12 weeks (± 28 days) up to approximately 3.5 years.
measure: Durable Response Rate (DRR)
timeFrame: Every 12 weeks (± 28 days) up to approximately 3.5 years.
measure: Disease Control Rate (DCR)
timeFrame: Every 12 weeks (± 28 days) up to approximately 3.5 years.
measure: Progression-free Survival (PFS)
timeFrame: Every 12 weeks (± 28 days) up to approximately 3.5 years.
measure: Overall Survival (OS)
timeFrame: Every 12 weeks (± 28 days) up to approximately 3.5 years.
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: University of California Los Angeles
state: California
city: New York
country: United States
facility: Columbia University Medical Center
state: New York
city: Stony Brook
country: United States
facility: Stony Brook University
state: New York
city: Liverpool
country: Australia
facility: Liverpool Hospital
state: New South Wales
city: Clayton
country: Australia
facility: Monash Medical Centre
state: Victoria
city: Murdoch
country: Australia
facility: Fiona Stanley Hospital
state: Western Australia
city: Nedlands
country: Australia
facility: Breast Cancer Research Centre - WA
state: Western Australia
city: Bruxelles
country: Belgium
facility: Universite Catholique de Louvain Cliniques Universitaires Saint Luc
city: Gent
country: Belgium
facility: Universitair Ziekenhuis Gent
city: Berlin
country: Germany
facility: Charite UniversitÃ¤tsmedizin Berlin, CharitÃ© Campus Virchow-Klinikum
city: Bonn
country: Germany
facility: UniversitÃ¤tsklinikum Bonn
city: TÃ¼bingen
country: Germany
facility: UniversitÃ¤tsklinik TÃ¼bingen
city: Barcelona
country: Spain
facility: Hospital del Mar
state: CataluÃ±a
city: Madrid
country: Spain
facility: Hospital General Universitario Gregorio MaraÃ±on
city: Madrid
country: Spain
facility: Hospital Universitario Ramon y Cajal
city: Bern
country: Switzerland
facility: Inselspital Bern
city: Geneva 14
country: Switzerland
facility: Hopitaux Universitaires de Geneve
Study officials:
affiliation: Amgen
name: MD
role: STUDY_DIRECTOR
References:
citation: 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.