Small Cell Lung Cancer
Conditions
Keywords
Small cell lung cancer, Ifinatamab deruxtecan, I-DXd
Brief summary
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).
Detailed 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.
Interventions
DRUGAmrubicin
Amrubicin will be administered per local SoC
DRUGLurbinectedin
Lurbinectedin will be administered per local SoC
DRUGIfinatamab deruxtecan
12 mg/kg intravenous dose on Day 1 of each 21-day cycle
DRUGTopotecan
Topotecan will be administered per local standard-of-care (SoC)
Sponsors
Daiichi Sankyo
Merck Sharp & Dohme LLC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival (OS) | From the date of randomization to the date of death due to any cause, up to approximately 3.7 years | OS is defined as the time interval from the date of randomization to the date of death due to any cause. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Objective Response (OR) Assessed by Blinded Independent Central Review (BICR) Per Response Evaluation Criteria In Solid Tumors Version 1.1 (RECIST v1.1) | Baseline up until documented progressive disease, death, lost to follow-up, or withdrawal by the participant, up to approximately 3.7 years | 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. |
| Number of Participants With OR Assessed by Investigator Per RECIST v1.1 | Baseline up until documented progressive disease, death, lost to follow-up, or withdrawal by the participant, up to approximately 3.7 years | 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. |
| Progression-free Survival (PFS) as Assessed by BICR and Investigator | Baseline up until documented progressive disease, death, lost to follow-up, or withdrawal by the participant, up to approximately 3.7 years | 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. |
| Duration of Response (DoR) as Assessed by BICR and Investigator | 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 | 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. |
| Disease Control as Assessed by BICR and Investigator | Baseline up until documented progressive disease, death, lost to follow-up, or withdrawal by the participant, up to approximately 3.7 years | 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 to Response (TTR) as Assessed by BICR and Investigator | 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 | 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. |
| Change from Baseline in The European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ)-C30 | Baseline up to 3.7 years | 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. |
| Change from Baseline in The European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Lung Cancer 29 (EORTC QLQ-LC29) | Baseline up to 3.7 years | 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. |
| Number of Participants With Treatment-emergent Adverse Events (TEAEs) | Up to 3.7 years | TEAEs are assessed based on NCI CTCAE v5.0. |
| 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 | Baseline up to 3.7 years | 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. |
| Pharmacokinetic Parameter Maximum Concentration (Cmax) for I-DXd, Total Anti-B7-H3 Antibody, and MAAA-1181a | 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) | Cmax will be assessed using non-compartmental methods in participants randomized to the I-DXd group. |
| Pharmacokinetic Parameter Time to Maximum Concentration (Tmax) for I-DXd, Total Anti-B7-H3 Antibody, and MAAA-1181a | 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) | Tmax will be assessed using non-compartmental methods in participants randomized to the I-DXd group. |
| 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 | 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) | 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 | 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) | AUCtau will be assessed using non-compartmental methods in participants randomized to the I-DXd group. |
Countries
Australia, Austria, Belgium, Brazil, Canada, China, Czechia, France, Germany, Greece, Hungary, Italy, Japan, Netherlands, Poland, Portugal, Romania, South Korea, Spain, Switzerland, Taiwan, Turkey (Türkiye), United States
Contacts
CONTACTDaiichi Sankyo Contact for Clinical Trial Information
STUDY_DIRECTORGlobal Clinical Director
Daiichi Sankyo
Outcome results
None listed