A Phase 1b/2, Multicenter, Open-label Study of Ifinatamab Deruxtecan (I-DXd), a B7-H3 Antibody-Drug Conjugate (ADC), in Combination With Atezolizumab With or Without Carboplatin as First-line Induction or Maintenance, in Subjects With Extensive-stage Small Cell Lung Cancer (ES-SCLC) (IDeate-Lung03)
Summary
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.
Detailed description
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.
Arms & interventions
- DrugIfinatamab deruxtecan
Intravenous administration
- DrugAtezolizumab
Intravenous administration
- DrugCarboplatin
Intravenous administration
Outcome measures
Primary
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
Secondary
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)
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)
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)
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)
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)
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 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)
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 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
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 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
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
Time frame: Baseline up to approximately 37 months
Eligibility criteria
Study locations (26)
University of Alabama -Birmingham
Birmingham, Alabama, 35233
Mayo Clinic Arizona
Phoenix, Arizona, 85054
David Geffen School of Medicine
Los Angeles, California, 90095
Hoag Memorial Hospital Presbyterian
Newport Beach, California, 92663
Mayo Clinic-Jacksonville
Jacksonville, Florida, 32224
Advent Health Orlando
Orlando, Florida, 32804
Moffitt Cancer Center
Tampa, Florida, 33612
Robert H. Lurie Comprehensive Cancer Center of Northwestern University
Chicago, Illinois, 60611
Henry Ford Hospital
Detroit, Michigan, 48202
Regents of the University of Minnesota
Minneapolis, Minnesota, 55455
Mayo Clinic
Rochester, Minnesota, 55905
Dartmouth-Hitchcock Medical Center
Lebanon, New Hampshire, 03766
Astera Cancer Care
East Brunswick, New Jersey, 08816
John Theurer Cancer Center At Hackensack Umc
Hackensack, New Jersey, 07601
New York University Cancer Center - Laura and Isaac Perlmutter Cancer Center At Nyu Langone
Mineola, New York, 11501
NYU Langone Hospital - Long Island
Mineola, New York, 11501
Memorial Sloan Kettering Cancer Center
New York, New York, 10021
Columbia University Hervert Irving Comprehensive Cancer Center
New York, New York, 10032
Montefiore Medical Center
New York, New York, 10461
Lancaster General Hospital - Ann B Barshinger Cancer Institute
Lancaster, Pennsylvania, 17601
University of Pennsylvania, Abramson Cancer Center
Philadelphia, Pennsylvania, 19104
Thomas Jefferson University Hospital - Central
Philadelphia, Pennsylvania, 19107
Scri Oncology Partners
Nashville, Tennessee, 37203
Next Virginia
Fairfax, Virginia, 22031
Northwest Cancer Specialists, P.C.-Vancouver
Vancouver, Washington, 98684
Medical College of Wisconsin
Milwaukee, Wisconsin, 53226