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

Extensive-stage Small-cell Lung Cancer Clinical Trial

— IDeate-Lung01  

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)

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT05280470
• Other study ID #: DS7300-127
• Secondary ID: 2022-000503-1320
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: March 9, 2022
• Est. completion date: April 17, 2025

Study information

• Verified date: June 2024
• Source: Daiichi Sankyo
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Active, not recruiting
• Enrollment: 187
• Est. completion date: April 17, 2025
• Est. primary completion date: January 31, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Extensive-stage Small-cell Lung Cancer
• Lung Neoplasms
• Small Cell Lung Carcinoma

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).

Locations

Country	Name	City	State
China	Jilin Cancer Hospital	Changchun
China	Hunan Cancer Hospital	Changsha
China	West China Hospital, Sichuan University	Chengdu Shi
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
France	Centre Hospitalier Intercommunal de Créteil	Créteil
France	Centre Leon Berard	Lyon
France	Hôpital Nord - Chu Marseille	Marseille cedex 20
France	CHU de Montpellier - Hôpital Arnaud de Villeneuve	Montpellier
France	Hopital Tenon	Paris
France	Institut Curie - Site de Paris	Paris Cedex 05
Germany	Evangelische Lungenklinik Berlin	Berlin
Germany	Universitaetsklinikum Essen	Essen
Japan	National Cancer Center Hospital	Chuo-ku
Japan	National Cancer Center Hospital East	Kashiwa
Japan	The Cancer Institute Hospital of Jfcr	Koto-ku
Japan	Osaka International Cancer Institute	Osaka
Japan	Kindai University Hospital	Osaka-Sayama
Japan	Shizuoka Cancer Center	Sunto-gun
Japan	Kanagawa Cancer Center	Yokohama
Korea, Republic of	National Cancer Center	Goyan-si
Korea, Republic of	Seoul National University Bundang Hospital	Seongnam-si
Korea, Republic of	Asan Medical Center	Seoul
Korea, Republic of	Samsung Medical Center	Seoul
Korea, Republic of	Seoul National University Hospital	Seoul
Spain	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 12 de Octubre	Madrid
Spain	Hospital Universitario Ramon Y Cajal	Madrid
Spain	Hospital Regional Universitario Malaga	Malaga
Spain	Hospital Virgen Macarena	Sevilla
Taiwan	Chang Gung Medical Foundation - Kaohsiung Branch	Kaohsiung
Taiwan	Taichung Veterans General Hospital	Taichung
Taiwan	National Cheng Kung University Hospital Nckuh	Tainan
Taiwan	Taipei Veterans General Hospital	Taipei
Taiwan	National Taiwan University Hospital	Taipei City
Taiwan	Chang Gung Memorial Hospital Linkou	Taoyuan
United States	Johns Hopkins Sidney Kimmel Comprehensive Cancer Center	Baltimore	Maryland
United States	Dana-Faeber Cancer Institute	Boston	Massachusetts
United States	University of Chicago Medical Center	Chicago	Illinois
United States	Henry Ford Hospital	Detroit	Michigan
United States	Duke University Health System	Durham	North Carolina
United States	Cancer and Hematology Centers of Western Michigan	Grand Rapids	Michigan
United States	Millennium Physicians Association, Llp	Houston	Texas
United States	The Cancer Specialists, Llc	Jacksonville	Florida
United States	Hackensack Meridian Health-Southern Ocean Medical Center	Manahawkin	New Jersey
United States	Sarah Cannon (Tennessee Oncology - Nashville)	Nashville	Tennessee
United States	Memorial Sloan-Kettering Cancer Center (Mskcc) - New York	New York	New York
United States	Washington University School of Medicine	Saint Louis	Missouri
United States	University of Washington Medical Center	Seattle	Washington
United States	Highlands Oncology Group	Springdale	Arkansas
United States	H. Lee Moffitt Cancer Center and Research Institute	Tampa	Florida

Sponsors (2)

Lead Sponsor	Collaborator
Daiichi Sankyo	Merck Sharp & Dohme LLC

Countries where clinical trial is conducted

United States,  China,  France,  Germany,  Japan,  Korea, Republic of,  Spain,  Taiwan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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.	Up to approximately 36 months
Secondary	Number of Participants With Treatment-Emergent Adverse Events (TEAEs) Following Treatment With I-DXd in Participants With Pretreated ES-SCLC	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.	Up to approximately 36 months
Secondary	Progression-Free Survival (PFS) Following Treatment With I-DXd in Participants With Pretreated ES-SCLC	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.	From enrollment until disease progression or death (whichever occurs first), up to approximately 36 months
Secondary	Duration of Response (DoR) Following Treatment With I-DXd in Participants With Pretreated ES-SCLC	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.	From enrollment until disease progression or death (whichever occurs first), up to approximately 36 months
Secondary	Overall Survival (OS) Following Treatment With I-DXd in Participants With Pretreated ES-SCLC	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.	From enrollment until death, up to approximately 36 months
Secondary	Time to Response (TTR) Following Treatment With I-DXd in Participants With Pretreated ES-SCLC	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.	From enrollment until disease progression or death (whichever occurs first), up to approximately 36 months
Secondary	Percentage of Participants With Objective Response Rate (ORR) Based on Investigator Assessment Following Treatment With I-DXd in Participants With Pretreated ES-SCLC	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.	Up to approximately 36 months
Secondary	Disease Control Rate (DCR) Following Treatment With I-DXd in Participants With Pretreated ES-SCLC	DCR is defined as percentage of participants with BOR of CR, PR, or stable disease, according to RECIST v1.1.	Up to approximately 36 months
Secondary	Maximum Plasma Concentration (Cmax) Following Treatment With I-DXd in Participants With Pretreated ES-SCLC	Cmax will be calculated using noncompartmental methods. Cmax will be assessed for I-DXd, total anti-B7-H3 antibody, and MAAA-1181a.	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)
Secondary	Time to Reach Maximum Serum Concentration (Tmax) Following Treatment With I-DXd in Participants With Pretreated ES-SCLC	Tmax will be calculated using noncompartmental methods. Tmax will be assessed for I-DXd, total anti-B7-H3 antibody, and MAAA-1181a.	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)
Secondary	Minimum Observed Concentration (Ctrough) Following Treatment With I-DXd in Participants With Pretreated ES-SCLC	Ctrough will be calculated using noncompartmental methods. Ctrough will be assessed for I-DXd, total anti-B7-H3 antibody, and MAAA-1181a.	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)
Secondary	Area Under the Curve (AUC) Following Treatment With I-DXd in Participants With Pretreated ES-SCLC	AUC will be calculated using noncompartmental methods. AUC will be assessed for I-DXd, total anti-B7-H3 antibody, and MAAA-1181a.	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)
Secondary	Terminal Half-Life (T1/2) Following Treatment With I-DXd in Participants With Pretreated ES-SCLC	T1/2 will be calculated using noncompartmental methods. T1/2 will be assessed for I-DXd, total anti-B7-H3 antibody, and MAAA-1181a.	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)
Secondary	Percentage of Participants Who Have Treatment-Emergent Antidrug Antibodies (ADA) Following Treatment With I-DXd in Participants With Pretreated ES-SCLC	The immunogenicity of I-DXd will be assessed.	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)