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)

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)

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.

Study Overview

• Status: Recruiting
• Conditions: Extensive Stage-small Cell Lung Cancer
• Intervention / Treatment: Drug: Ifinatamab deruxtecan; Drug: Atezolizumab; Drug: Carboplatin

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.

• Study Type: Interventional
• Enrollment (Estimated): 123
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: (Asia) Daiichi Sankyo Contact for Clinical Trial Information; Phone Number: +81-3-6225-1111 (M-F 9-5 JST; Email: dsclinicaltrial@daiichisankyo.co.jp
• Study Contact Backup: Name: (US) Daiichi Sankyo Contact for Clinical Trial Information; Phone Number: 9089926400; Email: CTRinfo_us@daiichisankyo.com

Study Locations

• France
  • Lille, France, 59037
    • Recruiting
    • Hopital Albert Calmette - CHU Lille
    • Contact: Principal Investigator
  • Lyon, France, 69008
    • Recruiting
    • Centre Leon Berard
    • Contact: Principal Investigator
  • Marseille, France, 13005
    • Recruiting
    • Hopital de La Timone
    • Contact: Principal Investigator
  • Paris, France, 75020
    • Recruiting
    • Hopital Tenon
    • Contact: Principal Investigator
  • Paris, France, 75005
    • Recruiting
    • Institut Curie - Site de Paris
    • Contact: Principal Investigator
  • Rennes, France, 35000
    • Recruiting
    • CHU Rennes - Hôpital Pontchaillou
    • Contact: Principal Investigator
  • Saint-Herblain, France, 44805
    • Recruiting
    • CHU Nantes - Hôpital Guillaume et René Laënnec
    • Contact: Principal Investigator
  • Suresnes, France, 92151
    • Recruiting
    • Hôpital Foch
    • Contact: Principal Investigator
  • Villejuif, France, 94805
    • Not yet recruiting
    • Institut Gustave Roussy
    • Contact: Principal Investigator
• Japan
  • Himeji-shi, Japan, 670-8520
    • Recruiting
    • NHO Himeji Medical Center
  • Hirakata-shi, Japan, 573-1191
    • Recruiting
    • Kansai Medical University Hospital
    • Contact: Principal Investigator
  • Kashiwa, Japan, 277-8577
    • Recruiting
    • National Cancer Center Hospital East
    • Contact: Principal Investigator
  • Kumamoto, Japan, 861-4193
    • Recruiting
    • Social Welfare Organization Saiseikai Imperial Gift Foundation, Inc. Saiseikai Kumamoto Hospital
    • Contact: Principal Investigator
  • Kōtoku, Japan, 135-8550
    • Recruiting
    • The Cancer Institute Hospital of JFCR
    • Contact: Principal Investigator
  • Nagaizumi-cho, Japan, 411-8777
    • Recruiting
    • Shizuoka Cancer Center
    • Contact: Principal Investigator
  • Niigata, Japan, 951-8566
    • Recruiting
    • Niigata Cancer Center Hospital
    • Contact: Principal Investigator
  • Okayama, Japan, 700-8558
    • Recruiting
    • Okayama University Hospital
    • Contact: Principal Investigator
  • Tokushima, Japan, 770-8503
    • Recruiting
    • Tokushima University Hospital
  • Toyoake-shi, Japan, 470-1192
    • Recruiting
    • Fujita Health University Hospital
  • Ōsaka-sayama, Japan, 589-8511
    • Recruiting
    • Kindai University Hospital
    • Contact: Principal Investigator
• Spain
  • Barcelona, Spain, 08036
    • Recruiting
    • Hospital Clinic De Barcelona
    • Contact: Principal Investigator
  • Barcelona, Spain, 8035
    • Recruiting
    • Hospital Universitari Vall d'Hebron
    • Contact: Principal Investigator
  • Girona, Spain, 17007
    • Recruiting
    • ICO Girona - Hospital Universitari de Girona Dr Josep Trueta
    • Contact: Principal Investigator
  • L'Hospitalet de Llobregat, Spain, 08908
    • Recruiting
    • ICO L'Hospitalet - Hospital Duran i Reynals
    • Contact: Principal Investigator
  • Madrid, Spain, 28034
    • Recruiting
    • Hospital Universitario Ramon y Cajal
    • Contact: Principal Investigator
  • Madrid, Spain, 28041
    • Recruiting
    • Hospital Universitario 12 de Octubre
    • Contact: Principal Investigator
  • Madrid, Spain, 28007
    • Recruiting
    • Hospital General Universitario Gregorio Marañon
    • Contact: Principal Investigator
  • Madrid, Spain, 28223
    • Recruiting
    • NEXT Madrid
    • Contact: Principal Investigator
  • Málaga, Spain, 29010
    • Recruiting
    • Hospital Regional Universitario de Malaga
    • Contact: Principal Investigator
  • Seville, Spain, 41013
    • Recruiting
    • Hospital Universitario Virgen del Rocio
    • Contact: Principal Investigator
  • Seville, Spain, 41009
    • Recruiting
    • Hospital Universitario Virgen Macarena
    • Contact: Principal Investigator
  • Vigo, Spain, 36312
    • Recruiting
    • Hospital Alvaro Cunqueiro
    • Contact: Principal Investigator
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35233
      • Recruiting
      • University of Alabama -Birmingham
      • Contact: Principal Investigator
  • Arizona
    • Phoenix, Arizona, United States, 85054
      • Recruiting
      • Mayo Clinic Arizona
      • Contact: Principal Investigator
  • California
    • Los Angeles, California, United States, 90095
      • Not yet recruiting
      • David Geffen School of Medicine
      • Contact: Principal Investigator
    • Newport Beach, California, United States, 92663
      • Recruiting
      • Hoag Memorial Hospital Presbyterian
      • Contact: Principal Investigator
  • Florida
    • Jacksonville, Florida, United States, 32224
      • Recruiting
      • Mayo Clinic-Jacksonville
      • Contact: Principal Investigator
    • Orlando, Florida, United States, 32804
      • Recruiting
      • Advent Health Orlando
      • Contact: Principal Investigator
    • Tampa, Florida, United States, 33612
      • Recruiting
      • Moffitt Cancer Center
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Recruiting
      • Robert H. Lurie Comprehensive Cancer Center of Northwestern University
      • Contact: Principal Investigator
  • Michigan
    • Detroit, Michigan, United States, 48202
      • Active, not recruiting
      • Henry Ford Hospital
  • Minnesota
    • Minneapolis, Minnesota, United States, 55455
      • Recruiting
      • Regents of the University of Minnesota
      • Contact: Principal Investigator
    • Rochester, Minnesota, United States, 55905
      • Recruiting
      • Mayo Clinic
      • Contact: Principal Investigator
  • New Hampshire
    • Lebanon, New Hampshire, United States, 03766
      • Recruiting
      • Dartmouth-Hitchcock Medical Center
      • Contact: Principal Investigator
  • New Jersey
    • East Brunswick, New Jersey, United States, 08816
      • Recruiting
      • Astera Cancer Care
    • Hackensack, New Jersey, United States, 07601
      • Recruiting
      • John Theurer Cancer Center At Hackensack UMC
      • Contact: Principal Investigator
  • New York
    • Mineola, New York, United States, 11501
      • Recruiting
      • NYU Langone Hospital - Long Island
      • Contact: Principal Investigator
    • Mineola, New York, United States, 11501
      • Recruiting
      • New York University Cancer Center - Laura and Isaac Perlmutter Cancer Center At Nyu Langone
      • Contact: Principal Investigator
    • New York, New York, United States, 10021
      • Recruiting
      • Memorial Sloan Kettering Cancer Center
      • Contact: Principal Investigator
    • New York, New York, United States, 10461
      • Recruiting
      • Montefiore Medical Center
    • New York, New York, United States, 10032
      • Recruiting
      • Columbia University Hervert Irving Comprehensive Cancer Center
      • Contact: Principal Investigator
  • Pennsylvania
    • Lancaster, Pennsylvania, United States, 17601
      • Recruiting
      • Lancaster General Hospital - Ann B Barshinger Cancer Institute
    • Philadelphia, Pennsylvania, United States, 19104
      • Recruiting
      • University of Pennsylvania, Abramson Cancer Center
    • Philadelphia, Pennsylvania, United States, 19107
      • Recruiting
      • Thomas Jefferson University Hospital - Central
      • Contact: Principal Investigator
  • Tennessee
    • Nashville, Tennessee, United States, 37203
      • Recruiting
      • SCRI Oncology Partners
      • Contact: Principal Investigator
  • Virginia
    • Fairfax, Virginia, United States, 22031
      • Recruiting
      • NEXT Virginia
      • Contact: Principal Investigator
  • Washington
    • Vancouver, Washington, United States, 98684
      • Recruiting
      • Northwest Cancer Specialists, P.C.-Vancouver
      • Contact: Principal Investigator
  • Wisconsin
    • Milwaukee, Wisconsin, United States, 53226
      • Recruiting
      • Medical College of Wisconsin
      • Contact: Principal Investigator

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

7

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cohort 1, Part A: Maintenance Only (I-DXd 12 mg/kg); Part A (Safety Run-in): Participants who must have received 4 cycles of 1L induction standard of care (SoC) therapy with best overall response of CR, PR, or SD will receive maintenance therapy only. Maintenance therapy consisting of I-DXd 12 mg/kg (or a lower dose based on data for I-DXd collected during the study) + atezolizumab 1200 mg IV Q3W. A 5-day surveillance period between each of the first 3 participants (up to a maximum of 9 participants) dosed is included as a safety measure.	Drug: Ifinatamab deruxtecan; Intravenous administration; Other Names: I-DXd; Drug: Atezolizumab; Intravenous administration
Experimental: Cohort 2, Part A: Induction + Maintenance (I-DXd 8 mg/kg); Part A (Safety Run-in): Participants who are treatment-naive, newly diagnosed with ES-SCLC will receive 4 cycles of 1L I-DXd induction therapy (8 mg/kg IV Q3W) + atezolizumab (1200 mg IV Q3W) + carboplatin (AUC 5 mg/ml×min IV Q3W) followed by maintenance therapy. Maintenance therapy consisting of I-DXd 8 mg/kg (or a lower dose based on data for I-DXd collected during the study) + atezolizumab 1200 mg IV Q3W.	Drug: Ifinatamab deruxtecan; Intravenous administration; Other Names: I-DXd; Drug: Atezolizumab; Intravenous administration; Drug: Carboplatin; Intravenous administration
Experimental: Cohort 2, Part A: Induction + Maintenance (I-DXd 12 mg/kg); Part A (Safety Run-in): Participants who are treatment-naive, newly diagnosed with ES-SCLC will receive 4 cycles of 1L I-DXd induction therapy (12 mg/kg IV Q3W) + atezolizumab (1200 mg IV Q3W) + carboplatin (AUC 5 mg/ml×min IV Q3W) followed by maintenance therapy. Maintenance therapy consisting of I-DXd 12 mg/kg (or a lower dose based on data for I-DXd collected during the study) + atezolizumab 1200 mg IV Q3W.	Drug: Ifinatamab deruxtecan; Intravenous administration; Other Names: I-DXd; Drug: Atezolizumab; Intravenous administration; Drug: Carboplatin; Intravenous administration
Experimental: Cohort 1, Part B: Maintenance (I-DXd 8 mg/kg); Part B: Participants who must have received 4 cycles of 1L induction standard of care (SoC) therapy with best overall response of CR, PR, or SD will receive maintenance therapy only starting at Cycle 1 Day 1. Maintenance therapy consisting of I-DXd 8 mg/kg (or a lower dose based on data for I-DXd collected during the study) + atezolizumab 1200 mg IV Q3W	Drug: Ifinatamab deruxtecan; Intravenous administration; Other Names: I-DXd; Drug: Atezolizumab; Intravenous administration
Experimental: Cohort 1, Part B: Maintenance (I-DXd 12 mg/kg); Part B: Participants who must have received 4 cycles of 1L induction standard of care (SoC) therapy with best overall response of CR, PR, or SD will receive maintenance therapy only starting at Cycle 1 Day 1. Maintenance therapy consisting of I-DXd 12 mg/kg (or a lower dose based on data for I-DXd collected during the study) + atezolizumab 1200 mg IV Q3W.	Drug: Ifinatamab deruxtecan; Intravenous administration; Other Names: I-DXd; Drug: Atezolizumab; Intravenous administration
Experimental: Cohort 2, Part B: Induction + Maintenance (I-DXd 8 mg/kg); Participants who are treatment-naive, newly diagnosed with ES-SCLC will receive 4 cycles of 1L I-DXd induction therapy (8 mg/kg IV Q3W) + atezolizumab (1200 mg IV Q3W) + carboplatin (AUC 5 mg/ml×min IV Q3W) followed by maintenance therapy. Maintenance therapy consisting of I-DXd 8 mg/kg (or a lower dose based on data for I-DXd collected during the study) + atezolizumab 1200 mg IV Q3W.	Drug: Ifinatamab deruxtecan; Intravenous administration; Other Names: I-DXd; Drug: Atezolizumab; Intravenous administration; Drug: Carboplatin; Intravenous administration
Experimental: Cohort 2, Part B: Induction + Maintenance (I-DXd 12 mg/kg); Participants who are treatment-naive, newly diagnosed with ES-SCLC will receive 4 cycles of IL I-DXd induction therapy (12 mg/kg IV Q3W) + atezolizumab (1200 mg IV Q3W) + carboplatin (AUC 5 mg/ml×minIV Q3W) followed by maintenance therapy. Maintenance therapy consisting of I-DXd 12 mg/kg (or a lower dose based on data for I-DXd collected during the study) + atezolizumab 1200 mg IV Q3W.	Drug: Ifinatamab deruxtecan; Intravenous administration; Other Names: I-DXd; Drug: Atezolizumab; Intravenous administration; Drug: Carboplatin; Intravenous administration

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
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

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-free Survival As Assessed by Blinded Independent Central Review and Investigator Following I-DXd in Combination With Atezolizumab With or Without Carboplatin (Part A and B)	Progression-free survival is defined as the time from the enrollment/randomization date to the earlier of the dates of the first documentation of disease progression assessed by BICR and investigator per RECIST v1.1 or death due to any cause.	From start date of study drug to the earlier date of the first objective documentation of radiographic disease progression assessed by BICR and investigator per RECIST v1.1 or death due to any cause, whichever occurs first, up to approximately 37 months
Objective Response Rate Assessed by Blinded Independent Central Review and Investigator Following I-DXd in Combination With Atezolizumab With Carboplatin (Part A and B of Cohort 2 Only)	Objective response rate (ORR) is defined as proportion of subjects who achieved a best overall response of confirmed complete response (CR) or confirmed partial response (PR) per BICR and investigator according to RECIST v1.1.	Baseline up until documented progressive disease, death, lost to follow-up, or withdrawal by the participant, up to approximately 37 months
Duration of Response As Assessed by Blinded Independent Central Review and Investigator Following I-DXd in Combination With Atezolizumab With Carboplatin (Part A and B of Cohort 2 Only)	Duration of response (DoR) is defined as the time from the date of the first documentation of objective response (confirmed complete response [CR] or confirmed partial response [PR]) to the date of the first documentation of progressive disease (PD) or death due to any cause, whichever occurs first. The DoR will be calculated for responding participants (confirmed PR or confirmed CR) only.	From the date of first documentation of confirmed response (CR or PR) to the first documentation of objective progression or to death due to any cause, whichever occurs first, up to approximately 37 months
Disease Control Rate As Assessed by Blinded Independent Central Review and Investigator Following I-DXd in Combination With Atezolizumab With Carboplatin (Part A and B of Cohort 2 Only)	Disease control rate is defined as the proportion of participants who have achieved a best overall response of confirmed CR, confirmed PR, or SD by BICR and investigator assessment per RECIST v1.1.	Baseline up until documented progressive disease, death, lost to follow-up, or withdrawal by the participant, up to approximately 37 months
Clinical Benefit Rate as Assessed by Blinded Independent Central Review and Investigator Following I-DXd in Combination With Atezolizumab With Carboplatin (Part A and B of Cohort 2 Only)	Clinical benefit rate (CBR) is defined as the proportion of participants who achieved a best overall response of confirmed CR, confirmed PR, or SD lasting for at least 180 days.	Baseline up until documented progressive disease, death, lost to follow-up, or withdrawal by the participant, up to approximately 37 months
Time to Response As Assessed by Blinded Independent Central Review and Investigator Following I-DXd in Combination With Atezolizumab With Carboplatin (Part A and B of Cohort 2 Only)	Time to response (TTR) is defined as the time from the date of enrollment/randomization to the date of the first documentation of objective response (confirmed CR or confirmed PR) in responding subjects.	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 37 months
Best Percentage Change in the Sum of Diameters (SoD) of Measurable Tumors As Assessed by Blinded Independent Central Review and Investigator Following I-DXd in Combination With Atezolizumab With Carboplatin (Part A and B of Cohort 2 Only)	The best percentage change in SoD is defined as the percentage change in the smallest SoD from all post-baseline tumor assessments, taking as reference the baseline SoD.	Baseline up to approximately 37 months
Overall Survival Following I-DXd in Combination With Atezolizumab With or Without Carboplatin (Part A and B)	Time from the date of enrollment/randomization to the date of death due to any cause.	From the start date of study drug to the date of death due to any cause, whichever occurs first, up to approximately 37 months
Pharmacokinetic Parameter Maximum Serum Concentration of I-DXd	Maximum serum concentration (Cmax) will be assessed using non-compartmental methods.	Cycle 1 Day 1 pre-dose up to Cycle 9 (and every 2 cycles thereafter up to 37 months) Day 1 pre-dose (each cycle is 21 days)
Pharmacokinetic Parameter Time to Maximum Serum Concentration of I-DXd	Time to maximum serum concentration (Tmax) will be assessed using non-compartmental methods.	Cycle 1 Day 1 pre-dose up to Cycle 9 (and every 2 cycles thereafter up to 37 months) Day 1 pre-dose (each cycle is 21 days)
Pharmacokinetic Parameter Area Under the Concentration Curve of I-DXd	Area under the concentration-time curve up to the last quantifiable time (AUClast) and Area under the concentration-time curve during dosing interval (AUCtau) will be assessed using non-compartmental methods.	Cycle 1 Day 1 pre-dose up to Cycle 9 (and every 2 cycles thereafter up to 37 months) Day 1 pre-dose (each cycle is 21 days)
The Number of Participants Who Are Anti-Drug Antibody (ADA)-Positive At Any Time and Who Have A Treatment-emergent Anti-Drug Antibody	The ADA prevalence, which is the percentage of participants who are ADA positive at any time point (baseline or postbaseline), as well as the ADA incidence, which is the proportion of participants having treatment-emergent ADA during the study period, will be reported.	Baseline up to approximately 37 months

Collaborators and Investigators

• Sponsor: Daiichi Sankyo
• Collaborators: Merck Sharp & Dohme LLC
• Investigators: Study Director: Global Clinical Leader, Daiichi Sankyo

Study record dates

Study Major Dates

• Study Start (Actual): July 22, 2024
• Primary Completion (Estimated): September 30, 2026
• Study Completion (Estimated): December 30, 2026

Study Registration Dates

• First Submitted: January 2, 2024
• First Submitted That Met QC Criteria: April 8, 2024
• First Posted (Actual): April 12, 2024

Study Record Updates

• Last Update Posted (Actual): February 6, 2026
• Last Update Submitted That Met QC Criteria: February 4, 2026
• Last Verified: February 1, 2026

More Information

Terms related to this study

• Keywords: I-DXd; Ifinatamab deruxtecan; Extensive stage-small cell lung cancer (ES-SCLC)
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Respiratory Tract Diseases; Lung Diseases; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Small Cell Lung Carcinoma; Organic Chemicals; Coordination Complexes; Carboplatin; atezolizumab
• Other Study ID Numbers: DS7300-189; 2023-509629-36 (Other Identifier: EU CT); 2031240089 (Other Identifier: JRCT)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: De-identified individual participant data (IPD) on completed studies and applicable supporting clinical trial documents may be available upon request at https://vivli.org/. In cases where clinical trial data and supporting documents are provided pursuant to our company policies and procedures, Daiichi Sankyo will continue to protect the privacy of our clinical trial participants. Details on data sharing criteria and the procedure for requesting access can be found at this web address: https://vivli.org/ourmember/daiichi-sankyo/
• IPD Sharing Time Frame: Completed studies that has reached a global end or completion with all data set collected and analyzed, and 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.
• IPD Sharing Access Criteria: Formal request from qualified scientific and medical researchers on IPD and clinical study documents on completed 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.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No