NCT06203210RecruitingPhase 3
A Phase 3, Multicenter, Randomized, Open-label Study of Ifinatamab Deruxtecan (I-DXd), a B7-H3 Antibody Drug Conjugate (ADC), Versus Treatment of Physician's Choice (TPC) in Subjects With Relapsed Small Cell Lung Cancer (SCLC) (IDeate-Lung02)
Conditions
Interventions
Drugs
Trial Snapshot
- Phase
- Phase 3
- Status
- Recruiting
- Sponsor
- Daiichi Sankyo
- Enrollment
- 540
- Locations
- 434
- Primary Endpoint
- Overall Survival (OS)
Study Overview
Brief Summary
This study is designed to compare the efficacy and safety of I-DXd with treatment of physician's choice in participants with relapsed small cell lung cancer (SCLC).
Detailed Description
The primary objective of this study is to assess whether treatment with I-DXd prolongs overall survival (OS) compared with treatment of physician's choice among participants with relapsed SCLC.
The secondary objectives of the study are to further evaluate the efficacy/safety of I-DXd, health economics and outcome research measures (including patient reported outcomes), immunogenicity of I-DXd, B7-H3 protein expression, and characterize the pharmacokinetics of I-DXd.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Participants must meet all the following criteria to be eligible for randomization into the study:
- •Sign and date the informed consent form (ICF) prior to the start of any study-specific qualification procedures.
- •Adults greater than or equal to (≥)18 years or the minimum legal adult age (whichever is greater) at the time the ICF is signed.
- •Has histologically or cytologically documented extensive-stage small cell lung cancer (ES-SCLC).
- •The participant must provide adequate baseline tumor samples with sufficient quantity and quality of tumor tissue content.
- •Has received prior therapy with only one prior platinum-based line as systemic therapy for SCLC with at least 2 cycles of therapy and a chemotherapy free-interval [CTFI] (duration from stop date of the platinum agent in 1L therapy to radiological PD) of ≥30 days.
- •Has at least 1 measurable lesion according to RECIST v1.1 as assessed by the investigator.
- •Has documentation of radiological disease progression on or after the most recent systemic therapy.
- •Has ECOG PS of less than or equal to (≤)1 within 7 days prior to Cycle 1 Day 1 (C1D1).
- •Participants with brain metastasis/leptomeningeal disease are eligible if protocol specified criteria are met.
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 homologue 3 (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.
- •Has received any of the comparators used in this study or any topoisomerase I inhibitor.
- •Has inadequate washout period before randomization as specified in the protocol.
- •Has any of the following conditions within the past 6 months: cerebrovascular accident, transient ischemic attack, or another arterial thromboembolic event.
- •Has uncontrolled or significant cardiovascular (CV) disease.
- •Has clinically significant corneal disease.
- •All of the following indicators of interstitial lung disease (ILD)/pneumonitis are excluded:
- •Any history of ILD/pneumonitis irrespective of steroid use, except for a history of radiation pneumonitis that did not require steroids.
- •Current diagnosis of ILD.
- •Clinical or radiographic suspicion of ILD for which the diagnosis of ILD cannot be ruled out. Radiographic findings may include presence of lung parenchymal fibrosis, combined fibrosis and emphysema (CPFE), and/or interstitial lung abnormalities such as reticular opacities, traction bronchiectasis, honeycombing, or extensive ground glass opacities. Screening computed tomography (CT) scans must be submitted for independent central radiology review and results before randomization.
- •Has clinically severe pulmonary compromise resulting from intercurrent pulmonary illnesses, including, but not limited to, any underlying pulmonary disorder and potential pulmonary involvement caused by any autoimmune, connective tissue, or inflammatory disorders, prior pneumonectomy, or requirement for supplemental oxygen.
Arms & Interventions
Treatment of Physician's Choice (TPC)
Active Comparator
Participants will be randomized to receive topotecan or lurbinectedin, or amrubicin, as per investigator's choice and per locally approved label (indicated dose and frequency), until a treatment discontinuation criteria are met as specified in the protocol.
Intervention: Amrubicin (Drug)
Treatment of Physician's Choice (TPC)
Active Comparator
Participants will be randomized to receive topotecan or lurbinectedin, or amrubicin, as per investigator's choice and per locally approved label (indicated dose and frequency), until a treatment discontinuation criteria are met as specified in the protocol.
Intervention: Lurbinectedin (Drug)
Treatment of Physician's Choice (TPC)
Active Comparator
Participants will be randomized to receive topotecan or lurbinectedin, or amrubicin, as per investigator's choice and per locally approved label (indicated dose and frequency), until a treatment discontinuation criteria are met as specified in the protocol.
Intervention: Topotecan (Drug)
Ifinatamab deruxtecan (I-DXd)
Experimental
Participants will be randomized to receive 12 milligrams per kilogram (mg/kg) I-DXd, intravenously (IV), as monotherapy on Day 1 of each 21-day cycle, once every 3 weeks (Q3W), until clinical or radiologic evidence of progression of disease determined by the investigator, unacceptable toxicity, withdrawal of informed consent, death, loss to follow-up, or other treatment discontinuation criteria are met as specified in the protocol.
Intervention: Ifinatamab deruxtecan (Drug)
Outcomes
Primary Outcomes
Overall Survival (OS)
Time Frame: From the date of randomization to the date of death due to any cause, up to approximately 3.7 years
OS is defined as the time interval from the date of randomization to the date of death due to any cause.
Number of Participants With Objective Response Rate Assessed by Blinded Independent Central Review
Time Frame: Baseline up until documented progressive disease, death, lost to follow-up, or withdrawal by the participant, up to approximately 5 years
Confirmed objective response rate (ORR) is defined as the sum of the complete response (CR) rate and partial response (PR) rate based on BICR by Response Evaluation Criteria In Solid Tumors (RECIST) v1.1.
Overall Survival
Time Frame: From the date of randomization to the date of death due to any cause, up to approximately 5 years
Secondary Outcomes
- Objective Response (OR) Assessed by Blinded Independent Central Review (BICR) Per Response Evaluation Criteria In Solid Tumors Version 1.1 (RECIST v1.1)(Baseline up until documented progressive disease, death, lost to follow-up, or withdrawal by the participant, up to approximately 3.7 years)
- Number of Participants With OR Assessed by Investigator Per RECIST v1.1(Baseline up until documented progressive disease, death, lost to follow-up, or withdrawal by the participant, up to approximately 3.7 years)
- Progression-free Survival (PFS) as Assessed by BICR and Investigator(Baseline up until documented progressive disease, death, lost to follow-up, or withdrawal by the participant, up to approximately 3.7 years)
- Duration of Response (DoR) as Assessed by BICR and Investigator(From the date of first documentation of BOR (CR or PR) to the first documentation of objective progression or to death due to any cause, whichever occurs first, up to approximately 3.7 years)
- Disease Control as Assessed by BICR and Investigator(Baseline up until documented progressive disease, death, lost to follow-up, or withdrawal by the participant, up to approximately 3.7 years)
- Time to Response (TTR) as Assessed by BICR and Investigator(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 3.7 years)
- Change from Baseline in The European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ)-C30(Baseline up to 3.7 years)
- Change from Baseline in The European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Lung Cancer 29 (EORTC QLQ-LC29)(Baseline up to 3.7 years)
- Number of Participants With Treatment-emergent Adverse Events (TEAEs)(Up to 3.7 years)
- Percentage of Participants Who are Anti-Drug Antibody (ADA)-Positive at Any Time (Baseline and Post-baseline) and Who Have a Treatment-emergent Anti-Drug Antibody(Baseline up to 3.7 years)
- Pharmacokinetic Parameter Maximum Concentration (Cmax) for I-DXd, Total Anti-B7-H3 Antibody, and MAAA-1181a(Cycle 1 before infusion (BI), end of infusion EOI), and 3, 6, 24, 72, 168, 336 and 504 hours (hrs) post dose; Cycle 2 BI and EOI; Cycle 3 BI, EOI and 6 hrs post dose; Cycles 4, 5, and every 2 cycles thereafter up to 3.7 years BI (each cycle is 21 days))
- Pharmacokinetic Parameter Time to Maximum Concentration (Tmax) for I-DXd, Total Anti-B7-H3 Antibody, and MAAA-1181a(Cycle 1 before infusion (BI), end of infusion EOI), and 3, 6, 24, 72, 168, 336 and 504 hours (hrs) post dose; Cycle 2 BI and EOI; Cycle 3 BI, EOI and 6 hrs post dose; Cycles 4, 5 and every 2 cycles thereafter up to 3.7 years BI (each cycle is 21 days))
- Pharmacokinetic Parameter Area Under the Plasma Concentration-Time Curve Up to the Last Quantifiable Time Point (AUClast) for I-DXd, Total Anti-B7-H3 Antibody, and MAAA-1181a(Cycle 1 before infusion (BI), end of infusion EOI), and 3, 6, 24, 72, 168, 336 and 504 hours (hrs) post dose; Cycle 2 BI and EOI; Cycle 3 BI, EOI and 6 hrs post dose; Cycles 4, 5, and every 2 cycles thereafter up to 3.7 years BI (each cycle is 21 days))
- Pharmacokinetic Parameter Area Under the Plasma Concentration-Time Curve dosing interval (AUCtau) for I-DXd, Total Anti-B7-H3 Antibody, and MAAA-1181a(Cycle 1 before infusion (BI), end of infusion EOI), and 3, 6, 24, 72, 168, 336 and 504 hours (hrs) post dose; Cycle 2 BI and EOI; Cycle 3 BI, EOI and 6 hrs post dose; Cycles 4, 5, and every 2 cycles thereafter up to 3.7 years BI (each cycle is 21 days))
- Number of Participants With Objective Response Rate Assessed by Investigator(Baseline up until documented progressive disease, death, lost to follow-up, or withdrawal by the participant, up to approximately 5 years)
- Progression-free Survival As Assessed by Blinded Independent Central Review and Investigator(Baseline up until documented progressive disease, death, lost to follow-up, or withdrawal by the participant, up to approximately 5 years)
- Duration of Response As Assessed by Blinded Independent Central Review and Investigator(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 5 years)
- Disease Control Rate As Assessed by Blinded Independent Central Review and Investigator(Baseline up until documented progressive disease, death, lost to follow-up, or withdrawal by the participant, up to approximately 5 years)
- Time to Response As Assessed by Blinded Independent Central Review and Investigator(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 5 years)
- Change from Baseline in The European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ)-C30(Baseline up to 5 years)
- Change from Baseline in The European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Lung Cancer 29 (EORTC QLQ-LC29)(Baseline up to 5 years)
- Overall Number of Participants With Treatment-emergent Adverse Events Following I-DXd Monotherapy(Baseline up to 5 years)
- 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 5 years)
- Pharmacokinetic Parameter Maximum Concentration for I-DXd, Total Anti-B7-H3 Antibody, and MAAA-1181a(Cycle 1 before infusion (BI), end of infusion EOI), and 3, 6, 24, 72, 168, 336, and 504 hours (hrs) post dose; Cycle 2 BI and EOI; Cycle 3 BI, EOI, and 6 hrs postdose; Cycles 4, 5, and every 2 cycles thereafter up to 5 years BI (each cycle is 21 days))
- Pharmacokinetic Parameter Time to Maximum Concentration for I-DXd, Total Anti-B7-H3 Antibody, and MAAA-1181a(Cycle 1 before infusion (BI), end of infusion EOI), and 3, 6, 24, 72, 168, 336, and 504 hours (hrs) post dose; Cycle 2 BI and EOI; Cycle 3 BI, EOI, and 6 hrs postdose; Cycles 4, 5, and every 2 cycles thereafter up to 5 years BI (each cycle is 21 days))
- Pharmacokinetic Parameter Area Under the Plasma Concentration-Time Curve for I-DXd, Total Anti-B7-H3 Antibody, and MAAA-1181a(Cycle 1 before infusion (BI), end of infusion EOI), and 3, 6, 24, 72, 168, 336, and 504 hours (hrs) post dose; Cycle 2 BI and EOI; Cycle 3 BI, EOI, and 6 hrs postdose; Cycles 4, 5, and every 2 cycles thereafter up to 5 years BI (each cycle is 21 days))
Investigators
Study Sites (434)
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