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RecruitingInterventionalPhase 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)

NCT ID: NCT06203210Sponsor: Daiichi SankyoLast updated: 2026-06-02

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.

Arms & interventions

  • DrugIfinatamab deruxtecan

    12 mg/kg intravenous dose on Day 1 of each 21-day cycle

  • DrugTopotecan

    Topotecan will be administered per local SoC.

  • DrugAmrubicin

    Amrubicin will be administered per local SoC.

  • DrugLurbinectedin

    Lurbinectedin will be administered per local SoC

Outcome measures

Primary

  • Number of Participants With Objective Response Rate Assessed by Blinded Independent Central Review

    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.

    Time frame: Baseline up until documented progressive disease, death, lost to follow-up, or withdrawal by the participant, up to approximately 5 years

  • Overall Survival

    Time frame: From the date of randomization to the date of death due to any cause, up to approximately 5 years

Secondary

  • Number of Participants With Objective Response Rate Assessed by Investigator

    Time frame: 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

    Time frame: 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

    Time frame: 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

    Time frame: 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

    Time frame: 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

    Time frame: 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)

    Time frame: Baseline up to 5 years

  • Overall Number of Participants With Treatment-emergent Adverse Events Following I-DXd Monotherapy

    Time frame: 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

    Time frame: Baseline up to 5 years

  • Pharmacokinetic Parameter Maximum Concentration for I-DXd, Total Anti-B7-H3 Antibody, and MAAA-1181a

    Time frame: 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

    Time frame: 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

    Time frame: 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)

Eligibility criteria

Sex: AllAge: 18 Years and olderHealthy volunteers: No
Inclusion Criteria Participants must meet all the following criteria to be eligible for randomization into the study: 1. Sign and date the informed consent form prior to the start of any study-specific qualification procedures. 2. Adults ≥18 years or the minimum legal adult age (whichever is greater) at the time the informed consent form is signed. 3. Has histologically or cytologically documented extensive-stage small cell lung cancer (ES-SCLC). 4. The participant must provide adequate baseline tumor samples with sufficient quantity and quality of tumor tissue content. 5. 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. 6. Has at least 1 measurable lesion according to RECIST v1.1 as assessed by the investigator. 7. Has documentation of radiological disease progression on or after the most recent systemic therapy. 8. Has ECOG PS of ≤1 within 7 days prior to Cycle 1 Day 1 (C1D1). 9. 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: 1. Has received prior treatment with orlotamab, enoblituzumab, or other B7 homologue 3 (B7-H3) targeted agents, including I-DXd. 2. Prior discontinuation of an antibody drug conjugate (ADC) that consists of an exatecan derivative (eg, trastuzumab deruxtecan) due to treatment-related toxicities. 3. Has received any of the comparators used in this study or any topoisomerase I inhibitor. 4. Has inadequate washout period before randomization as specified in the protocol. 5. Has any of the following conditions within the past 6 months: cerebrovascular accident, transient ischemic attack, or another arterial thromboembolic event. 6. Has uncontrolled or significant cardiovascular disease. 7. Has clinically significant corneal disease. 8. 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. 9. 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.

Study locations (30)

Highlands Oncology Group

Springdale, Arkansas, 72762

Recruiting
Principal Investigator · Contact

Clinical Research Providence Medical Foundation

Fullerton, California, 92835

Recruiting
Principal Investigator · Contact

UCLA Hematology-Oncology

Los Angeles, California, 90095

Recruiting
Principal Investigator · Contact

UCSF Mission Bay Mission Hall

San Francisco, California, 94115

Recruiting
Principal Investigator · Contact

University of Miami Hospital and Clinics Sylvester Comprehensive Cancer Center

Miami, Florida, 33136

Recruiting
Principal Investigator · Contact

AdventHealth Orlando, Cancer Institute

Orlando, Florida, 32804

Recruiting
Principal Investigator · Contact

H. Lee Moffitt Cancer Center and Research Institute, Inc

Tampa, Florida, 33612

Not Yet Recruiting
Principal Investigator · Contact

Rush MD Anderson Cancer Center

Chicago, Illinois, 60612

Recruiting
Principal Investigator · Contact

Baptist Health Lexington

Lexington, Kentucky, 40503

Recruiting
Principal Investigator · Contact

University of Maryland Greenebaum Comprehensive Cancer Center

Baltimore, Maryland, 21201

Recruiting
Principal Investigator · Contact

John Hopkins School of Medicine

Baltimore, Maryland, 21287

Recruiting
Principal Investigator · Contact

Dana-Farber Cancer Institute

Boston, Massachusetts, 02216

Recruiting
Principal Investigator · Contact

Henry Ford Health System

Detroit, Michigan, 48202

Not Yet Recruiting
Principal Investigator · Contact

Mercy Clinic Oncology and Hematology Sindelar Cancer Center

St Louis, Missouri, 63128

Recruiting
Principal Investigator · Contact

University of Nebraska Medical Center

Omaha, Nebraska, 68198-6811

Recruiting
Principal Investigator · Contact

Dartmouth-Hitchcock Medical Center

Lebanon, New Hampshire, 03766

Recruiting
Principal Investigator · Contact

Astera Cancer Care

East Brunswick, New Jersey, 08816

Recruiting
Principal Investigator · Contact

Hackensack Meridian Health Jsumc

Neptune City, New Jersey, 07753

Recruiting
Principal Investigator · Contact

Clinical Research Alliance, Inc

Lake Success, New York, 11042

Recruiting
Principal Investigator · Contact

Laura and Isaac Perlmutter Cancer Center at NYU Langone Health Long Island

New York, New York, 10016

Recruiting
Principal Investigator · Contact

New York University Cancer Center - Laura and Isaac

New York, New York, 10016

Recruiting

Montefiore Medical Center Prime

The Bronx, New York, 10461

Not Yet Recruiting
Principal Investigator · Contact

Cleveland Clinic Mercy Hospital

Canton, Ohio, 44708

Recruiting
Principal Investigator · Contact

Oncology/Hematology Care Clinical Trials, Llc

Cincinnati, Ohio, 45236

Recruiting
Principal Investigator · Contact

Providence Portland Medical Center

Portland, Oregon, 97213

Not Yet Recruiting
Principal Investigator · Contact

THE WEST CLINIC, PLLC dba West Cancer Center

Germantown, Tennessee, 38138

Recruiting
Principal Investigator · Contact

Houston Methodist Cancer Center

Houston, Texas, 77030

Recruiting
Principal Investigator · Contact

University of Texas Md Anderson Cancer Center

Houston, Texas, 77030

Recruiting
Principal Investigator · Contact

Texas Oncology, P.A. - Tyler

Tyler, Texas, 75702

Recruiting
Principal Investigator · Contact

Medical College of Wisconsin

Milwaukee, Wisconsin, 53226

Not Yet Recruiting
Principal Investigator · Contact

References

  • Owonikoko TK, Byers L, Cheng Y, Hayashi H, Paz-Ares L, Perol M, Hu H, Qian M, Garcia CR, Godard J, Tang M, Rudin CM. IDeate-Lung02: a Phase 3 study of second-line ifinatamab deruxtecan in patients with relapsed small cell lung cancer. Future Oncol. 2025 Oct;21(25):3275-3282. doi: 10.1080/14796694.2025.2565995. Epub 2025 Oct 7.(PubMed)
A Study of Ifinatamab Deruxtecan Versus Treatment of Physician's Choice in Subjects With Relapsed Small Cell Lung Cancer | Cancerify