MelanomaPhase 2NCT02014441
Single-arm Trial to Evaluate the Biodistribution and Shedding of Talimogene Laherparepvec
A Phase 2 study testing Talimogene laherparepvec in people with Melanoma, run by Amgen at 14 sites in 2 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 100 years
- Conditions the study is for
- Melanoma
- What is being tested?
- Talimogene laherparepvec
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 61 participants
- Where
- 14 sitesin 2 countries
- Study dates
- 7 Apr 2014to 19 Apr 2018
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 100 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
Trial locations and contacts
14 sites in 2 countries.
14 sites in 2 countries
United States11 sites
Research Site
Albuquerque, New Mexico, 87106
Research Site
Dallas, Texas, 75230
Research Site
Fridley, Minnesota, 55432
Research Site
Germantown, Tennessee, 38138
Research Site
Indianapolis, Indiana, 46202
Research Site
Louisville, Kentucky, 40202
Research Site
Minneapolis, Minnesota, 55407
Research Site
New Brunswick, New Jersey, 08903
Research Site
Salt Lake City, Utah, 84112
Research Site
Tampa, Florida, 33612
Research Site
Winston-Salem, North Carolina, 27157
Canada3 sites
Research Site
Calgary, Alberta, T2N 4N2
Research Site
Edmonton, Alberta, T6G 1Z2
Research Site
Montreal, Quebec, H3T 1E2
About this study
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
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.
- Conditions
- Melanoma
- Being tested
- Talimogene laherparepvec
- Medical subject headings
- Melanoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Talimogene laherparepvecDrug
Also called IMLYGIC®, OncoVEX^GM-CSF
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.
| Study group | Role | What they receive |
|---|---|---|
| Talimogene Laherparepvec | Experimental | 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. Receives: Drug: Talimogene laherparepvec |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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 outcomes (34)
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.
Measured: 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).
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.
Measured: 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).
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.
Measured: 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).
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.
Measured: 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).
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.
Measured: 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).
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.
Measured: 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).
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.
Measured: 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).
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.
Measured: 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).
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.
Measured: 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).
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.
Measured: 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).
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.
Measured: 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.
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.
Measured: 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.
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.
Measured: 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.
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.
Measured: 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.
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.
Measured: 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.
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.
Measured: 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.
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.
Measured: 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.
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.
Measured: 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.
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.
Measured: From 30 to 60 days after the last dose of talimogene laherparepvec (the median [minimum, maximum] duration of treatment was 23 [3, 141] weeks).
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.
Measured: From 30 to 60 days after the last dose of talimogene laherparepvec (the median [minimum, maximum] duration of treatment was 23 [3, 141] weeks).
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.
Measured: From 30 to 60 days after the last dose of talimogene laherparepvec (the median [minimum, maximum] duration of treatment was 23 [3, 141] weeks).
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.
Measured: From 30 to 60 days after the last dose of talimogene laherparepvec (the median [minimum, maximum] duration of treatment was 23 [3, 141] weeks).
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.
Measured: From 30 to 60 days after the last dose of talimogene laherparepvec (the median [minimum, maximum] duration of treatment was 23 [3, 141] weeks).
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.
Measured: 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.
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.
Measured: From 30 to 60 days after the last dose of talimogene laherparepvec (the median [minimum, maximum] duration of treatment was 23 [3, 141] weeks).
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.
Measured: From 30 to 60 days after the last dose of talimogene laherparepvec (the median [minimum, maximum] duration of treatment was 23 [3, 141] weeks).
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.
Measured: 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).
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.
Measured: 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).
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.
Measured: 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).
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.
Measured: 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).
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.
Measured: 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).
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.
Measured: 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).
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.
Measured: 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).
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.
Measured: 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).
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Dec 2013 (estimated)
- Study start7 Apr 2014
- Primary completion25 Jan 2016
- Study completion19 Apr 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for MelanomaStudies of the same condition, open and under way.
- More trials run by AmgenThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 61 participants (actual)
Sponsor and investigators
- Lead sponsor
- Amgen
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- MD, Study director, Amgen
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02014441
- Sponsor's protocol ID
- 20120324
- Status last verified
- Nov 2019
- First submitted
- 22 Nov 2013
- Last updated
- 20 Nov 2019
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Publications
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.
PubMed 31409575
Study at a glance
From the registry record, last updated by the sponsor on 20 Nov 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT02014441
- Acronym / sponsor ID
- 20120324
- Conditions
- Melanoma
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 61 participants (actual)
- Lead sponsor
- AmgenIndustry (pharma, biotech, devices)
- Study start
- 7 Apr 2014 (actual)
- Primary completion
- 25 Jan 2016 (actual)
- Study completion
- 19 Apr 2018 (actual)
- First posted
- 18 Dec 2013 (estimated)
- Results
- Posted 14 Feb 2017
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Talimogene Laherparepvec | Experimental | Drug: Talimogene laherparepvecTalimogene 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. |
Who may qualify
- Ages
- 18 to 100 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (1 listed)
- 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 (1 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Talimogene laherparepvecAlso: IMLYGIC®, OncoVEX^GM-CSFTalimogene 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. | Drug | Talimogene Laherparepvec |
Primary outcome
Percentage of Participants With Detectable Talimogene Laherparepvec Deoxyribonucleic Acid (DNA) During the First Three Cycles
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).
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.
34 secondary outcomes
Percentage of Participants With Clearance of Talimogene Laherparepvec DNA From Blood
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).
Percentage of Participants With Clearance of Talimogene Laherparepvec DNA From Urine
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).
Percentage of Samples With Detectable Talimogene Laherparepvec DNA on the Exterior of the Occlusive Dressing During the First Three Cycles
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).
Percentage of Samples With Detectable Talimogene Laherparepvec Virus on the Exterior of the Occlusive Dressing During the First Three Cycles
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).
Percentage of Participants With Detectable Talimogene Laherparepvec DNA on the Exterior of the Occlusive Dressing During the First Three Cycles
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).
Percentage of Participants With Detectable Talimogene Laherparepvec Virus on the Exterior of the Occlusive Dressing During the First Three Cycles
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).
Percentage of Samples From the Surface of Injected Lesions With Detectable Talimogene Laherparepvec DNA During the First Three Cycles
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).
Percentage of Samples From the Surface of Injected Lesions With Detectable Talimogene Laherparepvec Virus During the First Three Cycles
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).
Percentage of Participants With Detectable Talimogene Laherparepvec DNA on the Surface of Injected Lesions During the First Three Cycles
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).
Percentage of Participants With Detectable Talimogene Laherparepvec Virus on the Surface of Injected Lesions During the First Three Cycles
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).
Percentage of Samples From Oral Mucosa With Detectable Talimogene Laherparepvec DNA During Treatment
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.
Percentage of Samples From Oral Mucosa With Detectable Talimogene Laherparepvec Virus During Treatment
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.
Percentage of Participants With Detectable Talimogene Laherparepvec DNA in Oral Mucosa During Treatment
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.
Percentage of Participants With Detectable Talimogene Laherparepvec Virus in Oral Mucosa During Treatment
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.
Percentage of Samples From the Anogenital Area With Detectable Talimogene Laherparepvec DNA During Treatment
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.
Percentage of Samples With Detectable Talimogene Laherparepvec Virus in Swabs From the Anogenital Area During Treatment
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.
Percentage of Participants With Detectable Talimogene Laherparepvec DNA in Swabs From the Anogenital Area During Treatment
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.
Percentage of Participants With Detectable Talimogene Laherparepvec Virus in Swabs From the Anogenital Area During Treatment
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.
Percentage of Samples From Oral Mucosa With Detectable Talimogene Laherparepvec DNA After the End of Treatment
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).
Percentage of Samples From Oral Mucosa With Detectable Talimogene Laherparepvec Virus After the End of Treatment
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).
Percentage of Participants With Detectable Talimogene Laherparepvec DNA in Oral Mucosa After the End of Treatment
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).
Percentage of Participants With Detectable Talimogene Laherparepvec Virus in Oral Mucosa After the End of Treatment
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).
Percentage of Samples From the Anogenital Area With Detectable Talimogene Laherparepvec DNA After the End of Treatment
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).
Percentage of Samples From the Anogenital Area With Detectable Talimogene Laherparepvec Virus After the End of Treatment
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.
Percentage of Participants With Detectable Talimogene Laherparepvec DNA in Swabs From the Anogenital Area After the End of Treatment
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).
Percentage of Participants With Detectable Talimogene Laherparepvec Virus in Swabs From the Anogenital Area After the End of Treatment
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).
Number of Samples With Detectable Talimogene Laherparepvec in Lesions Suspected to be Herpetic in Origin
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).
Best Overall Response
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).
Objective Response Rate
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).
Time to Response
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).
Duration of Response
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).
Durable Response Rate
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).
Overall Survival
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).
Number of Participants With Adverse Events (AEs)
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).
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Nov 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 31409575Andtbacka 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.
- AmgenTrials clinical trials websiteLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
MD study director
Amgen
14 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Talimogene laherparepvec in people with Melanoma, run by Amgen at 14 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 1 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 20 Nov 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 14 sites in United States, Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 14 Feb 2017). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Percentage of Participants With Detectable Talimogene Laherparepvec Deoxyribonucleic Acid (DNA) During the First Three Cycles (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).). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02014441, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 Nov 2019.