A Study of Ifinatamab Deruxtecan Versus Treatment of Physician's Choice in Subjects With Relapsed Small Cell Lung Cancer (IDeate-Lung02)

Daiichi Sankyo

Status and phase: Enrolling; Phase 3

Conditions: Small Cell Lung Cancer

Treatments: Drug: Amrubicin; Drug: Lurbinectedin; Drug: Ifinatamab deruxtecan; Drug: Topotecan

Study type: Interventional

Funder types: Industry

Identifiers

NCT06203210

2031230631 (Other Identifier)

DS7300-188

2023-509628-16-00 (Other Identifier)

Details and patient eligibility

About

This study is designed to compare the efficacy and safety of I-DXd with treatment of physician's choice in participants with relapsed small cell lung cancer (SCLC).

Full description

The primary objective of this study is to assess whether treatment with I-DXd prolongs overall survival (OS) compared with treatment of physician's choice among participants with relapsed SCLC.

The secondary objectives of the study are to further evaluate the efficacy/safety of I-DXd, health economics and outcome research measures (including patient reported outcomes), immunogenicity of I-DXd, B7-H3 protein expression, and characterize the pharmacokinetics of I-DXd.

Enrollment: 540 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

Inclusion Criteria

Participants must meet all the following criteria to be eligible for randomization into the study:

1. Sign and date the informed consent form (ICF) prior to the start of any study-specific qualification procedures.
2. Adults greater than or equal to (≥)18 years or the minimum legal adult age (whichever is greater) at the time the ICF is signed.
3. Has histologically or cytologically documented extensive-stage small cell lung cancer (ES-SCLC).
4. The participant 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 [CTFI] (duration from stop date of the platinum agent in 1L therapy to radiological PD) 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 less than or equal to (≤)1 within 7 days prior to Cycle 1 Day 1 (C1D1).
9. Participants with brain metastasis/leptomeningeal disease are eligible if protocol specified criteria are met.

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 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 (CV) disease.

7. Has clinically significant corneal disease.

8. All of the following indicators of interstitial lung disease (ILD)/pneumonitis are excluded:

   1. Any history of ILD/pneumonitis irrespective of steroid use, except for a history of radiation pneumonitis that did not require steroids.
   2. Current diagnosis of ILD.
   3. Clinical or radiographic suspicion of ILD for which the diagnosis of ILD cannot be ruled out. Radiographic findings may include presence of lung parenchymal fibrosis, combined fibrosis and emphysema (CPFE), and/or interstitial lung abnormalities such as reticular opacities, traction bronchiectasis, honeycombing, or extensive ground glass opacities. Screening computed tomography (CT) scans must be submitted for independent central radiology review and results before randomization.

9. Has clinically severe pulmonary compromise resulting from intercurrent pulmonary illnesses, including, but not limited to, any underlying pulmonary disorder and potential pulmonary involvement caused by any autoimmune, connective tissue, or inflammatory disorders, prior pneumonectomy, or requirement for supplemental oxygen.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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540 participants in 2 patient groups

Ifinatamab deruxtecan (I-DXd)

Experimental group

Description:

Participants will be randomized to receive 12 milligrams per kilogram (mg/kg) I-DXd, intravenously (IV), as monotherapy on Day 1 of each 21-day cycle, once every 3 weeks (Q3W), until clinical or radiologic evidence of progression of disease determined by the investigator, unacceptable toxicity, withdrawal of informed consent, death, loss to follow-up, or other treatment discontinuation criteria are met as specified in the protocol.

Treatment:

Drug: Ifinatamab deruxtecan

Treatment of Physician's Choice (TPC)

Active Comparator group

Description:

Participants will be randomized to receive topotecan or lurbinectedin, or amrubicin, as per investigator's choice and per locally approved label (indicated dose and frequency), until a treatment discontinuation criteria are met as specified in the protocol.

Treatment:

Drug: Topotecan

Drug: Lurbinectedin

Drug: Amrubicin