Clinical trial NCT02211131: Efficacy and Safety of Talimogene Laherparepvec Neoadjuvant Treatment Plus Surgery Versus Surgery Alone for Melanoma
Official title: A Phase 2, Multicenter, Randomized, Open-label Trial Assessing the Efficacy and Safety of Talimogene Laherparepvec Neoadjuvant Treatment Plus Surgery Versus Surgery Alone for Resectable, Stage IIIB to IVM1a Melanoma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Completely Resectable Stage IIIB, IIIC, or IVM1a Melanoma
Lead sponsor: Amgen
Sponsor class: INDUSTRY
First posted: 2014-08-07
Enrollment: 150
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This is a phase 2, multicenter, randomized, open-label study to estimate the efficacy of talimogene laherparepvec as a neoadjuvant treatment followed by surgery compared to surgery alone in subjects with completely resectable stage IIIB, IIIC, or IVM1a melanoma.

Detailed description: This is a phase 2, multicenter, randomized, open-label study to estimate the efficacy of talimogene laherparepvec as a neoadjuvant treatment followed by surgery compared to surgery alone in subjects with completely resectable stage IIIB, IIIC, or IVM1a melanoma.

Arm 1: Talimogene laherparepvec for 6 doses followed by surgical resection of melanoma tumor lesion(s).

Arm 2: Immediate surgical resection of melanoma tumor lesion(s) Following surgery, adjuvant systemic therapy and/or radiotherapy may be administered at the investigator's discretion and per the institutional standard of care.

Subjects will be followed for safety approximately 30 (+15) days after surgery and for disease recurrence, subsequent anticancer therapy, and survival every 3 months (±30 days) for first 3 years after the end of the safety follow-up period and then every 6 months (±30 days) until death, subject withdraws full consent, or up to 5 years after the last subject is randomized.

Eligibility criteria: Inclusion Criteria:

* Histologically confirmed diagnosis of stage IIIB, IIIC or IVM1a melanoma eligible for complete surgical resection.
* Prior systemic, regional and radiation anticancer therapies for melanoma must have been completed at least 3 months prior to randomization.
* Subject must have measurable disease and must be a candidate for intralesional therapy with at least one injectable cutaneous, subcutaneous, or nodal melanoma lesion (≥ 10 mm in longest diameter) or with multiple injectable lesions that in aggregate have a longest diameter of ≥ 10 mm.
* Subject must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 and must have a serum lactate dehydrogenase (LDH) ≤ 1.0 X upper limit of normal and adequate hematologic, hepatic, renal, and coagulation organ function- Other criteria may apply

Exclusion Criteria:

* Subject must not have primary ocular or mucosal melanoma, or history or evidence of melanoma associated with immunodeficiency states (eg, hereditary immune deficiency, organ transplant, or leukemia).
* Subject must not have history or evidence of symptomatic autoimmune pneumonitis, glomerulonephritis, vasculitis, or other symptomatic autoimmune disease.
* Subject must not have evidence of clinically significant immunosuppression or active herpetic skin lesions or prior complications of herpes simplex type 1 (HSV-1) infection (eg, herpetic keratitis or encephalitis) and must not require intermittent or chronic systemic treatment with an antiherpetic drug (eg, acyclovir), other than intermittent topical use.
* Subject known to have acute or chronic active hepatitis B, hepatitis C, or human immunodeficiency virus infection will also be excluded.
* Subject must not have been treated previously with talimogene laherparepvec or tumor vaccine.

Other criteria may apply

Primary outcomes:
measure: Recurrence-Free Survival (RFS)
timeFrame: 24 months after last participant was randomized (data cutoff date of 30 April 2019)
Secondary outcomes:
measure: RFS
timeFrame: 5 years after the last participant was randomized (last subject last visit occurred 28 April 2022)
measure: Kaplan-Meier (K-M) Estimate of RFS Rate at 1 Year, 2 Years, 3 Years, and 5 Years
timeFrame: 5 years after the last participant was randomized (last subject last visit occurred on 28 April 2022)
measure: Histopathology Tumor-Free Margin (R0) Surgical Resection Rate
timeFrame: 18 weeks after last participant randomized (data cutoff date of 30 April 2019)
measure: Pathological Complete Response (pCR) Rate
timeFrame: 18 weeks after last participant randomized (data cutoff date of 30 April 2019)
measure: Local Recurrence-Free Survival (LRFS)
timeFrame: 5 years after the last participant was randomized (last subject last visit occurred on 28 April 2022)
measure: Regional Recurrence-Free Survival (RRFS)
timeFrame: 5 years after the last participant was randomized (last subject last visit occurred on 28 April 2022)
measure: Distant Metastases-Free Survival (DMFS)
timeFrame: 5 years after the last participant was randomized (last subject last visit occurred on 28 April 2022)
measure: Overall Survival (Kaplan-Meier)
timeFrame: 5 years after the last participant was randomized (last subject last visit occurred on 28 April 2022)
measure: Kaplan-Meier Estimate of OS at 1 Year, 2 Years, 3 Years, and 5 Years
timeFrame: 5 years after the last participant was randomized (last subject last visit occurred on 28 April 2022)
measure: Best Overall Tumor Response Per Investigator Response Rate (Talimogene Laherparepvec Arm Only)
timeFrame: 18 months after last participant randomized (data cutoff date of 30 April 2019).
measure: Lesion Objective Response Rate: Injected Lesions (Talimogene Laherparepvec Arm Only)
timeFrame: 18 months after last participant randomized (data cutoff date of 30 April 2019).
measure: Lesion Objective Response Rate: Uninjected Lesions (Talimogene Laherparepvec Arm Only)
timeFrame: 18 months after last participant randomized (data cutoff date of 30 April 2019).
measure: Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), Fatal Adverse Events (AEs), and TEAEs Leading to Discontinuations or Interruptions
timeFrame: Adverse Events are reported from first day of study drug or the surgery through 30 days after the last dose of study drug or 30 days after the surgery, whichever is later. Median duration of treatment was 11.14 weeks (range 0.1 to 12.3 weeks).
measure: Number of Participants With Talimogene Laherparepvec-Related TEAEs, SAEs, Fatal AEs, and TEAEs Leading to Discontinuations or Interruptions
timeFrame: Adverse Events are reported from first day of study drug or the surgery through 30 days after the last administration of talimogene laherparepvec or 30 days after the surgical resection of melanoma tumor lesion(s), whichever is later.
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Research Site
state: Alabama
city: Duarte
country: United States
facility: Research Site
state: California
city: Orange
country: United States
facility: Research Site
state: California
city: San Francisco
country: United States
facility: Research Site
state: California
city: Santa Monica
country: United States
facility: Research Site
state: California
city: Daytona Beach
country: United States
facility: Research Site
state: Florida
city: Gainesville
country: United States
facility: Research Site
state: Florida
city: Tampa
country: United States
facility: Research Site
state: Florida
city: Louisville
country: United States
facility: Research Site
state: Kentucky
city: Worcester
country: United States
facility: Research Site
state: Massachusetts
city: Omaha
country: United States
facility: Research Site
state: Nebraska
city: New Brunswick
country: United States
facility: Research Site
state: New Jersey
city: New York
country: United States
facility: Research Site
state: New York
city: New York
country: United States
facility: Research Site
state: New York
city: Chapel Hill
country: United States
facility: Research Site
state: North Carolina
city: Columbus
country: United States
facility: Research Site
state: Ohio
city: Philadelphia
country: United States
facility: Research Site
state: Pennsylvania
city: Memphis
country: United States
facility: Research Site
state: Tennessee
city: Dallas
country: United States
facility: Research Site
state: Texas
city: Dallas
country: United States
facility: Research Site
state: Texas
city: Houston
country: United States
facility: Research Site
state: Texas
city: Salt Lake City
country: United States
facility: Research Site
state: Utah
city: North Sydney
country: Australia
facility: Research Site
state: New South Wales
city: Woodville South
country: Australia
facility: Research Site
state: South Australia
city: Heidelberg
country: Australia
facility: Research Site
state: Victoria
city: Florianopolis
country: Brazil
facility: Research Site
state: Santa Catarina
city: Barretos
country: Brazil
facility: Research Site
state: São Paulo
city: Rio de Janeiro
country: Brazil
facility: Research Site
city: Dijon
country: France
facility: Research Site
city: Marseille cedex 05
country: France
facility: Research Site
city: Paris
country: France
facility: Research Site
city: Pierre Benite Cedex
country: France
facility: Research Site
city: Toulouse cedex 9
country: France
facility: Research Site
city: Athens
country: Greece
facility: Research Site
city: Heraklion - Crete
country: Greece
facility: Research Site
city: Poznan
country: Poland
facility: Research Site
city: Warszawa
country: Poland
facility: Research Site
city: Wroclaw
country: Poland
facility: Research Site
city: Moscow
country: Russian Federation
facility: Research Site
city: Saint-Petersburg
country: Russian Federation
facility: Research Site
city: Saint-Petersburg
country: Russian Federation
facility: Research Site
city: Malaga
country: Spain
facility: Research Site
state: Andalucía
city: Pamplona
country: Spain
facility: Research Site
state: Navarra
city: Madrid
country: Spain
facility: Research Site
city: Chur
country: Switzerland
facility: Research Site
city: Zürich
country: Switzerland
facility: Research Site
Study officials:
affiliation: Amgen
name: MD
role: STUDY_DIRECTOR
References:
citation: Dummer R, Gyorki DE, Hyngstrom J, Berger AC, Conry R, Demidov L, Sharma A, Treichel SA, Radcliffe H, Gorski KS, Anderson A, Chan E, Faries M, Ross MI. Neoadjuvant talimogene laherparepvec plus surgery versus surgery alone for resectable stage IIIB-IVM1a melanoma: a randomized, open-label, phase 2 trial. Nat Med. 2021 Oct;27(10):1789-1796. doi: 10.1038/s41591-021-01510-7. Epub 2021 Oct 4.