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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)

NCT06362252 · Daiichi Sankyo
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Official title
A Phase 1b/2, Multicenter, Open-label Study of Ifinatamab Deruxtecan (I-DXd), a B7-H3 Antibody-Drug Conjugate (ADC), in Combination With Atezolizumab With or Without Carboplatin as First-line Induction or Maintenance, in Subjects With Extensive-stage Small Cell Lung Cancer (ES-SCLC) (IDeate-Lung03)
About this study
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
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
Study design
Enrollment target: 123 participants
Allocation: randomized
Masking: none
Age groups: adult, older_adult
Timeline
Starts: 2024-07-22
Estimated completion: 2026-12-30
Last updated: 2026-02-06
Interventions
Drug: Ifinatamab deruxtecanDrug: AtezolizumabDrug: Carboplatin
Primary outcomes
  • Number of Participants Reporting Dose-limiting Toxicities Following I-DXd in Combination With Atezolizumab With or Without Carboplatin (Part A) (Cycle 1 Day 1 up to Cycle 1 Day 21 (each cycle is 21 days))
  • Overall Number of Participants With Treatment-emergent Adverse Events Following I-DXd in Combination With Atezolizumab With or Without Carboplatin (Part A and B) (Baseline up to 37 months)
Sponsor
Daiichi Sankyo · industry
With: Merck Sharp & Dohme LLC
Contacts & investigators
Contact(US) Daiichi Sankyo Contact for Clinical Trial Information · contact · CTRinfo_us@daiichisankyo.com · 9089926400
Contact(Asia) Daiichi Sankyo Contact for Clinical Trial Information · contact · dsclinicaltrial@daiichisankyo.co.jp · +81-3-6225-1111 (M-F 9-5 JST
InvestigatorGlobal Clinical Leader · study_director, Daiichi Sankyo
All locations (58)
University of Alabama -BirminghamRecruiting
Birmingham, Alabama, United States
Mayo Clinic ArizonaRecruiting
Phoenix, Arizona, United States
David Geffen School of MedicineNot Yet Recruiting
Los Angeles, California, United States
Hoag Memorial Hospital PresbyterianRecruiting
Newport Beach, California, United States
Mayo Clinic-JacksonvilleRecruiting
Jacksonville, Florida, United States
Advent Health OrlandoRecruiting
Orlando, Florida, United States
Moffitt Cancer CenterRecruiting
Tampa, Florida, United States
Robert H. Lurie Comprehensive Cancer Center of Northwestern UniversityRecruiting
Chicago, Illinois, United States
Henry Ford HospitalActive Not Recruiting
Detroit, Michigan, United States
Regents of the University of MinnesotaRecruiting
Minneapolis, Minnesota, United States
Mayo ClinicRecruiting
Rochester, Minnesota, United States
Dartmouth-Hitchcock Medical CenterRecruiting
Lebanon, New Hampshire, United States
Astera Cancer CareRecruiting
East Brunswick, New Jersey, United States
John Theurer Cancer Center At Hackensack UmcRecruiting
Hackensack, New Jersey, United States
New York University Cancer Center - Laura and Isaac Perlmutter Cancer Center At Nyu LangoneRecruiting
Mineola, New York, United States
NYU Langone Hospital - Long IslandRecruiting
Mineola, New York, United States
Memorial Sloan Kettering Cancer CenterRecruiting
New York, New York, United States
Columbia University Hervert Irving Comprehensive Cancer CenterRecruiting
New York, New York, United States
Montefiore Medical CenterRecruiting
New York, New York, United States
Lancaster General Hospital - Ann B Barshinger Cancer InstituteRecruiting
Lancaster, Pennsylvania, United States
University of Pennsylvania, Abramson Cancer CenterRecruiting
Philadelphia, Pennsylvania, United States
Thomas Jefferson University Hospital - CentralRecruiting
Philadelphia, Pennsylvania, United States
Scri Oncology PartnersRecruiting
Nashville, Tennessee, United States
Next VirginiaRecruiting
Fairfax, Virginia, United States
Northwest Cancer Specialists, P.C.-VancouverRecruiting
Vancouver, Washington, United States
Medical College of WisconsinRecruiting
Milwaukee, Wisconsin, United States
Hopital Albert Calmette - Chu LilleRecruiting
Lille, France
Centre Léon BérardRecruiting
Lyon, France
Hôpital de la TimoneRecruiting
Marseille, France
Institut Curie - Site de ParisRecruiting
Paris, France
Hopital TenonRecruiting
Paris, France
Chu Rennes - Hopital PontchaillouRecruiting
Rennes, France
CHU Nantes - Hôpital Guillaume et René LaënnecRecruiting
Saint-Herblain, France
Hôpital FochRecruiting
Suresnes, France
Institut Gustave RoussyNot Yet Recruiting
Villejuif, France
NHO Himeji Medical CenterRecruiting
Himeji-shi, Japan
Kansai Medical University HospitalRecruiting
Hirakata-shi, Japan
National Cancer Center Hospital EastRecruiting
Kashiwa, Japan
The Cancer Institute Hospital of JfcrRecruiting
Kōtoku, Japan
Social Welfare Organization Saiseikai Imperial Gift Foundation, Inc. Saiseikai Kumamoto HospitalRecruiting
Kumamoto, Japan
Shizuoka Cancer CenterRecruiting
Nagaizumi-cho, Japan
Niigata Cancer Center HospitalRecruiting
Niigata, Japan
Okayama University HospitalRecruiting
Okayama, Japan
Kindai University HospitalRecruiting
Ōsaka-sayama, Japan
Tokushima University HospitalRecruiting
Tokushima, Japan
Fujita Health University HospitalRecruiting
Toyoake-shi, Japan
Hospital Clinic de BarcelonaRecruiting
Barcelona, Spain
Hospital Universitari Vall D'HebronRecruiting
Barcelona, Spain
Ico Girona - Hospital Universitari de Girona Dr Josep TruetaRecruiting
Girona, Spain
ICO l'Hospitalet - Hospital Duran i ReynalsRecruiting
L'Hospitalet de Llobregat, Spain
Hospital General Universitario Gregorio MarañonRecruiting
Madrid, Spain
Hospital Universitario Ramon Y CajalRecruiting
Madrid, Spain
Hospital Universitario 12 de OctubreRecruiting
Madrid, Spain
Next MadridRecruiting
Madrid, Spain
Hospital Regional Universitario de MalagaRecruiting
Málaga, Spain
Hospital Universitario Virgen MacarenaRecruiting
Seville, Spain
Hospital Universitario Virgen Del RocioRecruiting
Seville, Spain
Hospital Alvaro CunqueiroRecruiting
Vigo, Spain
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) · TrialPath