A Phase I/II Study of Pembrolizumab (MK-3475) in Children With Advanced Melanoma or a PD-L1 Positive Advanced, Relapsed or Refractory Solid Tumor or Lymphoma (KEYNOTE-051)
概览
- 阶段
- 1 期
- 干预措施
- Pembrolizumab
- 疾病 / 适应症
- Melanoma
- 发起方
- Merck Sharp & Dohme LLC
- 入组人数
- 370
- 试验地点
- 28
- 主要终点
- ORR by RECIST 1.1 per Site Assessment for MSI-H or TMBH Solid Tumors (Each Cohort Evaluated Separately)
- 状态
- 招募中
- 最后更新
- 上个月
概览
简要总结
Researchers are looking for new ways to treat children with different types of melanoma (skin cancer), solid tumors, and lymphomas (blood cancers) that are any of these:
- Advanced, which means cancer spread in the body or cannot be removed with surgery
- Relapsed, which means cancer has come back after it had responded to previous treatment (responded means it stopped growing, gets smaller, or disappeared)
- Refractory, which means cancer did not respond to previous treatment
Pembrolizumab is an immunotherapy, which is a treatment that helps the immune system fight cancer. Researchers want to learn if different doses of pembrolizumab can cause at least 1 of the types of cancer to get smaller or go away.
With Amendment 8, enrolment of participants with solid tumours and participants 6 months to under 12 years old with melanoma were closed. Enrolment of participants 12-18 years old with melanoma continues. Enrolment of participants who have tumours with specific traits (microsatellite-instability-high (MSI-H), and tumour-mutational burden-high ≥10 mutation/Mb (TMB-H)) also continues.
研究者
入排标准
入选标准
- •Between 6 months and \<18 years of age on day of signing informed consent is documented.
- •Histologically- or cytologically-documented, locally-advanced, or metastatic solid malignancy or lymphoma that is incurable and has failed prior standard therapy, or for which no standard therapy exists, or for which no standard therapy is considered appropriate
- •Any number of prior treatment regimens
- •Tissue (or lymph node biopsy for rrcHL participants) available from an archival tissue sample or, if appropriate, a newly obtained core or excisional biopsy of a tumor lesion not previously irradiated
- •Advanced melanoma or PD-L1-positive advanced, relapsed, or refractory solid tumor or lymphoma
- •Measurable disease based on RECIST 1.1 (Or based on IWG \[Cheson, 2007\] \[i.e., measurement must be \>15 mm in longest diameter or \>10 mm in short axis\] for rrcHL participants)
- •Participants with neuroblastoma with only metaiodobenzylguanidine (MIBG)-positive evaluable disease may be enrolled
- •Lansky Play Scale ≥50 for participants from 6 months up to and including 16 years of age; or Karnofsky score ≥50 for participants \>16 years of age
- •Adequate organ function
- •Female participants of childbearing potential should have a negative urine or serum pregnancy test within 72 hours before the first dose of study medication
排除标准
- •Currently participating and receiving study therapy in, or has participated in a study of an investigational agent and received study therapy or used an investigational device within 4 weeks of the date of allocation/randomization
- •Diagnosis of immunodeficiency or receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the date of allocation/randomization
- •Prior systemic anti-cancer therapy including investigational agent within 2 weeks prior to study Day 1 or not recovered from adverse events due to a previously administered agent
- •Prior radiotherapy within 2 weeks of start of study treatment
- •Known additional malignancy that is progressing or requires active treatment with the exception of basal cell carcinoma of the skin, squamous cell carcinoma of the skin or carcinoma in situ (eg, breast carcinoma, cervical carcinoma in situ) with potentially curative therapy, or in situ cervical cancer
- •Known active central nervous system (CNS) metastases and/or carcinomatous meningitis
- •Tumor(s) involving the brain stem
- •Severe hypersensitivity (≥ Grade 3) to pembrolizumab and/or any of its excipients
- •Active autoimmune disease that has required systemic treatment in past 2 years; replacement therapy (such as thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is acceptable
- •Has a history of (non-infectious) pneumonitis that required steroids or current pneumonitis.
研究组 & 干预措施
Melanoma
Participants aged 6 months to \<18 years with melanoma receive pembrolizumab, starting dose 2 mg/kg (maximum dose 200 mg), intravenously (IV) once every 3 weeks (Q3W). Enrollment of participants aged 6 months to \<12 years with melanoma was closed with Amendment 8. Enrollment of participants aged ≥12 years to ≤18 years with melanoma continues.
干预措施: Pembrolizumab
Solid Tumors and Other Lymphomas
Participants aged 6 months to \<18 years with solid tumors and other lymphomas receive pembrolizumab, starting dose 2 mg/kg (maximum dose 200 mg), IV Q3W. Initial enrollment limited to programmed death-ligand 1 (PD-L1)-positive participants. PD-L1-negative participants may enroll if responses are observed. Enrollment of participants with solid tumors and other lymphomas was closed with Amendment 8.
干预措施: Pembrolizumab
rrcHL
Participants aged 3 years to \<18 years with rrcHL receive pembrolizumab, starting dose 2 mg/kg (maximum dose 200 mg), IV Q3W.
干预措施: Pembrolizumab
MSI-H
Participants aged 6 months to \<18 years with microsatellite-instability-high (MSI-H) solid tumors receive pembrolizumab, starting dose 2 mg/kg (maximum dose 200 mg), IV Q3W.
干预措施: Pembrolizumab
TMB-H
Participants aged 6 months to \<18 years with tumor-mutational burden-high ≥10 mutation/Mb (TMB-H) solid tumors receive pembrolizumab, starting dose 2 mg/kg (maximum dose 200 mg), IV Q3W.
干预措施: Pembrolizumab
Adjuvant Melanoma
Participants aged 12 years to \<18 years with resected high-risk Stage IIB, IIC, III, or IV melanoma receive pembrolizumab, starting dose 2 mg/kg (maximum dose 200 mg), intravenously (IV) once every 3 weeks (Q3W).
干预措施: Pembrolizumab
结局指标
主要结局
ORR by RECIST 1.1 per Site Assessment for MSI-H or TMBH Solid Tumors (Each Cohort Evaluated Separately)
时间窗: Up to 2 years
The ORR is assessed by RECIST 1.1 per site assessment. The ORR is defined as the percentage of participants who have a response (complete response, CR or partial response, PR) prior to disease progression. Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm. Partial Response (PR): At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.
Number of Participants Experiencing Adverse Events (AEs)
时间窗: Up to 27 months
An adverse event (AE) is defined as any unfavorable and unintended sign including an abnormal laboratory finding, symptom or disease associated with the use of a medical treatment or procedure, regardless of whether it is considered related to the medical treatment or procedure, that occurs during the course of the study.
ORR by International Working Group (IWG) Response Criteria (Cheson, 2007) per BICR Assessment for rrcHL Cohort
时间窗: Up to approximately 2 years
The ORR is assessed by blinded independent central review utilizing the International Working Group \[IWG\] response assessment criteria per Cheson 2007 by BICR. The ORR is defined as the percentage of participants who have a response (complete response, CR or partial response, PR) prior to disease progression. CR is the disappearance of all evidence of disease and PR is the regression of measurable disease and no new sites. Participants with missing data are considered non-responders.
Objective Response Rate (ORR) by Response Evaluation Criteria in Solid Tumors and Other Lymphoma Version 1.1 (RECIST 1.1) per Site Assessment (Each Disease Indication Evaluated Separately)
时间窗: Up to 2 years
The ORR is assessed by RECIST 1.1 per site assessment. The ORR is defined as the percentage of participants who have a response (complete response, CR or partial response, PR) prior to disease progression. Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm. Partial Response (PR): At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.
Number of Participants with Dose-Limiting Toxicities (DLTs)
时间窗: Cycle 1 (Up to 21 days)
Number of participants experiencing toxicities that are possibly, probably, or definitely related to study therapy; that meet pre-defined severity criteria; and result in a change in the given dose.
Number of Participants Discontinuing Study Drug Due to AEs
时间窗: Up to 2 years
An adverse event (AE) is defined as any unfavorable and unintended sign including an abnormal laboratory finding, symptom or disease associated with the use of a medical treatment or procedure, regardless of whether it is considered related to the medical treatment or procedure, that occurs during the course of the study.
次要结局
- ORR by IWG Response Criteria (Cheson, 2007) per Site Assessment (rrcHL Cohort)(Up to 2 years)
- DOR per IWG 2007 (Cheson, 2007) Response by Site Assessment (rrcHL Cohort)(Up to approximately 2 years)
- PFS using IWG 2007 Criteria (Chesson 2007) by BICR Assessment (rrcHL Cohort)(Up to approximately 2 years)
- PFS using IWG 2007 Criteria (Chesson, 2007) by Site Assessment (rrcHL Cohort)(Up to approximately 2 years)
- Overall Survival(Up to approximately 2 years)
- DOR per Immune-related Response Evaluation Criteria in Solid Tumors (irRECIST) by Site Assessment (MSI-H and TMB-H, Each Cohort Is Evaluated Separately)(Up to approximately 2 years)
- PFS using RECIST 1.1 Criteria by Site Assessment (MSI-H and TMB-H, Each Cohort Evaluated Separately)(Up to approximately 2 years)
- Disease Control Rate by RECIST 1.1 Using Site Assessment (Solid Tumors and Other Lymphoma, Each Disease Indication Evaluated Separately)(Up to approximately 2 years)
- Objective irRECIST Response Rate by Site Assessment (Each Disease Indication Evaluated Separately)(Up to approximately 2 years)
- DOR per RECIST 1.1 by Site Assessment (Advanced Melanoma, Solid Tumors and Other Lymphoma, Each Disease Indication Is Evaluated Separately)(Up to approximately 2 years)
- DOR per IWG 2007 (Cheson, 2007) Response by BICR Assessment (rrcHL Cohort)(Up to approximately 2 years)
- DOR per Immune-related Response Evaluation Criteria in Solid Tumors (irRECIST) by Site Assessment (Solid Tumors and Other Lymphoma, Each Disease Indication Evaluated Separately)(Up to approximately 2 years)
- Disease Control Rate by irRECIST Using Site Assessment (Solid Tumors and Other Lymphomas, Each Disease Indication Evaluated Separately)(Up to approximately 2 years)
- Area Under the Concentration Curve (AUC) for Pembrolizumab(Predose Cycles 1, 2, 4, 8 and every 4 cycles thereafter, and within 30 minutes post infusion at Cycles 1 and 8. Additional single pharmacokinetic samples obtained in Cycle 1 between 72 to 168 hours post-dose, and Cycle 1 at 336 hours post-dose)
- DOR per RECIST 1.1 by Site Assessment (MSI-H and TMBH, Each Cohort Is Evaluated Separately)(Up to approximately 2 years)
- Progression-free Survival (PFS) Using RECIST 1.1 Criteria by Site Assessment (Solid Tumors and Other Lymphoma, Each Disease Indication Evaluated Separately)(Up to approximately 2 years)
- PFS Using irRECIST Criteria by Site Assessment(Up to approximately 2 years)
- Disease Control Rate by RECIST 1.1 Using Site Assessment (MSIH and TMB-H, Each Cohort Evaluated Separately)(Up to approximately 2 years)