A Study of Ifinatamab Deruxtecan Versus Treatment of Physician's Choice in Subjects With Relapsed Small Cell Lung Cancer (IDeate-Lung02)

• ClinicalTrials.gov Identifier: NCT06203210
• Recruitment Status: Not yet recruiting
• First Posted: January 12, 2024
• Last Update Posted: April 22, 2024
• Sponsor: Daiichi Sankyo
• Collaborator: Merck Sharp & Dohme LLC
• Information provided by (Responsible Party): Daiichi Sankyo

Tracking Information

• First Submitted Date: January 2, 2024
• First Posted Date: January 12, 2024
• Last Update Posted Date: April 22, 2024
• Estimated Study Start Date: June 10, 2024
• Estimated Primary Completion Date: April 30, 2027 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: April 19, 2024)

• Number of Participants With Objective Response Rate Assessed by Blinded Independent Central Review [ Time Frame: Baseline up until documented progressive disease, death, lost to follow-up, or withdrawal by the participant, up to approximately 4.5 years ]
  Confirmed objective response rate (ORR) is defined as the sum of the complete response (CR) rate and partial response (PR) rate based on BICR by Response Evaluation Criteria In Solid Tumors (RECIST) v1.1.
• Overall Survival [ Time Frame: From the date of randomization to the date of death due to any cause, whichever occurs first, up to approximately 4.5 years ]

Original Primary Outcome Measures (submitted: January 2, 2024)

• Number of Participants With Objective Response Rate Assessed by Blinded Independent Central Review Following I-DXd Monotherapy [ Time Frame: Baseline up until documented progressive disease, death, lost to follow-up, or withdrawal by the participant, up to approximately 46 months] ]
  Confirmed objective response rate (ORR) is defined as the sum of the complete response (CR) rate and partial response (PR) rate based on BICR by Response Evaluation Criteria In Solid Tumors (RECIST) v1.1.
• Overall Survival Following I-DXd Monotherapy [ Time Frame: From the start date of study drug to the date of death due to any cause, whichever occurs first, up to approximately 46 months ]

Current Secondary Outcome Measures (submitted: April 19, 2024)

• Number of Participants With Objective Response Rate Assessed by Investigator [ Time Frame: Baseline up until documented progressive disease, death, lost to follow-up, or withdrawal by the participant, up to approximately 4.5 years ]
  Confirmed objective response rate (ORR) is defined as the sum of the complete response (CR) rate and partial response (PR) rate based on investigator by Response Evaluation Criteria In Solid Tumors (RECIST) v1.1.
• Progression-free Survival As Assessed by Blinded Independent Central Review and Investigator [ Time Frame: Baseline up until documented progressive disease, death, lost to follow-up, or withdrawal by the participant, up to approximately 4.5 years ]
  PFS is defined as the time interval from the date of randomization to the date of disease progression as per BICR and investigator assessment or death due to any cause.
• Duration of Response As Assessed by Blinded Independent Central Review and Investigator [ Time Frame: From the date of first documentation of confirmed response (CR or PR) to the first documentation of objective progression or to death due to any cause, whichever occurs first, up to approximately 4.5 years ]
  Duration of response (DoR) is defined as the time from the date of the first documentation of objective response (complete response [CR] or partial response [PR]) to the date of the first documentation of progressive disease (PD) or death. The DoR will be calculated for responding participants (PR or CR) only.
• Disease Control Rate As Assessed by Blinded Independent Central Review and Investigator [ Time Frame: Baseline up until documented progressive disease, death, lost to follow-up, or withdrawal by the participant, up to approximately 4.5 years ]
  Disease control rate is defined as the proportion of participants who have achieved a best overall response of confirmed CR, confirmed PR, or SD (or non-CR/non-PD) by BICR and investigator assessment per RECIST v1.1.
• Time to Response As Assessed by Blinded Independent Central Review and Investigator [ Time Frame: From the start date of study drug to the date of the first documentation of response (CR or PR) that is subsequently confirmed, up to approximately 4.5 years ]
  TTR is defined as the time from the date of randomization to the first documentation of objective tumor response (CR or PR) that is subsequently confirmed by BICR and investigator assessment .Time to response (TTR) will be calculated for confirmed responders only.
• Change from Baseline in The European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ)-C30 [ Time Frame: Baseline up to 4.5 years ]
  This 30-item questionnaire assesses global health status (GHS)/quality of life (QoL), subject functioning, and general cancer symptoms and has a recall period of one week. All scores for the EORTC QLQ-C30 instrument are linearly transformed to a 0 to 100 metric, where a higher score on GHS/QoL and functioning scales indicates a better outcome and a higher score for the symptom scales indicates worse outcomes.
• Change from Baseline in The European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Lung Cancer 29 (EORTC QLQ-LC29) [ Time Frame: Baseline up to 4.5 years ]
  The LC29 is a self-reported 29-item questionnaire that measures SCLC-related symptoms and the side effects of treatments and has a recall period of one week. All scores range from 0 to 100, with a higher score indicating a worse outcome.
• Overall Number of Participants With Treatment-emergent Adverse Events Following I-DXd Monotherapy [ Time Frame: Baseline up to 4.5 years ]
  TEAEs are assessed based on NCI CTCAE v5.0.
• The Number of Participants Who Are Anti-Drug Antibody (ADA)-Positive At Any Time and Who Have A Treatment-emergent Anti-Drug Antibody [ Time Frame: Baseline up to 4.5 years ]
  The ADA prevalence, which is the percentage of participants who are ADA positive at any time point (baseline or post-baseline), as well as the ADA incidence, which is the proportion of participants having treatment-emergent ADA during the study period, will only be reported in participants receiving I-DXd.
• Pharmacokinetic Parameter Maximum Concentration for I-DXd, Total Anti-B7-H3 Antibody, and MAAA-1181a [ Time Frame: Cycle 1 before infusion (BI), end of infusion EOI), and 3, 6, 24, 72, 168, 336, and 504 hours (hrs) post dose; Cycle 2 BI and EOI; Cycle 3 BI, EOI, and 6 hrs postdose; Cycles 4, 5, and every 2 cycles thereafter up to 4.5 years BI (each cycle is 21 days) ]
  Maximum concentration (Cmax) will be assessed using non-compartmental methods in participants randomized to the I-DXd group.
• Pharmacokinetic Parameter Time to Maximum Concentration for I-DXd, Total Anti-B7-H3 Antibody, and MAAA-1181a [ Time Frame: Cycle 1 before infusion (BI), end of infusion EOI), and 3, 6, 24, 72, 168, 336, and 504 hours (hrs) post dose; Cycle 2 BI and EOI; Cycle 3 BI, EOI, and 6 hrs postdose; Cycles 4, 5, and every 2 cycles thereafter up to 4.5 years BI (each cycle is 21 days) ]
  Time to maximum concentration (Tmax) will be assessed using non-compartmental methods in participants randomized to the I-DXd group.
• Pharmacokinetic Parameter Area Under the Plasma Concentration-Time Curve for I-DXd, Total Anti-B7-H3 Antibody, and MAAA-1181a [ Time Frame: Cycle 1 before infusion (BI), end of infusion EOI), and 3, 6, 24, 72, 168, 336, and 504 hours (hrs) post dose; Cycle 2 BI and EOI; Cycle 3 BI, EOI, and 6 hrs postdose; Cycles 4, 5, and every 2 cycles thereafter up to 4.5 years BI (each cycle is 21 days) ]
  Area under the plasma concentration-time curve up to the last quantifiable time point (AUClast) and area under the plasma concentration-time curve dosing interval (AUCtau) will be assessed using non-compartmental methods in participants randomized to the I-DXd group.

Original Secondary Outcome Measures (submitted: January 2, 2024)

• Number of Participants With Objective Response Rate Assessed by Investigator Following I-DXd Monotherapy [ Time Frame: Baseline up until documented progressive disease, death, lost to follow-up, or withdrawal by the participant, up to approximately 46 months ]
  Confirmed objective response rate (ORR) is defined as the sum of the complete response (CR) rate and partial response (PR) rate based on investigator by Response Evaluation Criteria In Solid Tumors (RECIST) v1.1.
• Progression-free Survival As Assessed by Blinded Independent Central Review and Investigator Following I-DXd Monotherapy [ Time Frame: From the start date of drug to the earlier date of the first objective documentation of radiographic disease progression as assessed by BICR and investigator per RECIST v1.1 or death due to any cause, whichever occurs first, up to approximately 46 months ]
• Duration of Response As Assessed by Blinded Independent Central Review and Investigator Following I-DXd Monotherapy [ Time Frame: From the date of first documentation of confirmed response (CR or PR) to the first documentation of objective progression or to death due to any cause, whichever occurs first, up to approximately 46 months ]
  Duration of response (DoR) is defined as the time from the date of the first documentation of objective response (complete response [CR] or partial response [PR]) to the date of the first documentation of progressive disease (PD) or death. The DoR will be calculated for responding participants (PR or CR) only.
• Disease Control Rate As Assessed by Blinded Independent Central Review and Investigator Following I-DXd Monotherapy [ Time Frame: Baseline up until documented progressive disease, death, lost to follow-up, or withdrawal by the participant, up to approximately 46 months ]
  Disease control rate is defined as the proportion of participants who have achieved a best overall response of confirmed CR, confirmed PR, or SD (or non-CR/non-PD) by BICR and investigator assessment per RECIST v1.1.
• Time to Response As Assessed by Blinded Independent Central Review and Investigator Following I-DXd Monotherapy [ Time Frame: From the start date of study drug to the date of the first documentation of response (CR or PR) that is subsequently confirmed, up to approximately 46 months ]
  Time to response (TTR) will be calculated for confirmed responders only.
• Change from Baseline in The European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ)-C30 [ Time Frame: Baseline up to 46 months ]
  This 30-item questionnaire assesses global health status (GHS)/quality of life (QoL), subject functioning, and general cancer symptoms and has a recall period of one week. All scores for the EORTC QLQ-C30 instrument are linearly transformed to a 0 to 100 metric, where a higher score on GHS/QoL and functioning scales indicates a better outcome and a higher score for the symptom scales indicates worse outcomes.
• Change from Baseline in The European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Lung Cancer 29 (EORTC QLQ-LC29) [ Time Frame: Baseline up to 46 months ]
  The LC29 is a self-reported 29-item questionnaire that measures SCLC-related symptoms and the side effects of treatments and has a recall period of one week. All scores range from 0 to 100, with a higher score indicating a worse outcome.
• Overall Number of Participants With Treatment-emergent Adverse Events Following I-DXd Monotherapy [ Time Frame: Baseline up to 46 months ]
• The Number of Participants Who Are Anti-Drug Antibody (ADA)-Positive At Any Time and Who Have A Treatment-emergent Anti-Drug Antibody [ Time Frame: Baseline up to 46 months ]
  The ADA prevalence, which is the percentage of participants who are ADA positive at any time point (baseline or post-baseline), as well as the ADA incidence, which is the proportion of participants having treatment-emergent ADA during the study period, will be reported.

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

Descriptive Information

• Brief Title: A Study of Ifinatamab Deruxtecan Versus Treatment of Physician's Choice in Subjects With Relapsed Small Cell Lung Cancer
• Official Title: A Phase 3, Multicenter, Randomized, Open-label Study of Ifinatamab Deruxtecan (I-DXd), a B7-H3 Antibody Drug Conjugate (ADC), Versus Treatment of Physician's Choice (TPC) in Subjects With Relapsed Small Cell Lung Cancer (SCLC) (IDeate-Lung02)
• Brief Summary: This study was designed to compare the efficacy and safety of I-DXd with treatment of physician's choice in participants with relapsed small cell lung cancer (SCLC).

Detailed Description

The primary objective of this study is to assess whether treatment with I-DXd improves objective response rate (ORR) and prolongs overall survival (OS) compared with treatment of physician's choice among participants with relapsed SCLC.

The secondary objectives of the study are to further evaluate the efficacy/safety of I-DXd, health economics and outcome research measures (including patient reported outcomes), immunogenicity of I-DXd, B7-H3 protein expression, and characterize the pharmacokinetics of I-DXd.

• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Small Cell Lung Cancer

Intervention

• Drug: Ifinatamab deruxtecan
  12 mg/kg intravenous dose on Day 1 of each 21-day cycle
  Other Name: I-DXd
• Drug: Topotecan
  Topotecan will be administered per local SoC.
• Drug: Amrubicin
  Amrubicin will be administered per local SoC.
• Drug: Lurbinectedin
  Lurbinectedin will be administered per local SoC

Study Arms

• Experimental: Ifinatamab deruxtecan (I-DXd)
  Participants randomized to receive 12 mg/kg I-DXd monotherapy on Day 1 of each 21-day cycle until unacceptable toxicity, progressive disease (PD), or withdrawal of consent as specified in the protocol.
  Intervention: Drug: Ifinatamab deruxtecan
• Active Comparator: Treatment of Physician's Choice (TPC)
  Participants randomized to receive topotecan, lurbinectedin, or amrubicin, as per investigator's choice and per locally approved label (indicated dose and frequency), until a treatment discontinuation criterion is met as specified in the protocol.
  Interventions:

  • Drug: Topotecan
  • Drug: Amrubicin
  • Drug: Lurbinectedin

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Not yet recruiting
• Estimated Enrollment (submitted: January 2, 2024): 468
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: February 22, 2029
• Estimated Primary Completion Date: April 30, 2027 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria

Participants must meet all the following criteria to be eligible for randomization into the study:

1. Sign and date the informed consent form prior to the start of any study-specific qualification procedures.
2. Adults ≥18 years or the minimum legal adult age (whichever is greater) at the time the informed consent form is signed.
3. Has histologically or cytologically documented SCLC.
4. The participant must provide adequate baseline tumor samples with sufficient quantity and quality of tumor tissue content.
5. Has received prior therapy with only one prior platinum-based line as systemic therapy for SCLC with at least 2 cycles of therapy and a chemotherapy-free interval of >30 days.
6. Has at least 1 measurable lesion according to RECIST v1.1 as assessed by the investigator.
7. Has documentation of radiological disease progression on or after the most recent systemic therapy.
8. Has ECOG PS of ≤1.
9. Subjects with untreated and asymptomatic brain metastases or subjects with treated brain metastases that are no longer symptomatic (ie, without neurologic signs or symptoms) and who require no treatment with steroids or anticonvulsants may be included in the study if they have recovered from the acute toxic effect of radiotherapy. Subjects must have a stable neurologic status for at least 2 weeks prior to the first dose of study drug.

Exclusion Criteria

Participants who meet any of the following criteria will be disqualified from entering the study:

1. Has received prior treatment with orlotamab, enoblituzumab, or other humanized anti-B7 homologue 3 (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. Has received any of the comparators used in this study or any topoisomerase I inhibitor.
4. Has inadequate washout period before randomization as specified in the protocol.
5. Has any of the following conditions within the past 6 months: cerebrovascular accident, transient ischemic attack, or another arterial thromboembolic event.
6. Has uncontrolled or significant cardiovascular disease.
7. Has clinically significant corneal disease.
8. Has 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.
9. Has clinically severe pulmonary compromise resulting from intercurrent pulmonary illnesses, including, but not limited to, any underlying pulmonary disorder and potential pulmonary involvement caused by any autoimmune, connective tissue, or inflammatory disorders, prior pneumonectomy, or requirement for supplemental oxygen.

Sex/Gender

• Sexes Eligible for Study: All

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

Contacts

Contact: Daiichi Sankyo Contact for Clinical Trial Information; 9089926400; CTRinfo@dsi.com

• Listed Location Countries: Australia, Belgium, Brazil, Canada, China, France, Germany, Hungary, Italy, Japan, Korea, Republic of, Netherlands, Poland, Portugal, Romania, Spain, Switzerland, Taiwan, Turkey, United Kingdom, United States

Administrative Information

• NCT Number: NCT06203210
• Other Study ID Numbers: DS7300-188; 2023-509628-16 ( Other Identifier: EU CT )
• Has Data Monitoring Committee: Yes

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

• 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 Director; Daiichi Sankyo

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