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JOURNAL ONKOLOGIE – STUDIE

Study of DS-1062a in Advanced or Metastatic Non-small Cell Lung Cancer With Actionable Genomic Alterations (TROPION-Lung05)

Rekrutierend

NCT-Nummer:
NCT04484142

Studienbeginn:
November 2020

Letztes Update:
07.01.2021

Wirkstoff:
DS-1062a

Indikation (Clinical Trials):
Lung Neoplasms, Carcinoma, Non-Small-Cell Lung

Geschlecht:
Alle

Altersgruppe:
Erwachsene (18+)

Phase:
Phase 2

Sponsor:
Daiichi Sankyo, Inc.

Collaborator:
AstraZeneca

Studienleiter

Global Clinical Leader
Study Director
Daiichi Sankyo, Inc.

Kontakt

(US sites only) Daiichi Sankyo Contact for Clinical Trial Information
Kontakt:
Phone: 908-992-6400
E-Mail: CTRinfo@dsi.com» Kontaktdaten anzeigen
(Asia sites) Daiichi Sankyo Contact for Clinical Trial Information
Kontakt:
Phone: +81-3-6225-1111(M-F 9-5 JST)
E-Mail: dsclinicaltrial@daiichisankyo.co.jp» Kontaktdaten anzeigen

Studienlocations (3 von 74)

Lungenkrebszentrum des NCT Heidelberg; Thoraxklinik Heidelberg
Im Neuenheimer Feld 672
69126 Heidelberg
DeutschlandNoch nicht rekrutierend» Google-Maps
Ansprechpartner:
Principal Investigator» Ansprechpartner anzeigen
Alle anzeigen

Studien-Informationen

Detailed Description:

This study will evaluate DS-1062a 6.0 mg/kg in participants with advanced or metastatic NSCLC

with actionable genomic alterations and who have been previously been treated with 1 or more

kinase inhibitors and platinum-based chemotherapy. The study will be divided into 3 periods:

Screening Period, Treatment Period, and Follow-up Period. The primary analysis of Objective

Response Rate (ORR) by blinded Independent Central Review (BICR) will be conducted after all

participants either have been followed for at least 9 months after the start of study

treatment or have discontinued from the study, whichever occurs first.

Ein-/Ausschlusskriterien

Inclusion Criteria:

Participants eligible for inclusion in the study must meet all inclusion criteria for this

study.

- Sign and date the inform consent form (ICF) prior to the start of any study- specific

qualification procedures.

- Adults ≥18 years (if the legal age of consent is >18 years old, then follow local

regulatory requirements)

- Has pathologically documented NSCLC that:

1. Has stage IIIB or stage IV NSCLC disease at the time of enrollment (based on the

American Joint Committee on Cancer, Eighth Edition).

2. Has one or more of the following documented activating genomic alterations: EGFR,

ALK, ROS1, NTRK, BRAF, MET exon 14 skipping, or RET.

Overexpression of any of the above, in the absence of activating mutations, is NOT

sufficient for enrollment

Participants with EGFR genomic alterations should be evaluated for the presence of EGFR

T790M mutation after relapse/progression on/after the most recent anti-EGFR TKI, unless

already known to carry this mutation. Participants with EGFR mutations (regardless of T790M

status) should comprise no less than 40% and no more than 50% of participants by the

conclusion of study enrollment.

- Has documentation of radiographic disease progression while on or after receiving the

most recent treatment regimen for advanced or metastatic NSCLC.

- Participant must meet at least the following for advanced or metastatic NSCLC:

1. Has progressed on or after at least one kinase inhibitor as specified in the

study protocol

2. Has progressed on or after at least 1 regimen of platinum-based chemotherapy

Up to 4 prior lines of therapy are allowed to be eligible for this study

- Willing and able to undergo a mandatory pre-treatment tumor biopsy

- Measurable disease based on local imaging assessment using RECIST v1.1.

- Eastern Cooperative Oncology Group performance status (ECOG PS) of 0 - 1 at screening.

Exclusion Criteria:

Participants meeting any exclusion criteria for this study will be excluded from this

study.

- Has spinal cord compression or clinically active central nervous system metastases,

defined as untreated and symptomatic, or requiring therapy with corticosteroids or

anticonvulsants to control associated symptoms. Participants with clinically inactive

brain metastases may be included in the study.

- Has leptomeningeal carcinomatosis.

- Has prior treatment with:

1. Any agent including antibody drug conjugate (ADC) containing a chemotherapeutic

agent targeting topoisomerase I.

2. TROP2-targeted therapy.

- Uncontrolled or significant cardiovascular disease:

1. History of myocardial infarction within 6 months prior to Cycle 1 Day 1.

2. History of uncontrolled angina pectoris within 6 months prior to Cycle 1 Day 1.

3. Symptomatic congestive heart failure (CHF) (New York Heart Association Class II

to IV) at screening. Participants with a history of Class II to IV CHF prior to

screening must have returned to Class I CHF and have LVEF ≥50% (by either an ECHO

or MUGA scan within 28 days of Cycle 1 Day 1) in order to be eligible.

4. History of serious cardiac arrhythmia requiring treatment.

5. LVEF <50% or institutional lower limit of normal by ECHO or MUGA scan.

6. Uncontrolled hypertension (resting systolic blood pressure >180 mmHg or diastolic

blood pressure >110 mmHg).

- Has a history of (non-infectious) interstitial lung disease (ILD)/pneumonitis that

required steroids, has current ILD/pneumonitis, or where suspected ILD/pneumonitis

cannot be ruled out by imaging at screening.

- Clinically severe pulmonary compromise resulting from intercurrent pulmonary illnesses

- Clinically significant corneal disease.

- Has other primary malignancies, except adequately resected non-melanoma skin cancer,

curatively treated in situ disease, or other solid tumors curatively treated, with no

evidence of disease for ≥3 years.

Studien-Rationale

Primary outcome:

1. Objective Response Rate (ORR) As Assessed by Blind Independent Central Review Per RECIST v1.1 Following DS-1062a Intravenous Infusion (Time Frame - From baseline until disease progression, death, or other protocol defined reason, up to approximately 23 months):
ORR is defined as the proportion of participants with a best overall response of confirmed complete response (CR) or confirmed partial response (PR). CR is defined as a disappearance of all target lesions and PR is defined as at least a 30% decrease in the sum of diameters of target lesions.



Secondary outcome:

1. Duration of Response (DOR) As Assessed by Blinded Independent Central Review and by Investigator Per RECIST v1.1 Following DS-1062a Intravenous Infusion (Time Frame - From baseline until disease progression, death, or other protocol defined reason, up to approximately 23 months):
DOR is defined as the time from the date of the first documentation of response (confirmed CR or confirmed PR) to the date of the first documentation of PD or death due to any cause, whichever occurs first.

2. Progression-free Survival (PFS) As Assessed by Blinded Independent Central Review and by Investigator Per RECIST v1.1 Following DS-1062a Intravenous (IV) Infusion (Time Frame - From baseline until disease progression, death, or other protocol defined reason, up to approximately 23 months):
PFS is defined as the time from the start of study treatment to the earlier of the dates of the first documentation of progressive disease or death due to any cause.

3. Overall Survival (OS) Following DS-1062a Intravenous Infusion (Time Frame - From baseline until death due to any cause, up to approximately 23 months):
OS is defined as the time from the start of study treatment to the date of death due to any cause.

4. Percentage of Participants Who Reported Treatment-emergent Adverse Events Following DS-1062a Intravenous Infusion in Participants with Advanced or Metastatic NSCLC with Actionable Genomic Alterations (Time Frame - From baseline up to approximately 23 months post treatment):
Reported treatment-emergent adverse events, serious adverse events, adverse events of interest, and those considered related to the study drug or study procedures, or that associated DS-1062a reduction, interruption, or discontinuation.

5. Pharmacokinetic Parameter Maximum Concentration (Cmax) of DS-1062a, Total Anti-TROP2 Antibody, and MAAA-1181a (Time Frame - Cycle 1, Day 1: predose (within 8 hours [h] of infusion), 30 minutes (min), 3 h, 5 h, 7 h postdose; Cycle 1, Day 2, Day 4, Day 8, and Day 15 postdose; Cycle 2 and Cycle 3, Day 1 predose (within 8 h) and postdose (within 1 h) (each cycle is 21 days))

6. Pharmacokinetic Parameter Time to Maximum Concentration (Tmax) of DS-1062a, Total Anti-TROP2 Antibody, and MAAA-1181a (Time Frame - Cycle 1, Day 1: predose (within 8 hours [h] of infusion), 30 minutes (min), 3 h, 5 h, 7 h postdose; Cycle 1, Day 2, Day 4, Day 8, and Day 15 postdose; Cycle 2 and Cycle 3, Day 1 predose (within 8 h) and postdose (within 1 h) (each cycle is 21 days))

7. Pharmacokinetic Parameter Area Under the Concentration-Time Curve (AUC) of DS-1062a, Total Anti-TROP2 Antibody, and MAAA-1181a (Time Frame - Cycle 1, Day 1: predose (within 8 hours [h] of infusion), 30 minutes (min), 3 h, 5 h, 7 h postdose; Cycle 1, Day 2, Day 4, Day 8, and Day 15 postdose; Cycle 2 and Cycle 3, Day 1 predose (within 8 h) and postdose (within 1 h) (each cycle is 21 days)):
AUC up to the last quantifiable time (AUClast) and AUC during dosing interval (AUCtau) will be assessed for DS-1062, total Anti-TROP2 antibody, and MAAA-1181a.

Geprüfte Regime

  • DS-1062a:
    DS-1062a will be administered as an intravenous (IV) infusion once every 3 weeks

Quelle: ClinicalTrials.gov


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