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

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

Tracking Information

• First Submitted Date: February 23, 2022
• First Posted Date: March 15, 2022
• Last Update Posted Date: April 9, 2024
• Actual Study Start Date: March 9, 2022
• Estimated Primary Completion Date: January 31, 2025 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: March 15, 2024)

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.

Original Primary Outcome Measures (submitted: March 4, 2022)

Percentage of Participants With Objective Response Rate (ORR) Based on Blinded Independent Central Review (BICR) Following Treatment With DS-7300a in Participants With Pretreated ES-SCLC [ Time Frame: Up to approximately 16 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.

Current Secondary Outcome Measures (submitted: March 15, 2024)

• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.

Original Secondary Outcome Measures (submitted: March 4, 2022)

• Number of Participants With Treatment-Emergent Adverse Events (TEAEs) Following Treatment With DS-7300a in Participants With Pretreated ES-SCLC [ Time Frame: Up to approximately 24 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.
• Progression-Free Survival (PFS) Following Treatment With DS-7300a in Participants With Pretreated ES-SCLC [ Time Frame: From enrollment until disease progression or death (whichever occurs first), up to approximately 24 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.
• Duration of Response (DoR) Following Treatment With DS-7300a in Participants With Pretreated ES-SCLC [ Time Frame: From enrollment until disease progression or death (whichever occurs first), up to approximately 24 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.
• Overall Survival (OS) Following Treatment With DS-7300a in Participants With Pretreated ES-SCLC [ Time Frame: From enrollment until death, up to approximately 24 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.
• Time to Response (TTR) Following Treatment With DS-7300a in Participants With Pretreated ES-SCLC [ Time Frame: From enrollment until disease progression or death (whichever occurs first), up to approximately 24 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.
• Percentage of Participants With Objective Response Rate (ORR) Based on Investigator Assessment Following Treatment With DS-7300a in Participants With Pretreated ES-SCLC [ Time Frame: Up to approximately 24 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.
• Disease Control Rate (DCR) Following Treatment With DS-7300a in Participants With Pretreated ES-SCLC [ Time Frame: Up to approximately 24 months ]
  DCR is defined as percentage of participants with BOR of CR, PR, or stable disease, according to RECIST v1.1 criteria.
• Maximum Plasma Concentration (Cmax) Following Treatment With DS-7300a 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 & every 2 cycles up to 24 months: Predose (each cycle is 21 days) ]
  Cmax will be calculated using noncompartmental methods. Cmax will be assessed for DS-7300a, total anti-B7-H3 antibody, and MAAA-1181a.
• Time to Reach Maximum Serum Concentration (Tmax) Following Treatment With DS-7300a 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 & every 2 cycles up to 24 months: Predose (each cycle is 21 days) ]
  Tmax will be calculated using noncompartmental methods. Tmax will be assessed for DS-7300a, total anti-B7-H3 antibody, and MAAA-1181a.
• Minimum Observed Concentration (Ctrough) Following Treatment With DS-7300a 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 & every 2 cycles up to 24 months: Predose (each cycle is 21 days) ]
  Ctrough will be calculated using noncompartmental methods. Ctrough will be assessed for DS-7300a, total anti-B7-H3 antibody, and MAAA-1181a.
• Area Under the Curve (AUC) Following Treatment With DS-7300a 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 & every 2 cycles up to 24 months: Predose (each cycle is 21 days) ]
  AUC will be calculated using noncompartmental methods. AUC will be assessed for DS-7300a, total anti-B7-H3 antibody, and MAAA-1181a.
• Terminal Half-Life (T1/2) Following Treatment With DS-7300a 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 & every 2 cycles up to 24 months: Predose (each cycle is 21 days) ]
  T1/2 will be calculated using noncompartmental methods. T1/2 will be assessed for DS-7300a, total anti-B7-H3 antibody, and MAAA-1181a.
• Percentage of Participants Who Have Treatment-Emergent Antidrug Antibodies (ADA) Following Treatment With DS-7300a in Participants With Pretreated ES-SCLC [ Time Frame: Up to approximately 24 months ]
  The immunogenicity of DS-7300a will be assessed.

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Ifinatamab Deruxtecan (I-DXd) in Subjects With Pretreated Extensive-Stage Small Cell Lung Cancer (ES-SCLC)
• 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)
• 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.

• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Extensive-stage Small-cell Lung Cancer

Intervention

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

Study Arms

• Experimental: Ifinatamab Deruxtecan (8 mg/kg)
  Participants will be randomized to receive I-DXd at 8 mg/kg.
  Intervention: Drug: Ifinatamab Deruxtecan (I-DXd)
• 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.

  Intervention: Drug: Ifinatamab Deruxtecan (I-DXd)

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: March 15, 2024): 180
• Original Estimated Enrollment (submitted: March 4, 2022): 80
• Estimated Study Completion Date: June 20, 2025
• Estimated Primary Completion Date: January 31, 2025 (Final data collection date for primary outcome measure)

Eligibility 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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

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

• Listed Location Countries: Austria, China, France, Germany, Japan, Korea, Republic of, Spain, Taiwan, United States

Administrative Information

• NCT Number: NCT05280470
• Other Study ID Numbers: DS7300-127; 2022-000503-13 ( EudraCT Number ); 2041220019 ( Other Identifier: jRCT )
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

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
• Supporting Materials: Statistical Analysis Plan (SAP)
• Supporting Materials: 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/

• Current Responsible Party: Daiichi Sankyo
• Original Responsible Party: Same as current
• Current Study Sponsor: Daiichi Sankyo
• Original Study Sponsor: Same as current
• Collaborators: Merck Sharp & Dohme LLC

Investigators

• Study Director: Global Clinical Leader; Daiichi Sankyo

• PRS Account: Daiichi Sankyo
• Verification Date: April 2024