GSK2132231A Antigen-Specific Cancer Immunotherapeutic as First-line Treatment of Patients With Unresectable Metastatic Melanoma
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 125
- 试验地点
- 64
- 主要终点
- One-year Overall Survival Rate (OSR) Estimated by Complete Case Method
研究概览
简要总结
The objective of this study is to evaluate the clinical activity of the GSK2132231A immunotherapeutic in patients with MAGE-A3 positive unresectable metastatic melanoma presenting with the predictive gene signature.
详细描述
In this study, patients were to receive a maximum of 24 doses of recMAGE-A3 + AS15 according four cycles over a period of four years. An active follow-phase (up to five years after registration into the study) was planned for all patients.
As of Amendment 2, there will no longer be an active follow-up of patients after discontinuation or completion of the treatment. The study will end approximately 30 days after the last dose will be administered.
In addition, no more biological samples will be collected for protocol research purposes. For each biological sample already collected in the scope of this study and not tested yet, testing will not be performed by default, except if a scientific rationale remains relevant.
Blood sampling for safety monitoring as per protocol will continue.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Single Group
- 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
- •Male or female patients with histologically proven metastatic cutaneous melanoma that is measurable.
- •Patients with regional or distant cutaneous, subcutaneous or lymph-node metastasis can be included in the study, provided the disease is not amenable to curative treatment with surgery. In terms of the AJCC 2002 classification, this includes patients with unresectable stage III melanoma including in-transit metastases or patient with stage IV M1a melanoma.
- •Written informed consent obtained from the patient prior to performance of any study specific procedure.
- •Patient is >= 18 years at the time of signature of the informed consent form.
- •The patient's tumor shows expression of MAGE-A3, as determined by RT-PCR analysis on a fresh tumor tissue sample obtained during the screening phase.
- •Fresh tissue from the same lesion as used for MAGE-A3 expression testing must be available for the testing of the predictive gene signature.
- •Formalin-fixed paraffin-embedded (FFPE) tissue must be available for complementary MAGE-A3 and gene signature testing.
- •Patient fully recovered from any previous intervention (i.e., biopsy).
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0 or
- •Adequate bone-marrow reserve, adequate renal function and adequate hepatic function as assessed by standard laboratory criteria
- •If the patient is female, she must be of non-childbearing potential, or if she is of childbearing potential, she must practice adequate contraception for at least 30 days prior to registration in the trial, have a negative pregnancy test and continue such precautions during the entire study treatment period and for 2 months after completion of the injection series.
- •In the opinion of the investigator, the patient can and will comply with the protocol requirements.
排除标准
- •Patients with unresectable stage IV M1b,c melanoma and patients with ocular and mucosal melanoma.
- •The patient has at any time received any systemic anticancer treatment.
- •Prior systemic treatment with an immunomodulator or loco-regional radiotherapy is permitted as prior adjuvant treatment provided that the last dose was administered at least 30 days before the registration into this trial;
- •Previous adjuvant treatment with a cancer vaccine containing a tumor antigen other than MAGE-A3 is allowed if the last administration took place at least 8 weeks before registration into the trial.
- •Prior isolated limb perfusion is permitted provided that the last dose was administered at least 30 days before registration into this trial
- •The patient is scheduled to receive any anti-cancer specific treatment, including radiotherapy, other immunotherapy, chemotherapy and immunomodulating agents.
- •The patient requires concomitant chronic treatment (more than 7 consecutive days) with systemic corticosteroids, or any other immunosuppressive agents.
- •The patient has a history of autoimmune disease such as, but not limited to, multiple sclerosis, lupus, and inflammatory bowel disease. Patients with vitiligo are not excluded.
- •The patient has a family history of congenital or hereditary immunodeficiency.
- •The patient is known to be positive for Human Immunodeficiency Virus (HIV).
- •History of allergic disease or reactions likely to be exacerbated by any component of the ASCI treatment.
- •The patient has previous or concomitant malignancies at other sites, except effectively treated non-melanoma skin cancer or carcinoma in situ of the cervix and effectively treated malignancy that has been in remission for over 5 years and is highly likely to have been cured.
- •The patient has psychiatric or addictive disorders
- •The patient has an uncontrolled bleeding disorder.
- •The patient has concurrent severe medical problems, unrelated to the malignancy, that would significantly limit full compliance with the study or expose the patient to unacceptable risk.
- •Use of any investigational or non-registered product (drug or vaccine) other than the study medication within the 30 days preceding the first investigational treatment injection or planned use during the study period.
- •Concurrently participating in another clinical study, at any time during the study period, in which the patient has been or will be exposed to an investigational or a non-investigational product (pharmaceutical product or device). For female patients: the patient is pregnant or lactating.
结局指标
主要结局
One-year Overall Survival Rate (OSR) Estimated by Complete Case Method
时间窗: Month 0 - Month 12
The 1-year overall survival rate (OSR) in the GS+ Population would be above 50% (target = 71%), a percentage which was reported together with its 95% confidence interval (CI). Maximum 1-year OSR of any currently available treatment in the MAGE-A3-positive population = 50% (P0). This median OS of 12 months is based on the observed median OS for MAGE-A3-positive patients, whose tumor did not present the predictive GS. The target 1-year OSR for patients presenting the predictive GS = 71% (P1). This corresponds to a median OS of 24 months when assuming an exponential distribution of OS.
Number of Patients Reported With Serious Adverse Events (SAEs)
时间窗: Month 0 - Month 49
Serious adverse events (SAEs) assessed included medical occurrences that result in death, are life threatening, require hospitalization or prolongation of hospitalization or result in disability/ incapacity. Events which were part of the natural course of the disease under study (i.e., disease progression, recurrence) were captured as part of the clinical activity outcome variables in this study; therefore these did not need to be reported as SAEs. Progression/recurrence of the tumor in a patient was recorded as part of the clinical assessment data collection, and deaths due to progressive disease was recorded on a specific form, but not as an SAE. However, if the investigator considered that there was a causal relationship between treatment or protocol design/procedures and the disease progression/recurrence, then the event was reported as an SAE. Any new primary cancer (non-related to the cancer under study) was reported as an SAE.
次要结局
- Time to Treatment Failure (TTF) by GS(Month 0 - Month 24)
- Duration of Stable Disease (SD), or Time-to-Progression (TTP) by GS(Month 0 - Month 24)
- Anti-MAGE-A3 Antibody Concentrations(PRE = Pre any dose, PII(W4) = Post-Dose 2 (Week 4), PVI(W12) = Post-Dose 6 (Week 12), PXII(W31) = Post-Dose 12 (Week 31), PXVI(W54) = Post-Dose 16 (Week 54), PXVII(M18) = Post-Dose 17 (Month 18), PXXIV(M49) = Post-Dose 24 (Month 49))
- Progression-free Survival (PFS) by GS(Month 0 - Month 24)
- Kaplan-Meier Estimates of the Progression-free Survival (PFS) at Months 6, 12 and 24, by Gene Signature(Month 6, Month 12, Month 24)
- Overall Survival (OS) by GS(Up to 5 years from the time of registration.)
- Number of Seropositive Patients for Protein D(PRE = Pre any dose, PII(W4) = Post-Dose 2 (Week 4), PVI(W12) = Post-Dose 6 (Week 12), PXII(W31) = Post-Dose 12 (Week 31), PXVI(W54) = Post-Dose 16 (Week 54), PXVII(M18) = Post-Dose 17 (Month 18), PXXIV(M49) = Post-Dose 24 (Month 49))
- Number of Patients With Abnormal Platelets (PLT) Values by Maximum Grade(Month 0 - Month 49 (each patient was censored out of the analysis at time of death))
- Number of Patients With Autoimmune Diseases or Immune-mediated Inflammatory Disorders(Month 0 - Month 49)
- Duration of Response (CR or PR)(Month 0 - Month 24)
- Concentrations of Antibodies Against Protein D (Anti-PD)(PRE = Pre any dose, PII(W4) = Post-Dose 2 (Week 4), PVI(W12) = Post-Dose 6 (Week 12), PXII(W31) = Post-Dose 12 (Week 31), PXVI(W54) = Post-Dose 16 (Week 54), PXVII(M18) = Post-Dose 17 (Month 18), PXXIV(M49) = Post-Dose 24 (Month 49))
- Number of Patients With Abnormal Alanine Aminotransferase (ALT) Values by Maximum Grade(Month 0 - Month 49 (each patient was censored out of the analysis at time of death))
- Number of Patients With Abnormal Alkaline Phosphatase (ALK) Values by Maximum Grade(Month 0 - Month 49 (each patient was censored out of the analysis at time of death))
- Number of Patients Reported With Unsolicited AE(s)(Through 30 days after the last administration of the study treatment, approximately 49 months)
- Number of Patients With Diseases Characteristics by GS(Month 0 - Month 49)
- Best Overall Response (BOR) by GS(Month 0 - Month 24)
- Number of Seropositive Patients for Anti-MAGE-A3(PRE = Pre any dose, PII(W4) = Post-Dose 2 (Week 4), PVI(W12) = Post-Dose 6 (Week 12), PXII(W31) = Post-Dose 12 (Week 31), PXVI(W54) = Post-Dose 16 (Week 54), PXVII(M18) = Post-Dose 17 (Month 18), PXXIV(M49) = Post-Dose 24 (Month 49).)
- Anti-MAGE-A3 Antibody Response(PII(W4) = Post-Dose 2 (Week 4), PVI(W12) = Post-Dose 6 (Week 12), PXII(W31) = Post-Dose 12 (Week 31), PXVI(W54) = Post-Dose 16 (Week 54), PXVII(M18) = Post-Dose 17 (Month 18), PXXIV(M49) = Post-Dose 24 (Month 49))
- Anti-PD Antibody Response(PII(W4) = Post-Dose 2 (Week 4), PVI(W12) = Post-Dose 6 (Week 12), PXII(W31) = Post-Dose 12 (Week 31), PXVI(W54) = Post-Dose 16 (Week 54), PXVII(M18) = Post-Dose 17 (Month 18), PXXIV(M49) = Post-Dose 24 (Month 49))
- Number of Patients With Abnormal Aspartate Aminotransferase (AST) Values by Maximum Grade(Month 0 - Month 49 (each patient was censored out of the analysis at time of death))
- Number of Patients With Abnormal Creatinine (CREA) Values by Maximum Grade(Month 0 - Month 49 (each patient was censored out of the analysis at time of death))
- Number of Patients With Abnormal Hemoglobin (HGB) Values by Maximum Grade(Month 0 - Month 49 (each patient was censored out of the analysis at time of death))
- Number of Patients With Abnormal Lymphopenia (LYM) Values by Maximum Grade(Month 0 - Month 49 (each patient was censored out of the analysis at time of death))
- Number of Patients With Abnormal Neutrophils (NEU) Values by Maximum Grade(Month 0 - Month 49 (each patient was censored out of the analysis at time of death))
- Number of Patients With Abnormal Bilirubine (BIL) Values by Maximum Grade(Month 0 - Month 49 (each patient was censored out of the analysis at time of death))
- Number of Patients With Abnormal Leukocytes (LEU) Values by Maximum Grade(Month 0 - Month 49 (each patient was censored out of the analysis at time of death))
- Number of Patients Reported With Unsolicited Adverse Events (AEs) by Maximum Grade.(Through 30 days after the last administration of the study treatment, approximately 49 months)