This study is designed to evaluate the safety and efficacy of ifinatamab deruxtecan (I-DXd) in combination with immune checkpoint inhibitor (ICI) atezolizumab with or without carboplatin in participants with extensive stage-small cell lung cancer (ES-SCLC) in the first-line (1L) setting.
This study consists of two parts and two cohorts: Part A (Phase 1b; Safety Run-in) and Part B (Phase 2; Dose Optimization), Cohort 1 (I-DXd in maintenance) and Cohort 2 (I-DXd in induction + maintenance). The primary objective of this study is to evaluate the safety and tolerability of I-DXd in combination with atezolizumab with or without carboplatin by assessing treatment-emergent adverse events (TEAEs) and other safety parameters which will inform optimal dose selection of I-DXd in the combination regimens (Dose Optimization Part B) of this study.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
123
Intravenous administration
Intravenous administration
Intravenous administration
Number of Participants Reporting Dose-limiting Toxicities Following I-DXd in Combination With Atezolizumab With or Without Carboplatin (Part A)
Time frame: Cycle 1 Day 1 up to Cycle 1 Day 21 (each cycle is 21 days)
Overall Number of Participants With Treatment-emergent Adverse Events Following I-DXd in Combination With Atezolizumab With or Without Carboplatin (Part A and B)
Time frame: Baseline up to 37 months
Progression-free Survival As Assessed by Blinded Independent Central Review and Investigator Following I-DXd in Combination With Atezolizumab With or Without Carboplatin (Part A and B)
Progression-free survival is defined as the time from the enrollment/randomization date to the earlier of the dates of the first documentation of disease progression assessed by BICR and investigator per RECIST v1.1 or death due to any cause.
Time frame: From start date of study drug to the earlier date of the first objective documentation of radiographic disease progression assessed by BICR and investigator per RECIST v1.1 or death due to any cause, whichever occurs first, up to approximately 37 months
Objective Response Rate Assessed by Blinded Independent Central Review and Investigator Following I-DXd in Combination With Atezolizumab With Carboplatin (Part A and B of Cohort 2 Only)
Objective response rate (ORR) is defined as proportion of subjects who achieved a best overall response of confirmed complete response (CR) or confirmed partial response (PR) per BICR and investigator according to RECIST v1.1.
Time frame: Baseline up until documented progressive disease, death, lost to follow-up, or withdrawal by the participant, up to approximately 37 months
Duration of Response As Assessed by Blinded Independent Central Review and Investigator Following I-DXd in Combination With Atezolizumab With Carboplatin (Part A and B of Cohort 2 Only)
Duration of response (DoR) is defined as the time from the date of the first documentation of objective response (confirmed complete response \[CR\] or confirmed partial response \[PR\]) to the date of the first documentation of progressive disease (PD) or death due to any cause, whichever occurs first. The DoR will be calculated for responding participants (confirmed PR or confirmed CR) only.
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University of Alabama -Birmingham
Birmingham, Alabama, United States
RECRUITINGMayo Clinic Arizona
Phoenix, Arizona, United States
RECRUITINGDavid Geffen School of Medicine
Los Angeles, California, United States
NOT_YET_RECRUITINGHoag Memorial Hospital Presbyterian
Newport Beach, California, United States
RECRUITINGMayo Clinic-Jacksonville
Jacksonville, Florida, United States
RECRUITINGAdvent Health Orlando
Orlando, Florida, United States
RECRUITINGMoffitt Cancer Center
Tampa, Florida, United States
RECRUITINGRobert H. Lurie Comprehensive Cancer Center of Northwestern University
Chicago, Illinois, United States
RECRUITINGHenry Ford Hospital
Detroit, Michigan, United States
ACTIVE_NOT_RECRUITINGRegents of the University of Minnesota
Minneapolis, Minnesota, United States
RECRUITING...and 48 more locations
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 37 months
Disease Control Rate As Assessed by Blinded Independent Central Review and Investigator Following I-DXd in Combination With Atezolizumab With Carboplatin (Part A and B of Cohort 2 Only)
Disease control rate is defined as the proportion of participants who have achieved a best overall response of confirmed CR, confirmed PR, or SD by BICR and investigator assessment per RECIST v1.1.
Time frame: Baseline up until documented progressive disease, death, lost to follow-up, or withdrawal by the participant, up to approximately 37 months
Clinical Benefit Rate as Assessed by Blinded Independent Central Review and Investigator Following I-DXd in Combination With Atezolizumab With Carboplatin (Part A and B of Cohort 2 Only)
Clinical benefit rate (CBR) is defined as the proportion of participants who achieved a best overall response of confirmed CR, confirmed PR, or SD lasting for at least 180 days.
Time frame: Baseline up until documented progressive disease, death, lost to follow-up, or withdrawal by the participant, up to approximately 37 months
Time to Response As Assessed by Blinded Independent Central Review and Investigator Following I-DXd in Combination With Atezolizumab With Carboplatin (Part A and B of Cohort 2 Only)
Time to response (TTR) is defined as the time from the date of enrollment/randomization to the date of the first documentation of objective response (confirmed CR or confirmed PR) in responding subjects.
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 37 months
Best Percentage Change in the Sum of Diameters (SoD) of Measurable Tumors As Assessed by Blinded Independent Central Review and Investigator Following I-DXd in Combination With Atezolizumab With Carboplatin (Part A and B of Cohort 2 Only)
The best percentage change in SoD is defined as the percentage change in the smallest SoD from all post-baseline tumor assessments, taking as reference the baseline SoD.
Time frame: Baseline up to approximately 37 months
Overall Survival Following I-DXd in Combination With Atezolizumab With or Without Carboplatin (Part A and B)
Time from the date of enrollment/randomization to the date of death due to any cause.
Time frame: From the start date of study drug to the date of death due to any cause, whichever occurs first, up to approximately 37 months
Pharmacokinetic Parameter Maximum Serum Concentration of I-DXd
Maximum serum concentration (Cmax) will be assessed using non-compartmental methods.
Time frame: Cycle 1 Day 1 pre-dose up to Cycle 9 (and every 2 cycles thereafter up to 37 months) Day 1 pre-dose (each cycle is 21 days)
Pharmacokinetic Parameter Time to Maximum Serum Concentration of I-DXd
Time to maximum serum concentration (Tmax) will be assessed using non-compartmental methods.
Time frame: Cycle 1 Day 1 pre-dose up to Cycle 9 (and every 2 cycles thereafter up to 37 months) Day 1 pre-dose (each cycle is 21 days)
Pharmacokinetic Parameter Area Under the Concentration Curve of I-DXd
Area under the concentration-time curve up to the last quantifiable time (AUClast) and Area under the concentration-time curve during dosing interval (AUCtau) will be assessed using non-compartmental methods.
Time frame: Cycle 1 Day 1 pre-dose up to Cycle 9 (and every 2 cycles thereafter up to 37 months) Day 1 pre-dose (each cycle is 21 days)
The Number of Participants Who Are Anti-Drug Antibody (ADA)-Positive At Any Time 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 postbaseline), as well as the ADA incidence, which is the proportion of participants having treatment-emergent ADA during the study period, will be reported.
Time frame: Baseline up to approximately 37 months