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
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- Amgen
- 入组人数
- 150
- 试验地点
- 1
- 主要终点
- Recurrence-Free Survival (RFS)
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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
研究组 & 干预措施
Surgery
Surgical resection of melanoma tumor lesion(s)
干预措施: Immediate surgical resection of melanoma lesion(s) (Procedure)
Talimogene Laherparepvec
Talimogene laherparepvec for 6 doses followed by surgical resection of melanoma tumor lesion(s).
干预措施: Talimogene Laherparepvec (Drug)
结局指标
主要结局
Recurrence-Free Survival (RFS)
时间窗: 24 months after last participant was randomized (data cutoff date of 30 April 2019)
Recurrence free survival (RFS) is defined as the time from randomization to the date of event, and is presented as a Kaplan Meier estimate of time to events. The event for RFS is defined as the first of local, regional, or distant recurrence of melanoma or death due to any cause. Participants without a histopathology tumor-free margin (R0) surgical outcome or those who withdrew prior to surgery were considered an event at randomization. Participants without an event were censored at their last evaluable tumor assessment.
次要结局
- RFS(5 years after the last participant was randomized (last subject last visit occurred 28 April 2022))
- Histopathology Tumor-Free Margin (R0) Surgical Resection Rate(18 weeks after last participant randomized (data cutoff date of 30 April 2019))
- Kaplan-Meier (K-M) Estimate of RFS Rate at 1 Year, 2 Years, 3 Years, and 5 Years(5 years after the last participant was randomized (last subject last visit occurred on 28 April 2022))
- Pathological Complete Response (pCR) Rate(18 weeks after last participant randomized (data cutoff date of 30 April 2019))
- Local Recurrence-Free Survival (LRFS)(5 years after the last participant was randomized (last subject last visit occurred on 28 April 2022))
- Regional Recurrence-Free Survival (RRFS)(5 years after the last participant was randomized (last subject last visit occurred on 28 April 2022))
- Distant Metastases-Free Survival (DMFS)(5 years after the last participant was randomized (last subject last visit occurred on 28 April 2022))
- Overall Survival (Kaplan-Meier)(5 years after the last participant was randomized (last subject last visit occurred on 28 April 2022))
- Kaplan-Meier Estimate of OS at 1 Year, 2 Years, 3 Years, and 5 Years(5 years after the last participant was randomized (last subject last visit occurred on 28 April 2022))
- Best Overall Tumor Response Per Investigator Response Rate (Talimogene Laherparepvec Arm Only)(18 months after last participant randomized (data cutoff date of 30 April 2019).)
- Lesion Objective Response Rate: Injected Lesions (Talimogene Laherparepvec Arm Only)(18 months after last participant randomized (data cutoff date of 30 April 2019).)
- Lesion Objective Response Rate: Uninjected Lesions (Talimogene Laherparepvec Arm Only)(18 months after last participant randomized (data cutoff date of 30 April 2019).)
- Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), Fatal Adverse Events (AEs), and TEAEs Leading to Discontinuations or Interruptions(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).)
- Number of Participants With Talimogene Laherparepvec-Related TEAEs, SAEs, Fatal AEs, and TEAEs Leading to Discontinuations or Interruptions(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.)