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

Active, not recruiting

• Conditions: Extensive-stage Small Cell Lung Cancer

• Registration Number: jRCT2041220019
• Lead Sponsor: Daiichi Sankyo Co., Ltd.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2022-05-19
• Study Start: 2022-07-22
• Last Update Posted: 2025-06-17

Recruitment & Eligibility

• Status: Not Recruiting
• Sex: All
• Target Recruitment: 180

Inclusion Criteria

1. Sign and date the informed consent form (ICF) prior to the start of any study-specific qualification procedures.
2. Participant must have at least one lesion, not previously irradiated, amenable to core biopsy.
3. Male or female subjects aged >=18 years
4. Histologically or cytologically documented ES-SCLC.
5. At least one measurable lesion according to RECIST v1.1 as assessed by the investigator.
6. 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.
7. Documentation of radiological disease progression on or after most recent systemic therapy.
8. Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1.

Exclusion Criteria

1. Prior treatment with orlotamab, enoblituzumab, or other B7-H3 targeted agents, including I-DXd.
2. Prior discontinuation of an antibody drug conjugate (ADC) that consists of an exatecan derivative (eg, trastuzumab deruxtecan) due to treatment-related toxicities.
3. 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.
4. Any of the following conditions within the past 6 months: cerebrovascular accident, transient ischemic attack, or another arterial thromboembolic event.
5. Clinically significant corneal disease.
6. Uncontrolled or significant cardiovascular disease.
7. 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.
8. Clinically severe pulmonary compromise resulting from intercurrent pulmonary illnesses.
9. Chronic steroid treatment (maximum 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.
10. 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.
11. History of allogeneic bone marrow, stem cell, or solid organ transplant.
12. 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.
13. History of hypersensitivity to the drug substances, inactive ingredients in the drug product or severe hypersensitivity reactions to other monoclonal antibodies.
14. Evidence of ongoing uncontrolled systemic bacterial, fungal, or viral infection.
15. Has active or uncontrolled hepatitis B or C infection.
16. Active, known, or suspected autoimmune disease.
17. Any evidence of severe or uncontrolled systemic diseases (including active bleeding diatheses, psychiatric illness/social situations, substance abuse).
18. Has received a live vaccine within 30 days prior to the first dose of study drug.
19. Female who is pregnant or breast-feeding or intends to become pregnant during the study.
20. 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.
21. Known human immunodeficiency virus (HIV) infection that is not well controlled.

Study & Design

• Study Type: Interventional
• Study Design: parallel assignment

Primary Outcome Measures

Name	Time	Method
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	Up to approximately 36 months	ORR was the 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.; - **CR**: Disappearance of all target lesions; - **PR**: At least a 30% decrease in the sum of diameters of target lesions