Small Cell Lung Cancer
Conditions
Keywords
Small cell lung cancer, Ifinatamab deruxtecan, I-DXd
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).
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.
Interventions
12 mg/kg intravenous dose on Day 1 of each 21-day cycle
DRUGTopotecan
Topotecan will be administered per local SoC.
DRUGAmrubicin
Amrubicin will be administered per local SoC.
DRUGLurbinectedin
Lurbinectedin will be administered per local SoC
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
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 any history of ILD/pneumonitis irrespective of steroid use, or current ILD, or suspected ILD, or ILD that cannot be ruled out by imaging at Screening. Participants may be eligible if they had history of radiation pneumonitis that did not require steroids. Examples of suspected ILD/pneumonitis by imaging include the presence of lung parenchymal fibrosis, such as combined pulmonary fibrosis and emphysema (CPFE) and any radiographic features consistent with ILA, including but not limited to, extensive ground glass opacities, reticular opacities, traction bronchiectasis, and honeycombing. 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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Objective Response Rate Assessed by Blinded Independent Central Review | Baseline up until documented progressive disease, death, lost to follow-up, or withdrawal by the participant, up to approximately 5 years | 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. |
| Overall Survival | From the date of randomization to the date of death due to any cause, up to approximately 5 years | — |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Objective Response Rate Assessed by Investigator | Baseline up until documented progressive disease, death, lost to follow-up, or withdrawal by the participant, up to approximately 5 years | 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. |
| Progression-free Survival As Assessed by Blinded Independent Central Review and Investigator | Baseline up until documented progressive disease, death, lost to follow-up, or withdrawal by the participant, up to approximately 5 years | 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. |
| Duration of Response As Assessed by Blinded Independent Central Review and Investigator | 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 | 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. |
| Disease Control Rate As Assessed by Blinded Independent Central Review and Investigator | Baseline up until documented progressive disease, death, lost to follow-up, or withdrawal by the participant, up to approximately 5 years | 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. |
| Time to Response As Assessed by Blinded Independent Central Review and Investigator | 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 | 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. |
| Change from Baseline in The European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ)-C30 | Baseline up to 5 years | 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. |
| Change from Baseline in The European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Lung Cancer 29 (EORTC QLQ-LC29) | Baseline up to 5 years | 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. |
| Overall Number of Participants With Treatment-emergent Adverse Events Following I-DXd Monotherapy | Baseline up to 5 years | TEAEs are assessed based on NCI CTCAE v5.0. |
| 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 5 years | 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. |
| Pharmacokinetic Parameter Maximum Concentration for I-DXd, Total Anti-B7-H3 Antibody, and MAAA-1181a | 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) | Maximum concentration (Cmax) will be assessed using non-compartmental methods in participants randomized to the I-DXd group. |
| Pharmacokinetic Parameter Time to Maximum Concentration for I-DXd, Total Anti-B7-H3 Antibody, and MAAA-1181a | 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) | Time to maximum concentration (Tmax) will be assessed using non-compartmental methods in participants randomized to the I-DXd group. |
| Pharmacokinetic Parameter Area Under the Plasma Concentration-Time Curve for I-DXd, Total Anti-B7-H3 Antibody, and MAAA-1181a | 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) | 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. |
Countries
Australia, Austria, Belgium, Brazil, Canada, China, Czechia, France, Germany, Greece, Hungary, Italy, Japan, Netherlands, Poland, Portugal, Romania, South Korea, Spain, Switzerland, Taiwan, Turkey (Türkiye), United Kingdom, United States
Contacts
CONTACTDaiichi Sankyo Contact for Clinical Trial Information
STUDY_DIRECTORGlobal Clinical Director
Daiichi Sankyo
Outcome results
None listed