A Phase 1b/2, Multicenter, Open-label Study of Ifinatamab Deruxtecan (I-DXd), a B7-H3 Antibody-Drug Conjugate (ADC), in Combination With Atezolizumab With or Without Carboplatin as First-line Induction or Maintenance, in Subjects With Extensive-stage Small Cell Lung Cancer (ES-SCLC) (IDeate-Lung03)
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 123
- 试验地点
- 109
- 主要终点
- Number of Participants Reporting Dose-limiting Toxicities Following I-DXd in Combination With Atezolizumab With or Without Carboplatin (Part A)
研究概览
简要总结
This study is designed to evaluate the safety and efficacy of ifinatamab deruxtecan (I-DXd) in combination with immune checkpoint inhibitor (ICI) atezolizumab with or without carboplatin in participants with extensive stage-small cell lung cancer (ES-SCLC) in the first-line (1L) setting.
详细描述
This study consists of two parts and two cohorts: Part A (Phase 1b; Safety Run-in) and Part B (Phase 2; Dose Optimization), Cohort 1 (I-DXd in maintenance) and Cohort 2 (I-DXd in induction + maintenance).
The primary objective of this study is to evaluate the safety and tolerability of I-DXd in combination with atezolizumab with or without carboplatin by assessing treatment-emergent adverse events (TEAEs) and other safety parameters which will inform optimal dose selection of I-DXd in the combination regimens (Dose Optimization Part B) of this study.
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
- •A full list of inclusion/
排除标准
- •are available in the protocol.
- •Inclusion Criteria
- •Participants must meet all of 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.
- •Adults ≥18 years or the minimum legal adult age (whichever is greater) at the time the ICF is signed.
- •Has histologically or cytologically confirmed diagnosis of ES-SCLC who will require first-line (IL) therapy.
- •For Cohort 1, participant has received 4 cycles of 1L induction therapy with carboplatin, etoposide, and atezolizumab for ES-SCLC with ongoing CR PR, CR, or SD per RECIST v1.1 assessed by the investigator.
- •For Cohort 2, participant has received no prior treatment for ES-SCLC.
- •For Cohort 2, participant has at least one measurable lesion according to RECIST v1.1 on computed tomography (CT) or magnetic resonance imaging (MRI) as assessed by the investigator.
- •For Cohort 2, participant must have at least one lesion, amenable to core biopsy, and must consent to provide a pretreatment biopsy tissue sample and on-treatment biopsy.
- •Has ECOG PS of ≤1 (assessed within 7 days before enrollment/randomization).
- •Has adequate organ and bone marrow function within 7 days before the start of study treatment as specified in the study protocol.
- •A female subject of childbearing potential (POCBP) is eligible to participate if the following conditions are met:
- •Subject is not pregnant as confirmed by highly sensitive pregnancy test during Screening (within 3 days prior to enrollment/randomization)
- •Subject does not breastfeed during the treatment period and for at least 8/5/6 months after last dose of I-DXd/atezolizumab/carboplatin, respectively.
- •Subject agrees to adhere to a contraceptive method that is highly effective and agrees not to donate eggs (ova, oocytes) to others or freeze/store eggs during the treatment period and for at least the time needed to eliminate each study drug after the last dose. The length of time required to continue contraception and avoid donating/freezing eggs after last dose for I-DXd/atezolizumab/carboplatin is 8/5/6 months, respectively. Preservation of eggs may be considered prior to first dose of study drug.
- •A male subject capable of producing sperm is eligible to participate if he agrees to the following during the intervention period and for at least the time needed to eliminate each study drug. The length of time required to continue contraception and avoid donating sperm after last dose for I-DXd/atezolizumab/carboplatin is 6/5/6 months, respectively.
- •Avoid donating sperm.
- •Adhere to either of the contraception methods: true abstinence from penile-vaginal intercourse or uses a penile/external condom when having penile-vaginal intercourse with a non-subject of childbearing potential plus partner use of an additional contraceptive method.
- •Is willing and able to comply with scheduled visits, drug administration plan, laboratory tests, other study procedures, and study restrictions.
- •Exclusion Criteria
- •Participants who meet any of the following criteria will be disqualified from entering the study:
- •Has received prior treatment with orlotamab, enoblituzumab, or other B7-H3 targeted agents, including I-DXd.
- •Prior discontinuation of an ADC that consists of an exatecan derivative (eg, trastuzumab deruxtecan) due to treatment-related toxicities.
- •Has received prior treatment with CD137 agonists or ICIs, including anti-cytotoxic T-cell lymphocyte-4, anti-PD-1, and anti-PD-L1 therapeutic antibodies, except for atezolizumab for Cohort
- •Has inadequate washout period before enrollment/randomization as specified in the study protocol.
- •Has any of the following within the past 6 months: cerebrovascular accident, transient ischemic attack, or another arterial thromboembolic event.
- •Has clinically active brain metastases, spinal cord compression, or leptomeningeal carcinomatosis, defined as untreated and symptomatic, or requiring therapy with steroids or anticonvulsants to control associated symptoms.
- •Has clinically significant corneal disease.
- •Has uncontrolled or significant cardiovascular disease,.
- •Has history of (non-infectious) ILD/pneumonitis that required corticosteroids, current ILD/pneumonitis, or suspected ILD/pneumonitis that cannot be ruled out by imaging at Screening.
- •Has clinically severe pulmonary compromise resulting from intercurrent pulmonary illnesses
- •Is on chronic steroid treatment (dose of 10 mg daily or more prednisone equivalent), except for low-dose inhaled steroids (for asthma/chronic obstructive pulmonary disease, topical steroids (for mild skin conditions), or intra-articular steroid injections.
- •Has history of malignancy other than SCLC within the 5 years prior to randomization/enrollment, except adequately resected non-melanoma skin cancer, curatively treated in situ disease, superficial gastrointestinal tract tumors, and non-muscle invasive bladder cancer curatively resected by endoscopic surgery.
- •Has history of allogeneic bone marrow, stem cell, or solid organ transplant.
- •Has unresolved toxicities from previous anticancer therapy, defined as toxicities (other than alopecia) not yet resolved to NCI-CTCAE V5.0, Grade ≤1 or baseline.
- •Has history of hypersensitivity to the drug substances, inactive ingredients in the drug product or severe hypersensitivity reactions to other monoclonal antibodies.
- •Has evidence of ongoing uncontrolled systemic bacterial, fungal, or viral infection.
- •Has active or uncontrolled human immunodeficiency virus (HIV) infection.
- •Has active or uncontrolled hepatitis B or C virus (HBV or HCV) infection.
- •Has history of autoimmune disease.
- •Has any evidence of severe or uncontrolled systemic diseases.
- •Has received a live vaccine within 30 days prior to the first dose of study drug.
- •Is a female who is pregnant or breastfeeding or planning to become pregnant.
- •Has 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; alter the absorption, distribution, metabolism, or excretion of the study drug; or confound the assessment of study results.
- •Has psychological, social, familial, or logistical factors that would prevent regular follow-up
研究组 & 干预措施
Cohort 1, Part A: Maintenance Only (I-DXd 12 mg/kg)
Part A (Safety Run-in): Participants who must have received 4 cycles of 1L induction standard of care (SoC) therapy with best overall response of CR, PR, or SD will receive maintenance therapy only. Maintenance therapy consisting of I-DXd 12 mg/kg (or a lower dose based on data for I-DXd collected during the study) + atezolizumab 1200 mg IV Q3W.
A 5-day surveillance period between each of the first 3 participants (up to a maximum of 9 participants) dosed is included as a safety measure.
干预措施: Ifinatamab deruxtecan (Drug)
Cohort 1, Part A: Maintenance Only (I-DXd 12 mg/kg)
Part A (Safety Run-in): Participants who must have received 4 cycles of 1L induction standard of care (SoC) therapy with best overall response of CR, PR, or SD will receive maintenance therapy only. Maintenance therapy consisting of I-DXd 12 mg/kg (or a lower dose based on data for I-DXd collected during the study) + atezolizumab 1200 mg IV Q3W.
A 5-day surveillance period between each of the first 3 participants (up to a maximum of 9 participants) dosed is included as a safety measure.
干预措施: Atezolizumab (Drug)
Cohort 2, Part A: Induction + Maintenance (I-DXd 8 mg/kg)
Part A (Safety Run-in): Participants who are treatment-naive, newly diagnosed with ES-SCLC will receive 4 cycles of 1L I-DXd induction therapy (8 mg/kg IV Q3W) + atezolizumab (1200 mg IV Q3W) + carboplatin (AUC 5 mg/ml×min IV Q3W) followed by maintenance therapy. Maintenance therapy consisting of I-DXd 8 mg/kg (or a lower dose based on data for I-DXd collected during the study) + atezolizumab 1200 mg IV Q3W.
干预措施: Ifinatamab deruxtecan (Drug)
Cohort 2, Part A: Induction + Maintenance (I-DXd 8 mg/kg)
Part A (Safety Run-in): Participants who are treatment-naive, newly diagnosed with ES-SCLC will receive 4 cycles of 1L I-DXd induction therapy (8 mg/kg IV Q3W) + atezolizumab (1200 mg IV Q3W) + carboplatin (AUC 5 mg/ml×min IV Q3W) followed by maintenance therapy. Maintenance therapy consisting of I-DXd 8 mg/kg (or a lower dose based on data for I-DXd collected during the study) + atezolizumab 1200 mg IV Q3W.
干预措施: Atezolizumab (Drug)
Cohort 2, Part A: Induction + Maintenance (I-DXd 8 mg/kg)
Part A (Safety Run-in): Participants who are treatment-naive, newly diagnosed with ES-SCLC will receive 4 cycles of 1L I-DXd induction therapy (8 mg/kg IV Q3W) + atezolizumab (1200 mg IV Q3W) + carboplatin (AUC 5 mg/ml×min IV Q3W) followed by maintenance therapy. Maintenance therapy consisting of I-DXd 8 mg/kg (or a lower dose based on data for I-DXd collected during the study) + atezolizumab 1200 mg IV Q3W.
干预措施: Carboplatin (Drug)
Cohort 2, Part A: Induction + Maintenance (I-DXd 12 mg/kg)
Part A (Safety Run-in): Participants who are treatment-naive, newly diagnosed with ES-SCLC will receive 4 cycles of 1L I-DXd induction therapy (12 mg/kg IV Q3W) + atezolizumab (1200 mg IV Q3W) + carboplatin (AUC 5 mg/ml×min IV Q3W) followed by maintenance therapy. Maintenance therapy consisting of I-DXd 12 mg/kg (or a lower dose based on data for I-DXd collected during the study) + atezolizumab 1200 mg IV Q3W.
干预措施: Ifinatamab deruxtecan (Drug)
Cohort 2, Part A: Induction + Maintenance (I-DXd 12 mg/kg)
Part A (Safety Run-in): Participants who are treatment-naive, newly diagnosed with ES-SCLC will receive 4 cycles of 1L I-DXd induction therapy (12 mg/kg IV Q3W) + atezolizumab (1200 mg IV Q3W) + carboplatin (AUC 5 mg/ml×min IV Q3W) followed by maintenance therapy. Maintenance therapy consisting of I-DXd 12 mg/kg (or a lower dose based on data for I-DXd collected during the study) + atezolizumab 1200 mg IV Q3W.
干预措施: Atezolizumab (Drug)
Cohort 2, Part A: Induction + Maintenance (I-DXd 12 mg/kg)
Part A (Safety Run-in): Participants who are treatment-naive, newly diagnosed with ES-SCLC will receive 4 cycles of 1L I-DXd induction therapy (12 mg/kg IV Q3W) + atezolizumab (1200 mg IV Q3W) + carboplatin (AUC 5 mg/ml×min IV Q3W) followed by maintenance therapy. Maintenance therapy consisting of I-DXd 12 mg/kg (or a lower dose based on data for I-DXd collected during the study) + atezolizumab 1200 mg IV Q3W.
干预措施: Carboplatin (Drug)
Cohort 1, Part B: Maintenance (I-DXd 8 mg/kg)
Part B: Participants who must have received 4 cycles of 1L induction standard of care (SoC) therapy with best overall response of CR, PR, or SD will receive maintenance therapy only starting at Cycle 1 Day 1. Maintenance therapy consisting of I-DXd 8 mg/kg (or a lower dose based on data for I-DXd collected during the study) + atezolizumab 1200 mg IV Q3W
干预措施: Ifinatamab deruxtecan (Drug)
Cohort 1, Part B: Maintenance (I-DXd 8 mg/kg)
Part B: Participants who must have received 4 cycles of 1L induction standard of care (SoC) therapy with best overall response of CR, PR, or SD will receive maintenance therapy only starting at Cycle 1 Day 1. Maintenance therapy consisting of I-DXd 8 mg/kg (or a lower dose based on data for I-DXd collected during the study) + atezolizumab 1200 mg IV Q3W
干预措施: Atezolizumab (Drug)
Cohort 1, Part B: Maintenance (I-DXd 12 mg/kg)
Part B: Participants who must have received 4 cycles of 1L induction standard of care (SoC) therapy with best overall response of CR, PR, or SD will receive maintenance therapy only starting at Cycle 1 Day 1. Maintenance therapy consisting of I-DXd 12 mg/kg (or a lower dose based on data for I-DXd collected during the study) + atezolizumab 1200 mg IV Q3W.
干预措施: Ifinatamab deruxtecan (Drug)
Cohort 1, Part B: Maintenance (I-DXd 12 mg/kg)
Part B: Participants who must have received 4 cycles of 1L induction standard of care (SoC) therapy with best overall response of CR, PR, or SD will receive maintenance therapy only starting at Cycle 1 Day 1. Maintenance therapy consisting of I-DXd 12 mg/kg (or a lower dose based on data for I-DXd collected during the study) + atezolizumab 1200 mg IV Q3W.
干预措施: Atezolizumab (Drug)
Cohort 2, Part B: Induction + Maintenance (I-DXd 8 mg/kg)
Participants who are treatment-naive, newly diagnosed with ES-SCLC will receive 4 cycles of 1L I-DXd induction therapy (8 mg/kg IV Q3W) + atezolizumab (1200 mg IV Q3W) + carboplatin (AUC 5 mg/ml×min IV Q3W) followed by maintenance therapy. Maintenance therapy consisting of I-DXd 8 mg/kg (or a lower dose based on data for I-DXd collected during the study) + atezolizumab 1200 mg IV Q3W.
干预措施: Ifinatamab deruxtecan (Drug)
Cohort 2, Part B: Induction + Maintenance (I-DXd 8 mg/kg)
Participants who are treatment-naive, newly diagnosed with ES-SCLC will receive 4 cycles of 1L I-DXd induction therapy (8 mg/kg IV Q3W) + atezolizumab (1200 mg IV Q3W) + carboplatin (AUC 5 mg/ml×min IV Q3W) followed by maintenance therapy. Maintenance therapy consisting of I-DXd 8 mg/kg (or a lower dose based on data for I-DXd collected during the study) + atezolizumab 1200 mg IV Q3W.
干预措施: Atezolizumab (Drug)
Cohort 2, Part B: Induction + Maintenance (I-DXd 8 mg/kg)
Participants who are treatment-naive, newly diagnosed with ES-SCLC will receive 4 cycles of 1L I-DXd induction therapy (8 mg/kg IV Q3W) + atezolizumab (1200 mg IV Q3W) + carboplatin (AUC 5 mg/ml×min IV Q3W) followed by maintenance therapy. Maintenance therapy consisting of I-DXd 8 mg/kg (or a lower dose based on data for I-DXd collected during the study) + atezolizumab 1200 mg IV Q3W.
干预措施: Carboplatin (Drug)
Cohort 2, Part B: Induction + Maintenance (I-DXd 12 mg/kg)
Participants who are treatment-naive, newly diagnosed with ES-SCLC will receive 4 cycles of IL I-DXd induction therapy (12 mg/kg IV Q3W) + atezolizumab (1200 mg IV Q3W) + carboplatin (AUC 5 mg/ml×minIV Q3W) followed by maintenance therapy. Maintenance therapy consisting of I-DXd 12 mg/kg (or a lower dose based on data for I-DXd collected during the study) + atezolizumab 1200 mg IV Q3W.
干预措施: Ifinatamab deruxtecan (Drug)
Cohort 2, Part B: Induction + Maintenance (I-DXd 12 mg/kg)
Participants who are treatment-naive, newly diagnosed with ES-SCLC will receive 4 cycles of IL I-DXd induction therapy (12 mg/kg IV Q3W) + atezolizumab (1200 mg IV Q3W) + carboplatin (AUC 5 mg/ml×minIV Q3W) followed by maintenance therapy. Maintenance therapy consisting of I-DXd 12 mg/kg (or a lower dose based on data for I-DXd collected during the study) + atezolizumab 1200 mg IV Q3W.
干预措施: Atezolizumab (Drug)
Cohort 2, Part B: Induction + Maintenance (I-DXd 12 mg/kg)
Participants who are treatment-naive, newly diagnosed with ES-SCLC will receive 4 cycles of IL I-DXd induction therapy (12 mg/kg IV Q3W) + atezolizumab (1200 mg IV Q3W) + carboplatin (AUC 5 mg/ml×minIV Q3W) followed by maintenance therapy. Maintenance therapy consisting of I-DXd 12 mg/kg (or a lower dose based on data for I-DXd collected during the study) + atezolizumab 1200 mg IV Q3W.
干预措施: Carboplatin (Drug)
结局指标
主要结局
Number of Participants Reporting Dose-limiting Toxicities Following I-DXd in Combination With Atezolizumab With or Without Carboplatin (Part A)
时间窗: Cycle 1 Day 1 up to Cycle 1 Day 21 (each cycle is 21 days)
Overall Number of Participants With Treatment-emergent Adverse Events Following I-DXd in Combination With Atezolizumab With or Without Carboplatin (Part A and B)
时间窗: Baseline up to 37 months
次要结局
- Progression-free Survival As Assessed by Blinded Independent Central Review and Investigator Following I-DXd in Combination With Atezolizumab With or Without Carboplatin (Part A and B)(From start date of study drug to the earlier date of the first objective documentation of radiographic disease progression assessed by BICR and investigator per RECIST v1.1 or death due to any cause, whichever occurs first, up to approximately 37 months)
- Objective Response Rate Assessed by Blinded Independent Central Review and Investigator Following I-DXd in Combination With Atezolizumab With Carboplatin (Part A and B of Cohort 2 Only)(Baseline up until documented progressive disease, death, lost to follow-up, or withdrawal by the participant, up to approximately 37 months)
- Duration of Response As Assessed by Blinded Independent Central Review and Investigator Following I-DXd in Combination With Atezolizumab With Carboplatin (Part A and B of Cohort 2 Only)(From the date of first documentation of confirmed response (CR or PR) to the first documentation of objective progression or to death due to any cause, whichever occurs first, up to approximately 37 months)
- Disease Control Rate As Assessed by Blinded Independent Central Review and Investigator Following I-DXd in Combination With Atezolizumab With Carboplatin (Part A and B of Cohort 2 Only)(Baseline up until documented progressive disease, death, lost to follow-up, or withdrawal by the participant, up to approximately 37 months)
- Clinical Benefit Rate as Assessed by Blinded Independent Central Review and Investigator Following I-DXd in Combination With Atezolizumab With Carboplatin (Part A and B of Cohort 2 Only)(Baseline up until documented progressive disease, death, lost to follow-up, or withdrawal by the participant, up to approximately 37 months)
- Time to Response As Assessed by Blinded Independent Central Review and Investigator Following I-DXd in Combination With Atezolizumab With Carboplatin (Part A and B of Cohort 2 Only)(From the start date of study drug to the date of the first documentation of response (CR or PR) that is subsequently confirmed, up to approximately 37 months)
- Best Percentage Change in the Sum of Diameters (SoD) of Measurable Tumors As Assessed by Blinded Independent Central Review and Investigator Following I-DXd in Combination With Atezolizumab With Carboplatin (Part A and B of Cohort 2 Only)(Baseline up to approximately 37 months)
- Overall Survival Following I-DXd in Combination With Atezolizumab With or Without Carboplatin (Part A and B)(From the start date of study drug to the date of death due to any cause, whichever occurs first, up to approximately 37 months)
- Pharmacokinetic Parameter Maximum Serum Concentration of I-DXd(Cycle 1 Day 1 pre-dose up to Cycle 9 (and every 2 cycles thereafter up to 37 months) Day 1 pre-dose (each cycle is 21 days))
- Pharmacokinetic Parameter Time to Maximum Serum Concentration of I-DXd(Cycle 1 Day 1 pre-dose up to Cycle 9 (and every 2 cycles thereafter up to 37 months) Day 1 pre-dose (each cycle is 21 days))
- Pharmacokinetic Parameter Area Under the Concentration Curve of I-DXd(Cycle 1 Day 1 pre-dose up to Cycle 9 (and every 2 cycles thereafter up to 37 months) Day 1 pre-dose (each cycle is 21 days))
- The Number of Participants Who Are Anti-Drug Antibody (ADA)-Positive At Any Time and Who Have A Treatment-emergent Anti-Drug Antibody(Baseline up to approximately 37 months)