Back to Trials
NCT06362252PHASE1, PHASE2Recruiting

A Study of I-DXd in Combination With Atezolizumab With or Without Carboplatin as First-Line Induction or Maintenance in Subjects With Extensive Stage-Small Cell Lung Cancer (IDeate-Lung03)

Daiichi Sankyo

Start Date

7/22/2024

Completion Date

12/30/2026

Summary

This study is designed to evaluate the safety and efficacy of ifinatamab deruxtecan (I-DXd) in combination with immune checkpoint inhibitor (ICI) atezolizumab with or without carboplatin in participants with extensive stage-small cell lung cancer (ES-SCLC) in the first-line (1L) setting.

Detailed Description

This study consists of two parts and two cohorts: Part A (Phase 1b; Safety Run-in) and Part B (Phase 2; Dose Optimization), Cohort 1 (I-DXd in maintenance) and Cohort 2 (I-DXd in induction + maintenance). The primary objective of this study is to evaluate the safety and tolerability of I-DXd in combination with atezolizumab with or without carboplatin by assessing treatment-emergent adverse events (TEAEs) and other safety parameters which will inform optimal dose selection of I-DXd in the combination regimens (Dose Optimization Part B) of this study.

Eligibility Criteria

Age Range: 18 years to No maximum

A full list of inclusion/exclusion criteria are available in the protocol. Inclusion Criteria Participants must meet all of the following criteria to be eligible for enrollment into the study: 1. Sign and date the informed consent form (ICF), 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 ICF is signed. 3. Has histologically or cytologically confirmed diagnosis of ES-SCLC who will require first-line (IL) therapy. 4. For Cohort 1, participant has received 4 cycles of 1L induction therapy with carboplatin, etoposide, and atezolizumab for ES-SCLC with ongoing CR PR, CR, or SD per RECIST v1.1 assessed by the investigator. For Cohort 2, participant has received no prior treatment for ES-SCLC. 5. For Cohort 2, participant has at least one measurable lesion according to RECIST v1.1 on computed tomography (CT) or magnetic resonance imaging (MRI) as assessed by the investigator. 6. For Cohort 2, participant must have at least one lesion, amenable to core biopsy, and must consent to provide a pretreatment biopsy tissue sample and on-treatment biopsy. 7. Has ECOG PS of ≤1 (assessed within 7 days before enrollment/randomization). 8. Has adequate organ and bone marrow function within 7 days before the start of study treatment as specified in the study protocol. 9. A female subject of childbearing potential (POCBP) is eligible to participate if the following conditions are met: 1. Subject is not pregnant as confirmed by highly sensitive pregnancy test during Screening (within 3 days prior to enrollment/randomization) 2. Subject does not breastfeed during the treatment period and for at least 8/5/6 months after last dose of I-DXd/atezolizumab/carboplatin, respectively. 3. Subject agrees to adhere to a contraceptive method that is highly effective and agrees not to donate eggs (ova, oocytes) to others or freeze/store eggs during the treatment period and for at least the time needed to eliminate each study drug after the last dose. The length of time required to continue contraception and avoid donating/freezing eggs after last dose for I-DXd/atezolizumab/carboplatin is 8/5/6 months, respectively. Preservation of eggs may be considered prior to first dose of study drug. 10. A male subject capable of producing sperm is eligible to participate if he agrees to the following during the intervention period and for at least the time needed to eliminate each study drug. The length of time required to continue contraception and avoid donating sperm after last dose for I-DXd/atezolizumab/carboplatin is 6/5/6 months, respectively. 1. Avoid donating sperm. 2. Adhere to either of the contraception methods: true abstinence from penile-vaginal intercourse or uses a penile/external condom when having penile-vaginal intercourse with a non-subject of childbearing potential plus partner use of an additional contraceptive method. 11. Is willing and able to comply with scheduled visits, drug administration plan, laboratory tests, other study procedures, and study restrictions. 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-H3 targeted agents, including I-DXd. 2. Prior discontinuation of an ADC that consists of an exatecan derivative (eg, trastuzumab deruxtecan) due to treatment-related toxicities. 3. Has received prior treatment with CD137 agonists or ICIs, including anti-cytotoxic T-cell lymphocyte-4, anti-PD-1, and anti-PD-L1 therapeutic antibodies, except for atezolizumab for Cohort 1. 4. Has inadequate washout period before enrollment/randomization as specified in the study protocol. 5. Has any of the following within the past 6 months: cerebrovascular accident, transient ischemic attack, or another arterial thromboembolic event. 6. Has clinically active brain metastases, spinal cord compression, or leptomeningeal carcinomatosis, defined as untreated and symptomatic, or requiring therapy with steroids or anticonvulsants to control associated symptoms. 7. Has clinically significant corneal disease. 8. Has uncontrolled or significant cardiovascular disease,. 9. Has history of (non-infectious) ILD/pneumonitis that required corticosteroids, current ILD/pneumonitis, or suspected ILD/pneumonitis that cannot be ruled out by imaging at Screening. 10. Has clinically severe pulmonary compromise resulting from intercurrent pulmonary illnesses 11. Is on chronic steroid treatment (dose of 10 mg daily or more prednisone equivalent), except for low-dose inhaled steroids (for asthma/chronic obstructive pulmonary disease, topical steroids (for mild skin conditions), or intra-articular steroid injections. 12. Has history of malignancy other than SCLC within the 5 years prior to randomization/enrollment, except adequately resected non-melanoma skin cancer, curatively treated in situ disease, superficial gastrointestinal tract tumors, and non-muscle invasive bladder cancer curatively resected by endoscopic surgery. 13. Has history of allogeneic bone marrow, stem cell, or solid organ transplant. 14. Has unresolved toxicities from previous anticancer therapy, defined as toxicities (other than alopecia) not yet resolved to NCI-CTCAE V5.0, Grade ≤1 or baseline. 15. Has history of hypersensitivity to the drug substances, inactive ingredients in the drug product or severe hypersensitivity reactions to other monoclonal antibodies. 16. Has evidence of ongoing uncontrolled systemic bacterial, fungal, or viral infection. 17. Has active or uncontrolled human immunodeficiency virus (HIV) infection. 18. Has active or uncontrolled hepatitis B or C virus (HBV or HCV) infection. 19. Has history of autoimmune disease. 20. Has any evidence of severe or uncontrolled systemic diseases. 21. Has received a live vaccine within 30 days prior to the first dose of study drug. 22. Is a female who is pregnant or breastfeeding or planning to become pregnant. 23. Has 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; alter the absorption, distribution, metabolism, or excretion of the study drug; or confound the assessment of study results. 24. Has psychological, social, familial, or logistical factors that would prevent regular follow-up

Interventions

DRUG

Ifinatamab deruxtecan

DRUG

Atezolizumab

DRUG

Carboplatin

Interested in This Trial?

Contact the trial locations directly using the information below to learn more about enrollment.

Expressing interest lets you review the study and consent before we connect you with the research site.

Conditions

Extensive Stage-small Cell Lung Cancer

Locations

University of Alabama -Birmingham

Birmingham, Alabama 35233

United States

Mayo Clinic Arizona

Phoenix, Arizona 85054

United States

David Geffen School of Medicine

Los Angeles, California 90095

United States

Hoag Memorial Hospital Presbyterian

Newport Beach, California 92663

United States

Mayo Clinic-Jacksonville

Jacksonville, Florida 32224

United States

Advent Health Orlando

Orlando, Florida 32804

United States

Moffitt Cancer Center

Tampa, Florida 33612

United States

Robert H. Lurie Comprehensive Cancer Center of Northwestern University

Chicago, Illinois 60611

United States

Henry Ford Hospital

Detroit, Michigan 48202

United States

Regents of the University of Minnesota

Minneapolis, Minnesota 55455

United States

Mayo Clinic

Rochester, Minnesota 55905

United States

Dartmouth-Hitchcock Medical Center

Lebanon, New Hampshire 03766

United States

Astera Cancer Care

East Brunswick, New Jersey 08816

United States

John Theurer Cancer Center At Hackensack Umc

Hackensack, New Jersey 07601

United States

New York University Cancer Center - Laura and Isaac Perlmutter Cancer Center At Nyu Langone

Mineola, New York 11501

United States

NYU Langone Hospital - Long Island

Mineola, New York 11501

United States

Memorial Sloan Kettering Cancer Center

New York, New York 10021

United States

Columbia University Hervert Irving Comprehensive Cancer Center

New York, New York 10032

United States

Montefiore Medical Center

New York, New York 10461

United States

Lancaster General Hospital - Ann B Barshinger Cancer Institute

Lancaster, Pennsylvania 17601

United States

University of Pennsylvania, Abramson Cancer Center

Philadelphia, Pennsylvania 19104

United States

Thomas Jefferson University Hospital - Central

Philadelphia, Pennsylvania 19107

United States

Scri Oncology Partners

Nashville, Tennessee 37203

United States

Next Virginia

Fairfax, Virginia 22031

United States

Northwest Cancer Specialists, P.C.-Vancouver

Vancouver, Washington 98684

United States

Medical College of Wisconsin

Milwaukee, Wisconsin 53226

United States

Hopital Albert Calmette - Chu Lille

Lille, 59037

France

Centre Léon Bérard

Lyon, 69008

France

Hôpital de la Timone

Marseille, 13005

France

Institut Curie - Site de Paris

Paris, 75005

France

Hopital Tenon

Paris, 75020

France

Chu Rennes - Hopital Pontchaillou

Rennes, 35000

France

CHU Nantes - Hôpital Guillaume et René Laënnec

Saint-Herblain, 44805

France

Hôpital Foch

Suresnes, 92151

France

Institut Gustave Roussy

Villejuif, 94805

France

NHO Himeji Medical Center

Himeji-shi, 670-8520

Japan

Kansai Medical University Hospital

Hirakata-shi, 573-1191

Japan

National Cancer Center Hospital East

Kashiwa, 277-8577

Japan

The Cancer Institute Hospital of Jfcr

Kōtoku, 135-8550

Japan

Social Welfare Organization Saiseikai Imperial Gift Foundation, Inc. Saiseikai Kumamoto Hospital

Kumamoto, 861-4193

Japan

Shizuoka Cancer Center

Nagaizumi-cho, 411-8777

Japan

Niigata Cancer Center Hospital

Niigata, 951-8566

Japan

Okayama University Hospital

Okayama, 700-8558

Japan

Kindai University Hospital

Ōsaka-sayama, 589-8511

Japan

Tokushima University Hospital

Tokushima, 770-8503

Japan

Fujita Health University Hospital

Toyoake-shi, 470-1192

Japan

Hospital Clinic de Barcelona

Barcelona, 08036

Spain

Hospital Universitari Vall D'Hebron

Barcelona, 8035

Spain

Ico Girona - Hospital Universitari de Girona Dr Josep Trueta

Girona, 17007

Spain

ICO l'Hospitalet - Hospital Duran i Reynals

L'Hospitalet de Llobregat, 08908

Spain

Hospital General Universitario Gregorio Marañon

Madrid, 28007

Spain

Hospital Universitario Ramon Y Cajal

Madrid, 28034

Spain

Hospital Universitario 12 de Octubre

Madrid, 28041

Spain

Next Madrid

Madrid, 28223

Spain

Hospital Regional Universitario de Malaga

Málaga, 29010

Spain

Hospital Universitario Virgen Macarena

Seville, 41009

Spain

Hospital Universitario Virgen Del Rocio

Seville, 41013

Spain

Hospital Alvaro Cunqueiro

Vigo, 36312

Spain