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).
Brief Title
A Study of Ifinatamab Deruxtecan Versus Treatment of Physician's Choice in Subjects With Relapsed Small Cell Lung Cancer
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.
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.
Central Contacts
Central Contact Role
Contact
Central Contact Phone
9089926400
Central Contact Email
CTRinfo@dsi.com
Completion Date
Completion Date Type
Estimated
Conditions
SMALL CELL LUNG CANCER
Eligibility 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.
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.
Inclusion 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.
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.
Gender
All
Gender Based
false
Keywords
Small cell lung cancer
Ifinatamab deruxtecan
I-DXd
Healthy Volunteers
No
Last Update Post Date
Last Update Post Date Type
Actual
Last Update Submit Date
Minimum Age
18 Years
NCT Id
NCT06203210
Org Class
Industry
Org Full Name
Daiichi Sankyo
Org Study Id
DS7300-188
Overall Status
Recruiting
Phases
Phase 3
Primary Completion Date
Primary Completion Date Type
Estimated
Official Title
A Phase 3, Multicenter, Randomized, Open-label Study of Ifinatamab Deruxtecan (I-DXd), a B7-H3 Antibody Drug Conjugate (ADC), Versus Treatment of Physician's Choice (TPC) in Subjects With Relapsed Small Cell Lung Cancer (SCLC) (IDeate-Lung02)
Primary Outcomes
Outcome Description
OS is defined as the time interval from the date of randomization to the date of death due to any cause.
Outcome Measure
Overall Survival (OS)
Outcome Time Frame
From the date of randomization to the date of death due to any cause, up to approximately 3.7 years
Secondary Ids
Secondary Id
2023-509628-16-00
Secondary Id
2031230631
Secondary Id
2023
Secondary Outcomes
Outcome Description
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.
Outcome Time Frame
Baseline up until documented progressive disease, death, lost to follow-up, or withdrawal by the participant, up to approximately 3.7 years
Outcome Measure
Objective Response (OR) Assessed by Blinded Independent Central Review (BICR) Per Response Evaluation Criteria In Solid Tumors Version 1.1 (RECIST v1.1)
Outcome Description
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.
Outcome Time Frame
Baseline up until documented progressive disease, death, lost to follow-up, or withdrawal by the participant, up to approximately 3.7 years
Outcome Measure
Number of Participants With OR Assessed by Investigator Per RECIST v1.1
Outcome Description
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.
Outcome Time Frame
Baseline up until documented progressive disease, death, lost to follow-up, or withdrawal by the participant, up to approximately 3.7 years
Outcome Measure
Progression-free Survival (PFS) as Assessed by BICR and Investigator
Outcome Description
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.
Outcome 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
Outcome Measure
Duration of Response (DoR) as Assessed by BICR and Investigator
Outcome Description
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.
Outcome Time Frame
Baseline up until documented progressive disease, death, lost to follow-up, or withdrawal by the participant, up to approximately 3.7 years
Outcome Measure
Disease Control as Assessed by BICR and Investigator
Outcome Description
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.
Outcome 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
Outcome Measure
Time to Response (TTR) as Assessed by BICR and Investigator
Outcome Description
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.
Outcome Time Frame
Baseline up to 3.7 years
Outcome Measure
Change from Baseline in The European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ)-C30
Outcome Description
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.
Outcome Time Frame
Baseline up to 3.7 years
Outcome Measure
Change from Baseline in The European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Lung Cancer 29 (EORTC QLQ-LC29)
Outcome Description
TEAEs are assessed based on NCI CTCAE v5.0.
Outcome Time Frame
Up to 3.7 years
Outcome Measure
Number of Participants With Treatment-emergent Adverse Events (TEAEs)
Outcome Description
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.
Outcome Time Frame
Baseline up to 3.7 years
Outcome Measure
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
Outcome Description
Cmax will be assessed using non-compartmental methods in participants randomized to the I-DXd group.
Outcome 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)
Outcome Measure
Pharmacokinetic Parameter Maximum Concentration (Cmax) for I-DXd, Total Anti-B7-H3 Antibody, and MAAA-1181a
Outcome Description
Tmax will be assessed using non-compartmental methods in participants randomized to the I-DXd group.
Outcome 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)
Outcome Measure
Pharmacokinetic Parameter Time to Maximum Concentration (Tmax) for I-DXd, Total Anti-B7-H3 Antibody, and MAAA-1181a
Outcome Description
AUClast will be assessed using non-compartmental methods in participants randomized to the I-DXd group.
Outcome 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)
Outcome Measure
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
Outcome Description
AUCtau will be assessed using non-compartmental methods in participants randomized to the I-DXd group.
Outcome 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)
Outcome Measure
Pharmacokinetic Parameter Area Under the Plasma Concentration-Time Curve dosing interval (AUCtau) for I-DXd, Total Anti-B7-H3 Antibody, and MAAA-1181a
Start Date
Start Date Type
Actual
Status Verified Date
First Post Date
First Post Date Type
Actual
First Submit Date
First Submit QC Date
Std Ages
Adult
Older Adult
Maximum Age Number (converted to Years and rounded down)
999
Minimum Age Number (converted to Years and rounded down)
18
Investigators
Investigator Type
Principal Investigator
Investigator Name
Balazs Halmos
Investigator Email
bahalmos@montefiore.org
Investigator Department
Medicine
Investigator Division
Oncology
Investigator Sponsor Organization
External
Study Department
Oncology (Medical/Hematologic)
Study Division
Medical and Hematologic Oncology
Categories Mesh Debug
Lung & Chest Cancers --- CARCINOMA, BRONCHOGENIC
Lung & Chest Cancers --- BRONCHIAL NEOPLASMS
Lung & Chest Cancers --- LUNG NEOPLASMS
Lung & Chest Cancers --- RESPIRATORY TRACT NEOPLASMS
Lung & Chest Cancers --- THORACIC NEOPLASMS
Cancer --- NEOPLASMS BY SITE
Cancer --- NEOPLASMS
COVID-19 --- LUNG DISEASES
Lung --- LUNG DISEASES
Asthma and Other Respiratory Diseases --- RESPIRATORY TRACT DISEASES
COVID-19 --- RESPIRATORY TRACT DISEASES
Lung --- RESPIRATORY TRACT DISEASES
MeSH Terms
SMALL CELL LUNG CARCINOMA
CARCINOMA, BRONCHOGENIC
BRONCHIAL NEOPLASMS
LUNG NEOPLASMS
RESPIRATORY TRACT NEOPLASMS
THORACIC NEOPLASMS
NEOPLASMS BY SITE
NEOPLASMS
LUNG DISEASES
RESPIRATORY TRACT DISEASES
TOPOTECAN
AMRUBICIN
PM 01183
CAMPTOTHECIN
ALKALOIDS
HETEROCYCLIC COMPOUNDS