Neoplasms

Respiratory Tract (Lung and Bronchial) Diseases

All Conditions

Rare Diseases

Lung Neoplasms

Small Cell Lung Carcinoma

Carcinoma

Respiratory Tract Neoplasms

Thoracic Neoplasms

Lung Diseases

Respiratory Tract Diseases

Carcinoma, Bronchogenic

Bronchial Neoplasms

Small Cell Lung Cancer

All Drugs and Chemicals

Antineoplastic Agents

Antibodies

Topotecan

Immunoglobulins

Amrubicin

Topoisomerase I Inhibitors

Enzyme Inhibitors

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.

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.

12 mg/kg intravenous dose on Day 1 of each 21-day cycle

Ifinatamab deruxtecan

Topotecan will be administered per local SoC.

Amrubicin will be administered per local SoC.

Lurbinectedin will be administered per local SoC

Lurbinectedin

Daiichi Sankyo Contact for Clinical Trial Information

Global Clinical Director

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).

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.

A Study of Ifinatamab Deruxtecan Versus Treatment of Physician's Choice in Subjects With Relapsed Small Cell Lung Cancer

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)

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/

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.

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.

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 (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 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.

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.

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.

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.

TEAEs are assessed based on NCI CTCAE v5.0.

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.

Maximum concentration (Cmax) will be assessed using non-compartmental methods in participants randomized to the I-DXd group.

Time to maximum concentration (Tmax) will be assessed using non-compartmental methods in participants randomized to the I-DXd group.

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.

Merck Sharp & Dohme LLC

Daiichi Sankyo

Atezolizumab

Carboplatin

Etoposide

Etoposide phosphate

Immune Checkpoint Inhibitors

Antineoplastic Agents, Immunological

Part A (Safety Run-in): Participants who must have completed 1L induction with 4 cycles of standard of care (SoC) with best overall response of CR, PR, or SD will receive maintenance therapy only (I-DXd 12 mg/kg IV Q3W + atezolizumab 1200 mg IV Q3W).

A 5-day surveillance period between each of the first 3 participants (up to a maximum of 9 participants) dosed is included as a safety measure.

Part A (Safety Run-in): Participants who are treatment-naive with ES-SCLC will receive 4 cycles of 1L I-DXd induction therapy (8 mg/kg IV Q3W) + atezolizumab (1200 mg IV Q3W) + carboplatin (AUC 5 IV Q3W) followed by maintenance therapy (I-DXd 8 mg/kg IV Q3W) + atezolizumab (1200 mg IV Q3W).

Part A (Safety Run-in): Participants who are treatment-naive with ES-SCLC will receive 4 cycles of I-DXd induction therapy (12 mg/kg IV Q3W) + atezolizumab (1200 mg IV Q3W) + carboplatin (AUC 5 IV Q3W) followed by maintenance therapy (I-DXd 12 mg/kg IV Q3W) + atezolizumab (1200 mg IV Q3W).

Part B (Dose Optimization): Participants who are treatment naive with ES-SCLC will receive 4 cycles of 1L SoC induction therapy (carboplatin AUC 5 IV Q3W, etoposide 100 mg/m\^2 IV Q3W, and atezolizumab 1200 mg IV Q3W) and only those patients with best overall response of CR, PR, or SD after completion of the induction will be re-randomized to maintenance therapy (I-DXd 8 mg/kg IV Q3W + atezolizumab 1200 mg IV Q3W).

Part B (Dose Optimization): Participants who are treatment naive with ES-SCLC will receive 4 cycles of 1L SoC induction therapy (carboplatin AUC 5 IV Q3W, etoposide 100 mg/m\^2 IV Q3W, and atezolizumab 1200 mg IV Q3W) and only those patients with best overall response of CR, PR, or SD after completion of the induction will be re-randomized to maintenance therapy (I-DXd 12 mg/kg IV Q3W + atezolizumab 1200 mg IV Q3W).

Participants who are treatment-naive with ES-SCLC will receive 4 cycles of 1L I-DXd induction therapy (8 mg/kg IV Q3W) + atezolizumab (1200 mg IV Q3W) + carboplatin (AUC 5 IV Q3W) followed by maintenance therapy (I-DXd 8 mg/kg IV Q3W) + atezolizumab (1200 mg IV Q3W).

Participants who are treatment-naive with ES-SCLC will receive 4 cycles of I-DXd induction therapy (12 mg/kg IV Q3W) + atezolizumab (1200 mg IV Q3W) + carboplatin (AUC 5 IV Q3W) followed by maintenance therapy (I-DXd 12 mg/kg IV Q3W) + atezolizumab (1200 mg IV Q3W).

(US) Daiichi Sankyo Contact for Clinical Trial Information

(Asia) Daiichi Sankyo Contact for Clinical Trial Information

Global Clinical Leader

This study is designed to evaluate the safety and efficacy of ifinatamab deruxtecan (I-DXd) in combination with immune checkpoint inhibitor (ICI) atezolizumab with or without carboplatin in participants with extensive stage-small cell lung cancer (ES-SCLC) in the first-line (1L) setting.

This study consists of two parts and two cohorts: Part A (Phase 1b; Safety Run-in) and Part B (Phase 2; Dose Optimization), Cohort 1 (I-DXd in maintenance) and Cohort 2 (I-DXd in induction + maintenance).

The primary objective of this study is to evaluate the safety and tolerability of I-DXd in combination with atezolizumab with or without carboplatin by assessing treatment-emergent adverse events (TEAEs) and other safety parameters which will inform optimal dose selection of I-DXd in the combination regimens (Dose Optimization Part B) of this study.

A Study of I-DXd in Combination With Atezolizumab With or Without Carboplatin as First-Line Induction or Maintenance in Subjects With Extensive Stage-Small Cell Lung Cancer (IDeate-Lung03)

A Phase 1b/2, Multicenter, Open-label Study of Ifinatamab Deruxtecan (I-DXd), a B7-H3 Antibody-Drug Conjugate (ADC), in Combination With Atezolizumab With or Without Carboplatin as First-line Induction or Maintenance, in Subjects With Extensive-stage Small Cell Lung Cancer (ES-SCLC) (IDeate-Lung03)

Confirmed objective response rate (ORR) is defined as the sum of the complete response (CR) rate and partial response (PR) rate based on BICR and investigator by Response Evaluation Criteria In Solid Tumors (RECIST) v1.1.

Clinical benefit rate (CBR) is defined as the proportion of participants who achieved a best overall response of confirmed CR, confirmed PR, or confirmed SD lasting for at least 180 days.

Time to response (TTR) will be calculated for confirmed responders only.

The best percentage change in SoD is defined as the percentage change in the smallest SoD from all post-baseline tumor assessments, taking as reference the baseline SoD.

Maximum serum concentration (Cmax) will be assessed using non-compartmental methods.

Time to maximum serum concentration (Tmax) will be assessed using non-compartmental methods.

Area under the concentration-time curve up to the last quantifiable time (AUClast) and Area under the concentration-time curve during dosing interval (AUCtau) will be assessed using non-compartmental methods.

The ADA prevalence, which is the percentage of participants who are ADA positive at any time point (baseline or postbaseline), as well as the ADA incidence, which is the proportion of participants having treatment-emergent ADA during the study period, will be reported.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
A Study of Ifinatamab Deruxtecan Versus Treatment of Physician's Choice in Subjects With Relapsed Small Cell Lung Cancer	NCT06203210	Small Cell Lung...	Ifinatamab deru... Topotecan Amrubicin Lurbinectedin	18 Years -	Daiichi Sankyo
A Study of I-DXd in Combination With Atezolizumab With or Without Carboplatin as First-Line Induction or Maintenance in Subjects With Extensive Stage-Small Cell Lung Cancer (IDeate-Lung03)	NCT06362252	Extensive Stage...	Ifinatamab deru... Atezolizumab Carboplatin Etoposide	18 Years -	Daiichi Sankyo

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