A Study of Ifinatamab Deruxtecan Versus Treatment of Physician's Choice in Subjects With Relapsed Small Cell Lung Cancer

Phase 3RecruitingNCT06203210

Daiichi Sankyo540 enrolled

Overview

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).

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

540

Conditions

Small Cell Lung Cancer

Interventions

Ifinatamab deruxtecanDRUG

12 mg/kg intravenous dose on Day 1 of each 21-day cycle

TopotecanDRUG

Topotecan will be administered per local standard-of-care (SoC)

AmrubicinDRUG

Amrubicin will be administered per local SoC

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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.

Locations (229)

Outcomes

Primary Outcomes

Overall Survival (OS)

OS is defined as the time interval from the date of randomization to the date of death due to any cause.

Time frame: From the date of randomization to the date of death due to any cause, up to approximately 3.7 years

Secondary Outcomes

Objective Response (OR) Assessed by Blinded Independent Central Review (BICR) Per Response Evaluation Criteria In Solid Tumors Version 1.1 (RECIST v1.1)

Objective response as assessed by BICR is defined as the best overall response (BOR) of confirmed complete response (CR) or confirmed partial response (PR) per BICR according to RECIST v1.1. CR is defined as the disappearance of all target and non-target lesions and normalization of tumor marker level. PR is defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters.

Time frame: Baseline up until documented progressive disease, death, lost to follow-up, or withdrawal by the participant, up to approximately 3.7 years

Number of Participants With OR Assessed by Investigator Per RECIST v1.1

Objective response as assessed by the investigator is defined as a BOR of confirmed CR or confirmed PR by the investigator according to RECIST v1.1. CR is defined as the disappearance of all target and non-target lesions and normalization of tumor marker level. PR is defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters.

Time frame: Baseline up until documented progressive disease, death, lost to follow-up, or withdrawal by the participant, up to approximately 3.7 years

Progression-free Survival (PFS) as Assessed by BICR and Investigator

PFS is defined as the time interval from randomization to the earlier date of the first documented radiographic disease progression or death due to any cause.

Time frame: Baseline up until documented progressive disease, death, lost to follow-up, or withdrawal by the participant, up to approximately 3.7 years

Central Contacts

Daiichi Sankyo Contact for Clinical Trial Information

CONTACT

9089926400 CTRinfo@dsi.com

Data from ClinicalTrials.gov

This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.

Lurbinectedin will be administered per local SoC

Highlands Oncology Group

Springdale, Arkansas, United States

RECRUITING

Clinical Research Providence Medical Foundation

Fullerton, California, United States

RECRUITING

UCLA Hematology-Oncology

Los Angeles, California, United States

RECRUITING

UCSF Mission Bay Mission Hall

San Francisco, California, United States

RECRUITING

University of Miami Hospital and Clinics Sylvester Comprehensive Cancer Center

Miami, Florida, United States

RECRUITING

AdventHealth Orlando, Cancer Institute

Orlando, Florida, United States

RECRUITING

H. Lee Moffitt Cancer Center and Research Institute, Inc

Tampa, Florida, United States

NOT_YET_RECRUITING

Rush MD Anderson Cancer Center

Chicago, Illinois, United States

RECRUITING

Baptist Health Lexington

Lexington, Kentucky, United States

RECRUITING

University of Maryland Greenebaum Comprehensive Cancer Center

Baltimore, Maryland, United States

RECRUITING

...and 219 more locations

Duration of Response (DoR) as Assessed by BICR and Investigator

DoR is defined as the time from the date of the first documentation of objective tumor response (CR or PR) that is subsequently confirmed to the date of the first documentation of objective tumor progressive or death to any cause, whichever occurs first. The DoR will be calculated for responding participants (PR or CR) only.

Time frame: From the date of first documentation of BOR (CR or PR) to the first documentation of objective progression or to death due to any cause, whichever occurs first, up to approximately 3.7 years

Disease Control as Assessed by BICR and Investigator

Disease control is defined as a BOR of confirmed CR, confirmed PR, or stable disease (SD). CR is defined as the disappearance of all target and non-target lesions and normalization of tumor marker level. PR is defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters. SD is defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum of diameters while on study. PD is defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study for target lesions and unequivocal progression of existing non-target lesions for non-target lesions.

Time frame: Baseline up until documented progressive disease, death, lost to follow-up, or withdrawal by the participant, up to approximately 3.7 years

Time to Response (TTR) as Assessed by BICR and Investigator

TTR is defined as the time from the date of randomization to the first documentation of objective tumor response (CR or PR) that is subsequently confirmed by BICR and investigator assessment. Time to response (TTR) will be calculated for confirmed responders only.

Time frame: 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 3.7 years

Change from Baseline in The European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ)-C30

EORTC QLQ-C30 is a 30-item questionnaire that assesses global health status (GHS)/quality of life (QoL), subject functioning, and general cancer symptoms. All scores for the EORTC QLQ-C30 instrument are linearly transformed to a 0 to 100 metric, where a higher score on GHS/QoL and functioning scales indicates a better outcome and a higher score for the symptom scales indicates worse outcomes.

Time frame: Baseline up to 3.7 years

Change from Baseline in The European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Lung Cancer 29 (EORTC QLQ-LC29)

The LC29 is a self-reported 29-item questionnaire that measures SCLC-related symptoms and the side effects of treatments and has a recall period of one week. All scores range from 0 to 100, with a higher score indicating a worse outcome.

Time frame: Baseline up to 3.7 years

Number of Participants With Treatment-emergent Adverse Events (TEAEs)

TEAEs are assessed based on NCI CTCAE v5.0.

Time frame: Up to 3.7 years

Percentage of Participants Who are Anti-Drug Antibody (ADA)-Positive at Any Time (Baseline and Post-baseline) 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 post-baseline), as well as the ADA incidence, which is the proportion of participants having treatment-emergent ADA during the study period, will only be reported in participants receiving I-DXd.

Time frame: Baseline up to 3.7 years

Pharmacokinetic Parameter Maximum Concentration (Cmax) for I-DXd, Total Anti-B7-H3 Antibody, and MAAA-1181a

Cmax will be assessed using non-compartmental methods in participants randomized to the I-DXd group.

Time frame: Cycle 1 before infusion (BI), end of infusion EOI), and 3, 6, 24, 72, 168, 336 and 504 hours (hrs) post dose; Cycle 2 BI and EOI; Cycle 3 BI, EOI and 6 hrs post dose; Cycles 4, 5, and every 2 cycles thereafter up to 3.7 years BI (each cycle is 21 days)

Pharmacokinetic Parameter Time to Maximum Concentration (Tmax) for I-DXd, Total Anti-B7-H3 Antibody, and MAAA-1181a

Tmax will be assessed using non-compartmental methods in participants randomized to the I-DXd group.

Time frame: Cycle 1 before infusion (BI), end of infusion EOI), and 3, 6, 24, 72, 168, 336 and 504 hours (hrs) post dose; Cycle 2 BI and EOI; Cycle 3 BI, EOI and 6 hrs post dose; Cycles 4, 5 and every 2 cycles thereafter up to 3.7 years BI (each cycle is 21 days)

Pharmacokinetic Parameter Area Under the Plasma Concentration-Time Curve Up to the Last Quantifiable Time Point (AUClast) for I-DXd, Total Anti-B7-H3 Antibody, and MAAA-1181a

AUClast will be assessed using non-compartmental methods in participants randomized to the I-DXd group.

Pharmacokinetic Parameter Area Under the Plasma Concentration-Time Curve dosing interval (AUCtau) for I-DXd, Total Anti-B7-H3 Antibody, and MAAA-1181a

AUCtau will be assessed using non-compartmental methods in participants randomized to the I-DXd group.