A Phase 2, Multicenter, Randomized, Open-label Study of DS-7300a, a B7-H3 Antibody Drug Conjugate (ADC), in Subjects With Pretreated Extensive-Stage Small Cell Lung Cancer (ES-SCLC) (IDeate-Lung01)
Ifinatamab Deruxtecan (I-DXd) in Subjects With Pretreated Extensive-Stage Small Cell Lung Cancer (ES-SCLC)
Inoguchi Akihiro
DAIICHI SANKYO Co.,Ltd.
1-2-58, Hiromachi, Shinagawa-ku, Tokyo
+81-3-6225-1111
dsclinicaltrial@daiichisankyo.co.jp
Contact for Clinical Trial Information
DAIICHI SANKYO Co.,Ltd.
1-2-58, Hiromachi, Shinagawa-ku, Tokyo
+81-3-6225-1111
dsclinicaltrial@daiichisankyo.co.jp
Recruiting
July. 08, 2022
July. 22, 2022
180
Interventional
randomized controlled trial
open(masking not used)
dose comparison control
parallel assignment
treatment purpose
1. Sign and date the informed consent form (ICF) prior to the start of any study-specific qualification procedures.
2. Participant must have at least one lesion, not previously irradiated, amenable to core biopsy.
3. Male or female subjects aged >=18 years
4. Histologically or cytologically documented ES-SCLC.
5. At least one measurable lesion according to RECIST v1.1 as assessed by the investigator.
6. Prior therapy with at least one platinum-based line as systemic therapy for extensive-stage disease with at least two cycles of therapy (except in the case of early objective PD) and beginning with protocol version 3.0, a minimum of two previous lines of systemic therapy.
7. Documentation of radiological disease progression on or after most recent systemic therapy.
8. Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1.
1. Prior treatment with orlotamab, enoblituzumab, or other 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. Clinically active brain metastases, spinal cord compression or leptomeningeal carcinomatosis, defined as untreated or symptomatic, or requiring therapy with steroids or anticonvulsants to control associated symptoms.
4. Any of the following conditions within the past 6 months: cerebrovascular accident, transient ischemic attack, or another arterial thromboembolic event.
5. Clinically significant corneal disease.
6. Uncontrolled or significant cardiovascular disease.
7. History of (non-infectious) interstitial lung disease (ILD)/pneumonitis that required corticosteroids, current ILD/pneumonitis, or suspected ILD/pneumonitis that cannot be ruled out by imaging at screening.
8. Clinically severe pulmonary compromise resulting from intercurrent pulmonary illnesses.
9. Chronic steroid treatment (maximum dose of 10 mg daily or more prednisone equivalent), except for low-dose inhaled steroids (for asthma/COPD) or topical steroids (for mild skin conditions) or intra-articular steroid injections.
10. History of malignancy other than SCLC within the 3 years prior to enrollment, except adequately resected non-melanoma skin cancer, curatively treated in situ disease, superficial gastrointestinal (GI) tract tumors and non-muscle invasive bladder cancer curatively resected by endoscopic surgery.
11. History of allogeneic bone marrow, stem cell, or solid organ transplant.
12. Unresolved toxicities from previous anticancer therapy, defined as toxicities (other than alopecia) not yet resolved to National Cancer Institute- Common Terminology Criteria for Adverse Events Version 5.0 (NCI-CTCAE V5.0), Grade <=1 or baseline.
13. History of hypersensitivity to the drug substances, inactive ingredients in the drug product or severe hypersensitivity reactions to other monoclonal antibodies.
14. Evidence of ongoing uncontrolled systemic bacterial, fungal, or viral infection.
15. Has active or uncontrolled hepatitis B or C infection.
16. Active, known, or suspected autoimmune disease.
17. Any evidence of severe or uncontrolled systemic diseases (including active bleeding diatheses, psychiatric illness/social situations, substance abuse).
18. Has received a live vaccine within 30 days prior to the first dose of study drug.
19. Female who is pregnant or breast-feeding or intends to become pregnant during the study.
20. Prior or ongoing clinically relevant illness, medical condition, surgical history, physical finding, or laboratory abnormality that, in the investigator's opinion, could affect the safety of the participant.
21. Known human immunodeficiency virus (HIV) infection that is not well controlled.
18age old over
No limit
Both
Extensive-stage Small Cell Lung Cancer
In the dose optimization part of the study (Part 1), participant will be randomized to receive Ifinatamab Deruxtecan (I-DXd) at 8 mg/kg or 12 mg/kg. In the extension part of the study (Part 2), participant will be randomized to receive Ifinatamab Deruxtecan (I-DXd) at 12 mg/kg.
I-DXd will be administered as intravenous (IV) on Day 1 of each 21-day cycle (every Q3W).
Percentage of Participants With Objective Response Rate (ORR) Based on Blinded Independent Central Review (BICR) Following Treatment With I-DXd in Participants With Pretreated ES-SCLC [ Time Frame: Up to approximately 36 months ]
ORR was the defined as the percentage of participants who achieved a best overall response (BOR) of confirmed Complete Response (CR) or Partial Response (PR), assessed by BICR based on RECIST version 1.1. CR was defined as a disappearance of all target lesions and PR was defined as at least a 30% decrease in the sum of diameters of target lesions.
1. Number of Participants With Treatment-Emergent Adverse Events (TEAEs) Following Treatment With I-DXd in Participants With Pretreated ES-SCLC [ Time Frame: Up to approximately 36 months ]
TEAEs are defined as new adverse events (AEs) that occur after the dose of study drug or as AEs that were present prior to the dose of study drug but which worsened in severity after the start of study drug.
2. Progression-Free Survival (PFS) Following Treatment With I-DXd in Participants With Pretreated ES-SCLC [ Time Frame: From enrollment until disease progression or death (whichever occurs first), up to approximately 36 months ]
PFS is defined as the time interval from the date of enrollment to the date of disease progression based on RECIST v1.1 criteria or death due to any cause. PFS will be assessed by BICR and investigator.
3. Duration of Response (DoR) Following Treatment With I-DXd in Participants With Pretreated ES-SCLC [ Time Frame: From enrollment until disease progression or death (whichever occurs first), up to approximately 36 months ]
DoR is defined as the time from the date of first documentation of objective tumor response (CR or PR) to the first documentation of objective tumor progression based on RECIST v1.1 criteria or to death due to any cause, whichever occurs first. DoR will be assessed by BICR and investigator.
4. Overall Survival (OS) Following Treatment With I-DXd in Participants With Pretreated ES-SCLC [ Time Frame: From enrollment until death, up to approximately 36 months ]
OS is defined as the time interval from the date of enrollment to the date of death due to any cause or last contact follow-up, whichever occurs first.
5. Time to Response (TTR) Following Treatment With I-DXd in Participants With Pretreated ES-SCLC [ Time Frame: From enrollment until disease progression or death (whichever occurs first), up to approximately 36 months ]
TTR is defined as the time from the date of enrollment to the first documentation of objective tumor response (CR or PR) based on RECIST v.1.1 criteria. TTR will be assessed by BICR and investigator.
6. Percentage of Participants With Objective Response Rate (ORR) Based on Investigator Assessment Following Treatment With I-DXd in Participants With Pretreated ES-SCLC [ Time Frame: Up to approximately 36 months ]
ORR was the defined as the percentage of participants who achieved a best overall response (BOR) of confirmed Complete Response (CR) or Partial Response (PR), assessed by investigator based on RECIST version 1.1. CR was defined as a disappearance of all target lesions and PR was defined as at least a 30% decrease in the sum of diameters of target lesions.
7. Disease Control Rate (DCR) Following Treatment With I-DXd in Participants With Pretreated ES-SCLC [ Time Frame: Up to approximately 36 months ]
DCR is defined as percentage of participants with BOR of CR, PR, or stable disease, according to RECIST v1.1 criteria.
8. Maximum Plasma Concentration (Cmax) Following Treatment With I-DXd in Participants With Pretreated ES-SCLC [ Time Frame: Cycle 1: Predose, end of infusion (EOI), 3, 6, & 24 hours post start of infusion (SOI), Days 4, 8, 15, & 22; Cycle 2: Predose & EOI; Cycle 3: Predose, EOI, 3 & 6 hours post SOI; Cycle 4,5 & every 2 cycles up to 36 months: Predose (each cycle is 21 days) ]
Cmax will be calculated using noncompartmental methods. Cmax will be assessed for I-DXd, total anti-B7-H3 antibody, and MAAA-1181a.
9. Time to Reach Maximum Serum Concentration (Tmax) Following Treatment With I-DXd in Participants With Pretreated ES-SCLC [ Time Frame: Cycle 1: Predose, end of infusion (EOI), 3, 6, & 24 hours post start of infusion (SOI), Days 4, 8, 15, & 22; Cycle 2: Predose & EOI; Cycle 3: Predose, EOI, 3 & 6 hours post SOI; Cycle 4, 5 & every 2 cycles up to 36 months: Predose (each cycle is 21 days) ]
Tmax will be calculated using noncompartmental methods. Tmax will be assessed for I-DXd, total anti-B7-H3 antibody, and MAAA-1181a.
10. Minimum Observed Concentration (Ctrough) Following Treatment With I-DXd in Participants With Pretreated ES-SCLC [ Time Frame: Cycle 1: Predose, end of infusion (EOI), 3, 6, & 24 hours post start of infusion (SOI), Days 4, 8, 15, & 22; Cycle 2: Predose & EOI; Cycle 3: Predose, EOI, 3 & 6 hours post SOI; Cycle 4, 5 & every 2 cycles up to 36 months: Predose (each cycle is 21 days) ]
Ctrough will be calculated using noncompartmental methods. Ctrough will be assessed for I-DXd, total anti-B7-H3 antibody, and MAAA-1181a.
11. Area Under the Curve (AUC) Following Treatment With I-DXd in Participants With Pretreated ES-SCLC [ Time Frame: Cycle 1: Predose, end of infusion (EOI), 3, 6, & 24 hours post start of infusion (SOI), Days 4, 8, 15, & 22; Cycle 2: Predose & EOI; Cycle 3: Predose, EOI, 3 & 6 hours post SOI; Cycle 4, 5 & every 2 cycles up to 36 months: Predose (each cycle is 21 days) ]
AUC will be calculated using noncompartmental methods. AUC will be assessed for I-DXd, total anti-B7-H3 antibody, and MAAA-1181a.
12. Terminal Half-Life (T1/2) Following Treatment With I-DXd in Participants With Pretreated ES-SCLC [ Time Frame: Cycle 1: Predose, end of infusion (EOI), 3, 6, & 24 hours post start of infusion (SOI), Days 4, 8, 15, & 22; Cycle 2: Predose & EOI; Cycle 3: Predose, EOI, 3 & 6 hours post SOI; Cycle 4, 5 & every 2 cycles up to 36 months: Predose (each cycle is 21 days) ]
T1/2 will be calculated using noncompartmental methods. T1/2 will be assessed for I-DXd, total anti-B7-H3 antibody, and MAAA-1181a.
13. Percentage of Participants Who Have Treatment-Emergent Antidrug Antibodies (ADA) Following Treatment With I-DXd in Participants With Pretreated ES-SCLC [ Time Frame: Cycle 1, Cycle 2, Cycle 3 and Cycle 4 Day 1: Predose; Cycle 5 Day 1 & every 2 cycles thereafter up to approximately 36 months: Predose; End of Termination Visit; 40-day Follow-up Visit (each cycle is 21 days) ]
The immunogenicity of I-DXd will be assessed.
De-identified individual participant data (IPD) on completed studies and applicable supporting clinical trial documents may be available upon request at https://vivli.org/. In cases where clinical trial data and supporting documents are provided pursuant to our company policies and procedures, Daiichi Sankyo will continue to protect the privacy of our clinical trial participants. Details on data sharing criteria and the procedure for requesting access can be found at this web address: https://vivli.org/ourmember/daiichi-sankyo/
Supporting Information:
- Study Protocol
- Statistical Analysis Plan (SAP)
- Informed Consent Form (ICF)
Time Frame: Completed studies that has reached a global end or completion with all data set collected and analyzed, and for which the medicine and indication have received European Union (EU) and United States (US), and/or Japan (JP) marketing approval on or after 01 January 2014 or by the US or EU or JP Health Authorities when regulatory submissions in all regions are not planned and after the primary study results have been accepted for publication.
Access Criteria: Formal request from qualified scientific and medical researchers on IPD and clinical study documents on completed clinical trials supporting products submitted and licensed in the United States, the European Union and/or Japan from 01 January 2014 and beyond for the purpose of conducting legitimate research. This must be consistent with the principle of safeguarding study participants' privacy and consistent with provision of informed consent.
URL: https://vivli.org/ourmember/daiichi-sankyo/
NCT05280470
ClinicalTrials.gov
United States/France/Germany/Spain/China/Taiwan/Korea
