IFINATAMAB DERUXTECAN for Small cell lung cancer (extensive-stage)

Inclusion criteria

• {"criterion_text":"- Sign and date the informed consent form (ICF), prior to the start of any study-specific qualification procedures.\n- 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. a. Avoid donating sperm. Note: Preservation of sperm should be considered prior to enrolment / randomization in this trial. b. Adhere to either of the following contraception methods: i. True abstinence from penile-vaginal intercourse, when this is in line with the preferred and usual lifestyle of the subject, OR ii. 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, as a condom may break or leak. Contraceptive use should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies. If the contraception requirements in the local label for any of the study drugs are more stringent than the requirements above, the local label requirements are to be followed. Note: If the subject is azoospermic (vasectomized or secondary to medical cause, documented from the site personnel’s review of the subject’s medical records, medical examination, or medical history interview), no contraception is required.\n- Is willing and able to comply with scheduled visits, drug administration plan, laboratory tests, other study procedures, and study restrictions.\n- Adults ≥18 years or the minimum legal adult age (whichever is greater) at the time the ICF is signed.\n- Has histologically or cytologically confirmed diagnosis of ES-SCLC.\n- For Cohort 1, subject has received 4 cycles of 1L induction therapy with carboplatin, etoposide, and atezolizumab for ES-SCLC with ongoing CR, PR, or SD per RECIST v1.1 assessed by the investigator. For Cohort 2, subject has received no prior treatment for ES-SCLC.\n- For Cohort 2, subject has at least one measurable lesion according to RECIST v1.1 on CT or MRI as assessed by the investigator.\n- For Cohort 2, subject must have at least one lesion, amenable to core biopsy, and must consent to provide a pretreatment biopsy tissue sample and on-treatment biopsy.\n- Has ECOG PS of ≤1 (assessed within 7 days before enrollment/randomization).\n- Has adequate organ and bone marrow function within 7 days before the start of study treatment as specified in the study protocol.\n- A female subject of childbearing potential (POCBP), as defined in Section 10.3.4 of the Protocol, is eligible to participate if the following conditions are met: a. Subject is not pregnant as confirmed by highly sensitive pregnancy test during Screening (within 3 days prior to enrollment/randomization) b. 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. c. Subject agrees to adhere to a contraceptive method that is highly effective (Section 10.3.4) 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 IDXd/atezolizumab/carboplatin is 8/5/6 months, respectively. Preservation of eggs may be considered prior to first dose of study drug."}

Exclusion criteria

• {"criterion_text":"- Has received prior treatment with orlotamab, enoblituzumab, or other B7-H3 targeted agents, including I-DXd.\n- Has clinically severe pulmonary compromise resulting from intercurrent pulmonary illnesses, as explained in the study protocol.\n- Is on chronic steroid treatment (dose of 10 mg daily or more prednisone equivalent), except for low-dose inhaled steroids (for asthma/chronic obstructive pulmonary disease, topical steroids (for mild skin conditions), or intra-articular steroid injections.\n- Has history of malignancy other than SCLC within the 3 years prior to randomization / enrolment, except adequately resected non-melanoma skin cancer, curatively treated in situ disease, superficial gastrointestinal tract tumours, and non-muscle invasive bladder cancer curatively resected by endoscopic surgery.\n- Has history of allogeneic bone marrow, stem cell, or solid organ transplant.\n- Has unresolved toxicities from previous anticancer therapy, defined as toxicities (other than alopecia) not yet resolved to NCI-CTCAE V5.0, Grade ≤1 or baseline.\n- Has history of hypersensitivity to the drug substances, inactive ingredients in the drug product or severe hypersensitivity reactions to other monoclonal antibodies.\n- Has evidence of ongoing uncontrolled systemic bacterial, fungal, or viral infection.\n- Has active or uncontrolled HIV infection. Subjects must be tested for HIV viral load during the Screening Period if acceptable by local regulations or IRBs/IECs, as explained in the study protocol.\n- Has active or uncontrolled hepatitis B or C infection. Hepatitis B and/or Hepatitis C screening tests are not required unless there is a known history of HBV infection or if mandated by local health authority. More details about subjects’ eligibility are explained in the study protocol.\n- Has history of autoimmune disease, as explained in the study protocol.\n- Prior discontinuation of an ADC that consists of an exatecan derivative (eg, trastuzumab deruxtecan) due to treatment-related toxicities.\n- Has any evidence of severe or uncontrolled systemic diseases, as included in the study protocol.\n- Has received a live vaccine within 30 days prior to the first dose of study drug.\n- Is a female who is pregnant or breastfeeding or planning to become pregnant.\n- Has 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 subject; alter the absorption, distribution, metabolism, or excretion of the study drug; or confound the assessment of study results.\n- Has psychological, social, familial, or logistical factors that would prevent regular follow-up.\n- Has received prior treatment with CD137 agonists or ICIs, including anti- cytotoxic T-cell lymphocyte-4, anti-PD-1, and anti-PD-L1 therapeutic antibodies, except for atezolizumab for Cohort 1.\n- Has inadequate washout period before enrolment / randomization as specified in the study protocol.\n- Has any of the following within the past 6 months: cerebrovascular accident, transient ischemic attack, or another arterial thromboembolic event.\n- Has clinically active brain metastases, spinal cord compression, or leptomeningeal carcinomatosis, defined as untreated and symptomatic, or requiring therapy with steroids or anticonvulsants to control associated symptoms.\n- Has clinically significant corneal disease.\n- Has uncontrolled or significant cardiovascular disease, as explained in the study protocol.\n- Has history of (non-infectious) ILD/pneumonitis that required corticosteroids, current ILD/pneumonitis, or suspected ILD/pneumonitis that cannot be ruled out by imaging at Screening."}

Primary endpoints

• {"endpoint_text":"- In the Part A, the endpoints are: DLTs, TEAEs, SAEs, AESIs, ECOG PS, vital sign measurements, standard clinical laboratory parameters (hematology, clinical chemistry, and urinalysis), ECG parameters, ECHO/MUGA scan findings, and ophthalmologic findings.\n- In the Part B, the endpoints are: TEAEs, SAEs, AESIs, ECOG PS, vital sign measurements, standard clinical laboratory parameters (hematology, clinical chemistry, and urinalysis), ECG parameters, ECHO/MUGA scan findings, and ophthalmologic findings.","definition_or_measurement_approach":"Safety and tolerability endpoints measured by incidence and assessment of dose-limiting toxicities (DLTs), treatment-emergent adverse events (TEAEs), serious adverse events (SAEs), adverse events of special interest (AESIs); functional status by ECOG performance status; vital sign measurements; standard clinical laboratory tests (hematology, clinical chemistry, urinalysis); electrocardiogram (ECG) parameters; ECHO/MUGA cardiac imaging findings; and ophthalmologic examinations."}

Secondary endpoints

• {"endpoint_text":"- PFS (progression free survival) is defined as the time from the enrollment / randomization date to the earlier of the dates of the first documentation of PD or death due to any cause.\n- ORR (objective response rate) is defined as the proportion of subjects who achieved a BOR of confirmed CR or confirmed PR.\n- DoR (duration of response) is defined as the time from the date of the first documentation of objective response (confirmed CR or confirmed PR) to the date of the first documentation of PD or death due to any cause, whichever occurs first.\n- DCR (disease control rate) is defined as the proportion of subjects who achieved a BOR of confirmed CR, confirmed PR, or SD.\n- CBR (clinical benefit rate) is defined as the proportion of subjects who achieved a BOR of confirmed CR, confirmed PR, or SD lasting for at least 180 days.\n- TTR (time to response) is defined as the time from the date of enrolment / randomization to the date of the first documentation of objective response (confirmed CR or PR) in responding subjects.\n- The best percentage change in the SoD (sum of diameters) of measurable tumors is defined as the percentage change in the smallest SoD from all post-baseline tumor assessments, taking as reference the baseline SoD.\n- OS (overall survival) is defined as the time from the date of enrollment/ randomization to the date of death due to any cause.\n- Plasma concentrations at each time point and PK parameters (Cmax, Tmax, AUClast, and AUCtau). If data permit, AUCinf,t1/2, CL, Vss, Vz, and Kel for I-DXd, total anti-B7-H3 antibody, and MAAA-1181a in the full PK sampling group. Serum concentrations at each time point for atezolizumab (if analyzed).\n- ADA prevalence (antidrug antibody): the proportion of all subjects having I-DXd ADA at any point in time (including pre-existing ADA at baseline and treatment-emergent ADA). ADA incidence: the proportion of subjects having treatment-emergent ADA during the study period. Titer and neutralizing antibodies may be determined when ADA is confirmed positive. Similar analysis may be conducted for atezolizumab (if analyzed).","definition_or_measurement_approach":"PFS, DoR, TTR, OS measured as time-to-event endpoints from enrollment/randomization to defined events (PD, response, death). ORR, DCR, CBR measured as proportions based on best overall response (BOR) assessed per RECIST v1.1. Tumor size change measured as percentage change in sum of diameters from baseline. PK endpoints measured by plasma/serum concentration sampling with calculation of Cmax, Tmax, AUC and other PK parameters. Immunogenicity assessed by ADA testing—prevalence and incidence, titers, and neutralizing activity if ADA positive."}

France

Earliest CTIS Part Ii Submission Date

15-07-2024

Latest Decision Or Authorization Date

05-05-2026

Processing Time Days

659

Number Of Sites

11

Number Of Participants

16

Spain

Earliest CTIS Part Ii Submission Date

19-07-2024

Latest Decision Or Authorization Date

10-05-2026

Processing Time Days

660

Number Of Sites

15

Number Of Participants

32

Primary sponsor

Full Name

Daiichi Sankyo Inc.

Organisation Type

Pharmaceutical company

Country Of Registered Address

United States

Contract research organisations

Name

PPD Development LP

Responsibilities

PK/ADA; Immunogenicity blood samples (ADA/NAb) for I-DXd

Name

IQVIA Limited

Responsibilities

Operational support roles listed (codes 1,10,11,12,13,2,5,9); contact eu_clinical_trials_information@iqvia.com

Name

Fortrea Inc.

Responsibilities

Biostatistician; Statistical Programming

Third parties

• {"country":"United States","full_name":"Suvoda LLC","duties_or_roles":"Sponsor duties codes: 3 (no textual duty provided); contact email: emclellan@suvoda.com","organisation_type":"Non-Pharmaceutical company"}
• {"country":"United States","full_name":"Mosaic Laboratories LLC","duties_or_roles":"Archival Tumor Tissue Sample, Fresh Tumor Biopsy Sample","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Icon Laboratory Services Inc.","duties_or_roles":"PK Sampling","organisation_type":"Laboratory/Research/Testing facility"}
• {"country":"United States","full_name":"Ventana Medical Systems Inc.","duties_or_roles":"Archival Tumor Tissue Sample; Fresh Tumor Biopsy Sample","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Eresearchtechnology Inc.","duties_or_roles":"Central Imaging, ILD Adjudication","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"PPD Development LP","duties_or_roles":"PK/ADA; Immunogenicity blood samples (ADA/NAb) for I-DXd","organisation_type":"Pharmaceutical company"}
• {"country":"Japan","full_name":"Daiichi Sankyo Co. Ltd.","duties_or_roles":"Archival Tumor Tissue Sample, Fresh Tumor Biopsy Sample","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Fortrea Inc.","duties_or_roles":"Biostatistician; Statistical Programming","organisation_type":"Pharmaceutical company"}
• {"country":"United Kingdom","full_name":"IQVIA Limited","duties_or_roles":"Multiple operational duties (codes 1,10,11,12,13,2,5,9) - contact eu_clinical_trials_information@iqvia.com","organisation_type":"Pharmaceutical company"}
• {"country":"United Kingdom","full_name":"Iqvia Laboratories Limited","duties_or_roles":"Sponsor duty code 4 (no textual duty provided)","organisation_type":"Non-Pharmaceutical company"}
• {"country":"United States","full_name":"Azenta US Inc.","duties_or_roles":"long-term storage of samples","organisation_type":"Pharmaceutical company"}