A Phase 3 Study of I-DXd in Subjects with Relapsed SCLC

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Daiichi Sankyo Inc.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

7 May 2026 → ongoing

Decision date (initial)

2025-11-03

Transition trial

No

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

Funding sources

Daiichi Sankyo, Inc.

External identifiers

EU CT number

2023-509628-16-00

ClinicalTrials.gov

NCT06203210

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Safety, Pharmacokinetic

To compare the efficacy of I-DXd with that of standard of care (SoC) in participants with SCLC using objective response rate (ORR) and overall survival (OS).

Secondary objectives 5

1. To further evaluate the efficacy of I-DXd compared to SoC using additional measurements.
2. To assess patient-reported outcomes (PROs) when comparing the impact on health-related quality of life of I DXd with SoC.
3. To evaluate the safety and tolerability of I-DXd compared to SoC. To evaluate whether I-DXd triggers an immune response.
4. To examine the level of B7-H3 protein in tumor tissue and understand its connection with tumor response
5. To evaluate the pharmacokinetics (PK) of I-DXd (how the participant’s body deals with I-DXd, including how it is absorbed, distributed, and removed from the body).

Conditions and MedDRA coding

Small Cell Lung Cancer (SCLC)

Study design 3 periods

Regulatory references

Scientific advice from competent authorities

European Medicines Agency, Pharmaceuticals And Medical Devices Agency, Food And Drug Administration

Plan to share IPD

Yes

IPD plan description

De-identified individual participant data (IPD) 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/

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 9

1. Sign and date the informed consent form 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 informed consent form is signed.
3. Has histologically or cytologically documented extensive-stage small cell lung cancer (ES-SCLC.).
4. The subject must provide adequate baseline tumor samples with sufficient quantity and quality of tumor tissue content.
5. Has received prior therapy with only one prior platinum-based line as systemic therapy for SCLC with at least 2 cycles of therapy and a chemotherapy-free interval of ≥30 days.
6. Has at least 1 measurable lesion according to RECIST v1.1 as assessed by the investigator.
7. Has documentation of radiological disease progression on or after the most recent systemic therapy.
8. Has ECOG PS of ≤1 within 7 days before C1D1.
9. Has no evidence of brain or leptomeningeal disease (spinal cord or central nervous system [CNS] metastases based on history and physical examination. For subjects with evidence of brain or leptomeningeal disease, they may be eligible if condition has been treated and a lack of progression within 4 weeks prior to initiation of study drug has been radiologically documented. Subjects must require no treatment with steroids or anticonvulsants and have a stable neurologic status for at least 2 weeks prior to the first dose of study drug.

Exclusion criteria 9

1. Has received prior treatment with orlotamab, enoblituzumab, or other B7 homologue 3 (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. Has received any of the comparators used in this study or any topoisomerase I inhibitor.
4. Has inadequate washout period before randomization as specified in the protocol .
5. Has any of the following conditions within the past 6 months: cerebrovascular accident, transient ischemic attack, or another arterial thromboembolic event.
6. Has uncontrolled or significant cardiovascular disease.
7. Has clinically significant corneal disease.
8. Has any history of ILD/pneumonitis irrespective of steroid use, or current ILD, or suspected ILD, or ILD that cannot be ruled out by imaging at Screening. Subjects may be eligible if they had history of radiation pneumonitis that did not require steroids.
9. Has clinically severe pulmonary compromise resulting from intercurrent pulmonary illnesses, including, but not limited to, any underlying pulmonary disorder (eg, pulmonary emboli within 3 months of randomization, severe asthma, severe chronic obstructive pulmonary disease (COPD), restrictive lung disease, pleural effusion, etc) and potential pulmonary involvement caused by any autoimmune, connective tissue, or inflammatory disorders (eg, rheumatoid arthritis, Sjögren’s syndrome, sarcoidosis, etc), prior pneumonectomy, or requirement for supplemental oxygen.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 2

1. Objective Response Rate (ORR): The percentage of participants who show a confirmed complete response (no detectable cancer) or confirmed partial response (reduced tumor size) as assessed by blinded independent central review.
2. Overall Survival (OS): The time interval from the date of randomization to the date of death due to any cause.

Secondary endpoints 1

1. ORR as assessed by the investigator, progression-free survival, duration of response, disease control rate, time to response, PROs measures of health-related quality of life, adverse events, antidrug antibody prevalence, correlation of B7-H3 protein expression in tumor tissue with clinical outcomes, and PK.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Comparator 2

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Daiichi Sankyo Inc.

Sponsor organisation

Daiichi Sankyo Inc.

Address

211 Mount Airy Road

City

Basking Ridge

Postcode

07920-2311

Country

United States

Scientific contact point

Organisation

Daiichi Sankyo Inc.

Contact name

Clinical Trial Office

Public contact point

Organisation

Daiichi Sankyo Inc.

Contact name

Clinical Trial Office

Third parties 21

Locations

13 EU/EEA countries · 107 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Oversight and notifications

Regulatory notifications under CTR Articles 38, 52, 53, 54 and 77

Temporary halts 10 · Art. 38 CTR

Urgent safety measures 1 · Art. 54 CTR

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 328 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

11 submissions — initial application plus substantial / non-substantial modifications