A Study of Ifinatamab Deruxtecan Versus Treatment of Physician's Choice in Subjects With Relapsed Small Cell Lung Cancer

Official title

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

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.

Interventions

• Drug Ifinatamab deruxtecan
  12 mg/kg intravenous dose on Day 1 of each 21-day cycle
• Drug Topotecan
  Topotecan will be administered per local standard-of-care (SoC)
• Drug Amrubicin
  Amrubicin will be administered per local SoC
• Drug Lurbinectedin
  Lurbinectedin will be administered per local SoC

Primary outcome measures

• 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]

Secondary outcome measures (12)

• Objective Response (OR) Assessed by Blinded Independent Central Review (BICR) Per Response Evaluation Criteria In Solid Tumors Version 1.1 (RECIST v1.1) [Time frame: 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 [Time frame: 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 [Time frame: 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 [Time frame: 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 [Time frame: 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 [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 3.7 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 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) [Time frame: Baseline up to 3.7 years]
• Number of Participants With Treatment-emergent Adverse Events (TEAEs) [Time frame: 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 [Time frame: Baseline up to 3.7 years]
• Pharmacokinetic Parameter Maximum Concentration (Cmax) 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 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 [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 post dose; Cycles 4, 5 and every 2 cycles thereafter up to 3.7 years BI (each cycle is 21 days)]

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 (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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

United States · 30 centers

• Highlands Oncology Group — Springdale
• Clinical Research Providence Medical Foundation — Fullerton
• UCLA Hematology-Oncology — Los Angeles
• UCSF Mission Bay Mission Hall — San Francisco
• University of Miami Hospital and Clinics Sylvester Comprehensive Cancer Center — Miami
• AdventHealth Orlando, Cancer Institute — Orlando
• H. Lee Moffitt Cancer Center and Research Institute, Inc — Tampa
• Rush MD Anderson Cancer Center — Chicago
• … and 22 more centers

China · 26 centers

• China-Japan Friendship Hospital — Beijing
• Beijing Cancer Hospital — Beijing
• Beijing Chest Hospital,Capital Medical University — Beijing
• Jilin Province Tumor Hospital — Changchun
• Hunan Cancer Hospital — Changsha
• Sichuan Cancer Hospital — Chengdu
• West China Hospital, Sichuan University — Chengdu
• Chongqing University Cancer Hospital — Chongqing
• … and 18 more centers

France · 18 centers

Center list to be confirmed — check the primary protocol.

Spain · 17 centers

Center list to be confirmed — check the primary protocol.

Italy · 16 centers

Center list to be confirmed — check the primary protocol.

Germany · 14 centers

Center list to be confirmed — check the primary protocol.

Japan · 13 centers

Center list to be confirmed — check the primary protocol.

Brazil · 11 centers

• Departmento de Pesquisa Clinica- Hospital de Amor de Barretos — Barretos
• Cepon - Centro de Pesquisas Oncolăgicas de Santa Catarina — Florianópolis
• Clínica de Neoplasias Litoral — Itajaí
• Hospital São Lucas Da Pucrs — Porto Alegre
• Cepho Centro de Estudos E Pesquisas de Hematologia E Oncologia — Santo André
• Fundacao Faculdade Regional de Medicina de Sao Jose Do Rio Preto — São José do Rio Preto
• ICESP Instituto do Câncer do Estado de São Paulo Octavio Frias de Oliveira — São Paulo
• Hospital Sirio-Libanes — São Paulo
• … and 3 more centers

South Korea · 9 centers

Center list to be confirmed — check the primary protocol.

Greece · 8 centers

Center list to be confirmed — check the primary protocol.

Taiwan · 8 centers

Center list to be confirmed — check the primary protocol.

Australia · 7 centers

• Ballarat Base Hospital — Ballarat
• Flinders Medical Centre (Fmc) — Bedford Park
• Chris O Brien Lifehouse — Camperdown
• Sunshine Hospital — St Albans
• St John of God Subiaco Hospital — Subiaco
• Townsville Cancer Centre — Townsville
• Princess Alexandra Hospital — Woolloongabba

Turkey (Türkiye) · 7 centers

Center list to be confirmed — check the primary protocol.

Belgium · 6 centers

• Cliniques Universitaires Saint-Luc — Brussels
• Universitair Ziekenhuis Antwerpen — Edegem
• Jessa Ziekenhuis Hospital — Hasselt
• Centre Hospitalier Universitaire de Liege — Liège
• AZ DELTA — Roeselare
• Chu Ucl Namur — Yvoir

Austria · 5 centers

• Landeskrankenhaus Feldkirch — Feldkirch
• Landesklinikum Krems — Krems
• Kepler University Hospital — Linz
• Wiener Gesundheitsverband Klinik Penzing — Vienna
• Klinik Floridsdorf — Vienna

Canada · 5 centers

• William Osler Health System - Brampton Civic Hospital — Brampton
• Cross Cancer Institute — Edmonton
• Institut Universitaire de Cardiologie et de Pneumologie de Quebec — Québec
• Princess Margaret Cancer Center — Toronto
• Cancercare Manitoba — Winnipeg

Hungary · 5 centers

Center list to be confirmed — check the primary protocol.

Poland · 5 centers

Center list to be confirmed — check the primary protocol.

Portugal · 5 centers

Center list to be confirmed — check the primary protocol.

Netherlands · 4 centers

Center list to be confirmed — check the primary protocol.

Romania · 4 centers

Center list to be confirmed — check the primary protocol.

Czechia · 3 centers

Center list to be confirmed — check the primary protocol.

Switzerland · 3 centers

Center list to be confirmed — check the primary protocol.

Publications

• 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. PMID 41055143

Identifiers

NCT: NCT06203210 · DS7300-188 · 2023-509628-16-00 · 2031230631

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗