An Open-label, Phase 2 Basket Study of SEA-CD40 Combination Therapies in Advanced Malignancies
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- Seagen Inc.
- 入组人数
- 77
- 试验地点
- 29
- 主要终点
- Confirmed Objective Response Rate (cORR) According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) Per Investigator Assessment
研究概览
简要总结
This trial is being done to see if an experimental drug (SEA-CD40) works when it's given with other cancer drugs to treat some types of cancer. It will also study side effects from the drug.
There are 2 parts in this trial. In one part, participants have melanoma that has come back after treatment or can't be removed by surgery. Participants in this part will get SEA-CD40 and pembrolizumab. In the other part, participants have non-small cell lung cancer (NSCLC) that has spread through their body. These participants will get SEA-CD40, pembrolizumab, carboplatin, and pemetrexed.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non 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 or cytologically confirmed unresectable malignancy defined as one of the following:
- •Cohort 1: Relapsed and/or refractory metastatic melanoma
- •Uveal/ocular melanoma is excluded
- •Must have progressed on treatment with an anti-PD-(L)1 mAb. PD-(L)1 treatment progression is defined as meeting all of the following criteria:
- •Has received at least 2 doses of an approved anti-PD-(L)1 mAb
- •Has demonstrated disease progression after PD-(L)1 as defined by RECIST v1.
- •Progressive disease has been documented within 12 weeks from the last dose of anti- PD-(L)1 mAb
- •Last dose of anti-PD-(L)1 must have been within 90 days prior to enrollment
- •Participants with a targetable BRAF mutation must have been treated with, been intolerant of, or declined treatment with BRAF/MEK targeted therapy prior to study entry
- •Cohort 2: Metastatic uveal melanoma
- •Must not have received prior treatment for advanced or metastatic disease except for prior adjuvant/neoadjuvant immunotherapy
- •No prior liver-directed therapy
- •Cohort 3: Metastatic PD-(L)1-naive melanoma
- •Uveal/ocular melanoma is excluded
- •Must not have received prior treatment for advanced or metastatic disease except for prior adjuvant/neoadjuvant immunotherapy.
- •For participants with a targetable BRAF mutation, prior BRAF/MEK targeted therapy is allowed if completed 4 weeks prior to first dose of study treatment.
- •Cohorts 4 and 5: Non-squamous NSCLC
- •Participants must have stage IV disease per AJCC 8th edition
- •No known driver mutations/alterations mutation for which targeted therapy is available
- •Must have non-squamous histology.
- •No prior therapy for metastatic disease
- •No prior treatment with anti-PD-(L)1 or PD-L2 agent or an antibody targeting other immuno-regulatory receptors or mechanisms
- •Able to provide archival tumor tissue from locations not radiated prior to biopsy. If archival tumor sample is not available a fresh baseline biopsy is required.
- •Eastern Cooperative Oncology Group (ECOG) Performance Status score of 0 or 1
- •Measurable disease per RECIST v1.1 at baseline
排除标准
- •History of another malignancy within 3 years of first dose of study drug
- •Active central nervous system (CNS) metastases and/or carcinomatous meningitis.
- •Previous exposure to CD40-targeted therapy
- •Currently on chronic systemic steroids in excess of physiologic replacement
- •Has had an allogeneic tissue/solid organ transplant.
- •History of autoimmune disease that has required systemic treatment in the past 2 years
研究组 & 干预措施
Melanoma Arm
SEA-CD40 + pembrolizumab
干预措施: SEA-CD40 (Drug)
Melanoma Arm
SEA-CD40 + pembrolizumab
干预措施: pembrolizumab (KEYTRUDA®) (Drug)
NSCLC Arm
SEA-CD40 + pembrolizumab + pemetrexed + carboplatin
干预措施: SEA-CD40 (Drug)
NSCLC Arm
SEA-CD40 + pembrolizumab + pemetrexed + carboplatin
干预措施: pembrolizumab (KEYTRUDA®) (Drug)
NSCLC Arm
SEA-CD40 + pembrolizumab + pemetrexed + carboplatin
干预措施: pemetrexed (Drug)
NSCLC Arm
SEA-CD40 + pembrolizumab + pemetrexed + carboplatin
干预措施: carboplatin (Drug)
结局指标
主要结局
Confirmed Objective Response Rate (cORR) According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) Per Investigator Assessment
时间窗: From start of study treatment until CR or PR (maximum up to 15.2 months)
cORR is defined as the percentage of participants achieving a confirmed complete response (CR) or partial response (PR) according to RECIST v1.1. CR: disappearance of all target, non-target lesions, all lymph nodes must be non-pathological in size (\<10 millimeter \[mm\] short axis), PR: at least 30% decrease in sum of diameters of target lesions, taking as reference baseline sum diameters persistence of one or more non-target lesions.
次要结局
- Number of Participants With Treatment Emergent Adverse Events (TEAEs), Treatment Related TEAEs, Greater Than or Equal to (>=) Grade 3 TEAEs, Treatment Emergent Serious Adverse Event (TESAE), Treatment Related TESAE(From first dose of the study treatment (Day 1) up to approximately 18.5 months)
- Number of Participants With Grade Shift From Baseline to Maximum Post-Baseline in Serum Chemistry Laboratory Abnormalities Assessed by NCI CTCAE(Baseline up to approximately 15.8 months)
- Number of Participants With Grade Shift From Baseline to Maximum Post-Baseline in Hematology Parameters Assessed by NCI CTCAE(Baseline up to approximately 15.8 months)
- Number of Participants With Treatment Interruptions, Dose Reductions, Treatment Discontinuations Due to Adverse Events(From first dose of the study treatment (Day 1) up to approximately 18.5 months)
- Disease Control Rate (DCR) Per Investigator Assessment(From the first dose of study treatment until the first documented CR, PR or SD or new anticancer therapies or death, whichever occurred first (maximum up to 15.2 months))
- Duration of Response (DOR) Per Investigator Assessment(From the first documentation of CR or PR to PD or death due to any cause or censoring, whichever occurred first (maximum up to 11.1 months))
- Progression Free Survival (PFS) Per Investigator Assessment(From first dose of study treatment to the date of PD or death due to any cause or censoring, whichever occurred first (maximum up to 13.9 months))
- Overall Survival (OS)(From start of study treatment to death due to any cause or censoring date (maximum up to 23.6 months))