Study of Talimogene Laherparepvec With Atezolizumab for Triple Negative Breast Cancer and Colorectal Cancer With Liver Metastases
Study Details
Study Description
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 |
|---|---|---|
|
Phase 1 |
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
Arms and Interventions
| 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 Names:
Biological: Atezolizumab
A monoclonal antibody given by intravenous injection.
Other Names:
|
| 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 Names:
Biological: Atezolizumab
A monoclonal antibody given by intravenous injection.
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Number of Participants Who Experienced a Dose-Limiting Toxicity (DLT) [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
- Objective Response Rate (ORR) [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.
- Best Overall Response (BOR) [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
- Duration of Response (DOR) [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.
- Lesion Level Response in Injected Tumor Lesions [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
- Lesion Level Response in Uninjected Tumor Lesions [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
- Durable Response Rate (DRR) [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.
- Disease Control Rate (DCR) [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.
- Progression-free Survival (PFS) [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.
- Overall Survival (OS) [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.
Eligibility Criteria
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.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | University of California Los Angeles | Los Angeles | California | United States | 90095 |
| 2 | Columbia University Medical Center | New York | New York | United States | 10032 |
| 3 | Stony Brook University | Stony Brook | New York | United States | 11794-9446 |
| 4 | Liverpool Hospital | Liverpool | New South Wales | Australia | 2170 |
| 5 | Monash Medical Centre | Clayton | Victoria | Australia | 3168 |
| 6 | Fiona Stanley Hospital | Murdoch | Western Australia | Australia | 6150 |
| 7 | Breast Cancer Research Centre - WA | Nedlands | Western Australia | Australia | 6009 |
| 8 | Universite Catholique de Louvain Cliniques Universitaires Saint Luc | Bruxelles | Belgium | 1200 | |
| 9 | Universitair Ziekenhuis Gent | Gent | Belgium | 9000 | |
| 10 | Charite Universitätsmedizin Berlin, Charité Campus Virchow-Klinikum | Berlin | Germany | 13353 | |
| 11 | Universitätsklinikum Bonn | Bonn | Germany | 53105 | |
| 12 | Universitätsklinik Tübingen | Tübingen | Germany | 72076 | |
| 13 | Hospital del Mar | Barcelona | Cataluña | Spain | 08003 |
| 14 | Hospital General Universitario Gregorio Marañon | Madrid | Spain | 28007 | |
| 15 | Hospital Universitario Ramon y Cajal | Madrid | Spain | 28034 | |
| 16 | Inselspital Bern | Bern | Switzerland | 3010 | |
| 17 | Hopitaux Universitaires de Geneve | Geneva 14 | Switzerland | 1211 |
Sponsors and Collaborators
- Amgen
- Roche-Genentech
Investigators
- Study Director: MD, Amgen
Study Documents (Full-Text)
More Information
Additional Information:
Publications
None provided.- 20140299
Study Results
Participant Flow
| Recruitment Details | Participants were enrolled at 15 research centers in Australia, Belgium, Germany, Spain, Switzerland and the United States. |
|---|---|
| Pre-assignment Detail | The results reported are based on a data snapshot date of October 2019 for participants with colorectal cancer and November 2020 for participants with triple negative breast cancer. Participants are still ongoing in this trial with final data collection expected in August 2022. |
| Arm/Group Title | Talimogene Laherparepvec With Atezolizumab: Triple Negative Breast Cancer (TNBC) | Talimogene Laherparepvec With Atezolizumab: Colorectal Cancer (CRC) |
|---|---|---|
| Arm/Group Description | Participants with TNBC with liver metastases were 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 was 21 days. Participants were 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 were also administered 1200 mg atezolizumab via intravenous injection on Day 1 of each cycle. | Participants with CRC with liver metastases were 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 was 21 days. Participants were administered 10^6 PFU/mL on Day 1 of Cycle 1 and 10^8 PFU/mL on Day 1 of each cycle thereafter. Participants were also administered 1200 mg atezolizumab via intravenous injection on Day 1 of each cycle. |
| Period Title: Overall Study | ||
| STARTED | 11 | 25 |
| Received Talimogene Laherparepvec | 8 | 23 |
| Received Atezolizumab | 10 | 24 |
| COMPLETED | 0 | 0 |
| NOT COMPLETED | 11 | 25 |
Baseline Characteristics
| Arm/Group Title | Talimogene Laherparepvec With Atezolizumab: Triple Negative Breast Cancer (TNBC) | Talimogene Laherparepvec With Atezolizumab: Colorectal Cancer (CRC) | Total |
|---|---|---|---|
| Arm/Group Description | Participants with TNBC with liver metastases were 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 was 21 days. Participants were 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 were also administered 1200 mg atezolizumab via intravenous injection on Day 1 of each cycle. | Participants with CRC with liver metastases were 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 was 21 days. Participants were administered 10^6 PFU/mL on Day 1 of Cycle 1 and 10^8 PFU/mL on Day 1 of each cycle thereafter. Participants were also administered 1200 mg atezolizumab via intravenous injection on Day 1 of each cycle. | Total of all reporting groups |
| Overall Participants | 11 | 25 | 36 |
| Age (Count of Participants) | |||
| <=18 years |
0
0%
|
0
0%
|
0
0%
|
| Between 18 and 65 years |
10
90.9%
|
15
60%
|
25
69.4%
|
| >=65 years |
1
9.1%
|
10
40%
|
11
30.6%
|
| Sex: Female, Male (Count of Participants) | |||
| Female |
11
100%
|
12
48%
|
23
63.9%
|
| Male |
0
0%
|
13
52%
|
13
36.1%
|
| Ethnicity (NIH/OMB) (Count of Participants) | |||
| Hispanic or Latino |
0
0%
|
1
4%
|
1
2.8%
|
| Not Hispanic or Latino |
11
100%
|
24
96%
|
35
97.2%
|
| Unknown or Not Reported |
0
0%
|
0
0%
|
0
0%
|
| Race (NIH/OMB) (Count of Participants) | |||
| American Indian or Alaska Native |
0
0%
|
0
0%
|
0
0%
|
| Asian |
0
0%
|
1
4%
|
1
2.8%
|
| Native Hawaiian or Other Pacific Islander |
0
0%
|
1
4%
|
1
2.8%
|
| Black or African American |
0
0%
|
1
4%
|
1
2.8%
|
| White |
10
90.9%
|
22
88%
|
32
88.9%
|
| More than one race |
0
0%
|
0
0%
|
0
0%
|
| Unknown or Not Reported |
1
9.1%
|
0
0%
|
1
2.8%
|
Outcome Measures
| Title | Number of Participants Who Experienced a Dose-Limiting Toxicity (DLT) |
|---|---|
| Description | 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. |
| Time Frame | From Day 1 up to the start of Cycle 3 (each cycle is 21 days) |
Outcome Measure Data
| Analysis Population Description |
|---|
| DLT Analysis Set: All participants who had opportunity to receive treatment for 2 cycles from the time of initial dose of study treatment and who had received 2 doses of talimogene laherparepvec and 2 doses of atezolizumab in combination or had a DLT during the DLT-evaluation period. |
| Arm/Group Title | Talimogene Laherparepvec With Atezolizumab: Triple Negative Breast Cancer (TNBC) | Talimogene Laherparepvec With Atezolizumab: Colorectal Cancer (CRC) |
|---|---|---|
| Arm/Group Description | Participants with TNBC with liver metastases were 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 was 21 days. Participants were 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 were also administered 1200 mg atezolizumab via intravenous injection on Day 1 of each cycle. | Participants with CRC with liver metastases were 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 was 21 days. Participants were administered 10^6 PFU/mL on Day 1 of Cycle 1 and 10^8 PFU/mL on Day 1 of each cycle thereafter. Participants were also administered 1200 mg atezolizumab via intravenous injection on Day 1 of each cycle. |
| Measure Participants | 5 | 18 |
| Count of Participants [Participants] |
0
0%
|
3
12%
|
| Title | Objective Response Rate (ORR) |
|---|---|
| Description | 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. |
| 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). |
Outcome Measure Data
| Analysis Population Description |
|---|
| Safety Analysis Set: All participants who received at least 1 dose of talimogene laherparepvec or atezolizumab. |
| Arm/Group Title | Talimogene Laherparepvec With Atezolizumab: Triple Negative Breast Cancer (TNBC) | Talimogene Laherparepvec With Atezolizumab: Colorectal Cancer (CRC) |
|---|---|---|
| Arm/Group Description | Participants with TNBC with liver metastases were 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 was 21 days. Participants were 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 were also administered 1200 mg atezolizumab via intravenous injection on Day 1 of each cycle. | Participants with CRC with liver metastases were 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 was 21 days. Participants were administered 10^6 PFU/mL on Day 1 of Cycle 1 and 10^8 PFU/mL on Day 1 of each cycle thereafter. Participants were also administered 1200 mg atezolizumab via intravenous injection on Day 1 of each cycle. |
| Measure Participants | 10 | 24 |
| Number (95% Confidence Interval) [Percentage of Participants] |
10.0
90.9%
|
0.0
0%
|
| Title | Best Overall Response (BOR) |
|---|---|
| Description | 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 |
| 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). |
Outcome Measure Data
| Analysis Population Description |
|---|
| Safety Analysis Set: All participants who received at least 1 dose of talimogene laherparepvec or atezolizumab. |
| Arm/Group Title | Talimogene Laherparepvec With Atezolizumab: Triple Negative Breast Cancer (TNBC) | Talimogene Laherparepvec With Atezolizumab: Colorectal Cancer (CRC) |
|---|---|---|
| Arm/Group Description | Participants with TNBC with liver metastases were 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 was 21 days. Participants were 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 were also administered 1200 mg atezolizumab via intravenous injection on Day 1 of each cycle. | Participants with CRC with liver metastases were 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 was 21 days. Participants were administered 10^6 PFU/mL on Day 1 of Cycle 1 and 10^8 PFU/mL on Day 1 of each cycle thereafter. Participants were also administered 1200 mg atezolizumab via intravenous injection on Day 1 of each cycle. |
| Measure Participants | 10 | 24 |
| CR |
0
0%
|
0
0%
|
| PR |
1
9.1%
|
0
0%
|
| SD |
1
9.1%
|
1
4%
|
| PD |
3
27.3%
|
4
16%
|
| UE |
3
27.3%
|
14
56%
|
| Not done |
2
18.2%
|
5
20%
|
| Title | Duration of Response (DOR) |
|---|---|
| Description | 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. |
| 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). |
Outcome Measure Data
| Analysis Population Description |
|---|
| Responders in Safety Analysis Set: All participants in safety analysis set who received at least 1 dose of talimogene laherparepvec or atezolizumab who had a best overall response of CR/PR at the time of analysis. |
| Arm/Group Title | Talimogene Laherparepvec With Atezolizumab: Triple Negative Breast Cancer (TNBC) | Talimogene Laherparepvec With Atezolizumab: Colorectal Cancer (CRC) |
|---|---|---|
| Arm/Group Description | Participants with TNBC with liver metastases were 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 was 21 days. Participants were 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 were also administered 1200 mg atezolizumab via intravenous injection on Day 1 of each cycle. | Participants with CRC with liver metastases were 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 was 21 days. Participants were administered 10^6 PFU/mL on Day 1 of Cycle 1 and 10^8 PFU/mL on Day 1 of each cycle thereafter. Participants were also administered 1200 mg atezolizumab via intravenous injection on Day 1 of each cycle. |
| Measure Participants | 1 | 0 |
| Median (Full Range) [Months] |
NA
|
| Title | Lesion Level Response in Injected Tumor Lesions |
|---|---|
| Description | 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 |
| 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). |
Outcome Measure Data
| Analysis Population Description |
|---|
| Injected Lesion Analysis Set: Any target lesion and new measurable lesion that was injected from the participants who had received at least 1 dose of talimogene laherparepvec or atezolizumab. |
| Arm/Group Title | Talimogene Laherparepvec With Atezolizumab: Triple Negative Breast Cancer (TNBC) | Talimogene Laherparepvec With Atezolizumab: Colorectal Cancer (CRC) |
|---|---|---|
| Arm/Group Description | Participants with TNBC with liver metastases were 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 was 21 days. Participants were 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 were also administered 1200 mg atezolizumab via intravenous injection on Day 1 of each cycle. | Participants with CRC with liver metastases were 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 was 21 days. Participants were administered 10^6 PFU/mL on Day 1 of Cycle 1 and 10^8 PFU/mL on Day 1 of each cycle thereafter. Participants were also administered 1200 mg atezolizumab via intravenous injection on Day 1 of each cycle. |
| Measure Participants | 10 | 24 |
| Measure Lesions | 13 | 28 |
| L-CRR - Hepatic |
0
|
0
|
| L-CRR - Overall |
0
|
0
|
| L-PRR - Hepatic |
1
|
0
|
| L-PRR - Overall |
1
|
0
|
| L-ORR - Hepatic |
1
|
0
|
| L-ORR - Overall |
1
|
0
|
| Title | Lesion Level Response in Uninjected Tumor Lesions |
|---|---|
| Description | 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 |
| 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). |
Outcome Measure Data
| Analysis Population Description |
|---|
| Uninjected Lesion Analysis Set: Any target lesion and new measurable lesion that was never injected from the participants who had received at least 1 dose of talimogene laherparepvec or atezolizumab. |
| Arm/Group Title | Talimogene Laherparepvec With Atezolizumab: Triple Negative Breast Cancer (TNBC) | Talimogene Laherparepvec With Atezolizumab: Colorectal Cancer (CRC) |
|---|---|---|
| Arm/Group Description | Participants with TNBC with liver metastases were 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 was 21 days. Participants were 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 were also administered 1200 mg atezolizumab via intravenous injection on Day 1 of each cycle. | Participants with CRC with liver metastases were 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 was 21 days. Participants were administered 10^6 PFU/mL on Day 1 of Cycle 1 and 10^8 PFU/mL on Day 1 of each cycle thereafter. Participants were also administered 1200 mg atezolizumab via intravenous injection on Day 1 of each cycle. |
| Measure Participants | 10 | 24 |
| Measure Lesions | 24 | 94 |
| L-CRR - Hepatic |
0
|
0
|
| L-CRR - Non-hepatic |
0
|
0
|
| L-CRR - Overall |
0
|
0
|
| L-PRR - Hepatic |
0
|
1
|
| L-PRR - Non-hepatic |
1
|
0
|
| L-PRR - Overall |
1
|
1
|
| L-ORR - Hepatic |
0
|
1
|
| L-ORR - Non-hepatic |
1
|
0
|
| L-ORR - Overall |
1
|
1
|
| Title | Durable Response Rate (DRR) |
|---|---|
| Description | DRR was defined as the percentage of participants with an objective response with a DOR of at least 6 months. |
| 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). |
Outcome Measure Data
| Analysis Population Description |
|---|
| Safety Analysis Set: All participants who received at least 1 dose of talimogene laherparepvec or atezolizumab. |
| Arm/Group Title | Talimogene Laherparepvec With Atezolizumab: Triple Negative Breast Cancer (TNBC) | Talimogene Laherparepvec With Atezolizumab: Colorectal Cancer (CRC) |
|---|---|---|
| Arm/Group Description | Participants with TNBC with liver metastases were 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 was 21 days. Participants were 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 were also administered 1200 mg atezolizumab via intravenous injection on Day 1 of each cycle. | Participants with CRC with liver metastases were 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 was 21 days. Participants were administered 10^6 PFU/mL on Day 1 of Cycle 1 and 10^8 PFU/mL on Day 1 of each cycle thereafter. Participants were also administered 1200 mg atezolizumab via intravenous injection on Day 1 of each cycle. |
| Measure Participants | 10 | 24 |
| Number (95% Confidence Interval) [Percentage of Participants] |
0.0
0%
|
0.0
0%
|
| Title | Disease Control Rate (DCR) |
|---|---|
| Description | DCR was defined as the percentage of participants that have a best overall response in one of the following categories: CR/PR/SD. |
| 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). |
Outcome Measure Data
| Analysis Population Description |
|---|
| Safety Analysis Set: All participants who received at least 1 dose of talimogene laherparepvec or atezolizumab. |
| Arm/Group Title | Talimogene Laherparepvec With Atezolizumab: Triple Negative Breast Cancer (TNBC) | Talimogene Laherparepvec With Atezolizumab: Colorectal Cancer (CRC) |
|---|---|---|
| Arm/Group Description | Participants with TNBC with liver metastases were 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 was 21 days. Participants were 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 were also administered 1200 mg atezolizumab via intravenous injection on Day 1 of each cycle. | Participants with CRC with liver metastases were 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 was 21 days. Participants were administered 10^6 PFU/mL on Day 1 of Cycle 1 and 10^8 PFU/mL on Day 1 of each cycle thereafter. Participants were also administered 1200 mg atezolizumab via intravenous injection on Day 1 of each cycle. |
| Measure Participants | 10 | 24 |
| Number (95% Confidence Interval) [Percentage of Participants] |
20.0
181.8%
|
4.2
16.8%
|
| Title | Progression-free Survival (PFS) |
|---|---|
| Description | 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. |
| 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). |
Outcome Measure Data
| Analysis Population Description |
|---|
| Safety Analysis Set: All participants who received at least 1 dose of talimogene laherparepvec or atezolizumab. |
| Arm/Group Title | Talimogene Laherparepvec With Atezolizumab: Triple Negative Breast Cancer (TNBC) | Talimogene Laherparepvec With Atezolizumab: Colorectal Cancer (CRC) |
|---|---|---|
| Arm/Group Description | Participants with TNBC with liver metastases were 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 was 21 days. Participants were 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 were also administered 1200 mg atezolizumab via intravenous injection on Day 1 of each cycle. | Participants with CRC with liver metastases were 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 was 21 days. Participants were administered 10^6 PFU/mL on Day 1 of Cycle 1 and 10^8 PFU/mL on Day 1 of each cycle thereafter. Participants were also administered 1200 mg atezolizumab via intravenous injection on Day 1 of each cycle. |
| Measure Participants | 10 | 24 |
| Median (95% Confidence Interval) [Months] |
5.4
|
3.0
|
| Title | Overall Survival (OS) |
|---|---|
| Description | 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. |
| 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). |
Outcome Measure Data
| Analysis Population Description |
|---|
| Safety Analysis Set: All participants who received at least 1 dose of talimogene laherparepvec or atezolizumab. |
| Arm/Group Title | Talimogene Laherparepvec With Atezolizumab: Triple Negative Breast Cancer (TNBC) | Talimogene Laherparepvec With Atezolizumab: Colorectal Cancer (CRC) |
|---|---|---|
| Arm/Group Description | Participants with TNBC with liver metastases were 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 was 21 days. Participants were 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 were also administered 1200 mg atezolizumab via intravenous injection on Day 1 of each cycle. | Participants with CRC with liver metastases were 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 was 21 days. Participants were administered 10^6 PFU/mL on Day 1 of Cycle 1 and 10^8 PFU/mL on Day 1 of each cycle thereafter. Participants were also administered 1200 mg atezolizumab via intravenous injection on Day 1 of each cycle. |
| Measure Participants | 10 | 24 |
| Median (95% Confidence Interval) [Months] |
19.2
|
3.8
|
Adverse Events
| Time Frame | Adverse events are reported from first dose through 30 days after last dose; max duration of treatment was 14.3 weeks for CRC cohort and 15.1 weeks for TNBC cohort. | |||
|---|---|---|---|---|
| Adverse Event Reporting Description | The TNBC cohort and CRC use different MedDRA versions respectively. MedDRA version 23.1 was used for the TNBC cohort and version 22.1 for the CRC cohort. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All cause mortality is presented for all participants who were enrolled in the study and were recorded from date of enrollment until data cut off. | |||
| Arm/Group Title | Talimogene Laherparepvec With Atezolizumab: Triple Negative Breast Cancer (TNBC) | Talimogene Laherparepvec With Atezolizumab: Colorectal Cancer (CRC) | ||
| Arm/Group Description | Participants with TNBC with liver metastases were 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 was 21 days. Participants were 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 were also administered 1200 mg atezolizumab via intravenous injection on Day 1 of each cycle. | Participants with CRC with liver metastases were 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 was 21 days. Participants were administered 10^6 PFU/mL on Day 1 of Cycle 1 and 10^8 PFU/mL on Day 1 of each cycle thereafter. Participants were also administered 1200 mg atezolizumab via intravenous injection on Day 1 of each cycle. | ||
All Cause Mortality |
||||
| Talimogene Laherparepvec With Atezolizumab: Triple Negative Breast Cancer (TNBC) | Talimogene Laherparepvec With Atezolizumab: Colorectal Cancer (CRC) | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 5/11 (45.5%) | 19/25 (76%) | ||
Serious Adverse Events |
||||
| Talimogene Laherparepvec With Atezolizumab: Triple Negative Breast Cancer (TNBC) | Talimogene Laherparepvec With Atezolizumab: Colorectal Cancer (CRC) | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 4/10 (40%) | 11/24 (45.8%) | ||
| Cardiac disorders | ||||
| Cardiac failure | 0/10 (0%) | 1/24 (4.2%) | ||
| Myocarditis | 0/10 (0%) | 1/24 (4.2%) | ||
| Gastrointestinal disorders | ||||
| Abdominal pain | 0/10 (0%) | 1/24 (4.2%) | ||
| Constipation | 0/10 (0%) | 1/24 (4.2%) | ||
| Intra-abdominal fluid collection | 0/10 (0%) | 1/24 (4.2%) | ||
| General disorders | ||||
| Pain | 0/10 (0%) | 1/24 (4.2%) | ||
| Pyrexia | 0/10 (0%) | 3/24 (12.5%) | ||
| Hepatobiliary disorders | ||||
| Hepatic haematoma | 1/10 (10%) | 0/24 (0%) | ||
| Immune system disorders | ||||
| Cytokine release syndrome | 1/10 (10%) | 1/24 (4.2%) | ||
| Hypersensitivity | 1/10 (10%) | 0/24 (0%) | ||
| Infections and infestations | ||||
| Abdominal infection | 1/10 (10%) | 0/24 (0%) | ||
| Pulmonary sepsis | 0/10 (0%) | 1/24 (4.2%) | ||
| Viral infection | 0/10 (0%) | 1/24 (4.2%) | ||
| Investigations | ||||
| Electrocardiogram QT prolonged | 0/10 (0%) | 1/24 (4.2%) | ||
| Platelet count decreased | 0/10 (0%) | 1/24 (4.2%) | ||
| Metabolism and nutrition disorders | ||||
| Hyponatraemia | 0/10 (0%) | 1/24 (4.2%) | ||
| Respiratory, thoracic and mediastinal disorders | ||||
| Dyspnoea | 0/10 (0%) | 1/24 (4.2%) | ||
| Respiratory failure | 0/10 (0%) | 1/24 (4.2%) | ||
| Vascular disorders | ||||
| Hypertension | 0/10 (0%) | 1/24 (4.2%) | ||
| Orthostatic hypotension | 1/10 (10%) | 0/24 (0%) | ||
Other (Not Including Serious) Adverse Events |
||||
| Talimogene Laherparepvec With Atezolizumab: Triple Negative Breast Cancer (TNBC) | Talimogene Laherparepvec With Atezolizumab: Colorectal Cancer (CRC) | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 8/10 (80%) | 23/24 (95.8%) | ||
| Blood and lymphatic system disorders | ||||
| Anaemia | 0/10 (0%) | 2/24 (8.3%) | ||
| Cardiac disorders | ||||
| Tachycardia | 0/10 (0%) | 5/24 (20.8%) | ||
| Ear and labyrinth disorders | ||||
| Ear congestion | 1/10 (10%) | 0/24 (0%) | ||
| Ear pain | 1/10 (10%) | 0/24 (0%) | ||
| Eye disorders | ||||
| Dry eye | 1/10 (10%) | 0/24 (0%) | ||
| Gastrointestinal disorders | ||||
| Abdominal pain | 1/10 (10%) | 2/24 (8.3%) | ||
| Abdominal pain lower | 1/10 (10%) | 0/24 (0%) | ||
| Abdominal pain upper | 0/10 (0%) | 3/24 (12.5%) | ||
| Constipation | 2/10 (20%) | 2/24 (8.3%) | ||
| Diarrhoea | 3/10 (30%) | 2/24 (8.3%) | ||
| Flatulence | 1/10 (10%) | 1/24 (4.2%) | ||
| Impaired gastric emptying | 1/10 (10%) | 0/24 (0%) | ||
| Nausea | 3/10 (30%) | 5/24 (20.8%) | ||
| Vomiting | 2/10 (20%) | 8/24 (33.3%) | ||
| General disorders | ||||
| Asthenia | 0/10 (0%) | 4/24 (16.7%) | ||
| Chills | 4/10 (40%) | 2/24 (8.3%) | ||
| Fatigue | 4/10 (40%) | 5/24 (20.8%) | ||
| General physical health deterioration | 0/10 (0%) | 2/24 (8.3%) | ||
| Influenza like illness | 1/10 (10%) | 1/24 (4.2%) | ||
| Injection site pain | 2/10 (20%) | 3/24 (12.5%) | ||
| Oedema peripheral | 0/10 (0%) | 5/24 (20.8%) | ||
| Pyrexia | 7/10 (70%) | 14/24 (58.3%) | ||
| Hepatobiliary disorders | ||||
| Hepatic pain | 1/10 (10%) | 2/24 (8.3%) | ||
| Immune system disorders | ||||
| Cytokine release syndrome | 1/10 (10%) | 1/24 (4.2%) | ||
| Infections and infestations | ||||
| Herpes virus infection | 1/10 (10%) | 0/24 (0%) | ||
| Urinary tract infection | 1/10 (10%) | 1/24 (4.2%) | ||
| Injury, poisoning and procedural complications | ||||
| Contusion | 1/10 (10%) | 0/24 (0%) | ||
| Infusion related reaction | 1/10 (10%) | 0/24 (0%) | ||
| Investigations | ||||
| Aspartate aminotransferase increased | 0/10 (0%) | 2/24 (8.3%) | ||
| Blood alkaline phosphatase increased | 1/10 (10%) | 2/24 (8.3%) | ||
| Hepatic enzyme increased | 0/10 (0%) | 2/24 (8.3%) | ||
| Lymphocyte count decreased | 1/10 (10%) | 0/24 (0%) | ||
| Platelet count decreased | 1/10 (10%) | 2/24 (8.3%) | ||
| Metabolism and nutrition disorders | ||||
| Decreased appetite | 0/10 (0%) | 5/24 (20.8%) | ||
| Hypokalaemia | 0/10 (0%) | 3/24 (12.5%) | ||
| Musculoskeletal and connective tissue disorders | ||||
| Arthralgia | 3/10 (30%) | 0/24 (0%) | ||
| Back pain | 2/10 (20%) | 0/24 (0%) | ||
| Bone pain | 1/10 (10%) | 0/24 (0%) | ||
| Musculoskeletal pain | 0/10 (0%) | 2/24 (8.3%) | ||
| Myalgia | 1/10 (10%) | 0/24 (0%) | ||
| Neck pain | 2/10 (20%) | 0/24 (0%) | ||
| Nervous system disorders | ||||
| Dizziness | 1/10 (10%) | 0/24 (0%) | ||
| Headache | 3/10 (30%) | 3/24 (12.5%) | ||
| Lethargy | 1/10 (10%) | 0/24 (0%) | ||
| Presyncope | 1/10 (10%) | 0/24 (0%) | ||
| Psychiatric disorders | ||||
| Anxiety | 1/10 (10%) | 0/24 (0%) | ||
| Renal and urinary disorders | ||||
| Dysuria | 0/10 (0%) | 2/24 (8.3%) | ||
| Reproductive system and breast disorders | ||||
| Benign prostatic hyperplasia | 0/10 (0%) | 2/24 (8.3%) | ||
| Vulvovaginal pruritus | 1/10 (10%) | 0/24 (0%) | ||
| Respiratory, thoracic and mediastinal disorders | ||||
| Cough | 2/10 (20%) | 3/24 (12.5%) | ||
| Dyspnoea | 1/10 (10%) | 2/24 (8.3%) | ||
| Epistaxis | 1/10 (10%) | 0/24 (0%) | ||
| Hiccups | 0/10 (0%) | 2/24 (8.3%) | ||
| Skin and subcutaneous tissue disorders | ||||
| Pruritus | 2/10 (20%) | 2/24 (8.3%) | ||
| Rash | 1/10 (10%) | 1/24 (4.2%) | ||
| Rash macular | 1/10 (10%) | 0/24 (0%) | ||
| Rash maculo-papular | 1/10 (10%) | 0/24 (0%) | ||
| Vascular disorders | ||||
| Hot flush | 1/10 (10%) | 0/24 (0%) | ||
Limitations/Caveats
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
The Clinical Trial Agreement generally does not restrict an investigator's discussion of trial results after completion. The Agreement permits Amgen a limited period of time to review material discussing trial results (typically up to 45 days and possible extension). Amgen may remove confidential information, but authors have final control and approval of publication content. For multicenter studies, the investigator agrees not to publish any results before the first multi-center publication.
Results Point of Contact
| Name/Title | Study Director |
|---|---|
| Organization | Amgen Inc. |
| Phone | 866-572-6436 |
| medinfo@amgen.com |
- 20140299