A Study of I-DXd in Combination With Atezolizumab With or Without Carboplatin as First-Line Induction or Maintenance in Subjects With Extensive Stage-Small Cell Lung Cancer (IDeate-Lung03)
- Conditions
- Extensive Stage-small Cell Lung Cancer
- Interventions
- Registration Number
- NCT06362252
- Lead Sponsor
- Daiichi Sankyo
- Brief 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.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 123
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Cohort 2, Part A: Induction + Maintenance (I-DXd 12 mg/kg) Ifinatamab deruxtecan Part A (Safety Run-in): Participants who are treatment-naive, newly diagnosed with ES-SCLC will receive 4 cycles of IL I-DXd induction therapy (12 mg/kg IV Q3W) + atezolizumab (1200 mg IV Q3W) + carboplatin (AUC 5 mg/ml×min IV Q3W) followed by maintenance therapy (I-DXd 12 mg/kg IV Q3W) + atezolizumab (1200 mg IV Q3W). Cohort 1, Part B: Maintenance (I-DXd 8 mg/kg) Ifinatamab deruxtecan Part B: Participants who must have received 4 cycles of 1L induction standard of care (SoC) therapy with best overall response of CR, PR, or SD will receive maintenance therapy only (I-DXd 8 mg/kg IV Q3W + atezolizumab 1200 mg IV Q3W), starting at Cycle 1 Day 1. Cohort 1, Part B: Maintenance (I-DXd 12 mg/kg) Ifinatamab deruxtecan Part B: Participants who must have received 4 cycles of 1L induction standard of care (SoC) therapy with best overall response of CR, PR, or SD will receive maintenance therapy only (I-DXd 12 mg/kg IV Q3W + atezolizumab 1200 mg IV Q3W), starting at Cycle 1 Day 1. Cohort 2, Part B: Induction + Maintenance (I-DXd 8 mg/kg) Ifinatamab deruxtecan Participants who are treatment-naive, newly diagnosed with ES-SCLC will receive 4 cycles of 1L I-DXd induction therapy (8 mg/kg IV Q3W) + atezolizumab (1200 mg IV Q3W) + carboplatin (AUC 5 mg/ml×min IV Q3W) followed by maintenance therapy (I-DXd 8 mg/kg IV Q3W) + atezolizumab (1200 mg IV Q3W). Cohort 2, Part B: Induction + Maintenance (I-DXd 12 mg/kg) Ifinatamab deruxtecan Participants who are treatment-naive, newly diagnosed with ES-SCLC will receive 4 cycles of IL I-DXd induction therapy (12 mg/kg IV Q3W) + atezolizumab (1200 mg IV Q3W) + carboplatin (AUC 5 mg/ml×minIV Q3W) followed by maintenance therapy (I-DXd 12 mg/kg IV Q3W) + atezolizumab (1200 mg IV Q3W). Cohort 1, Part A: Maintenance Only (I-DXd 12 mg/kg) Ifinatamab deruxtecan Part A (Safety Run-in): Participants who must have received 4 cycles of 1L induction standard of care (SoC) therapy with best overall response of CR, PR, or SD will receive maintenance therapy only (I-DXd 12 mg/kg IV Q3W + atezolizumab 1200 mg IV Q3W). A 5-day surveillance period between each of the first 3 participants (up to a maximum of 9 participants) dosed is included as a safety measure. Cohort 1, Part A: Maintenance Only (I-DXd 12 mg/kg) Atezolizumab Part A (Safety Run-in): Participants who must have received 4 cycles of 1L induction standard of care (SoC) therapy with best overall response of CR, PR, or SD will receive maintenance therapy only (I-DXd 12 mg/kg IV Q3W + atezolizumab 1200 mg IV Q3W). A 5-day surveillance period between each of the first 3 participants (up to a maximum of 9 participants) dosed is included as a safety measure. Cohort 2, Part A: Induction + Maintenance (I-DXd 8 mg/kg) Ifinatamab deruxtecan Part A (Safety Run-in): Participants who are treatment-naive, newly diagnosed with ES-SCLC will receive 4 cycles of 1L I-DXd induction therapy (8 mg/kg IV Q3W) + atezolizumab (1200 mg IV Q3W) + carboplatin (AUC 5 mg/ml×min IV Q3W) followed by maintenance therapy (I-DXd 8 mg/kg IV Q3W) + atezolizumab (1200 mg IV Q3W). Cohort 2, Part A: Induction + Maintenance (I-DXd 8 mg/kg) Atezolizumab Part A (Safety Run-in): Participants who are treatment-naive, newly diagnosed with ES-SCLC will receive 4 cycles of 1L I-DXd induction therapy (8 mg/kg IV Q3W) + atezolizumab (1200 mg IV Q3W) + carboplatin (AUC 5 mg/ml×min IV Q3W) followed by maintenance therapy (I-DXd 8 mg/kg IV Q3W) + atezolizumab (1200 mg IV Q3W). Cohort 2, Part A: Induction + Maintenance (I-DXd 8 mg/kg) Carboplatin Part A (Safety Run-in): Participants who are treatment-naive, newly diagnosed with ES-SCLC will receive 4 cycles of 1L I-DXd induction therapy (8 mg/kg IV Q3W) + atezolizumab (1200 mg IV Q3W) + carboplatin (AUC 5 mg/ml×min IV Q3W) followed by maintenance therapy (I-DXd 8 mg/kg IV Q3W) + atezolizumab (1200 mg IV Q3W). Cohort 2, Part A: Induction + Maintenance (I-DXd 12 mg/kg) Atezolizumab Part A (Safety Run-in): Participants who are treatment-naive, newly diagnosed with ES-SCLC will receive 4 cycles of IL I-DXd induction therapy (12 mg/kg IV Q3W) + atezolizumab (1200 mg IV Q3W) + carboplatin (AUC 5 mg/ml×min IV Q3W) followed by maintenance therapy (I-DXd 12 mg/kg IV Q3W) + atezolizumab (1200 mg IV Q3W). Cohort 2, Part A: Induction + Maintenance (I-DXd 12 mg/kg) Carboplatin Part A (Safety Run-in): Participants who are treatment-naive, newly diagnosed with ES-SCLC will receive 4 cycles of IL I-DXd induction therapy (12 mg/kg IV Q3W) + atezolizumab (1200 mg IV Q3W) + carboplatin (AUC 5 mg/ml×min IV Q3W) followed by maintenance therapy (I-DXd 12 mg/kg IV Q3W) + atezolizumab (1200 mg IV Q3W). Cohort 1, Part B: Maintenance (I-DXd 8 mg/kg) Atezolizumab Part B: Participants who must have received 4 cycles of 1L induction standard of care (SoC) therapy with best overall response of CR, PR, or SD will receive maintenance therapy only (I-DXd 8 mg/kg IV Q3W + atezolizumab 1200 mg IV Q3W), starting at Cycle 1 Day 1. Cohort 1, Part B: Maintenance (I-DXd 12 mg/kg) Atezolizumab Part B: Participants who must have received 4 cycles of 1L induction standard of care (SoC) therapy with best overall response of CR, PR, or SD will receive maintenance therapy only (I-DXd 12 mg/kg IV Q3W + atezolizumab 1200 mg IV Q3W), starting at Cycle 1 Day 1. Cohort 2, Part B: Induction + Maintenance (I-DXd 8 mg/kg) Atezolizumab Participants who are treatment-naive, newly diagnosed with ES-SCLC will receive 4 cycles of 1L I-DXd induction therapy (8 mg/kg IV Q3W) + atezolizumab (1200 mg IV Q3W) + carboplatin (AUC 5 mg/ml×min IV Q3W) followed by maintenance therapy (I-DXd 8 mg/kg IV Q3W) + atezolizumab (1200 mg IV Q3W). Cohort 2, Part B: Induction + Maintenance (I-DXd 8 mg/kg) Carboplatin Participants who are treatment-naive, newly diagnosed with ES-SCLC will receive 4 cycles of 1L I-DXd induction therapy (8 mg/kg IV Q3W) + atezolizumab (1200 mg IV Q3W) + carboplatin (AUC 5 mg/ml×min IV Q3W) followed by maintenance therapy (I-DXd 8 mg/kg IV Q3W) + atezolizumab (1200 mg IV Q3W). Cohort 2, Part B: Induction + Maintenance (I-DXd 12 mg/kg) Atezolizumab Participants who are treatment-naive, newly diagnosed with ES-SCLC will receive 4 cycles of IL I-DXd induction therapy (12 mg/kg IV Q3W) + atezolizumab (1200 mg IV Q3W) + carboplatin (AUC 5 mg/ml×minIV Q3W) followed by maintenance therapy (I-DXd 12 mg/kg IV Q3W) + atezolizumab (1200 mg IV Q3W). Cohort 2, Part B: Induction + Maintenance (I-DXd 12 mg/kg) Carboplatin Participants who are treatment-naive, newly diagnosed with ES-SCLC will receive 4 cycles of IL I-DXd induction therapy (12 mg/kg IV Q3W) + atezolizumab (1200 mg IV Q3W) + carboplatin (AUC 5 mg/ml×minIV Q3W) followed by maintenance therapy (I-DXd 12 mg/kg IV Q3W) + atezolizumab (1200 mg IV Q3W).
- Primary Outcome Measures
Name Time Method Number of Participants Reporting Dose-limiting Toxicities Following I-DXd in Combination With Atezolizumab With or Without Carboplatin (Part A) 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) Baseline up to 37 months
- Secondary Outcome Measures
Name Time Method 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) 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 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.
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) Baseline up until documented progressive disease, death, lost to follow-up, or withdrawal by the participant, up to approximately 37 months 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.
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) 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 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.
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) Baseline up until documented progressive disease, death, lost to follow-up, or withdrawal by the participant, up to approximately 37 months 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.
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) Baseline up until documented progressive disease, death, lost to follow-up, or withdrawal by the participant, up to approximately 37 months 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 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) 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 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.
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) Baseline up to approximately 37 months 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.
Overall Survival Following I-DXd in Combination With Atezolizumab With or Without Carboplatin (Part A and B) From the start date of study drug to the date of death due to any cause, whichever occurs first, up to approximately 37 months Time from the date of enrollment/randomization to the date of death due to any cause.
Pharmacokinetic Parameter Maximum Serum Concentration of I-DXd 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) Maximum serum concentration (Cmax) will be assessed using non-compartmental methods.
Pharmacokinetic Parameter Time to Maximum Serum Concentration of I-DXd 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) Time to maximum serum concentration (Tmax) will be assessed using non-compartmental methods.
Pharmacokinetic Parameter Area Under the Concentration Curve of I-DXd 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) 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.
The Number of Participants Who Are Anti-Drug Antibody (ADA)-Positive At Any Time and Who Have A Treatment-emergent Anti-Drug Antibody Baseline up to approximately 37 months 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.
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Trial Locations
- Locations (50)
University of Alabama -Birmingham
🇺🇸Birmingham, Alabama, United States
David Geffen School of Medicine
🇺🇸Los Angeles, California, United States
Hoag Memorial Hospital Presbyterian
🇺🇸Newport Beach, California, United States
Mayo Clinic-Jacksonville
🇺🇸Jacksonville, Florida, United States
Adventhealth Orlando
🇺🇸Orlando, Florida, United States
Robert H. Lurie Comprehensive Cancer Center of Northwestern University
🇺🇸Chicago, Illinois, United States
Henry Ford Hospital
🇺🇸Detroit, Michigan, United States
Regents of the University of Minnesota
🇺🇸Minneapolis, Minnesota, United States
Mayo Clinic
🇺🇸Rochester, Minnesota, United States
Dartmouth-Hitchcock Medical Center
🇺🇸Lebanon, New Hampshire, United States
Astera Cancer Care
🇺🇸East Brunswick, New Jersey, United States
John Theurer Cancer Center At Hackensack Umc
🇺🇸Hackensack, New Jersey, United States
New York University Cancer Center - Laura and Isaac Perlmutter Cancer Center At Nyu Langone
🇺🇸Mineola, New York, United States
NYU Langone Hospital - Long Island
🇺🇸Mineola, New York, United States
Memorial Sloan Kettering Cancer Center
🇺🇸New York, New York, United States
Columbia University Hervert Irving Comprehensive Cancer Center
🇺🇸New York, New York, United States
Thomas Jefferson University Hospital - Central
🇺🇸Philadelphia, Pennsylvania, United States
Scri Oncology Partners
🇺🇸Nashville, Tennessee, United States
Next Virginia
🇺🇸Fairfax, Virginia, United States
Northwest Cancer Specialists, P.C.-Vancouver
🇺🇸Vancouver, Washington, United States
Medical College of Wisconsin
🇺🇸Milwaukee, Wisconsin, United States
Hopital Albert Calmette - Chu Lille
🇫🇷Lille Cedex, France
Centre Léon Bérard
🇫🇷Lyon, France
Assistance Publique-Hă"Pitaux de Marseille
🇫🇷Marseille, France
Institut Curie - Site de Paris
🇫🇷Paris Cedex 05, France
Hopital Tenon
🇫🇷Paris, France
Chu Rennes - Hopital Pontchaillou
🇫🇷Rennes cedex 09, France
Chu Nantes - Hă"Pital Guillaume Et Renă Laă<Nnec
🇫🇷Saint Herblain, France
Hă"Pital Foch
🇫🇷Suresnes Cedex, France
Institut Gustave Roussy
🇫🇷Villejuif, France
Kansai Medical University Hospital
🇯🇵Hirakata-shi, Japan
National Cancer Center Hospital East
🇯🇵Kashiwa, Japan
The Cancer Institute Hospital of Jfcr
🇯🇵Koto-ku, Japan
Social Welfare Organization Saiseikai Imperial Gift Foundation, Inc. Saiseikai Kumamoto Hospital
🇯🇵Kumamoto, Japan
Shizuoka Cancer Center
🇯🇵Nagaizumi-chō, Japan
Niigata Cancer Center Hospital
🇯🇵Niigata, Japan
Okayama University Hospital
🇯🇵Okayama, Japan
Kindai University Hospital
🇯🇵Osaka-Sayama, Japan
Hospital Clinic de Barcelona
🇪🇸Barcelona, Spain
Hospital Universitari Vall D'Hebron
🇪🇸Barcelona, Spain
Ico Girona - Hospital Universitari de Girona Dr Josep Trueta
🇪🇸Girona, Spain
Ico L'Hospitalet - Hospital Duran I Reynals
🇪🇸L'Hospitalet de Llobregat, Spain
Hospital General Universitario Gregorio Marañon
🇪🇸Madrid, Spain
Hospital Universitario Ramon Y Cajal
🇪🇸Madrid, Spain
Hospital Universitario 12 de Octubre
🇪🇸Madrid, Spain
Next Madrid
🇪🇸Madrid, Spain
Hospital Regional Universitario de Malaga
🇪🇸Malaga, Spain
Hospital Universitario Virgen Macarena
🇪🇸Sevilla, Spain
Hospital Universitario Virgen Del Rocio
🇪🇸Sevilla, Spain
Hospital Alvaro Cunqueiro
🇪🇸Vigo, Spain