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)
Overview
- Phase
- Phase 3
- Intervention
- Ifinatamab deruxtecan
- Conditions
- Not specified
- Sponsor
- Daiichi Sankyo
- Enrollment
- 540
- Locations
- 453
- Primary Endpoint
- Number of Participants With Objective Response Rate Assessed by Blinded Independent Central Review
- Status
- Recruiting
- Last Updated
- 2 months ago
Overview
Brief Summary
This study was 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 improves objective response rate (ORR) and 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.
Investigators
Clinical Trial Office
Scientific
Daiichi Sankyo Inc.
Eligibility Criteria
Inclusion Criteria
- •Participants must meet all the following criteria to be eligible for randomization into the study:
- •Sign and date the informed consent form 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 informed consent form 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 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 ≤1 within 7 days prior to Cycle 1 Day 1 (C1D1).
- •Has no evidence of brain or leptomeningeal disease (spinal cord or central nervous system \[CNS\] metastases) based on history and physical examination. Subjects must require no treatment with steroids or anticonvulsants and have a stable neurologic status for at least 2 weeks prior to the first dose of study drug.
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 disease.
- •Has clinically significant corneal disease.
- •Has any history of ILD/pneumonitis irrespective of steroid use, or current ILD, or suspected ILD, or ILD that cannot be ruled out by imaging at Screening. Participants may be eligible if they had history of radiation pneumonitis that did not require steroids.
- •Examples of suspected ILD/pneumonitis by imaging include the presence of lung parenchymal fibrosis, such as combined pulmonary fibrosis and emphysema (CPFE) and any radiographic features consistent with ILA, including but not limited to, extensive ground glass opacities, reticular opacities, traction bronchiectasis, and honeycombing.
Arms & Interventions
Ifinatamab deruxtecan (I-DXd)
Participants randomized to receive 12 mg/kg I-DXd monotherapy on Day 1 of each 21-day cycle until unacceptable toxicity, progressive disease (PD), or withdrawal of consent as specified in the protocol.
Intervention: Ifinatamab deruxtecan
Treatment of Physician's Choice (TPC)
Participants randomized to receive topotecan, lurbinectedin, or amrubicin, as per investigator's choice and per locally approved label (indicated dose and frequency), until a treatment discontinuation criterion is met as specified in the protocol.
Intervention: Topotecan
Treatment of Physician's Choice (TPC)
Participants randomized to receive topotecan, lurbinectedin, or amrubicin, as per investigator's choice and per locally approved label (indicated dose and frequency), until a treatment discontinuation criterion is met as specified in the protocol.
Intervention: Amrubicin
Treatment of Physician's Choice (TPC)
Participants randomized to receive topotecan, lurbinectedin, or amrubicin, as per investigator's choice and per locally approved label (indicated dose and frequency), until a treatment discontinuation criterion is met as specified in the protocol.
Intervention: Lurbinectedin
Outcomes
Primary Outcomes
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
- 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))