Metastatic Triple Negative Breast CancerPhase 1NCT03256344
Study of Talimogene Laherparepvec With Atezolizumab for Triple Negative Breast Cancer and Colorectal Cancer With Liver Metastases
A Phase 1 study testing Talimogene Laherparepvec and Atezolizumab in people with Metastatic Triple Negative Breast Cancer and Metastatic Colorectal Cancer, run by Amgen at 17 sites in 6 countries.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 to 99 years
- Conditions the study is for
- Metastatic Triple Negative Breast Cancer, Metastatic Colorectal Cancer
- What is being tested?
- Talimogene Laherparepvec and Atezolizumab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 36 participants
- Where
- 17 sitesin 6 countries
- Study dates
- 19 Mar 2018to 3 Dec 2021
- Phase
- Phase 1
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 99 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Show all 10Show fewer
- 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.
Who cannot join
- 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.
Show all 9Show fewer
- 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.
Trial locations and contacts
17 sites in 6 countries.
17 sites in 6 countries
Australia4 sites
Monash Medical Centre
Clayton, Victoria, 3168
Liverpool Hospital
Liverpool, New South Wales, 2170
Fiona Stanley Hospital
Murdoch, Western Australia, 6150
Breast Cancer Research Centre - WA
Nedlands, Western Australia, 6009
United States3 sites
University of California Los Angeles
Los Angeles, California, 90095
Columbia University Medical Center
New York, New York, 10032
Stony Brook University
Stony Brook, New York, 11794-9446
Germany3 sites
Charite Universitätsmedizin Berlin, Charité Campus Virchow-Klinikum
Berlin, 13353
Universitätsklinikum Bonn
Bonn, 53105
Universitätsklinik Tübingen
Tübingen, 72076
Spain3 sites
Hospital del Mar
Barcelona, Cataluña, 08003
Hospital General Universitario Gregorio Marañon
Madrid, 28007
Hospital Universitario Ramon y Cajal
Madrid, 28034
Belgium2 sites
Universite Catholique de Louvain Cliniques Universitaires Saint Luc
Brussels, 1200
Universitair Ziekenhuis Gent
Ghent, 9000
Switzerland2 sites
Inselspital Bern
Bern, 3010
Hopitaux Universitaires de Geneve
Geneva, 1211
About this study
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
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.
Read the 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.
- Being tested
- Talimogene Laherparepvec, Atezolizumab
- Keywords
- Liver Metastases
- Medical subject headings
- Triple Negative Breast Neoplasms, Colorectal Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Talimogene LaherparepvecBiological
Also called IMLYGIC
Virally based anti-cancer immunotherapy given by direct injection into tumors.
AtezolizumabBiological
Also called MPDL3280A
A monoclonal antibody given by intravenous injection.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: Biological: Talimogene Laherparepvec; Biological: Atezolizumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: From Day 1 up to the start of Cycle 3 (each cycle is 21 days)
Secondary outcomes (9)
Objective Response Rate (ORR)
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.
Measured: Every 12 weeks (± 28 days) up to approximately 3.5 years.
Best Overall Response (BOR)
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
Measured: Every 12 weeks (± 28 days) up to approximately 3.5 years.
Duration of Response (DOR)
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.
Measured: Every 12 weeks (± 28 days) up to approximately 3.5 years.
Lesion Level Response in Injected Tumor Lesions
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
Measured: Every 12 weeks (± 28 days) up to approximately 3.5 years.
Lesion Level Response in Uninjected Tumor Lesions
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
Measured: Every 12 weeks (± 28 days) up to approximately 3.5 years.
Durable Response Rate (DRR)
DRR was defined as the percentage of participants with an objective response with a DOR of at least 6 months.
Measured: Every 12 weeks (± 28 days) up to approximately 3.5 years.
Disease Control Rate (DCR)
DCR was defined as the percentage of participants that have a best overall response in one of the following categories: CR/PR/SD.
Measured: Every 12 weeks (± 28 days) up to approximately 3.5 years.
Progression-free Survival (PFS)
PFS was defined as time from first dose to the date of first of confirmed disease progression per modified irRC-RECIST criteria, or death (whichever occurred first). Results were estimated using the Kaplan-Meier method.
Measured: Every 12 weeks (± 28 days) up to approximately 3.5 years.
Overall Survival (OS)
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.
Measured: Every 12 weeks (± 28 days) up to approximately 3.5 years.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Aug 2017
- Study start19 Mar 2018
- Primary completion26 May 2020
- Study completion3 Dec 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Metastatic Triple Negative Breast CancerStudies of the same condition, open and under way.
- More trials run by AmgenThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Other
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 36 participants (actual)
Sponsor and investigators
- Lead sponsor
- Amgen
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Roche-Genentech
- Responsible party
- Sponsor
- Investigators
- MD, Study director, Amgen
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03256344
- Sponsor's protocol ID
- 20140299
- Status last verified
- May 2024
- First submitted
- 8 Aug 2017
- Last updated
- 14 May 2024
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: De-identified individual patient data for variables necessary to address the specific research question in an approved data sharing request
Publications
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.
PubMed 36863095
Study at a glance
From the registry record, last updated by the sponsor on 14 May 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT03256344
- Acronym / sponsor ID
- 20140299
- Keywords
- Liver Metastases
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 36 participants (actual)
- Lead sponsor
- AmgenIndustry (pharma, biotech, devices)
- Collaborators
- Roche-Genentech
- Study start
- 19 Mar 2018 (actual)
- Primary completion
- 26 May 2020 (actual)
- Study completion
- 3 Dec 2021 (actual)
- First posted
- 22 Aug 2017 (actual)
- Results
- Posted 9 Jun 2021
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Other
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Talimogene Laherparepvec with Atezolizumab: Triple Negative Breast Cancer (TNBC) | Experimental | Biological: Talimogene Laherparepvec, Biological: AtezolizumabParticipants 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. |
| Talimogene Laherparepvec with Atezolizumab: Colorectal Cancer (CRC) | Experimental | Biological: Talimogene Laherparepvec, Biological: AtezolizumabParticipants 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. |
Who may qualify
- Ages
- 18 to 99 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- 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.
Key exclusion criteria (9 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Talimogene LaherparepvecAlso: IMLYGICVirally based anti-cancer immunotherapy given by direct injection into tumors. | Biological | Talimogene Laherparepvec with Atezolizumab: Colorectal Cancer (CRC), Talimogene Laherparepvec with Atezolizumab: Triple Negative Breast Cancer (TNBC) |
| AtezolizumabAlso: MPDL3280AA monoclonal antibody given by intravenous injection. | Biological | Talimogene Laherparepvec with Atezolizumab: Colorectal Cancer (CRC), Talimogene Laherparepvec with Atezolizumab: Triple Negative Breast Cancer (TNBC) |
Primary outcome
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.
9 secondary outcomes
Objective Response Rate (ORR)
Time frame: Every 12 weeks (± 28 days) up to approximately 3.5 years.
Best Overall Response (BOR)
Time frame: Every 12 weeks (± 28 days) up to approximately 3.5 years.
Duration of Response (DOR)
Time frame: Every 12 weeks (± 28 days) up to approximately 3.5 years.
Lesion Level Response in Injected Tumor Lesions
Time frame: Every 12 weeks (± 28 days) up to approximately 3.5 years.
Lesion Level Response in Uninjected Tumor Lesions
Time frame: Every 12 weeks (± 28 days) up to approximately 3.5 years.
Durable Response Rate (DRR)
Time frame: Every 12 weeks (± 28 days) up to approximately 3.5 years.
Disease Control Rate (DCR)
Time frame: Every 12 weeks (± 28 days) up to approximately 3.5 years.
Progression-free Survival (PFS)
Time frame: Every 12 weeks (± 28 days) up to approximately 3.5 years.
Overall Survival (OS)
Time frame: Every 12 weeks (± 28 days) up to approximately 3.5 years.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 May 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 36863095Hecht 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.
- AmgenTrials clinical trials websiteLink provided by the sponsor.
- Individual participant dataSharing planned: Yes. De-identified individual patient data for variables necessary to address the specific research question in an approved data sharing request
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Triple-Negative Breast Cancer (TNBC), Brain Metastases
RecruitingObservational study
Collection of CSF Samples From Participants With Metastatic Triple Negative Breast Cancer (TNBC) and HER2+ Breast Cancer With no Prior History Nor Active Radiographically Detectable Brain Metastases
Breast Cancer, Breast Carcinoma
RecruitingPhase 1/2
A Study of MR001 in Patients With Locally Recurrent or Metastatic Advanced Triple-Negative Breast Cancer (TNBC)
Triple-Negative Breast Cancer (TNBC)
RecruitingPhase 2
A Clinical Study to Evaluate the Efficacy and Safety of JS212 Monotherapy or Combination Therapy in Recurrent or Metastatic Triple-negative Breast Cancer(TNBC)
Triple-negative Breast Cancer
RecruitingPhase 1
A Study With NKT3964 for Adults With Advanced/Metastatic Solid Tumors
Solid Tumor, Advanced Solid Tumor
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
MD study director
Amgen
17 sites in 6 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Talimogene Laherparepvec and Atezolizumab in people with Metastatic Triple Negative Breast Cancer and Metastatic Colorectal Cancer, run by Amgen at 17 sites in 6 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 10 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 14 May 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 17 sites in Australia, United States, Germany, Spain, Belgium and 1 more country. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 9 Jun 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03256344, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 May 2024.