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Ifinatamab Deruxtecan (I-DXd) in Subjects With Pretreated Extensive-Stage Small Cell Lung Cancer (ES-SCLC) (IDeate-Lung01)

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ClinicalTrials.gov Identifier: NCT05280470
Recruitment Status : Recruiting
First Posted : March 15, 2022
Last Update Posted : April 9, 2024
Sponsor:
Collaborator:
Merck Sharp & Dohme LLC
Information provided by (Responsible Party):
Daiichi Sankyo

Study Description
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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.

Condition or disease Intervention/treatment Phase
Extensive-stage Small-cell Lung Cancer Drug: Ifinatamab Deruxtecan (I-DXd) Phase 2

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.
Study Design
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 180 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 2, Multicenter, Randomized, Open-label Study of Ifinatamab Deruxtecan (I-DXd), a B7-H3 Antibody Drug Conjugate (ADC), in Subjects With Pretreated Extensive-stage Small Cell Lung Cancer (ES-SCLC) (IDeate-Lung01)
Actual Study Start Date : March 9, 2022
Estimated Primary Completion Date : January 31, 2025
Estimated Study Completion Date : June 20, 2025

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Lung Cancer

Arms and Interventions
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Arm Intervention/treatment
Experimental: Ifinatamab Deruxtecan (8 mg/kg)
Participants will be randomized to receive I-DXd at 8 mg/kg.
 Drug: Ifinatamab Deruxtecan (I-DXd)
I-DXd will be administered as an intravenous (IV) infusion on Day 1 of each 21-day cycle (every Q3W).
Other Name: DS-7300a
Experimental: Ifinatamab Deruxtecan (12 mg/kg)

Participants will be randomized to receive I-DXd at 12 mg/kg.

In Part 2, all participants will receive I-DXd 12 mg/kg.

 Drug: Ifinatamab Deruxtecan (I-DXd)
I-DXd will be administered as an intravenous (IV) infusion on Day 1 of each 21-day cycle (every Q3W).
Other Name: DS-7300a


Outcome Measures
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Primary Outcome Measures :
  1. 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 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 :
  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 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 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. 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. 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.

  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.

  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.


Eligibility Criteria
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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

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.

Exclusion Criteria:

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.
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05280470


Contacts
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Contact: (US contact) Daiichi Sankyo Contact for Clinical Trial Information 908-992-6400 CTRinfo@dsi.com
Contact: Daiichi Sankyo Contact for Clinical Trial Information +81-3-6225-1111(M-F 9-5 JST) dsclinicaltrial@daiichisankyo.co.jp

Locations
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Sponsors and Collaborators
Daiichi Sankyo
Merck Sharp & Dohme LLC
Investigators
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Study Director: Global Clinical Leader Daiichi Sankyo
More Information
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Responsible Party: Daiichi Sankyo
ClinicalTrials.gov Identifier: NCT05280470    
Other Study ID Numbers: DS7300-127
2022-000503-13 ( EudraCT Number )
2041220019 ( Other Identifier: jRCT )
First Posted: March 15, 2022    Key Record Dates
Last Update Posted: April 9, 2024
Last Verified: April 2024
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: De-identified individual participant data (IPD) 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 Materials: Study Protocol
Statistical Analysis Plan (SAP)
Informed Consent Form (ICF)
Time Frame: Studies 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 from 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/

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Daiichi Sankyo:
Relapsed/Refractory Extensive-stage Small-cell Lung Cancer
DS-7300a
B7-H3 Antibody Drug Conjugate
Ifinatamab Deruxtecan
I-DXd
Additional relevant MeSH terms:
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Lung Neoplasms
Small Cell Lung Carcinoma
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
 Neoplasms
Lung Diseases
Respiratory Tract Diseases
Carcinoma, Bronchogenic
Bronchial Neoplasms