Extensive Stage-small Cell Lung Cancer
Conditions
Keywords
Extensive stage-small cell lung cancer (ES-SCLC), Ifinatamab deruxtecan, I-DXd
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.
Interventions
Intravenous administration
DRUGAtezolizumab
Intravenous administration
DRUGCarboplatin
Intravenous administration
Sponsors
Daiichi Sankyo
Merck Sharp & Dohme LLC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
A full list of inclusion/
Exclusion criteria
are available in the protocol. Inclusion Criteria Participants must meet all of the following criteria to be eligible for enrollment into the study: 1. Sign and date the informed consent form (ICF), 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 ICF is signed. 3. Has histologically or cytologically confirmed diagnosis of ES-SCLC who will require first-line (IL) therapy. 4. For Cohort 1, participant has received 4 cycles of 1L induction therapy with carboplatin, etoposide, and atezolizumab for ES-SCLC with ongoing CR PR, CR, or SD per RECIST v1.1 assessed by the investigator. For Cohort 2, participant has received no prior treatment for ES-SCLC. 5. For Cohort 2, participant has at least one measurable lesion according to RECIST v1.1 on computed tomography (CT) or magnetic resonance imaging (MRI) as assessed by the investigator. 6. For Cohort 2, participant must have at least one lesion, amenable to core biopsy, and must consent to provide a pretreatment biopsy tissue sample and on-treatment biopsy. 7. Has ECOG PS of ≤1 (assessed within 7 days before enrollment/randomization). 8. Has adequate organ and bone marrow function within 7 days before the start of study treatment as specified in the study protocol. 9. A female subject of childbearing potential (POCBP) is eligible to participate if the following conditions are met: 1. Subject is not pregnant as confirmed by highly sensitive pregnancy test during Screening (within 3 days prior to enrollment/randomization) 2. Subject does not breastfeed during the treatment period and for at least 8/5/6 months after last dose of I-DXd/atezolizumab/carboplatin, respectively. 3. Subject agrees to adhere to a contraceptive method that is highly effective and agrees not to donate eggs (ova, oocytes) to others or freeze/store eggs during the treatment period and for at least the time needed to eliminate each study drug after the last dose. The length of time required to continue contraception and avoid donating/freezing eggs after last dose for I-DXd/atezolizumab/carboplatin is 8/5/6 months, respectively. Preservation of eggs may be considered prior to first dose of study drug. 10. A male subject capable of producing sperm is eligible to participate if he agrees to the following during the intervention period and for at least the time needed to eliminate each study drug. The length of time required to continue contraception and avoid donating sperm after last dose for I-DXd/atezolizumab/carboplatin is 6/5/6 months, respectively. 1. Avoid donating sperm. 2. Adhere to either of the contraception methods: true abstinence from penile-vaginal intercourse or uses a penile/external condom when having penile-vaginal intercourse with a non-subject of childbearing potential plus partner use of an additional contraceptive method. 11. Is willing and able to comply with scheduled visits, drug administration plan, laboratory tests, other study procedures, and study restrictions.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
Countries
France, Japan, Spain, United States
Contacts
STUDY_DIRECTORGlobal Clinical Leader
Daiichi Sankyo
CONTACT(US) Daiichi Sankyo Contact for Clinical Trial Information
CONTACT(Asia) Daiichi Sankyo Contact for Clinical Trial Information
Outcome results
None listed