Overview

This trial is active, not recruiting.

Condition melanoma
Treatment talimogene laherparepvec
Phase phase 2
Target filgrastim
Sponsor Amgen
Start date April 2014
End date January 2016
Trial size 61 participants
Trial identifier NCT02014441, 20120324

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.

United States No locations recruiting
Other countries No locations recruiting

Study Design

Intervention model single group assignment
Primary purpose treatment
Masking no masking
Arm
(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.
talimogene laherparepvec IMLYGIC®
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 Outcomes

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).

Secondary Outcomes

Measure
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
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
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
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
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
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
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
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
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
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 37) 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
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 37) 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
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 37) 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
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 Anogenital Area With Detectable Talimogene Laherparepvec DNA
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 37) 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
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 37) 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
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 37) 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
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 After the End of Treatment
time frame: 30 to 60 days after the last dose of talimogene laherparepvec.
Percentage of Samples From Oral Mucosa With Detectable Talimogene Laherparepvec Virus After the End of Treatment
time frame: 30 to 60 days after the last dose of talimogene laherparepvec.
Percentage of Participants With Detectable Talimogene Laherparepvec DNA in Oral Mucosa After the End of Treatment
time frame: 30 to 60 days after the last dose of talimogene laherparepvec.
Percentage of Participants With Detectable Talimogene Laherparepvec Virus in Oral Mucosa After the End of Treatment
time frame: 30 to 60 days after the last dose of talimogene laherparepvec.
Percentage of Samples From the Anogenital Area With Detectable Talimogene Laherparepvec DNA After the End of Treatment
time frame: 30 to 60 days after the last dose of talimogene laherparepvec.
Percentage of Samples From the Anogenital Area With Detectable Talimogene Laherparepvec Virus After the End of Treatment
time frame: 30 to 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: 30 to 60 days after the last dose of talimogene laherparepvec.
Percentage of Participants With Detectable Talimogene Laherparepvec Virus in Swabs From the Anogenital Area After the End of Treatment
time frame: 30 to 60 days after the last dose of talimogene laherparepvec.
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 21.0 weeks (range: 3 to 73 weeks).
Best Overall Response
time frame: Tumor response was assessed at weeks 12 and 24 and then at least every 3 months up to 6 months after end of treatment; median actual follow-up time was 21.0 weeks (range: 3 to 73 weeks).
Objective Response Rate
time frame: Tumor response was assessed at weeks 12 and 24 and thenat least every 3 months up to 6 months after end of treatment; The median actual follow-up time was 21.0 weeks (range: 3 to 73 weeks).
Time to Response
time frame: Tumor response was assessed at weeks 12 and 24 and then at least every 3 months up to 6 months after end of treatment; The median actual follow-up time was 21.0 weeks (range: 3 to 73 weeks).
Duration of Response
time frame: Tumor response was assessed at weeks 12 and 24 and then at least every 3 months up to 6 months after end of treatment; The median actual follow-up time was 21.0 weeks (range: 3 to 73 weeks).
Durable Response Rate
time frame: Tumor response was assessed at weeks 12 and 24 and then at least every 3 months up to 6 months after end of treatment; The median actual follow-up time was 21.0 weeks (range: 3 to 73 weeks).
Overall Survival
time frame: From first dose of talimogene laherparepvec up to the data cut-off date. The median actual follow-up time was 21.0 weeks (range: 3 to 73 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 treatment duration was 21.1 weeks.

Eligibility Criteria

All participants from 18 years up to 100 years old.

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.

Additional Information

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
Trial information was received from ClinicalTrials.gov and was last updated in February 2017.
Information provided to ClinicalTrials.gov by Amgen.