Ifinatamab Deruxtecan (I-DXd) in Subjects With Pretreated Extensive-Stage Small Cell Lung Cancer (ES-SCLC)
- Conditions
- Extensive-stage Small-cell Lung Cancer
- Interventions
- Drug: Ifinatamab Deruxtecan (I-DXd)
- Registration Number
- NCT05280470
- Lead Sponsor
- Daiichi Sankyo
- Brief Summary
This 2-part study intends to define the recommended Phase 2 dose of ifinatamab deruxtecan (I-DXd) based on the efficacy, safety, and pharmacokinetics (PK) results observed in participants with Extensive-stage Small Cell Lung Cancer (ES-SCLC) who received at least 1 prior line of platinum-based chemotherapy and a maximum of 3 prior lines of therapy (Part 1) and a minimum of two previous lines of systemic therapy (Part 2). This study will also investigate I-DXd anti-tumor activity in this population.
- Detailed Description
This study will consist of 2 parts: dose optimization (Part 1) and extension (Part 2). In the dose optimization part of the study (Part 1), approximately 80 participants with at least 1 prior line of platinum-based chemotherapy and a maximum of 3 prior lines of therapy will be enrolled. Two I-DXd doses will be tested (8 mg/kg Q3W and 12 mg/kg Q3W). In the extension part of the study (Part 2), approximately 70 participants with a minimum of two previous lines of systemic therapy will be enrolled. I-DXd will be administered at the selected dose of 12 mg/kg Q3W.
In Part 1, eligible participants will be randomized in a 1:1 ratio to receive one of the two dose levels of I-DXd. Randomization will be stratified by:
1. Prior receipt or of an anti-programmed death-ligand 1 (PD-\[L\]1) antibody (yes/no)
2. The chemotherapy-free interval (CTFI) from completion of the first-line therapy to the date of documented radiological Progressive Disease of \<90 days vs. ≥90 days in second-line participants as well as the number of lines of therapy. Thus, the stratification factor includes three categories: (1) second-line participants with CTFI \<90 days, (2) second-line participants with CTFI ≥90 days, and (3) third- and fourth-line participants.
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 187
Participants must meet all the following criteria to be eligible for enrollment into the study:
- Sign and date the informed consent form (ICF) prior to the start of any study-specific qualification procedures.
- Participant must have at least one lesion, not previously irradiated, amenable to core biopsy.
- Male or female subjects aged ≥18 years (follow local regulatory requirements if the legal age of consent for study participation is >18 years old).
- Histologically or cytologically documented ES-SCLC.
- At least one measurable lesion according to RECIST v1.1 as assessed by the investigator.
- 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.
- Documentation of radiological disease progression on or after most recent systemic therapy.
- Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1.
Participants who meet any of the following criteria will be disqualified from entering the study:
- Prior treatment with orlotamab, enoblituzumab, or other B7-H3 targeted agents, including I-DXd.
- Prior discontinuation of an antibody drug conjugate (ADC) that consists of an exatecan derivative (eg, trastuzumab deruxtecan) due to treatment-related toxicities.
- 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.
- Any of the following conditions within the past 6 months: cerebrovascular accident, transient ischemic attack, or another arterial thromboembolic event.
- Clinically significant corneal disease.
- Uncontrolled or significant cardiovascular disease.
- 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.
- Clinically severe pulmonary compromise resulting from intercurrent pulmonary illnesses,
- Chronic steroid treatment (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.
- 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.
- History of allogeneic bone marrow, stem cell, or solid organ transplant.
- 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.
- History of hypersensitivity to the drug substances, inactive ingredients in the drug product or severe hypersensitivity reactions to other monoclonal antibodies.
- Evidence of ongoing uncontrolled systemic bacterial, fungal, or viral infection.
- Has active or uncontrolled hepatitis B or C infection.
- Active, known, or suspected autoimmune disease.
- Any evidence of severe or uncontrolled systemic diseases (including active bleeding diatheses, psychiatric illness/social situations, substance abuse).
- Has received a live vaccine within 30 days prior to the first dose of study drug.
- Female who is pregnant or breast-feeding or intends to become pregnant during the study.
- 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.
- Known human immunodeficiency virus (HIV) infection that is not well controlled.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Ifinatamab Deruxtecan (8 mg/kg) Ifinatamab Deruxtecan (I-DXd) Participants will be randomized to receive I-DXd at 8 mg/kg. Ifinatamab Deruxtecan (12 mg/kg) Ifinatamab Deruxtecan (I-DXd) Participants will be randomized to receive I-DXd at 12 mg/kg. In Part 2, all participants will receive I-DXd 12 mg/kg.
- Primary Outcome Measures
Name Time Method 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 Up to approximately 36 months ORR was 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. For all target, non-target, and new lesions, CR was defined as a disappearance of all lesions and PR was defined as at least a 30% decrease in the sum of diameters of all lesions.
- Secondary Outcome Measures
Name Time Method Overall Survival (OS) Following Treatment With I-DXd in Participants With Pretreated ES-SCLC 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.
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) Following Treatment With I-DXd in Participants With Pretreated ES-SCLC 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.
Duration of Response (DoR) Following Treatment With I-DXd in Participants With Pretreated ES-SCLC 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 or to death due to any cause, whichever occurs first. DoR will be assessed by BICR and investigator.
Progression-Free Survival (PFS) Following Treatment With I-DXd in Participants With Pretreated ES-SCLC 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 or death due to any cause. PFS will be assessed by BICR and investigator.
Time to Response (TTR) Following Treatment With I-DXd in Participants With Pretreated ES-SCLC 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. TTR will be assessed by BICR and investigator.
Percentage of Participants With Objective Response Rate (ORR) Based on Investigator Assessment Following Treatment With I-DXd in Participants With Pretreated ES-SCLC 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. For all target, non-target, and new lesions, CR was defined as a disappearance of all lesions and PR was defined as at least a 30% decrease in the sum of diameters of all lesions.
Disease Control Rate (DCR) Following Treatment With I-DXd in Participants With Pretreated ES-SCLC 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.
Maximum Plasma Concentration (Cmax) Following Treatment With I-DXd in Participants With Pretreated ES-SCLC 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.
Time to Reach Maximum Serum Concentration (Tmax) Following Treatment With I-DXd in Participants With Pretreated ES-SCLC 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.
Minimum Observed Concentration (Ctrough) Following Treatment With I-DXd in Participants With Pretreated ES-SCLC 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.
Area Under the Curve (AUC) Following Treatment With I-DXd in Participants With Pretreated ES-SCLC 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.
Terminal Half-Life (T1/2) Following Treatment With I-DXd in Participants With Pretreated ES-SCLC 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.
Percentage of Participants Who Have Treatment-Emergent Antidrug Antibodies (ADA) Following Treatment With I-DXd in Participants With Pretreated ES-SCLC 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.
Related Research Topics
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Trial Locations
- Locations (58)
Highlands Oncology Group
🇺🇸Springdale, Arkansas, United States
The Cancer Specialists, Llc
🇺🇸Jacksonville, Florida, United States
Johns Hopkins Sidney Kimmel Comprehensive Cancer Center
🇺🇸Baltimore, Maryland, United States
Universitaetsklinikum Essen
🇩🇪Essen, Germany
H. Lee Moffitt Cancer Center and Research Institute
🇺🇸Tampa, Florida, United States
University of Chicago Medical Center
🇺🇸Chicago, Illinois, United States
Dana-Faeber Cancer Institute
🇺🇸Boston, Massachusetts, United States
Henry Ford Hospital
🇺🇸Detroit, Michigan, United States
Cancer and Hematology Centers of Western Michigan
🇺🇸Grand Rapids, Michigan, United States
Washington University School of Medicine
🇺🇸Saint Louis, Missouri, United States
Hackensack Meridian Health-Southern Ocean Medical Center
🇺🇸Manahawkin, New Jersey, United States
Montefiore Medical Center Prime
🇺🇸Bronx, New York, United States
Memorial Sloan-Kettering Cancer Center (Mskcc) - New York
🇺🇸New York, New York, United States
Duke University Health System
🇺🇸Durham, North Carolina, United States
Sarah Cannon (Tennessee Oncology - Nashville)
🇺🇸Nashville, Tennessee, United States
Millennium Physicians Association, Llp
🇺🇸Houston, Texas, United States
University of Washington Medical Center
🇺🇸Seattle, Washington, United States
Jilin Cancer Hospital
🇨🇳Changchun, China
Hunan Cancer Hospital
🇨🇳Changsha, China
West China Hospital, Sichuan University
🇨🇳Chengdu, China
Guangdong Provincial People'S Hospital
🇨🇳Guangdong, China
Zhejiang Cancer Hospital
🇨🇳Hangzhou, China
Linyi Cancer Hospital
🇨🇳Linyi, China
Fudan University Shanghai Cancer Center
🇨🇳Shanghai, China
Union Hospital of Tongji Medical College Huazhong University of Science and Technology
🇨🇳Wuhan, China
Centre Hospitalier Intercommunal de Créteil
🇫🇷Créteil, France
Centre Leon Berard
🇫🇷Lyon, France
Hôpital Nord - Chu Marseille
🇫🇷Marseille cedex 20, France
Hopital Arnaud de Villeneuve
🇫🇷Montpellier cedex 05, France
CHU de Montpellier - Hôpital Arnaud de Villeneuve
🇫🇷Montpellier, France
Institut Curie - Site de Paris
🇫🇷Paris Cedex 05, France
Hopital Tenon
🇫🇷Paris, France
Evangelische Lungenklinik Berlin
🇩🇪Berlin, Germany
National Cancer Center Hospital
🇯🇵Chuo-ku, Japan
National Cancer Center Hospital East
🇯🇵Kashiwa, Japan
The Cancer Institute Hospital of Jfcr
🇯🇵Koto-ku, Japan
Shizuoka Cancer Center
🇯🇵Nagaizumi-chō, Japan
Kindai University Hospital
🇯🇵Osaka-Sayama, Japan
Osaka International Cancer Institute
🇯🇵Osaka, Japan
Kanagawa Cancer Center
🇯🇵Yokohama, Japan
National Cancer Center
🇰🇷Goyang-si, Korea, Republic of
Seoul National University Bundang Hospital
🇰🇷Seongnam-si, Korea, Republic of
Seoul National University Hospital
🇰🇷Seoul, Korea, Republic of
Samsung Medical Center
🇰🇷Seoul, Korea, Republic of
Asan Medical Center
🇰🇷Seoul, Korea, Republic of
Complejo Hospitalario Universitario A Coruña
🇪🇸A Coruña, Spain
Hospital Universitario Vall Dhebron
🇪🇸Barcelona, Spain
Ico L'Hospitalet - Hospital Duran I Reynals
🇪🇸L'Hospitalet de Llobregat, Spain
Hospital Universitario Ramon Y Cajal
🇪🇸Madrid, Spain
Hospital Universitario 12 de Octubre
🇪🇸Madrid, Spain
Hospital Regional Universitario Malaga
🇪🇸Malaga, Spain
Hospital Virgen Macarena
🇪🇸Sevilla, Spain
Chang Gung Medical Foundation - Kaohsiung Branch
🇨🇳Kaohsiung, Taiwan
Taichung Veterans General Hospital
🇨🇳Taichung, Taiwan
National Cheng Kung University Hospital Nckuh
🇨🇳Tainan, Taiwan
National Taiwan University Hospital
🇨🇳Taipei, Taiwan
Taipei Veterans General Hospital
🇨🇳Taipei, Taiwan
Chang Gung Memorial Hospital Linkou
🇨🇳Taoyuan, Taiwan