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

Phase 2Active Not RecruitingNCT05280470

Daiichi Sankyo187 enrolled

Overview

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.

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

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

187

Conditions

Extensive-stage Small-cell Lung Cancer

Interventions

Ifinatamab Deruxtecan (I-DXd)DRUG

I-DXd will be administered as an intravenous (IV) infusion on Day 1 of each 21-day cycle (every Q3W).

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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.

Locations (58)

Outcomes

Primary Outcomes

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.

Time frame: Up to approximately 36 months

Secondary Outcomes

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.

Time frame: Up to approximately 36 months

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.

Time frame: From enrollment until disease progression or death (whichever occurs first), up to approximately 36 months

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.

Time frame: From enrollment until disease progression or death (whichever occurs first), up to approximately 36 months

Data from ClinicalTrials.gov

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