Ifinatamab Deruxtecan (I-DXd) in Subjects With Pretreated Extensive-Stage Small Cell Lung Cancer (ES-SCLC)

NCT05280470 | Active Not Recruiting Phase 2 FDA Drug

• 3 other identifiers: DS7300-1272022-000503-132041220019
• Study Type: interventional
• Target: 187
• Locations: 8 countries
• Sites: 58

Brief Summary

This 2-part study intends to define the recommended Phase 2 dose of ifinatamab deruxtecan (I-DXd) based on the efficacy, safety, and pharmacokinetics (PK) results observed in participants with Extensive-stage Small Cell Lung Cancer (ES-SCLC) who received at least 1 prior line of platinum-based chemotherapy and a maximum of 3 prior lines of therapy (Part 1) and a minimum of two previous lines of systemic therapy (Part 2). This study will also investigate I-DXd anti-tumor activity in this population.

Conditions

Extensive-stage Small-cell Lung Cancer

Keywords

Relapsed/Refractory Extensive-stage Small-cell Lung Cancer; DS-7300a; B7-H3 Antibody Drug Conjugate; Ifinatamab Deruxtecan; I-DXd

Outcome Measures

Primary Outcomes (1)

• Percentage of Participants With Objective Response Rate (ORR) Based on Blinded Independent Central Review (BICR) Following Treatment With I-DXd in Participants With Pretreated ES-SCLC

  ORR was defined as the percentage of participants who achieved a best overall response (BOR) of confirmed Complete Response (CR) or Partial Response (PR), assessed by BICR based on RECIST version 1.1. For all target, non-target, and new lesions, CR was defined as a disappearance of all lesions and PR was defined as at least a 30% decrease in the sum of diameters of all lesions.

  Up to approximately 36 months

Secondary Outcomes (13)

• Number of Participants With Treatment-Emergent Adverse Events (TEAEs) Following Treatment With I-DXd in Participants With Pretreated ES-SCLC

  Up to approximately 36 months

• Progression-Free Survival (PFS) Following Treatment With I-DXd in Participants With Pretreated ES-SCLC

  From enrollment until disease progression or death (whichever occurs first), up to approximately 36 months

• Duration of Response (DoR) Following Treatment With I-DXd in Participants With Pretreated ES-SCLC

  From enrollment until disease progression or death (whichever occurs first), up to approximately 36 months

• Overall Survival (OS) Following Treatment With I-DXd in Participants With Pretreated ES-SCLC

  From enrollment until death, up to approximately 36 months

• Time to Response (TTR) Following Treatment With I-DXd in Participants With Pretreated ES-SCLC

  From enrollment until disease progression or death (whichever occurs first), up to approximately 36 months

Study Arms (2)

Ifinatamab Deruxtecan (8 mg/kg)

EXPERIMENTAL

Participants will be randomized to receive I-DXd at 8 mg/kg.

Drug: Ifinatamab Deruxtecan (I-DXd)

Ifinatamab Deruxtecan (12 mg/kg)

EXPERIMENTAL

Participants will be randomized to receive I-DXd at 12 mg/kg. This arm will consist of participants from Part 1 and Part 2 who receive I-DXd 12 mg/kg.

Drug: Ifinatamab Deruxtecan (I-DXd)

Interventions

Ifinatamab Deruxtecan (I-DXd) DRUG

I-DXd will be administered as an intravenous (IV) infusion on Day 1 of each 21-day cycle (every Q3W).

Also known as: DS-7300a

Ifinatamab Deruxtecan (12 mg/kg); Ifinatamab Deruxtecan (8 mg/kg)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Participants must meet all 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.
• Participant must have at least one lesion, not previously irradiated, amenable to core biopsy.
• Male or female subjects aged ≥18 years (follow local regulatory requirements if the legal age of consent for study participation is \>18 years old).
• Histologically or cytologically documented ES-SCLC.
• At least one measurable lesion according to RECIST v1.1 as assessed by the investigator.
• Prior therapy with at least one platinum-based line as systemic therapy for extensive-stage disease with at least two cycles of therapy (except in the case of early objective PD) and beginning with protocol version 3.0, a minimum of two previous lines of systemic therapy.
• Documentation of radiological disease progression on or after most recent systemic therapy.
• Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1.

You may not qualify if:

• Participants who meet any of the following criteria will be disqualified from entering the study:
• Prior treatment with orlotamab, enoblituzumab, or other 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.
• Clinically active brain metastases, spinal cord compression or leptomeningeal carcinomatosis, defined as untreated or symptomatic, or requiring therapy with steroids or anticonvulsants to control associated symptoms.
• Any of the following conditions within the past 6 months: cerebrovascular accident, transient ischemic attack, or another arterial thromboembolic event.
• Clinically significant corneal disease.
• Uncontrolled or significant cardiovascular disease.
• History of (non-infectious) interstitial lung disease (ILD)/pneumonitis that required corticosteroids, current ILD/pneumonitis, or suspected ILD/pneumonitis that cannot be ruled out by imaging at screening.
• Clinically severe pulmonary compromise resulting from intercurrent pulmonary illnesses,
• Chronic steroid treatment (dose of 10 mg daily or more prednisone equivalent), except for low-dose inhaled steroids (for asthma/COPD) or topical steroids (for mild skin conditions) or intra-articular steroid injections.
• History of malignancy other than SCLC within the 3 years prior to enrollment, except adequately resected non-melanoma skin cancer, curatively treated in situ disease, superficial gastrointestinal (GI) tract tumors and non-muscle invasive bladder cancer curatively resected by endoscopic surgery.
• History of allogeneic bone marrow, stem cell, or solid organ transplant.
• Unresolved toxicities from previous anticancer therapy, defined as toxicities (other than alopecia) not yet resolved to National Cancer Institute- Common Terminology Criteria for Adverse Events Version 5.0 (NCI-CTCAE V5.0), Grade ≤1 or baseline.
• History of hypersensitivity to the drug substances, inactive ingredients in the drug product or severe hypersensitivity reactions to other monoclonal antibodies.
• Evidence of ongoing uncontrolled systemic bacterial, fungal, or viral infection.

Sponsors & Collaborators

• Daiichi Sankyo: lead
• Merck Sharp & Dohme LLC: collaborator

Study Sites (58)

Highlands Oncology Group

Springdale, Arkansas, 72762, United States

Location

The Cancer Specialists, Llc

Jacksonville, Florida, 32256, United States

Location

H. Lee Moffitt Cancer Center and Research Institute

Tampa, Florida, 33612, United States

Location

University of Chicago Medical Center

Chicago, Illinois, 60637, United States

Location

Johns Hopkins Sidney Kimmel Comprehensive Cancer Center

Baltimore, Maryland, 21287, United States

Location

Dana-Faeber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

Henry Ford Hospital

Detroit, Michigan, 48202, United States

Location

Cancer and Hematology Centers of Western Michigan

Grand Rapids, Michigan, 49503, United States

Location

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

Hackensack Meridian Health-Southern Ocean Medical Center

Manahawkin, New Jersey, 08050, United States

Location

Memorial Sloan-Kettering Cancer Center (Mskcc) - New York

New York, New York, 10065, United States

Location

Montefiore Medical Center Prime

The Bronx, New York, 10461, United States

Location

Duke University Health System

Durham, North Carolina, 27703, United States

Location

Sarah Cannon (Tennessee Oncology - Nashville)

Nashville, Tennessee, 37203, United States

Location

Millennium Physicians Association, Llp

Houston, Texas, 77090, United States

Location

University of Washington Medical Center

Seattle, Washington, 98195, United States

Location

Jilin Cancer Hospital

Changchun, 130012, China

Location

Hunan Cancer Hospital

Changsha, 410013, China

Location

West China Hospital, Sichuan University

Chengdu, 610041, China

Location

Guangdong Provincial People'S Hospital

Guangdong, 510000, China

Location

Zhejiang Cancer Hospital

Hangzhou, 310022, China

Location

Linyi Cancer Hospital

Linyi, 276000, China

Location

Fudan University Shanghai Cancer Center

Shanghai, 200032, China

Location

Union Hospital of Tongji Medical College Huazhong University of Science and Technology

Wuhan, 430022, China

Location

Centre Hospitalier Intercommunal de Créteil

Créteil, 94000, France

Location

Centre Leon Berard

Lyon, 69008, France

Location

Hôpital Nord - Chu Marseille

Marseille, 13915, France

Location

CHU de Montpellier - Hôpital Arnaud de Villeneuve

Montpellier, 34295, France

Location

Hopital Arnaud de Villeneuve

Montpellier, 34295, France

Location

Institut Curie - Site de Paris

Paris, 75005, France

Location

Hopital Tenon

Paris, 75020, France

Location

Evangelische Lungenklinik Berlin

Berlin, 13125, Germany

Location

Universitaetsklinikum Essen

Essen, 45147, Germany

Location

National Cancer Center Hospital

Chūōku, 104-0045, Japan

Location

National Cancer Center Hospital East

Kashiwa, 277-8577, Japan

Location

The Cancer Institute Hospital of Jfcr

Kōtoku, 135-8550, Japan

Location

Shizuoka Cancer Center

Nagaizumi-chō, 411-8777, Japan

Location

Osaka International Cancer Institute

Osaka, 541-8567, Japan

Location

Kindai University Hospital

Ōsaka-sayama, 589-8511, Japan

Location

Kanagawa Cancer Center

Yokohama, 241-8515, Japan

Location

National Cancer Center

Goyang-si, 10408, South Korea

Location

Seoul National University Bundang Hospital

Seongnam-si, 13620, South Korea

Location

Seoul National University Hospital

Seoul, 03080, South Korea

Location

Samsung Medical Center

Seoul, 06351, South Korea

Location

Asan Medical Center

Seoul, 5505, South Korea

Location

Complejo Hospitalario Universitario A Coruña

A Coruña, 15006, Spain

Location

Hospital Universitario Vall Dhebron

Barcelona, 08035, Spain

Location

Ico L'Hospitalet - Hospital Duran I Reynals

L'Hospitalet de Llobregat, 08908, Spain

Location

Hospital Universitario Ramon Y Cajal

Madrid, 28034, Spain

Location

Hospital Universitario 12 de Octubre

Madrid, 28041, Spain

Location

Hospital Regional Universitario Malaga

Málaga, 29011, Spain

Location

Hospital Virgen Macarena

Seville, 41009, Spain

Location

Chang Gung Medical Foundation - Kaohsiung Branch

Kaohsiung City, 83301, Taiwan

Location

Taichung Veterans General Hospital

Taichung, 40705, Taiwan

Location

National Cheng Kung University Hospital Nckuh

Tainan, 704, Taiwan

Location

National Taiwan University Hospital

Taipei, 10002, Taiwan

Location

Taipei Veterans General Hospital

Taipei, 11217, Taiwan

Location

Chang Gung Memorial Hospital Linkou

Taoyuan District, 333, Taiwan

Location

Related Publications (1)

• Rudin CM, Johnson ML, Paz-Ares L, Nishio M, Hann CL, Girard N, Rocha P, Hayashi H, Sakai T, Kim YJ, Hu H, Qian M, Singh J, Godard J, Tang M, Ahn MJ. Ifinatamab Deruxtecan in Patients With Extensive-Stage Small Cell Lung Cancer: Primary Analysis of the Phase II IDeate-Lung01 Trial. J Clin Oncol. 2026 Feb;44(4):261-273. doi: 10.1200/JCO-25-02142. Epub 2025 Oct 14.

  PMID: 41086386 DERIVED

MeSH Terms

Conditions

Small Cell Lung Carcinoma

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Study Officials

• Global Clinical Leader

  Daiichi Sankyo

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 23, 2022
• First Posted: March 15, 2022
• Study Start: March 9, 2022
• Primary Completion: March 3, 2025
• Study Completion (Estimated): December 15, 2026
• Last Updated: February 25, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: Studies for which the medicine and indication have received European Union (EU) and United States (US), and/or Japan (JP) marketing approval on or after 01 January 2014 or by the US or EU or JP Health Authorities when regulatory submissions in all regions are not planned and after the primary study results have been accepted for publication.
• Access Criteria: Formal request from qualified scientific and medical researchers on IPD and clinical study documents from clinical trials supporting products submitted and licensed in the United States, the European Union and/or Japan from 01 January 2014 and beyond for the purpose of conducting legitimate research. This must be consistent with the principle of safeguarding study participants' privacy and consistent with provision of informed consent.

Locations

DE (2); FR (7); US (16); TW (6); ES (7); KR (5); JP (7); CN (8)