Clinical trial NCT05280470: 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)
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: Extensive-stage Small-cell Lung Cancer
Keywords: Relapsed/Refractory Extensive-stage Small-cell Lung Cancer
DS-7300a
B7-H3 Antibody Drug Conjugate
Ifinatamab Deruxtecan
I-DXd
Lead sponsor: Daiichi Sankyo
Sponsor class: INDUSTRY
Collaborators: name: Merck Sharp & Dohme LLC
First posted: 2022-03-15
Enrollment: 187
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: 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
timeFrame: Up to approximately 36 months
Secondary outcomes:
measure: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) Following Treatment With I-DXd in Participants With Pretreated ES-SCLC
timeFrame: Up to approximately 36 months
measure: Progression-Free Survival (PFS) Following Treatment With I-DXd in Participants With Pretreated ES-SCLC
timeFrame: From enrollment until disease progression or death (whichever occurs first), up to approximately 36 months
measure: Duration of Response (DoR) Following Treatment With I-DXd in Participants With Pretreated ES-SCLC
timeFrame: From enrollment until disease progression or death (whichever occurs first), up to approximately 36 months
measure: Overall Survival (OS) Following Treatment With I-DXd in Participants With Pretreated ES-SCLC
timeFrame: From enrollment until death, up to approximately 36 months
measure: Time to Response (TTR) Following Treatment With I-DXd in Participants With Pretreated ES-SCLC
timeFrame: From enrollment until disease progression or death (whichever occurs first), up to approximately 36 months
measure: Percentage of Participants With Objective Response Rate (ORR) Based on Investigator Assessment Following Treatment With I-DXd in Participants With Pretreated ES-SCLC
timeFrame: Up to approximately 36 months
measure: Disease Control Rate (DCR) Following Treatment With I-DXd in Participants With Pretreated ES-SCLC
timeFrame: Up to approximately 36 months
measure: Maximum Plasma Concentration (Cmax) Following Treatment With I-DXd in Participants With Pretreated ES-SCLC
timeFrame: 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)
measure: Time to Reach Maximum Serum Concentration (Tmax) Following Treatment With I-DXd in Participants With Pretreated ES-SCLC
timeFrame: 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)
measure: Minimum Observed Concentration (Ctrough) Following Treatment With I-DXd in Participants With Pretreated ES-SCLC
timeFrame: 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)
measure: Area Under the Curve (AUC) Following Treatment With I-DXd in Participants With Pretreated ES-SCLC
timeFrame: 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)
measure: Terminal Half-Life (T1/2) Following Treatment With I-DXd in Participants With Pretreated ES-SCLC
timeFrame: 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)
measure: Percentage of Participants Who Have Treatment-Emergent Antidrug Antibodies (ADA) Following Treatment With I-DXd in Participants With Pretreated ES-SCLC
timeFrame: 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)
Other outcomes:
Locations:
city: Springdale
country: United States
facility: Highlands Oncology Group
state: Arkansas
city: Jacksonville
country: United States
facility: The Cancer Specialists, Llc
state: Florida
city: Tampa
country: United States
facility: H. Lee Moffitt Cancer Center and Research Institute
state: Florida
city: Chicago
country: United States
facility: University of Chicago Medical Center
state: Illinois
city: Baltimore
country: United States
facility: Johns Hopkins Sidney Kimmel Comprehensive Cancer Center
state: Maryland
city: Boston
country: United States
facility: Dana-Faeber Cancer Institute
state: Massachusetts
city: Detroit
country: United States
facility: Henry Ford Hospital
state: Michigan
city: Grand Rapids
country: United States
facility: Cancer and Hematology Centers of Western Michigan
state: Michigan
city: Saint Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
city: Manahawkin
country: United States
facility: Hackensack Meridian Health-Southern Ocean Medical Center
state: New Jersey
city: Bronx
country: United States
facility: Montefiore Medical Center Prime
state: New York
city: New York
country: United States
facility: Memorial Sloan-Kettering Cancer Center (Mskcc) - New York
state: New York
city: Durham
country: United States
facility: Duke University Health System
state: North Carolina
city: Nashville
country: United States
facility: Sarah Cannon (Tennessee Oncology - Nashville)
state: Tennessee
city: Houston
country: United States
facility: Millennium Physicians Association, Llp
state: Texas
city: Seattle
country: United States
facility: University of Washington Medical Center
state: Washington
city: Changchun
country: China
facility: Jilin Cancer Hospital
city: Changsha
country: China
facility: Hunan Cancer Hospital
city: Chengdu
country: China
facility: West China Hospital, Sichuan University
city: Guangdong
country: China
facility: Guangdong Provincial People'S Hospital
city: Hangzhou
country: China
facility: Zhejiang Cancer Hospital
city: Linyi
country: China
facility: Linyi Cancer Hospital
city: Shanghai
country: China
facility: Fudan University Shanghai Cancer Center
city: Wuhan
country: China
facility: Union Hospital of Tongji Medical College Huazhong University of Science and Technology
city: Créteil
country: France
facility: Centre Hospitalier Intercommunal de Créteil
city: Lyon
country: France
facility: Centre Leon Berard
city: Marseille cedex 20
country: France
facility: Hôpital Nord - Chu Marseille
city: Montpellier cedex 05
country: France
facility: Hopital Arnaud de Villeneuve
city: Montpellier
country: France
facility: CHU de Montpellier - Hôpital Arnaud de Villeneuve
city: Paris Cedex 05
country: France
facility: Institut Curie - Site de Paris
city: Paris
country: France
facility: Hopital Tenon
city: Berlin
country: Germany
facility: Evangelische Lungenklinik Berlin
city: Essen
country: Germany
facility: Universitaetsklinikum Essen
city: Chuo-ku
country: Japan
facility: National Cancer Center Hospital
city: Kashiwa
country: Japan
facility: National Cancer Center Hospital East
city: Koto-ku
country: Japan
facility: The Cancer Institute Hospital of Jfcr
city: Nagaizumi-chō
country: Japan
facility: Shizuoka Cancer Center
city: Osaka-Sayama
country: Japan
facility: Kindai University Hospital
city: Osaka
country: Japan
facility: Osaka International Cancer Institute
city: Yokohama
country: Japan
facility: Kanagawa Cancer Center
city: Goyang-si
country: Korea, Republic of
facility: National Cancer Center
city: Seongnam-si
country: Korea, Republic of
facility: Seoul National University Bundang Hospital
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center
city: Seoul
country: Korea, Republic of
facility: Asan Medical Center
city: A Coruña
country: Spain
facility: Complejo Hospitalario Universitario A Coruña
city: Barcelona
country: Spain
facility: Hospital Universitario Vall Dhebron
city: L'Hospitalet de Llobregat
country: Spain
facility: Ico L'Hospitalet - Hospital Duran I Reynals
city: Madrid
country: Spain
facility: Hospital Universitario Ramon Y Cajal
city: Madrid
country: Spain
facility: Hospital Universitario 12 de Octubre
city: Malaga
country: Spain
facility: Hospital Regional Universitario Malaga
city: Sevilla
country: Spain
facility: Hospital Virgen Macarena
city: Kaohsiung
country: Taiwan
facility: Chang Gung Medical Foundation - Kaohsiung Branch
city: Taichung
country: Taiwan
facility: Taichung Veterans General Hospital
city: Tainan
country: Taiwan
facility: National Cheng Kung University Hospital Nckuh
city: Taipei
country: Taiwan
facility: National Taiwan University Hospital
city: Taipei
country: Taiwan
facility: Taipei Veterans General Hospital
city: Taoyuan
country: Taiwan
facility: Chang Gung Memorial Hospital Linkou
Study officials:
affiliation: Daiichi Sankyo
name: Global Clinical Leader
role: STUDY_DIRECTOR
References: