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

Phase 1

• Conditions: Pretreated Extensive-stage Small Cell Lung Cancer (ES-SCLC); MedDRA version: 21.1Level: PTClassification code 10041068Term: Small cell lung cancer extensive stageSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2022-000503-13-DE
• Lead Sponsor: Daiichi Sankyo, Inc.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2022-10-28
• Last Update Posted: 22 July 2024

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 191

Inclusion Criteria

1.Sign and date the ICF prior to the start of any study- specific qualification procedures
2.Subject must have at least one lesion, not previously irradiated, amenable to core biopsy and must consent to provide a pretreatment biopsy tissue sample and on-treatment biopsy. Fresh pretreatment biopsy may be waived for subjects who consent to provide archival tumor tissue from a biopsy performed within 6 months of consent and performed after treatment with their most recent cancer therapy regimen. If, after all efforts have been made, the fresh pretreatment biopsy is not feasible or the procedure is unsuccessful and an appropriate archival sample is not available, the subject may be considered for study eligibility only after discussion with the Sponsor
3.Male or female subjects aged =18 years
4.Histologically or cytologically documented ES-SCLC
5.At least one measurable lesion according to RECIST v1.1 as assessed by the investigator
6.Prior therapy with at least one prior platinum-based line as systemic therapy for extensive-stage disease with at least two cycles of therapy (except in case of early objective PD) and, beginning with protocol version 3.0, a minimum of two previous lines of systemic therapy. Subjects with or without prior immune-checkpoint inhibitor therapy are eligible. Subject must not have received more than three previous lines of systemic therapy (rechallenge with platinum chemotherapy will be considered as one separated prior line of therapy). Subjects treated with a platinum-based line of therapy for prior limited stage (LS)-SCLC may be eligible for the study if the disease has progressed on treatment or within 6 months from treatment completion: the platinum-based line of therapy will count as one prior line of therapy. One line of therapy will be defined as 1 or more drugs received prior to newly documented disease progression in the locally advanced or metastatic setting. Any switch between carboplatin and cisplatin for toxicity reasons will be regarded as one line overall
7.Documentation of radiological disease progression on or after most recent systemic therapy
8.ECOG PS of 0 or 1
9.Life-expectancy =3 months
10.Required baseline local laboratory data (within 7 days prior to Cycle 1 Day 1):
a.ALT and AST:
- =3 × ULN in subjects with no liver metastasis or
- =5.0 × ULN in subjects with liver metastasis
b.Total bilirubin =1.5 × ULN if no liver metastases or =3 × ULN in the presence of documented Gilbert’s syndrome (undocumented hyperbilirubinemia) or liver metastases at baseline
c.ANC =1.5 × 109/L (hematopoietic growth factors [eg, G-CSF, GM-CSF] support allowed up to 14 days before screening laboratory tests)
d.Platelet count =100 × 109/L (platelet transfusion is allowed up to 14 days before screening laboratory tests)
e.Hemoglobin =8.5 g/dL (transfusion and/or growth factor support allowed up to 14 days before screening laboratory tests)
f.Creatinine clearance =30 mL/min, as calculated using the Cockcroft-Gault equation
g.International normalized ratio (INR)/prothrombin time (PT) and either partial thromboplastin time (PTT) or activated partial thromboplastin time (aPTT) =1.5 × ULN, except for subjects receiving anti vitamin K derivative anticoagulant therapy who must have prothrombin time international normalization ratio within the therapeutic range as deemed appropriate by the investigator
11.If the subject is a female of childbearing potential, she must have a negative serum pregnancy test within 7 days befo

Exclusion Criteria

1.Prior treatment with orlotamab, enoblituzumab, or other B7-H3 targeted agents including I-DXd
2.Prior discontinuation of an ADC that consists of an exatecan derivative (eg, trastuzumab deruxtecan)
3.Inadequate washout period before randomization, defined as
a.Major surgery (placement of vascular access will not be regarded as a major surgery) <4 weeks; surgery for low invasive cases (eg, colostomy, <4 weeks)
b Radiation therapy to the lung >30 Gy <6 months; palliative radiotherapy affecting lung areas at lower dose <3 weeks; any other palliative radiotherapy <2 weeks
c.Cranial irradiation, including WBRT and SRS, =2 weeks
d.Any systemic anticancer therapy <3 weeks or 5 half-lives whichever is longer and <6 weeks for nitrosoureas or mitomycin C
e.Antibody-based anticancer therapy <3 weeks
f.Chloroquine or hydroxychloroquine =14 days
g.Hormonal therapy <2 weeks
4.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
5.Any of the following conditions within the past 6 months: cerebrovascular accident, transient ischemic attack or another arterial thromboembolic event
6.Clinically significant corneal disease
7.Uncontrolled or significant cardiovascular disease including
a.Corrected QT interval (by Fridericia’s formula) >470 ms (females) or >450 ms (males) based on average of the screening triplicate 12-lead ECG determinations
b.Diagnosed or suspected long QT syndrome or known family history of long QT syndrome
c.History of clinically relevant ventricular arrhythmias, such as ventricular tachycardia, ventricular fibrillation or Torsade de Pointes
d.Bradycardia of less than 50 bpm unless the subject has a pacemaker
e.History of second-or third-degree heart block
f.Acute myocardial infarction within 6 months prior to screening
g.Uncontrolled angina pectoris within 6 months prior to screening
h.CHF defined as NYHA Class II to IV
i.Coronary/peripheral artery bypass graft or any coronary/peripheral angioplasty within 6 months prior to screening
j.Grade =3 hypertension
k.Complete left or right bundle branch block
l.LVEF <50% by either an ECHO or a MUGA scan
8.History of (non-infectious) ILD/pneumonitis that required corticosteroids, current ILD/pneumonitis, or suspected ILD/pneumonitis that cannot be ruled out by imaging at screening
9.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 complete pneumonectomy, or requirement for supplemental oxygen
10.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
11.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 GI tumors and non-muscle invasive bladder cancer curatively resected by endoscopic surgery
12.History of allogeneic bone marrow, stem cell, or solid organ transplant
13.Unresolved toxicities from previous anticancer therapy, defined as toxicities (other than alopecia) not yet resolved to NCI-CTCAE V5.0 Grade =1 or baseline
14.History of

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: To assess the antitumor activity of I-DXd in subjects with pretreated ES-SCLC;Secondary Objective: - To further assess the antitumor activity of I-DXd in subjects with pretreated ES-SCLC<br>- To assess the safety and tolerability of I-DXd in subjects with pretreated ES-SCLC<br>- To evaluate the PK of I-DXd<br>- To assess the immunogenicity of I-DXd;Primary end point(s): Objective response rate (ORR), defined as the proportion of subjects with a BOR of confirmed CR or confirmed PR assessed by blinded independent central review (BICR) based on RECIST v1.1.;Timepoint(s) of evaluation of this end point: Every 6 weeks (±7 days) in the first 36 weeks after Day 1 of Cycle 1, and thereafter every 12 weeks (±7 days).