Back to resultsSingle-arm Trial to Evaluate the Biodistribution and Shedding of Talimogene Laherparepvec
Primary Purpose
Melanoma
Status
Completed
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
Talimogene laherparepvec
Sponsored by
About this trial
This is an interventional treatment trial for Melanoma
Eligibility Criteria
Key Inclusion Criteria:
Male or female age ≥ 18 years with histologically confirmed diagnosis of melanoma and unresected stage IIIB, IIIC, IVM1a, IVM1b, or IVM1c regardless of prior line of therapy. Subject is candidate for intralesional therapy administration into cutaneous, subcutaneous, or nodal disease and must also have measurable disease, serum lactate dehydrogenase ≤ 1.5 x upper limit of normal, and Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1, and adequate hematologic, hepatic, and renal organ function.
Key Exclusion Criteria:
Subject must not have clinically active cerebral metastases, greater than 3 visceral metastases (this does not include lung metastases or any nodal metastases associated with visceral organs) or any bone metastases melanoma, primary ocular or mucosal melanoma, history or evidence of symptomatic autoimmune pneumonitis, glomerulonephritis, vasculitis, or symptomatic autoimmune disease, or evidence of immunosuppression for any reason. Subject known to have acute or chronic active hepatitis B or hepatitis C infection, or human immunodeficiency virus infection will also be excluded. Subject who has active herpetic skin lesions or prior complications of herpes simplex virus type 1 ( HSV-1) infection (eg, herpetic keratitis or encephalitis), and/or requires intermittent or chronic systemic (intravenous or oral) treatment with an antiherpetic drug (eg, acyclovir), other than intermittent topical use will also be excuded. Subject must not have received previous treatment with talimogene laherparepvec.
Sites / Locations
- Research Site
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Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Talimogene Laherparepvec
Arm Description
Talimogene laherparepvec was administered by intralesional injection into injectable cutaneous, subcutaneous, and nodal lesions at an initial dose of 10⁶ plaque-forming units (PFU) per mL followed by a dose of 10⁸ PFU/mL 21 days after the initial dose and every 14 days thereafter. Participants were treated with talimogene laherparepvec until they achieved a complete response (CR), all injectable tumors had disappeared, clinically relevant (resulting in clinical deterioration or requiring change of therapy) disease progression per modified World Health Organization (WHO) response criteria beyond 6 months of therapy, or intolerance of study treatment, whichever occurred first.
Outcomes
Primary Outcome Measures
Percentage of Participants With Detectable Talimogene Laherparepvec Deoxyribonucleic Acid (DNA) During the First Three Cycles
Talimogene laherparepvec DNA was measured using a quantitative polymerase chain reaction (qPCR) method. The percentage of participants with detectable talimogene laherparepvec DNA in blood or urine at any time during cycles 1 to 3 is reported. The first cycle was 21 days in length, and subsequent cycles were 14 days in length.
Secondary Outcome Measures
Percentage of Participants With Clearance of Talimogene Laherparepvec DNA From Blood
A participant was defined as having cleared talimogene laherparepvec if a negative blood sample was obtained following a prior positive test and if there were no subsequent positive tests.
Percentage of Participants With Clearance of Talimogene Laherparepvec DNA From Urine
A participant was defined as having cleared talimogene laherparepvec if a negative urine sample was obtained following a prior positive test and if there were no subsequent positive tests.
Percentage of Samples With Detectable Talimogene Laherparepvec DNA on the Exterior of the Occlusive Dressing During the First Three Cycles
Talimogene laherparepvec DNA was measured using a quantitative polymerase chain reaction (qPCR) method. The percentage of swab samples from the exterior of the occlusive dressing with detectable talimogene laherparepvec DNA at any time during cycles 1 to 3 is reported.
Percentage of Samples With Detectable Talimogene Laherparepvec Virus on the Exterior of the Occlusive Dressing During the First Three Cycles
If the result of the qPCR testing was positive, then a 50% tissue culture infective dose (TCID50) assay was performed on the swab sample to measure viral infectivity. The percentage of swab samples from the exterior of the occlusive dressing with detectable talimogene laherparepvec virus at any time during cycles 1 to 3 is reported.
Percentage of Participants With Detectable Talimogene Laherparepvec DNA on the Exterior of the Occlusive Dressing During the First Three Cycles
Talimogene laherparepvec DNA was measured using a quantitative polymerase chain reaction (qPCR) method. The percentage of participants with detectable talimogene laherparepvec DNA on the exterior of the occlusive dressing at any time during cycles 1 to 3 is reported.
Percentage of Participants With Detectable Talimogene Laherparepvec Virus on the Exterior of the Occlusive Dressing During the First Three Cycles
If the result of the qPCR testing was positive, then a 50% tissue culture infective dose (TCID50) assay was performed on the swab sample to measure viral infectivity. The percentage of participants with detectable talimogene laherparepvec virus on the exterior of the occlusive dressing at any time during cycles 1 to 3 is reported.
Percentage of Samples From the Surface of Injected Lesions With Detectable Talimogene Laherparepvec DNA During the First Three Cycles
Talimogene laherparepvec DNA was measured using a quantitative polymerase chain reaction (qPCR) method. The percentage of swab samples from the surface of injected lesions with detectable talimogene laherparepvec DNA at any time during cycles 1 to 3 is reported.
Percentage of Samples From the Surface of Injected Lesions With Detectable Talimogene Laherparepvec Virus During the First Three Cycles
If the result of the qPCR testing was positive, then a 50% tissue culture infective dose (TCID50) assay was performed on the swab sample to measure viral infectivity. The percentage of samples taken from the surface of injected lesions with detectable talimogene laherparepvec virus at any time during cycles 1 to 3 is reported.
Percentage of Participants With Detectable Talimogene Laherparepvec DNA on the Surface of Injected Lesions During the First Three Cycles
Talimogene laherparepvec DNA was measured using a quantitative polymerase chain reaction (qPCR) method. The percentage of participants with detectable talimogene laherparepvec DNA swabs taken from the surface of injected lesions at any time during cycles 1 to 3 is reported.
Percentage of Participants With Detectable Talimogene Laherparepvec Virus on the Surface of Injected Lesions During the First Three Cycles
If the result of the qPCR testing was positive, then a 50% tissue culture infective dose (TCID50) assay was performed on the swab sample to measure viral infectivity. The percentage of participants with detectable talimogene laherparepvec virus on swabs taken from the surface of injected lesions at any time during cycles 1 to 3 is reported.
Percentage of Samples From Oral Mucosa With Detectable Talimogene Laherparepvec DNA During Treatment
Talimogene laherparepvec DNA was measured using a quantitative polymerase chain reaction (qPCR) method. The percentage of swab samples from oral mucosa with detectable talimogene laherparepvec DNA at any time during treatment is reported.
Percentage of Samples From Oral Mucosa With Detectable Talimogene Laherparepvec Virus During Treatment
If the result of the qPCR testing was positive, then a 50% tissue culture infective dose (TCID50) assay was performed on the swab sample to measure viral infectivity. The percentage of samples taken from oral mucosa with detectable talimogene laherparepvec virus at any time during treatment is reported.
Percentage of Participants With Detectable Talimogene Laherparepvec DNA in Oral Mucosa During Treatment
Talimogene laherparepvec DNA was measured using a quantitative polymerase chain reaction (qPCR) method. The percentage of participants with detectable talimogene laherparepvec DNA on swabs taken from oral mucosa at any time during treatment is reported.
Percentage of Participants With Detectable Talimogene Laherparepvec Virus in Oral Mucosa During Treatment
If the result of the qPCR testing was positive, then a 50% tissue culture infective dose (TCID50) assay was performed on the swab sample to measure viral infectivity. The percentage of participants with detectable talimogene laherparepvec virus in swabs taken from oral mucosa at any time during treatment is reported.
Percentage of Samples From the Anogenital Area With Detectable Talimogene Laherparepvec DNA During Treatment
Talimogene laherparepvec DNA was measured using a quantitative polymerase chain reaction (qPCR) method. The percentage of swab samples from the anogenital area with detectable talimogene laherparepvec DNA at any time during treatment is reported.
Percentage of Samples With Detectable Talimogene Laherparepvec Virus in Swabs From the Anogenital Area During Treatment
If the result of the qPCR testing was positive, then a 50% tissue culture infective dose (TCID50) assay was performed on the swab sample to measure viral infectivity. The percentage of samples with detectable talimogene laherparepvec virus in swabs taken from the anogenital area at any time during treatment is reported.
Percentage of Participants With Detectable Talimogene Laherparepvec DNA in Swabs From the Anogenital Area During Treatment
Talimogene laherparepvec DNA was measured using a quantitative polymerase chain reaction (qPCR) method. The percentage of participants with detectable talimogene laherparepvec DNA in swabs from the anogenital area at any time during treatment is reported.
Percentage of Participants With Detectable Talimogene Laherparepvec Virus in Swabs From the Anogenital Area During Treatment
If the result of the qPCR testing was positive, then a 50% tissue culture infective dose (TCID50) assay was performed on the swab sample to measure viral infectivity. The percentage of participants with detectable talimogene laherparepvec virus in swabs taken from the anogenital area at any time during treatment is reported.
Percentage of Samples From Oral Mucosa With Detectable Talimogene Laherparepvec DNA After the End of Treatment
Talimogene laherparepvec DNA was measured using a quantitative polymerase chain reaction (qPCR) method. The percentage of swab samples from oral mucosa with detectable talimogene laherparepvec DNA after the end of treatment is reported.
Percentage of Samples From Oral Mucosa With Detectable Talimogene Laherparepvec Virus After the End of Treatment
If the result of the qPCR testing was positive, then a 50% tissue culture infective dose (TCID50) assay was performed on the swab sample to measure viral infectivity.
Percentage of Participants With Detectable Talimogene Laherparepvec DNA in Oral Mucosa After the End of Treatment
Talimogene laherparepvec DNA was measured using a quantitative polymerase chain reaction (qPCR) method. The percentage of participants with detectable talimogene laherparepvec DNA in swabs taken from oral mucosa after the end of treatment is reported.
Percentage of Participants With Detectable Talimogene Laherparepvec Virus in Oral Mucosa After the End of Treatment
If the result of the qPCR testing was positive, then a 50% tissue culture infective dose (TCID50) assay was performed on the swab sample to measure viral infectivity.
Percentage of Samples From the Anogenital Area With Detectable Talimogene Laherparepvec DNA After the End of Treatment
Talimogene laherparepvec DNA was measured using a quantitative polymerase chain reaction (qPCR) method. The percentage of swab samples from the anogenital area with detectable talimogene laherparepvec DNA after the end of treatment is reported.
Percentage of Samples From the Anogenital Area With Detectable Talimogene Laherparepvec Virus After the End of Treatment
If the result of the qPCR testing was positive, then a 50% tissue culture infective dose (TCID50) assay was performed on the swab sample to measure viral infectivity.
Percentage of Participants With Detectable Talimogene Laherparepvec DNA in Swabs From the Anogenital Area After the End of Treatment
Talimogene laherparepvec DNA was measured using a quantitative polymerase chain reaction (qPCR) method. The percentage of participants with detectable talimogene laherparepvec DNA in swabs from the anogenital area after the end of treatment is reported.
Percentage of Participants With Detectable Talimogene Laherparepvec Virus in Swabs From the Anogenital Area After the End of Treatment
If the result of the qPCR testing was positive, then a 50% tissue culture infective dose (TCID50) assay was performed on the swab sample to measure viral infectivity.
Number of Samples With Detectable Talimogene Laherparepvec in Lesions Suspected to be Herpetic in Origin
Any lesion such as a cold sore or vesicle thought to be herpetic in origin was evaluated by the investigator and swabbed if HSV infection was suspected. Quantitative PCR was performed on the swab sample to evaluate whether talimogene laherparepvec DNA was detectable in the sample.
Best Overall Response
Response was assessed according to modified World Health Organization (WHO) criteria using both clinical (cutaneous, subcutaneous, or nodal tumor measurement by caliper) and radiological imaging (computed tomography (CT), magnetic resonance imaging (MRI), or ultrasound of the chest, abdomen, and pelvis and all other sites of disease).
Complete response: disappearance of all index and non-index lesions.
Partial Response: ≥ 50% reduction in size of all index lesions and any new measurable lesions.
Stable disease: Neither sufficient tumor shrinkage of index lesion to qualify for response nor sufficient tumor increase of index lesion to qualify for progressive disease, assessed a minimum interval of 77 days from the first dose of study drug.
Progressive Disease: ≥ 25% increase in size of index lesions or appearance of one or more non-index lesions.
Objective Response Rate
Response was assessed according to modified World Health Organization (WHO) criteria using both clinical (cutaneous, subcutaneous, or nodal tumor measurement by caliper) and radiological imaging (computed tomography, magnetic resonance imaging or ultrasound of the chest, abdomen, and pelvis and all other sites of disease). Objective response rate is defined as the percentage of participants with either a complete response or partial response. Subsequent confirmation was not required.
Complete response: disappearance of all index and non-index lesions.
Partial Response: ≥ 50% reduction in size of all index lesions and any new measurable lesions.
Time to Response
Time to response was defined as the interval from the first dose of talimogene laherparepvec to the first event of complete response or partial response per modified WHO criteria; participants who did not respond were censored at the last evaluable tumor assessment.
Duration of Response
Duration of response (DOR) was calculated only for those participants with an objective response and defined as the longest interval from an initial objective response (complete response or partial response) to disease progression per the modified WHO criteria or death, whichever occurred earlier; otherwise, DOR was censored at the last evaluable tumor assessment for participants who did not die or progress.
Durable Response Rate
Response was assessed according to modified World Health Organization (WHO) criteria using both clinical (cutaneous, subcutaneous, or nodal tumor measurement by caliper) and radiological imaging (computed tomography, magnetic resonance imaging or ultrasound of the chest, abdomen, and pelvis and all other sites of disease). Durable response rate is defined as the percentage of participants with a complete response or partial response maintained continuously for at least 6 months (183 days).
Complete response: disappearance of all index and non-index lesions.
Partial Response:≥ 50% reduction in size of all index lesions and any new measurable lesions.
Overall Survival
Overall Survival (OS) was defined as the interval from first dose of talimogene laherparepvec to death from any cause; participants still alive were censored at the last known alive date.
Number of Participants With Adverse Events (AEs)
The Common Terminology Criteria for Adverse Events version 3.0 was used to grade severity of adverse events, based on the following general guideline: Grade 1 = Mild AE Grade 2 = Moderate AE Grade 3 = Severe AE Grade 4 = Life-threatening or disabling AE Grade 5 = Death related to AE. A serious adverse event was defined as an adverse event that meets at least 1 of the following serious criteria:
fatal
life threatening
requires in-patient hospitalization or prolongation of existing hospitalization
results in persistent or significant disability/incapacity
congenital anomaly/birth defect
other medically important serious event
Treatment-related adverse events (TRAEs) are defined as adverse events possibly caused by talimogene laherparepvec, as assessed by the investigator.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT02014441
Brief Title
Single-arm Trial to Evaluate the Biodistribution and Shedding of Talimogene Laherparepvec
Official Title
A Phase 2, Multicenter, Single-arm Trial to Evaluate the Biodistribution and Shedding of Talimogene Laherparepvec in Subjects With Unresected, Stage IIIB to IVM1c Melanoma
Study Type
Interventional
2. Study Status
Record Verification Date
November 2019
Overall Recruitment Status
Completed
Study Start Date
April 7, 2014 (Actual)
Primary Completion Date
January 25, 2016 (Actual)
Study Completion Date
April 19, 2018 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Amgen
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief Summary
The primary objective was to estimate the proportion of participants with detectable talimogene laherparepvec deoxyribonucleic acid (DNA) in the blood and urine at any time after administration of talimogene laherparepvec within the first 3 cycles.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Melanoma
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
61 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Talimogene Laherparepvec
Arm Type
Experimental
Arm Description
Talimogene laherparepvec was administered by intralesional injection into injectable cutaneous, subcutaneous, and nodal lesions at an initial dose of 10⁶ plaque-forming units (PFU) per mL followed by a dose of 10⁸ PFU/mL 21 days after the initial dose and every 14 days thereafter.
Participants were treated with talimogene laherparepvec until they achieved a complete response (CR), all injectable tumors had disappeared, clinically relevant (resulting in clinical deterioration or requiring change of therapy) disease progression per modified World Health Organization (WHO) response criteria beyond 6 months of therapy, or intolerance of study treatment, whichever occurred first.
Intervention Type
Drug
Intervention Name(s)
Talimogene laherparepvec
Other Intervention Name(s)
IMLYGIC®, OncoVEX^GM-CSF
Intervention Description
Talimogene laherparepvec will be administered by intralesion injection at an initial dose of up to 4.0 mL of 10^6 PFU/mL. The second and subsequent doses will will be up to 4.0 mL 10^8 PFU/mL. The second dose should be administered 21 days from the initial dose. All subsequent doses should be given every 14 days.
Primary Outcome Measure Information:
Title
Percentage of Participants With Detectable Talimogene Laherparepvec Deoxyribonucleic Acid (DNA) During the First Three Cycles
Description
Talimogene laherparepvec DNA was measured using a quantitative polymerase chain reaction (qPCR) method. The percentage of participants with detectable talimogene laherparepvec DNA in blood or urine at any time during cycles 1 to 3 is reported. The first cycle was 21 days in length, and subsequent cycles were 14 days in length.
Time Frame
Cycles 1 and 2 on days 1 (pre-dose and 1, 4, and 8 hours post-dose), 2, 3, 8, and 15 (cycle 1 only), cycle 3 on day 1 (pre-dose) and day 8, and cycle 4 on day 1 (pre-dose).
Secondary Outcome Measure Information:
Title
Percentage of Participants With Clearance of Talimogene Laherparepvec DNA From Blood
Description
A participant was defined as having cleared talimogene laherparepvec if a negative blood sample was obtained following a prior positive test and if there were no subsequent positive tests.
Time Frame
Cycles 1 and 2 on days 1 (pre-dose and 1, 4, and 8 hours post-dose), 2, 3, 8, and 15 (cycle 1 only), cycle 3 on day 1 (pre-dose) and day 8, and cycle 4 on day 1 (pre-dose).
Title
Percentage of Participants With Clearance of Talimogene Laherparepvec DNA From Urine
Description
A participant was defined as having cleared talimogene laherparepvec if a negative urine sample was obtained following a prior positive test and if there were no subsequent positive tests.
Time Frame
Cycles 1 and 2 on days 1 (pre-dose and 1, 4, and 8 hours post-dose), 2, 3, 8, and 15 (cycle 1 only), cycle 3 on day 1 (pre-dose) and day 8, and cycle 4 on day 1 (pre-dose).
Title
Percentage of Samples With Detectable Talimogene Laherparepvec DNA on the Exterior of the Occlusive Dressing During the First Three Cycles
Description
Talimogene laherparepvec DNA was measured using a quantitative polymerase chain reaction (qPCR) method. The percentage of swab samples from the exterior of the occlusive dressing with detectable talimogene laherparepvec DNA at any time during cycles 1 to 3 is reported.
Time Frame
Cycle 1 on days 2, 3, 8, and 15, cycle 2 on days 1 (pre-dose), 2, 3, and 8, cycle 3 on day 1 (pre-dose) and day 8, and cycle 4 on day 1 (pre-dose).
Title
Percentage of Samples With Detectable Talimogene Laherparepvec Virus on the Exterior of the Occlusive Dressing During the First Three Cycles
Description
If the result of the qPCR testing was positive, then a 50% tissue culture infective dose (TCID50) assay was performed on the swab sample to measure viral infectivity. The percentage of swab samples from the exterior of the occlusive dressing with detectable talimogene laherparepvec virus at any time during cycles 1 to 3 is reported.
Time Frame
Cycle 1 on days 2, 3, 8, and 15, cycle 2 on days 1 (pre-dose), 2, 3, and 8, cycle 3 on day 1 (pre-dose) and day 8, and cycle 4 on day 1 (pre-dose).
Title
Percentage of Participants With Detectable Talimogene Laherparepvec DNA on the Exterior of the Occlusive Dressing During the First Three Cycles
Description
Talimogene laherparepvec DNA was measured using a quantitative polymerase chain reaction (qPCR) method. The percentage of participants with detectable talimogene laherparepvec DNA on the exterior of the occlusive dressing at any time during cycles 1 to 3 is reported.
Time Frame
Cycle 1 on days 2, 3, 8, and 15, cycle 2 on days 1 (pre-dose), 2, 3, and 8, cycle 3 on day 1 (pre-dose) and day 8, and cycle 4 on day 1 (pre-dose).
Title
Percentage of Participants With Detectable Talimogene Laherparepvec Virus on the Exterior of the Occlusive Dressing During the First Three Cycles
Description
If the result of the qPCR testing was positive, then a 50% tissue culture infective dose (TCID50) assay was performed on the swab sample to measure viral infectivity. The percentage of participants with detectable talimogene laherparepvec virus on the exterior of the occlusive dressing at any time during cycles 1 to 3 is reported.
Time Frame
Cycle 1 on days 2, 3, 8, and 15, cycle 2 on days 1 (pre-dose), 2, 3, and 8, cycle 3 on day 1 (pre-dose) and day 8, and cycle 4 on day 1 (pre-dose).
Title
Percentage of Samples From the Surface of Injected Lesions With Detectable Talimogene Laherparepvec DNA During the First Three Cycles
Description
Talimogene laherparepvec DNA was measured using a quantitative polymerase chain reaction (qPCR) method. The percentage of swab samples from the surface of injected lesions with detectable talimogene laherparepvec DNA at any time during cycles 1 to 3 is reported.
Time Frame
Cycle 1 on days 2, 3, 8, and 15, cycle 2 on days 1 (pre-dose), 2, 3, and 8, cycle 3 on day 1 (pre-dose) and day 8, and cycle 4 on day 1 (pre-dose).
Title
Percentage of Samples From the Surface of Injected Lesions With Detectable Talimogene Laherparepvec Virus During the First Three Cycles
Description
If the result of the qPCR testing was positive, then a 50% tissue culture infective dose (TCID50) assay was performed on the swab sample to measure viral infectivity. The percentage of samples taken from the surface of injected lesions with detectable talimogene laherparepvec virus at any time during cycles 1 to 3 is reported.
Time Frame
Cycle 1 on days 2, 3, 8, and 15, cycle 2 on days 1 (pre-dose), 2, 3, and 8, cycle 3 on day 1 (pre-dose) and day 8, and cycle 4 on day 1 (pre-dose).
Title
Percentage of Participants With Detectable Talimogene Laherparepvec DNA on the Surface of Injected Lesions During the First Three Cycles
Description
Talimogene laherparepvec DNA was measured using a quantitative polymerase chain reaction (qPCR) method. The percentage of participants with detectable talimogene laherparepvec DNA swabs taken from the surface of injected lesions at any time during cycles 1 to 3 is reported.
Time Frame
Cycle 1 on days 2, 3, 8, and 15, cycle 2 on days 1 (pre-dose), 2, 3, and 8, cycle 3 on day 1 (pre-dose) and day 8, and cycle 4 on day 1 (pre-dose).
Title
Percentage of Participants With Detectable Talimogene Laherparepvec Virus on the Surface of Injected Lesions During the First Three Cycles
Description
If the result of the qPCR testing was positive, then a 50% tissue culture infective dose (TCID50) assay was performed on the swab sample to measure viral infectivity. The percentage of participants with detectable talimogene laherparepvec virus on swabs taken from the surface of injected lesions at any time during cycles 1 to 3 is reported.
Time Frame
Cycle 1 on days 2, 3, 8, and 15, cycle 2 on days 1 (pre-dose), 2, 3, and 8, cycle 3 on day 1 (pre-dose) and day 8, and cycle 4 on day 1 (pre-dose).
Title
Percentage of Samples From Oral Mucosa With Detectable Talimogene Laherparepvec DNA During Treatment
Description
Talimogene laherparepvec DNA was measured using a quantitative polymerase chain reaction (qPCR) method. The percentage of swab samples from oral mucosa with detectable talimogene laherparepvec DNA at any time during treatment is reported.
Time Frame
Cycle 1 on days 1 (pre-dose), 8, and 15, cycles 2 and 3 on days 1 (pre-dose), and 8, cycle 4 and subsequent cycles (up to 47) on day 1 (pre-dose), cycle 25 on day 1 (pre-dose) and day 8.
Title
Percentage of Samples From Oral Mucosa With Detectable Talimogene Laherparepvec Virus During Treatment
Description
If the result of the qPCR testing was positive, then a 50% tissue culture infective dose (TCID50) assay was performed on the swab sample to measure viral infectivity. The percentage of samples taken from oral mucosa with detectable talimogene laherparepvec virus at any time during treatment is reported.
Time Frame
Cycle 1 on days 1 (pre-dose), 8, and 15, cycles 2 and 3 on days 1 (pre-dose), and 8, cycle 4 and subsequent cycles (up to 47) on day 1 (pre-dose), Cycle 25 on day 1 (pre-dose) and day 8.
Title
Percentage of Participants With Detectable Talimogene Laherparepvec DNA in Oral Mucosa During Treatment
Description
Talimogene laherparepvec DNA was measured using a quantitative polymerase chain reaction (qPCR) method. The percentage of participants with detectable talimogene laherparepvec DNA on swabs taken from oral mucosa at any time during treatment is reported.
Time Frame
Cycle 1 on days 1 (pre-dose), 8, and 15, cycles 2 and 3 on days 1 (pre-dose), and 8, cycle 4 and subsequent cycles (up to 47) on day 1 (pre-dose), Cycle 25 on day 1 (pre-dose) and day 8.
Title
Percentage of Participants With Detectable Talimogene Laherparepvec Virus in Oral Mucosa During Treatment
Description
If the result of the qPCR testing was positive, then a 50% tissue culture infective dose (TCID50) assay was performed on the swab sample to measure viral infectivity. The percentage of participants with detectable talimogene laherparepvec virus in swabs taken from oral mucosa at any time during treatment is reported.
Time Frame
Cycle 1 on days 1 (pre-dose), 8, and 15, cycles 2 and 3 on days 1 (pre-dose), and 8, cycle 4 and subsequent cycles (up to 47) on day 1 (pre-dose), Cycle 25 on day 1 (pre-dose) and day 8.
Title
Percentage of Samples From the Anogenital Area With Detectable Talimogene Laherparepvec DNA During Treatment
Description
Talimogene laherparepvec DNA was measured using a quantitative polymerase chain reaction (qPCR) method. The percentage of swab samples from the anogenital area with detectable talimogene laherparepvec DNA at any time during treatment is reported.
Time Frame
Cycle 1 on days 1 (pre-dose), 8, and 15, cycles 2 and 3 on days 1 (pre-dose), and 8, cycle 4 and subsequent cycles (up to 50) on day 1 (pre-dose), Cycle 25 on day 1 (pre-dose) and day 8.
Title
Percentage of Samples With Detectable Talimogene Laherparepvec Virus in Swabs From the Anogenital Area During Treatment
Description
If the result of the qPCR testing was positive, then a 50% tissue culture infective dose (TCID50) assay was performed on the swab sample to measure viral infectivity. The percentage of samples with detectable talimogene laherparepvec virus in swabs taken from the anogenital area at any time during treatment is reported.
Time Frame
Cycle 1 on days 1 (pre-dose), 8, and 15, cycles 2 and 3 on days 1 (pre-dose), and 8, cycle 4 and subsequent cycles (up to 50) on day 1 (pre-dose), Cycle 25 on day 1 (pre-dose) and day 8.
Title
Percentage of Participants With Detectable Talimogene Laherparepvec DNA in Swabs From the Anogenital Area During Treatment
Description
Talimogene laherparepvec DNA was measured using a quantitative polymerase chain reaction (qPCR) method. The percentage of participants with detectable talimogene laherparepvec DNA in swabs from the anogenital area at any time during treatment is reported.
Time Frame
Cycle 1 on days 1 (pre-dose), 8, and 15, cycles 2 and 3 on days 1 (pre-dose), and 8, cycle 4 and subsequent cycles (up to 50) on day 1 (pre-dose), Cycle 25 on day 1 (pre-dose) and day 8.
Title
Percentage of Participants With Detectable Talimogene Laherparepvec Virus in Swabs From the Anogenital Area During Treatment
Description
If the result of the qPCR testing was positive, then a 50% tissue culture infective dose (TCID50) assay was performed on the swab sample to measure viral infectivity. The percentage of participants with detectable talimogene laherparepvec virus in swabs taken from the anogenital area at any time during treatment is reported.
Time Frame
Cycle 1 on days 1 (pre-dose), 8, and 15, cycles 2 and 3 on days 1 (pre-dose), and 8, cycle 4 and subsequent cycles (up to 50) on day 1 (pre-dose), Cycle 25 on day 1 (pre-dose) and day 8.
Title
Percentage of Samples From Oral Mucosa With Detectable Talimogene Laherparepvec DNA After the End of Treatment
Description
Talimogene laherparepvec DNA was measured using a quantitative polymerase chain reaction (qPCR) method. The percentage of swab samples from oral mucosa with detectable talimogene laherparepvec DNA after the end of treatment is reported.
Time Frame
From 30 to 60 days after the last dose of talimogene laherparepvec (the median [minimum, maximum] duration of treatment was 23 [3, 141] weeks).
Title
Percentage of Samples From Oral Mucosa With Detectable Talimogene Laherparepvec Virus After the End of Treatment
Description
If the result of the qPCR testing was positive, then a 50% tissue culture infective dose (TCID50) assay was performed on the swab sample to measure viral infectivity.
Time Frame
From 30 to 60 days after the last dose of talimogene laherparepvec (the median [minimum, maximum] duration of treatment was 23 [3, 141] weeks).
Title
Percentage of Participants With Detectable Talimogene Laherparepvec DNA in Oral Mucosa After the End of Treatment
Description
Talimogene laherparepvec DNA was measured using a quantitative polymerase chain reaction (qPCR) method. The percentage of participants with detectable talimogene laherparepvec DNA in swabs taken from oral mucosa after the end of treatment is reported.
Time Frame
From 30 to 60 days after the last dose of talimogene laherparepvec (the median [minimum, maximum] duration of treatment was 23 [3, 141] weeks).
Title
Percentage of Participants With Detectable Talimogene Laherparepvec Virus in Oral Mucosa After the End of Treatment
Description
If the result of the qPCR testing was positive, then a 50% tissue culture infective dose (TCID50) assay was performed on the swab sample to measure viral infectivity.
Time Frame
From 30 to 60 days after the last dose of talimogene laherparepvec (the median [minimum, maximum] duration of treatment was 23 [3, 141] weeks).
Title
Percentage of Samples From the Anogenital Area With Detectable Talimogene Laherparepvec DNA After the End of Treatment
Description
Talimogene laherparepvec DNA was measured using a quantitative polymerase chain reaction (qPCR) method. The percentage of swab samples from the anogenital area with detectable talimogene laherparepvec DNA after the end of treatment is reported.
Time Frame
From 30 to 60 days after the last dose of talimogene laherparepvec (the median [minimum, maximum] duration of treatment was 23 [3, 141] weeks).
Title
Percentage of Samples From the Anogenital Area With Detectable Talimogene Laherparepvec Virus After the End of Treatment
Description
If the result of the qPCR testing was positive, then a 50% tissue culture infective dose (TCID50) assay was performed on the swab sample to measure viral infectivity.
Time Frame
30 toFrom 30 to 60 days after the last dose of talimogene laherparepvec (the median [minimum, maximum] duration of treatment was 23 [3, 141] weeks). 60 days after the last dose of talimogene laherparepvec.
Title
Percentage of Participants With Detectable Talimogene Laherparepvec DNA in Swabs From the Anogenital Area After the End of Treatment
Description
Talimogene laherparepvec DNA was measured using a quantitative polymerase chain reaction (qPCR) method. The percentage of participants with detectable talimogene laherparepvec DNA in swabs from the anogenital area after the end of treatment is reported.
Time Frame
From 30 to 60 days after the last dose of talimogene laherparepvec (the median [minimum, maximum] duration of treatment was 23 [3, 141] weeks).
Title
Percentage of Participants With Detectable Talimogene Laherparepvec Virus in Swabs From the Anogenital Area After the End of Treatment
Description
If the result of the qPCR testing was positive, then a 50% tissue culture infective dose (TCID50) assay was performed on the swab sample to measure viral infectivity.
Time Frame
From 30 to 60 days after the last dose of talimogene laherparepvec (the median [minimum, maximum] duration of treatment was 23 [3, 141] weeks).
Title
Number of Samples With Detectable Talimogene Laherparepvec in Lesions Suspected to be Herpetic in Origin
Description
Any lesion such as a cold sore or vesicle thought to be herpetic in origin was evaluated by the investigator and swabbed if HSV infection was suspected. Quantitative PCR was performed on the swab sample to evaluate whether talimogene laherparepvec DNA was detectable in the sample.
Time Frame
From first dose until 60 days after last dose of talimogene laherparepvec; The median actual follow-up time was 28.9 weeks (range: 4 to 151 weeks).
Title
Best Overall Response
Description
Response was assessed according to modified World Health Organization (WHO) criteria using both clinical (cutaneous, subcutaneous, or nodal tumor measurement by caliper) and radiological imaging (computed tomography (CT), magnetic resonance imaging (MRI), or ultrasound of the chest, abdomen, and pelvis and all other sites of disease).
Complete response: disappearance of all index and non-index lesions.
Partial Response: ≥ 50% reduction in size of all index lesions and any new measurable lesions.
Stable disease: Neither sufficient tumor shrinkage of index lesion to qualify for response nor sufficient tumor increase of index lesion to qualify for progressive disease, assessed a minimum interval of 77 days from the first dose of study drug.
Progressive Disease: ≥ 25% increase in size of index lesions or appearance of one or more non-index lesions.
Time Frame
Tumor response was assessed at weeks 12 and 24 and then at least every 3 months up to the end of treatment; median duration of treatment was 23.1 weeks (range: 3 to 141 weeks).
Title
Objective Response Rate
Description
Response was assessed according to modified World Health Organization (WHO) criteria using both clinical (cutaneous, subcutaneous, or nodal tumor measurement by caliper) and radiological imaging (computed tomography, magnetic resonance imaging or ultrasound of the chest, abdomen, and pelvis and all other sites of disease). Objective response rate is defined as the percentage of participants with either a complete response or partial response. Subsequent confirmation was not required.
Complete response: disappearance of all index and non-index lesions.
Partial Response: ≥ 50% reduction in size of all index lesions and any new measurable lesions.
Time Frame
Tumor response was assessed at weeks 12 and 24 and then at least every 3 months up to the end of treatment; median duration of treatment was 23.1 weeks (range: 3 to 141 weeks).
Title
Time to Response
Description
Time to response was defined as the interval from the first dose of talimogene laherparepvec to the first event of complete response or partial response per modified WHO criteria; participants who did not respond were censored at the last evaluable tumor assessment.
Time Frame
Tumor response was assessed at weeks 12 and 24 and then at least every 3 months up to the end of treatment; median duration of treatment was 23.1 weeks (range: 3 to 141 weeks).
Title
Duration of Response
Description
Duration of response (DOR) was calculated only for those participants with an objective response and defined as the longest interval from an initial objective response (complete response or partial response) to disease progression per the modified WHO criteria or death, whichever occurred earlier; otherwise, DOR was censored at the last evaluable tumor assessment for participants who did not die or progress.
Time Frame
Tumor response was assessed at weeks 12 and 24 and then at least every 3 months up to the end of treatment; median duration of treatment was 23.1 weeks (range: 3 to 141 weeks).
Title
Durable Response Rate
Description
Response was assessed according to modified World Health Organization (WHO) criteria using both clinical (cutaneous, subcutaneous, or nodal tumor measurement by caliper) and radiological imaging (computed tomography, magnetic resonance imaging or ultrasound of the chest, abdomen, and pelvis and all other sites of disease). Durable response rate is defined as the percentage of participants with a complete response or partial response maintained continuously for at least 6 months (183 days).
Complete response: disappearance of all index and non-index lesions.
Partial Response:≥ 50% reduction in size of all index lesions and any new measurable lesions.
Time Frame
Tumor response was assessed at weeks 12 and 24 and then at least every 3 months up to the end of treatment; median duration of treatment was 23.1 weeks (range: 3 to 141 weeks).
Title
Overall Survival
Description
Overall Survival (OS) was defined as the interval from first dose of talimogene laherparepvec to death from any cause; participants still alive were censored at the last known alive date.
Time Frame
From first dose until 60 days after last dose of talimogene laherparepvec; The median actual follow-up time was 28.9 weeks (range: 4 to 151 weeks).
Title
Number of Participants With Adverse Events (AEs)
Description
The Common Terminology Criteria for Adverse Events version 3.0 was used to grade severity of adverse events, based on the following general guideline: Grade 1 = Mild AE Grade 2 = Moderate AE Grade 3 = Severe AE Grade 4 = Life-threatening or disabling AE Grade 5 = Death related to AE. A serious adverse event was defined as an adverse event that meets at least 1 of the following serious criteria:
fatal
life threatening
requires in-patient hospitalization or prolongation of existing hospitalization
results in persistent or significant disability/incapacity
congenital anomaly/birth defect
other medically important serious event
Treatment-related adverse events (TRAEs) are defined as adverse events possibly caused by talimogene laherparepvec, as assessed by the investigator.
Time Frame
From the first administration of talimogene laherparepvec up to 30 days after the last administration of talimogene laherparepvec; median duration of treatment was 23.1 weeks (range: 3 to 141 weeks).
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
100 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Key Inclusion Criteria:
Male or female age ≥ 18 years with histologically confirmed diagnosis of melanoma and unresected stage IIIB, IIIC, IVM1a, IVM1b, or IVM1c regardless of prior line of therapy. Subject is candidate for intralesional therapy administration into cutaneous, subcutaneous, or nodal disease and must also have measurable disease, serum lactate dehydrogenase ≤ 1.5 x upper limit of normal, and Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1, and adequate hematologic, hepatic, and renal organ function.
Key Exclusion Criteria:
Subject must not have clinically active cerebral metastases, greater than 3 visceral metastases (this does not include lung metastases or any nodal metastases associated with visceral organs) or any bone metastases melanoma, primary ocular or mucosal melanoma, history or evidence of symptomatic autoimmune pneumonitis, glomerulonephritis, vasculitis, or symptomatic autoimmune disease, or evidence of immunosuppression for any reason. Subject known to have acute or chronic active hepatitis B or hepatitis C infection, or human immunodeficiency virus infection will also be excluded. Subject who has active herpetic skin lesions or prior complications of herpes simplex virus type 1 ( HSV-1) infection (eg, herpetic keratitis or encephalitis), and/or requires intermittent or chronic systemic (intravenous or oral) treatment with an antiherpetic drug (eg, acyclovir), other than intermittent topical use will also be excuded. Subject must not have received previous treatment with talimogene laherparepvec.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
MD
Organizational Affiliation
Amgen
Official's Role
Study Director
Facility Information:
Facility Name
Research Site
City
Tampa
State/Province
Florida
ZIP/Postal Code
33612
Country
United States
Facility Name
Research Site
City
Indianapolis
State/Province
Indiana
ZIP/Postal Code
46202
Country
United States
Facility Name
Research Site
City
Louisville
State/Province
Kentucky
ZIP/Postal Code
40202
Country
United States
Facility Name
Research Site
City
Fridley
State/Province
Minnesota
ZIP/Postal Code
55432
Country
United States
Facility Name
Research Site
City
Minneapolis
State/Province
Minnesota
ZIP/Postal Code
55407
Country
United States
Facility Name
Research Site
City
New Brunswick
State/Province
New Jersey
ZIP/Postal Code
08903
Country
United States
Facility Name
Research Site
City
Albuquerque
State/Province
New Mexico
ZIP/Postal Code
87106
Country
United States
Facility Name
Research Site
City
Winston-Salem
State/Province
North Carolina
ZIP/Postal Code
27157
Country
United States
Facility Name
Research Site
City
Germantown
State/Province
Tennessee
ZIP/Postal Code
38138
Country
United States
Facility Name
Research Site
City
Dallas
State/Province
Texas
ZIP/Postal Code
75230
Country
United States
Facility Name
Research Site
City
Salt Lake City
State/Province
Utah
ZIP/Postal Code
84112
Country
United States
Facility Name
Research Site
City
Calgary
State/Province
Alberta
ZIP/Postal Code
T2N 4N2
Country
Canada
Facility Name
Research Site
City
Edmonton
State/Province
Alberta
ZIP/Postal Code
T6G 1Z2
Country
Canada
Facility Name
Research Site
City
Montreal
State/Province
Quebec
ZIP/Postal Code
H3T 1E2
Country
Canada
12. IPD Sharing Statement
Citations:
PubMed Identifier
31409575
Citation
Andtbacka RHI, Amatruda T, Nemunaitis J, Zager JS, Walker J, Chesney JA, Liu K, Hsu CP, Pickett CA, Mehnert JM. Biodistribution, shedding, and transmissibility of the oncolytic virus talimogene laherparepvec in patients with melanoma. EBioMedicine. 2019 Sep;47:89-97. doi: 10.1016/j.ebiom.2019.07.066. Epub 2019 Aug 10.
Results Reference
background
Links:
URL
http://www.amgentrials.com
Description
AmgenTrials clinical trials website
Learn more about this trial
Single-arm Trial to Evaluate the Biodistribution and Shedding of Talimogene Laherparepvec
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