Brief Summary
This study was 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 improves objective response rate (ORR) and 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.
Categories
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 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 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 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 prior to Cycle 1 Day 1 (C1D1).
9. Has no evidence of brain or leptomeningeal disease (spinal cord or central nervous system \[CNS\] metastases) based on history and physical examination. 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
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 disease.
7. Has clinically significant corneal disease.
8. Has history of (non-infectious) interstitial lung disease (ILD)/pneumonitis that required corticosteroids, current ILD/pneumonitis, or suspected ILD/pneumonitis that cannot be ruled out by imaging at Screening.
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 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 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 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 prior to Cycle 1 Day 1 (C1D1).
9. Has no evidence of brain or leptomeningeal disease (spinal cord or central nervous system \[CNS\] metastases) based on history and physical examination. 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
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 disease.
7. Has clinically significant corneal disease.
8. Has history of (non-infectious) interstitial lung disease (ILD)/pneumonitis that required corticosteroids, current ILD/pneumonitis, or suspected ILD/pneumonitis that cannot be ruled out by imaging at Screening.
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 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 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 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 prior to Cycle 1 Day 1 (C1D1).
9. Has no evidence of brain or leptomeningeal disease (spinal cord or central nervous system \[CNS\] metastases) based on history and physical examination. 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.
Participants must meet all the following criteria to be eligible for randomization into the study:
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 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 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 prior to Cycle 1 Day 1 (C1D1).
9. Has no evidence of brain or leptomeningeal disease (spinal cord or central nervous system \[CNS\] metastases) based on history and physical examination. 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.
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
Confirmed objective response rate (ORR) is defined as the sum of the complete response (CR) rate and partial response (PR) rate based on BICR by Response Evaluation Criteria In Solid Tumors (RECIST) v1.1.
Outcome Measure
Number of Participants With Objective Response Rate Assessed by Blinded Independent Central Review
Outcome Time Frame
Baseline up until documented progressive disease, death, lost to follow-up, or withdrawal by the participant, up to approximately 5 years
Outcome Measure
Overall Survival
Outcome Time Frame
From the date of randomization to the date of death due to any cause, up to approximately 5 years
Secondary Ids
Secondary Id
2023-509628-16-00
Secondary Id
2031230631
Secondary Outcomes
Outcome Description
Confirmed objective response rate (ORR) is defined as the sum of the complete response (CR) rate and partial response (PR) rate based on investigator by Response Evaluation Criteria In Solid Tumors (RECIST) v1.1.
Outcome Time Frame
Baseline up until documented progressive disease, death, lost to follow-up, or withdrawal by the participant, up to approximately 5 years
Outcome Measure
Number of Participants With Objective Response Rate Assessed by Investigator
Outcome Description
PFS is defined as the time interval from the date of randomization to the date of disease progression as per BICR and investigator assessment 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 5 years
Outcome Measure
Progression-free Survival As Assessed by Blinded Independent Central Review and Investigator
Outcome Description
Duration of response (DoR) is defined as the time from the date of the first documentation of objective response (complete response \[CR\] or partial response \[PR\]) to the date of the first documentation of progressive disease (PD) or death. The DoR will be calculated for responding participants (PR or CR) only.
Outcome Time Frame
From the date of first documentation of confirmed response (CR or PR) to the first documentation of objective progression or to death due to any cause, whichever occurs first, up to approximately 5 years
Outcome Measure
Duration of Response As Assessed by Blinded Independent Central Review and Investigator
Outcome Description
Disease control rate is defined as the proportion of participants who have achieved a best overall response of confirmed CR, confirmed PR, or SD (or non-CR/non-PD) by BICR and investigator assessment per RECIST v1.1.
Outcome Time Frame
Baseline up until documented progressive disease, death, lost to follow-up, or withdrawal by the participant, up to approximately 5 years
Outcome Measure
Disease Control Rate As Assessed by Blinded Independent Central Review 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 5 years
Outcome Measure
Time to Response As Assessed by Blinded Independent Central Review and Investigator
Outcome Description
This 30-item questionnaire assesses global health status (GHS)/quality of life (QoL), subject functioning, and general cancer symptoms and has a recall period of one week. 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 5 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 5 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
Baseline up to 5 years
Outcome Measure
Overall Number of Participants With Treatment-emergent Adverse Events Following I-DXd Monotherapy
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 5 years
Outcome Measure
The Number of Participants Who Are Anti-Drug Antibody (ADA)-Positive At Any Time and Who Have A Treatment-emergent Anti-Drug Antibody
Outcome Description
Maximum concentration (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 postdose; Cycles 4, 5, and every 2 cycles thereafter up to 5 years BI (each cycle is 21 days)
Outcome Measure
Pharmacokinetic Parameter Maximum Concentration for I-DXd, Total Anti-B7-H3 Antibody, and MAAA-1181a
Outcome Description
Time to maximum concentration (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 postdose; Cycles 4, 5, and every 2 cycles thereafter up to 5 years BI (each cycle is 21 days)
Outcome Measure
Pharmacokinetic Parameter Time to Maximum Concentration for I-DXd, Total Anti-B7-H3 Antibody, and MAAA-1181a
Outcome Description
Area under the plasma concentration-time curve up to the last quantifiable time point (AUClast) and area under the plasma concentration-time curve dosing interval (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 postdose; Cycles 4, 5, and every 2 cycles thereafter up to 5 years BI (each cycle is 21 days)
Outcome Measure
Pharmacokinetic Parameter Area Under the Plasma Concentration-Time Curve 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