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

NCT ID: NCT05280470

Last Updated: 2025-10-28

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 187 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-03-09
• Study Completion Date: 2026-12-15

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.

Detailed Description

This study will consist of 2 parts: dose optimization (Part 1) and extension (Part 2). In the dose optimization part of the study (Part 1), approximately 80 participants with at least 1 prior line of platinum-based chemotherapy and a maximum of 3 prior lines of therapy will be enrolled. Two I-DXd doses will be tested (8 mg/kg Q3W and 12 mg/kg Q3W). In the extension part of the study (Part 2), approximately 70 participants with a minimum of two previous lines of systemic therapy will be enrolled. I-DXd will be administered at the selected dose of 12 mg/kg Q3W.

In Part 1, eligible participants will be randomized in a 1:1 ratio to receive one of the two dose levels of I-DXd. Randomization will be stratified by:

1. Prior receipt or of an anti-programmed death-ligand 1 (PD-[L]1) antibody (yes/no)

2. The chemotherapy-free interval (CTFI) from completion of the first-line therapy to the date of documented radiological Progressive Disease of <90 days vs. ≥90 days in second-line participants as well as the number of lines of therapy. Thus, the stratification factor includes three categories: (1) second-line participants with CTFI <90 days, (2) second-line participants with CTFI ≥90 days, and (3) third- and fourth-line participants.

Conditions

Extensive-stage Small-cell Lung Cancer

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Ifinatamab Deruxtecan (8 mg/kg)

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

Group Type: EXPERIMENTAL

Ifinatamab Deruxtecan (I-DXd)

Intervention Type: DRUG

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

Ifinatamab Deruxtecan (12 mg/kg)

Participants will be randomized to receive I-DXd at 12 mg/kg.

In Part 2, all participants will receive I-DXd 12 mg/kg.

Group Type: EXPERIMENTAL

Ifinatamab Deruxtecan (I-DXd)

Intervention Type: DRUG

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

Interventions

Ifinatamab Deruxtecan (I-DXd)

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

Intervention Type: DRUG

Other Intervention Names

DS-7300a

Eligibility Criteria

Inclusion Criteria

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.

Exclusion Criteria

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.
• Has active or uncontrolled hepatitis B or C infection.
• Active, known, or suspected autoimmune disease.
• Any evidence of severe or uncontrolled systemic diseases (including active bleeding diatheses, psychiatric illness/social situations, substance abuse).
• Has received a live vaccine within 30 days prior to the first dose of study drug.
• Female who is pregnant or breast-feeding or intends to become pregnant during the study.
• Prior or ongoing clinically relevant illness, medical condition, surgical history, physical finding, or laboratory abnormality that, in the investigator's opinion, could affect the safety of the participant.
• Known human immunodeficiency virus (HIV) infection that is not well controlled.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Merck Sharp & Dohme LLC

INDUSTRY

Sponsor Role: collaborator

Daiichi Sankyo

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Global Clinical Leader

Role: STUDY_DIRECTOR

Daiichi Sankyo

Locations

Highlands Oncology Group

Springdale, Arkansas, United States

The Cancer Specialists, Llc

Jacksonville, Florida, United States

H. Lee Moffitt Cancer Center and Research Institute

Tampa, Florida, United States

University of Chicago Medical Center

Chicago, Illinois, United States

Johns Hopkins Sidney Kimmel Comprehensive Cancer Center

Baltimore, Maryland, United States

Dana-Faeber Cancer Institute

Boston, Massachusetts, United States

Henry Ford Hospital

Detroit, Michigan, United States

Cancer and Hematology Centers of Western Michigan

Grand Rapids, Michigan, United States

Washington University School of Medicine

St Louis, Missouri, United States

Hackensack Meridian Health-Southern Ocean Medical Center

Manahawkin, New Jersey, United States

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

New York, New York, United States

Montefiore Medical Center Prime

The Bronx, New York, United States

Duke University Health System

Durham, North Carolina, United States

Sarah Cannon (Tennessee Oncology - Nashville)

Nashville, Tennessee, United States

Millennium Physicians Association, Llp

Houston, Texas, United States

University of Washington Medical Center

Seattle, Washington, United States

Jilin Cancer Hospital

Changchun, , China

Hunan Cancer Hospital

Changsha, , China

West China Hospital, Sichuan University

Chengdu, , China

Guangdong Provincial People'S Hospital

Guangdong, , China

Zhejiang Cancer Hospital

Hangzhou, , China

Linyi Cancer Hospital

Linyi, , China

Fudan University Shanghai Cancer Center

Shanghai, , China

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

Wuhan, , China

Centre Hospitalier Intercommunal de Créteil

Créteil, , France

Centre Leon Berard

Lyon, , France

Hôpital Nord - Chu Marseille

Marseille, , France

CHU de Montpellier - Hôpital Arnaud de Villeneuve

Montpellier, , France

Hopital Arnaud de Villeneuve

Montpellier, , France

Institut Curie - Site de Paris

Paris, , France

Hopital Tenon

Paris, , France

Evangelische Lungenklinik Berlin

Berlin, , Germany

Universitaetsklinikum Essen

Essen, , Germany

National Cancer Center Hospital

Chūōku, , Japan

National Cancer Center Hospital East

Kashiwa, , Japan

The Cancer Institute Hospital of Jfcr

Kōtoku, , Japan

Shizuoka Cancer Center

Nagaizumi-chō, , Japan

Osaka International Cancer Institute

Osaka, , Japan

Kindai University Hospital

Ōsaka-sayama, , Japan

Kanagawa Cancer Center

Yokohama, , Japan

National Cancer Center

Goyang-si, , South Korea

Seoul National University Bundang Hospital

Seongnam-si, , South Korea

Seoul National University Hospital

Seoul, , South Korea

Samsung Medical Center

Seoul, , South Korea

Asan Medical Center

Seoul, , South Korea

Complejo Hospitalario Universitario A Coruña

A Coruña, , Spain

Hospital Universitario Vall Dhebron

Barcelona, , Spain

Ico L'Hospitalet - Hospital Duran I Reynals

L'Hospitalet de Llobregat, , Spain

Hospital Universitario Ramon Y Cajal

Madrid, , Spain

Hospital Universitario 12 de Octubre

Madrid, , Spain

Hospital Regional Universitario Malaga

Málaga, , Spain

Hospital Virgen Macarena

Seville, , Spain

Chang Gung Medical Foundation - Kaohsiung Branch

Kaohsiung City, , Taiwan

Taichung Veterans General Hospital

Taichung, , Taiwan

National Cheng Kung University Hospital Nckuh

Tainan City, , Taiwan

National Taiwan University Hospital

Taipei, , Taiwan

Taipei Veterans General Hospital

Taipei, , Taiwan

Chang Gung Memorial Hospital Linkou

Taoyuan District, , Taiwan

Countries

United States; China; France; Germany; Japan; South Korea; Spain; Taiwan

Other Identifiers

2022-000503-13

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

2041220019

Identifier Type: OTHER

Identifier Source: secondary_id

DS7300-127

Identifier Type: -

Identifier Source: org_study_id