NCT05280470进行中（未招募）2 期
A Phase 2, Multicenter, Randomized, Open-label Study of Ifinatamab Deruxtecan (I-DXd), a B7-H3 Antibody Drug Conjugate (ADC), in Subjects With Pretreated Extensive-stage Small Cell Lung Cancer (ES-SCLC) (IDeate-Lung01)
适应症
干预措施
相关药物
试验速览
- 阶段
- 2 期
- 状态
- 进行中（未招募）
- 入组人数
- 187
- 试验地点
- 115
- 主要终点
- Percentage of Participants With Objective Response Rate (ORR) Based on Blinded Independent Central Review (BICR) Following Treatment With I-DXd in Participants With Pretreated ES-SCLC
研究概览
简要总结
This 2-part study intends to define the recommended Phase 2 dose of ifinatamab deruxtecan (I-DXd) based on the efficacy, safety, and pharmacokinetics (PK) results observed in participants with Extensive-stage Small Cell Lung Cancer (ES-SCLC) who received at least 1 prior line of platinum-based chemotherapy and a maximum of 3 prior lines of therapy (Part 1) and a minimum of two previous lines of systemic therapy (Part 2). This study will also investigate I-DXd anti-tumor activity in this population.
详细描述
This study will consist of 2 parts: dose optimization (Part 1) and extension (Part 2). In the dose optimization part of the study (Part 1), approximately 80 participants with at least 1 prior line of platinum-based chemotherapy and a maximum of 3 prior lines of therapy will be enrolled. Two I-DXd doses will be tested (8 mg/kg once every 3 weeks and 12 mg/kg once every 3 weeks). In the extension part of the study (Part 2), approximately 70 participants with a minimum of two previous lines of systemic therapy will be enrolled. I-DXd will be administered at the selected dose of 12 mg/kg once every 3 weeks (Q3W).
In Part 1, eligible participants will be randomized in a 1:1 ratio to receive one of the two dose levels of I-DXd. Randomization will be stratified by:
- Prior receipt or of an anti-programmed death-ligand 1 (PD-[L]1) antibody (yes/no)
- The chemotherapy-free interval (CTFI) from completion of the first-line therapy to the date of documented radiological Progressive Disease of <90 days vs. ≥90 days in second-line participants as well as the number of lines of therapy. Thus, the stratification factor includes three categories: (1) second-line participants with CTFI <90 days, (2) second-line participants with CTFI ≥90 days, and (3) third- and fourth-line participants.
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
- •Participants must meet all the following criteria to be eligible for enrollment into the study:
- •Sign and date the informed consent form (ICF) prior to the start of any study-specific qualification procedures.
- •Participant must have at least one lesion, not previously irradiated, amenable to core biopsy.
- •Male or female subjects aged ≥18 years (follow local regulatory requirements if the legal age of consent for study participation is >18 years old).
- •Histologically or cytologically documented ES-SCLC.
- •At least one measurable lesion according to RECIST v1.1 as assessed by the investigator.
- •Prior therapy with at least one platinum-based line as systemic therapy for extensive-stage disease with at least two cycles of therapy (except in the case of early objective PD) and beginning with protocol version 3.0, a minimum of two previous lines of systemic therapy.
- •Documentation of radiological disease progression on or after most recent systemic therapy.
- •Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1.
排除标准
- •Participants who meet any of the following criteria will be disqualified from entering the study:
- •Prior treatment with orlotamab, enoblituzumab, or other B7-H3 targeted agents, including I-DXd.
- •Prior discontinuation of an antibody drug conjugate (ADC) that consists of an exatecan derivative (eg, trastuzumab deruxtecan) due to treatment-related toxicities.
- •Clinically active brain metastases, spinal cord compression or leptomeningeal carcinomatosis, defined as untreated or symptomatic, or requiring therapy with steroids or anticonvulsants to control associated symptoms.
- •Any of the following conditions within the past 6 months: cerebrovascular accident, transient ischemic attack, or another arterial thromboembolic event.
- •Clinically significant corneal disease.
- •Uncontrolled or significant cardiovascular disease.
- •History of (non-infectious) interstitial lung disease (ILD)/pneumonitis that required corticosteroids, current ILD/pneumonitis, or suspected ILD/pneumonitis that cannot be ruled out by imaging at screening.
- •Clinically severe pulmonary compromise resulting from intercurrent pulmonary illnesses,
- •Chronic steroid treatment (dose of 10 mg daily or more prednisone equivalent), except for low-dose inhaled steroids (for asthma/COPD) or topical steroids (for mild skin conditions) or intra-articular steroid injections.
- •History of malignancy other than SCLC within the 3 years prior to enrollment, except adequately resected non-melanoma skin cancer, curatively treated in situ disease, superficial gastrointestinal (GI) tract tumors and non-muscle invasive bladder cancer curatively resected by endoscopic surgery.
- •History of allogeneic bone marrow, stem cell, or solid organ transplant.
- •Unresolved toxicities from previous anticancer therapy, defined as toxicities (other than alopecia) not yet resolved to National Cancer Institute- Common Terminology Criteria for Adverse Events Version 5.0 (NCI-CTCAE V5.0), Grade ≤1 or baseline.
- •History of hypersensitivity to the drug substances, inactive ingredients in the drug product or severe hypersensitivity reactions to other monoclonal antibodies.
- •Evidence of ongoing uncontrolled systemic bacterial, fungal, or viral infection.
- •Has active or uncontrolled hepatitis B or C infection.
- •Active, known, or suspected autoimmune disease.
- •Any evidence of severe or uncontrolled systemic diseases (including active bleeding diatheses, psychiatric illness/social situations, substance abuse).
- •Has received a live vaccine within 30 days prior to the first dose of study drug.
- •Female who is pregnant or breast-feeding or intends to become pregnant during the study.
- •Prior or ongoing clinically relevant illness, medical condition, surgical history, physical finding, or laboratory abnormality that, in the investigator's opinion, could affect the safety of the participant.
- •Known human immunodeficiency virus (HIV) infection that is not well controlled.
研究组 & 干预措施
Ifinatamab Deruxtecan (8 mg/kg)
Experimental
Participants will be randomized to receive I-DXd at 8 mg/kg.
干预措施: Ifinatamab Deruxtecan (I-DXd) (Drug)
Ifinatamab Deruxtecan (12 mg/kg)
Experimental
Participants will be randomized to receive I-DXd at 12 mg/kg.
This arm will consist of participants from Part 1 and Part 2 who receive I-DXd 12 mg/kg.
干预措施: Ifinatamab Deruxtecan (I-DXd) (Drug)
结局指标
主要结局
Percentage of Participants With Objective Response Rate (ORR) Based on Blinded Independent Central Review (BICR) Following Treatment With I-DXd in Participants With Pretreated ES-SCLC
时间窗: Up to approximately 36 months
ORR was defined as the percentage of participants who achieved a best overall response (BOR) of confirmed Complete Response (CR) or Partial Response (PR), assessed by BICR based on RECIST version 1.1. For all target, non-target, and new lesions, CR was defined as a disappearance of all lesions and PR was defined as at least a 30% decrease in the sum of diameters of all lesions.
次要结局
- Overall Survival (OS) Following Treatment With I-DXd in Participants With Pretreated ES-SCLC(From enrollment until death, up to approximately 36 months)
- Number of Participants With Treatment-Emergent Adverse Events (TEAEs) Following Treatment With I-DXd in Participants With Pretreated ES-SCLC(Up to approximately 36 months)
- Duration of Response (DoR) Following Treatment With I-DXd in Participants With Pretreated ES-SCLC(From enrollment until disease progression or death (whichever occurs first), up to approximately 36 months)
- Progression-Free Survival (PFS) Following Treatment With I-DXd in Participants With Pretreated ES-SCLC(From enrollment until disease progression or death (whichever occurs first), up to approximately 36 months)
- Time to Response (TTR) Following Treatment With I-DXd in Participants With Pretreated ES-SCLC(From enrollment until disease progression or death (whichever occurs first), up to approximately 36 months)
- Percentage of Participants With Objective Response Rate (ORR) Based on Investigator Assessment Following Treatment With I-DXd in Participants With Pretreated ES-SCLC(Up to approximately 36 months)
- Disease Control Rate (DCR) Following Treatment With I-DXd in Participants With Pretreated ES-SCLC(Up to approximately 36 months)
- Maximum Plasma Concentration (Cmax) Following Treatment With I-DXd in Participants With Pretreated ES-SCLC(Cycle 1: Predose, end of infusion (EOI), 3, 6, & 24 hours post start of infusion (SOI), Days 4, 8, 15, & 22; Cycle 2: Predose & EOI; Cycle 3: Predose, EOI, 3 & 6 hours post SOI; Cycle 4, 5 & every 2 cycles up to 36 months: Predose (each cycle is 21 days))
- Time to Reach Maximum Serum Concentration (Tmax) Following Treatment With I-DXd in Participants With Pretreated ES-SCLC(Cycle 1: Predose, end of infusion (EOI), 3, 6, & 24 hours post start of infusion (SOI), Days 4, 8, 15, & 22; Cycle 2: Predose & EOI; Cycle 3: Predose, EOI, 3 & 6 hours post SOI; Cycle 4, 5 & every 2 cycles up to 36 months: Predose (each cycle is 21 days))
- Minimum Observed Concentration (Ctrough) Following Treatment With I-DXd in Participants With Pretreated ES-SCLC(Cycle 1: Predose, end of infusion (EOI), 3, 6, & 24 hours post start of infusion (SOI), Days 4, 8, 15, & 22; Cycle 2: Predose & EOI; Cycle 3: Predose, EOI, 3 & 6 hours post SOI; Cycle 4, 5 & every 2 cycles up to 36 months: Predose (each cycle is 21 days))
- Area Under the Curve (AUC) Following Treatment With I-DXd in Participants With Pretreated ES-SCLC(Cycle 1: Predose, end of infusion (EOI), 3, 6, & 24 hours post start of infusion (SOI), Days 4, 8, 15, & 22; Cycle 2: Predose & EOI; Cycle 3: Predose, EOI, 3 & 6 hours post SOI; Cycle 4, 5 & every 2 cycles up to 36 months: Predose (each cycle is 21 days))
- Terminal Half-Life (T1/2) Following Treatment With I-DXd in Participants With Pretreated ES-SCLC(Cycle 1: Predose, end of infusion (EOI), 3, 6, & 24 hours post start of infusion (SOI), Days 4, 8, 15, & 22; Cycle 2: Predose & EOI; Cycle 3: Predose, EOI, 3 & 6 hours post SOI; Cycle 4, 5 & every 2 cycles up to 36 months: Predose (each cycle is 21 days))
- Percentage of Participants Who Have Treatment-Emergent Antidrug Antibodies (ADA) Following Treatment With I-DXd in Participants With Pretreated ES-SCLC(Cycle 1, Cycle 2, Cycle 3 and Cycle 4 Day 1: Predose; Cycle 5 Day 1 & every 2 cycles thereafter up to approximately 36 months: Predose; End of Termination Visit; 40-day Follow-up Visit (each cycle is 21 days))
研究者
研究点 (115)
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