Clinical trial NCT02014441: 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
Overall status: COMPLETED
Phase: PHASE2
Conditions: Melanoma
Lead sponsor: Amgen
Sponsor class: INDUSTRY
First posted: 2013-12-18
Enrollment: 61
Sex: ALL
Minimum age (years): 18
Maximum age (years): 100
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


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.

Primary outcomes:
measure: Percentage of Participants With Detectable Talimogene Laherparepvec Deoxyribonucleic Acid (DNA) During the First Three Cycles
timeFrame: 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:
measure: Percentage of Participants With Clearance of Talimogene Laherparepvec DNA From Blood
timeFrame: 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).
measure: Percentage of Participants With Clearance of Talimogene Laherparepvec DNA From Urine
timeFrame: 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).
measure: Percentage of Samples With Detectable Talimogene Laherparepvec DNA on the Exterior of the Occlusive Dressing During the First Three Cycles
timeFrame: 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).
measure: Percentage of Samples With Detectable Talimogene Laherparepvec Virus on the Exterior of the Occlusive Dressing During the First Three Cycles
timeFrame: 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).
measure: Percentage of Participants With Detectable Talimogene Laherparepvec DNA on the Exterior of the Occlusive Dressing During the First Three Cycles
timeFrame: 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).
measure: Percentage of Participants With Detectable Talimogene Laherparepvec Virus on the Exterior of the Occlusive Dressing During the First Three Cycles
timeFrame: 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).
measure: Percentage of Samples From the Surface of Injected Lesions With Detectable Talimogene Laherparepvec DNA During the First Three Cycles
timeFrame: 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).
measure: Percentage of Samples From the Surface of Injected Lesions With Detectable Talimogene Laherparepvec Virus During the First Three Cycles
timeFrame: 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).
measure: Percentage of Participants With Detectable Talimogene Laherparepvec DNA on the Surface of Injected Lesions During the First Three Cycles
timeFrame: 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).
measure: Percentage of Participants With Detectable Talimogene Laherparepvec Virus on the Surface of Injected Lesions During the First Three Cycles
timeFrame: 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).
measure: Percentage of Samples From Oral Mucosa With Detectable Talimogene Laherparepvec DNA During Treatment
timeFrame: 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.
measure: Percentage of Samples From Oral Mucosa With Detectable Talimogene Laherparepvec Virus During Treatment
timeFrame: 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.
measure: Percentage of Participants With Detectable Talimogene Laherparepvec DNA in Oral Mucosa During Treatment
timeFrame: 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.
measure: Percentage of Participants With Detectable Talimogene Laherparepvec Virus in Oral Mucosa During Treatment
timeFrame: 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.
measure: Percentage of Samples From the Anogenital Area With Detectable Talimogene Laherparepvec DNA During Treatment
timeFrame: 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.
measure: Percentage of Samples With Detectable Talimogene Laherparepvec Virus in Swabs From the Anogenital Area During Treatment
timeFrame: 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.
measure: Percentage of Participants With Detectable Talimogene Laherparepvec DNA in Swabs From the Anogenital Area During Treatment
timeFrame: 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.
measure: Percentage of Participants With Detectable Talimogene Laherparepvec Virus in Swabs From the Anogenital Area During Treatment
timeFrame: 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.
measure: Percentage of Samples From Oral Mucosa With Detectable Talimogene Laherparepvec DNA After the End of Treatment
timeFrame: From 30 to 60 days after the last dose of talimogene laherparepvec (the median [minimum, maximum] duration of treatment was 23 [3, 141] weeks).
measure: Percentage of Samples From Oral Mucosa With Detectable Talimogene Laherparepvec Virus After the End of Treatment
timeFrame: From 30 to 60 days after the last dose of talimogene laherparepvec (the median [minimum, maximum] duration of treatment was 23 [3, 141] weeks).
measure: Percentage of Participants With Detectable Talimogene Laherparepvec DNA in Oral Mucosa After the End of Treatment
timeFrame: From 30 to 60 days after the last dose of talimogene laherparepvec (the median [minimum, maximum] duration of treatment was 23 [3, 141] weeks).
measure: Percentage of Participants With Detectable Talimogene Laherparepvec Virus in Oral Mucosa After the End of Treatment
timeFrame: From 30 to 60 days after the last dose of talimogene laherparepvec (the median [minimum, maximum] duration of treatment was 23 [3, 141] weeks).
measure: Percentage of Samples From the Anogenital Area With Detectable Talimogene Laherparepvec DNA After the End of Treatment
timeFrame: From 30 to 60 days after the last dose of talimogene laherparepvec (the median [minimum, maximum] duration of treatment was 23 [3, 141] weeks).
measure: Percentage of Samples From the Anogenital Area With Detectable Talimogene Laherparepvec Virus After the End of Treatment
timeFrame: 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.
measure: Percentage of Participants With Detectable Talimogene Laherparepvec DNA in Swabs From the Anogenital Area After the End of Treatment
timeFrame: From 30 to 60 days after the last dose of talimogene laherparepvec (the median [minimum, maximum] duration of treatment was 23 [3, 141] weeks).
measure: Percentage of Participants With Detectable Talimogene Laherparepvec Virus in Swabs From the Anogenital Area After the End of Treatment
timeFrame: From 30 to 60 days after the last dose of talimogene laherparepvec (the median [minimum, maximum] duration of treatment was 23 [3, 141] weeks).
measure: Number of Samples With Detectable Talimogene Laherparepvec in Lesions Suspected to be Herpetic in Origin
timeFrame: 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).
measure: Best Overall Response
timeFrame: 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).
measure: Objective Response Rate
timeFrame: 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).
measure: Time to Response
timeFrame: 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).
measure: Duration of Response
timeFrame: 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).
measure: Durable Response Rate
timeFrame: 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).
measure: Overall Survival
timeFrame: 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).
measure: Number of Participants With Adverse Events (AEs)
timeFrame: 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).
Other outcomes:
Locations:
city: Tampa
country: United States
facility: Research Site
state: Florida
city: Indianapolis
country: United States
facility: Research Site
state: Indiana
city: Louisville
country: United States
facility: Research Site
state: Kentucky
city: Fridley
country: United States
facility: Research Site
state: Minnesota
city: Minneapolis
country: United States
facility: Research Site
state: Minnesota
city: New Brunswick
country: United States
facility: Research Site
state: New Jersey
city: Albuquerque
country: United States
facility: Research Site
state: New Mexico
city: Winston-Salem
country: United States
facility: Research Site
state: North Carolina
city: Germantown
country: United States
facility: Research Site
state: Tennessee
city: Dallas
country: United States
facility: Research Site
state: Texas
city: Salt Lake City
country: United States
facility: Research Site
state: Utah
city: Calgary
country: Canada
facility: Research Site
state: Alberta
city: Edmonton
country: Canada
facility: Research Site
state: Alberta
city: Montreal
country: Canada
facility: Research Site
state: Quebec
Study officials:
affiliation: Amgen
name: MD
role: STUDY_DIRECTOR
References:
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.