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JOURNAL ONKOLOGIE – STUDIE

Study of DS-1062a Versus Docetaxel in Previously Treated Advanced or Metastatic Non-small Cell Lung Cancer Without Actionable Genomic Alterations (TROPION-LUNG01)

Rekrutierend

NCT-Nummer:
NCT04656652

Studienbeginn:
Dezember 2020

Letztes Update:
14.07.2021

Wirkstoff:
DS-1062a, Docetaxel

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

Geschlecht:
Alle

Altersgruppe:
Erwachsene (18+)

Phase:
Phase 3

Sponsor:
Daiichi Sankyo, Inc.

Collaborator:
AstraZeneca

Studienleiter

Global Clinical Leader
Study Director
Daiichi Sankyo, Inc.

Kontakt

Daiichi Sankyo Contact for Clinical Trial Information
Kontakt:
Phone: 908-992-6400
E-Mail: CTRinfo@dsi.com
» Kontaktdaten anzeigen

Studienlocations
(3 von 195)

Icon Cancer Centre
04101 South Brisbane
AustraliaZurückgezogen» Google-Maps
Fondazione IRCCS Ca Granda Ospedale Maggiore Policlinico
20122 Milano
ItalyAbgebrochen» Google-Maps
Seoul National University Bundang Hospital
13620 Seongnam-si
Korea, Republic ofAbgebrochen» Google-Maps
Federal State Budgetary Institution - N.N. Blokhin National Medical Research Center of Oncology
115478 Moscow
Russian FederationNoch 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 vs docetaxel 75 mg/m^2 in participants with

advanced or metastatic NSCLC without actionable genomic alterations and who have been

previously treated with platinum-based chemotherapy and α-PD-1/α-PD-L1 monoclonal antibody,

either in combination or sequentially. The study will be divided into 3 periods: Screening

Period, Treatment Period, and Follow-up Period.

Ein-/Ausschlusskriterien

Inclusion Criteria:

Participants eligible for inclusion in the study must meet all inclusion criteria within 28

days of randomization into the 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)

- Life expectancy ≥3 months

- Has pathologically documented NSCLC that:

1. Has stage IIIB, IIIC, or stage IV NSCLC disease at the time of randomization

(based on the American Joint Committee on Cancer, Eighth Edition)

2. Has documented negative test results for epidermal growth factor receptor (EGFR)

and anaplastic lymphoma kinase (ALK)

3. Has no known genomic alterations in ROS proto-oncogene 1 (ROS1), neurotrophic

tyrosine receptor kinase (NTRK), proto oncogene B-raf (BRAF), or other actionable

driver oncogenes with approved therapies (actionable genomic alteration)

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

most recent treatment regimen for advanced or metastatic NSCLC

- Participant must meet 1 of the following prior therapy requirements for advanced or

metastatic NSCLC:

1. Received platinum-based chemotherapy in combination with α-PD-1/α-PD-L1

monoclonal antibody as the only prior line of therapy

- Includes participants who received prior platinum-based chemo/radiotherapy

with maintenance α-PD-1/α-PD-L1 monoclonal antibody for Stage III disease

and relapsed/progressed within 6 months from the last dose of platinum-based

chemotherapy

- Includes participants who received prior platinum-based chemo/radiotherapy

(with or without maintenance α-PD-1/α-PD-L1 monoclonal antibody) for Stage

III disease and subsequently received α-PD-1/α-PD-L1 monoclonal antibody

therapy (with or without platinum-based chemotherapy) for recurrent disease

2. Received platinum-based chemotherapy and α-PD-1/α-PD-L1 monoclonal antibody (in

either order) sequentially as the only 2 prior lines of therapy

- Must undergo a mandatory pre-treatment tumor biopsy procedure or, if available, a

tumor biopsy that was recently collected (within 3 months of Screening) after

completion of the most recent anticancer treatment regimen and of adequate size may be

substituted for the mandatory pre-treatment biopsy procedure collected during

Screening.

- Archival tumor tissue from initial diagnosis is required, to the extent that archival

tumor tissue is available

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

- Eastern Cooperative Oncology Group performance status (ECOG PS) of 0 or 1 at Screening

- Within 7 days before Cycle 1 Day 1, has adequate bone marrow, hepatic, and renal

function

- Left ventricular ejection fraction (LVEF) ≥50% by either echocardiogram (ECHO) or

multigated acquisition (MUGA) scan within 28 days before Cycle 1 Day 1

- Adequate blood clotting function defined as international normalized ratio/prothrombin

time and either partial thromboplastin or activated partial thromboplastin time ≤1.5 ×

upper limit of normal (ULN)

- Adequate treatment washout period before Cycle 1 Day 1

- Females of childbearing potential must have a negative serum pregnancy test at

screening and must be willing to use highly effective birth control from the time of

enrollment up to 7 months after the last dose of DS-1062a or for at least 6 months

after the last dose of docetaxel

- Males must be surgically sterile or must use a condom in addition to highly effective

birth control if his partners are of reproductive potential from the time of

enrollment and for at least 4 months after last dose of DS-1062a or for at least 6

months after the last dose of docetaxel

- Male participants must not freeze or donate sperm from the time of Screening and

throughout the study period and for at least 4 months after the last dose of DS-1062a

or for at least 6 months after the last dose of docetaxel

- Female participants must not donate, or retrieve for their own use, ova from the time

of Screening and throughout the study period and for at least 7 months after the last

dose of DS-1062a and for at least 6 months after the last dose of docetaxel

Exclusion Criteria:

- Mixed small-cell lung cancer (SCLC) and NSCLC histology

- 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. Participants with treated brain

metastases who are no longer symptomatic and who require no treatment with

corticosteroids or anticonvulsants may be included in the study if they have recovered

from the acute toxic effect of radiotherapy.

- Has leptomeningeal carcinomatosis or metastasis

- Had prior treatment with:

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

agent targeting topoisomerase I

- TROP2-targeted therapy

- Docetaxel as monotherapy or in combination with other agents

- Had prior treatment with platinum-based chemotherapy and prior immunotherapy for Stage

II NSCLC disease (eg, in the neo-adjuvant or adjuvant setting) without subsequently

meeting the prior therapy requirements for Stage III or metastatic NSCLC disease

- Has NSCLC disease that is eligible for definitive local therapy alone

- Uncontrolled or significant cardiovascular disease, including:

- Mean QT interval corrected for heart rate using Fridericia's formula >470 msec

(based on the average of Screening triplicate 12-lead electrocardiogram [ECG]

determinations).

- History of myocardial infarction within 6 months before Cycle 1 Day 1

- History of uncontrolled angina pectoris within 6 months before Cycle 1 Day 1

- 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 before Cycle 1 Day 1) in order to be eligible.

- History of serious cardiac arrhythmia requiring treatment

- LVEF <50% by ECHO or MUGA scan within 28 days before Cycle 1 Day 1

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

blood pressure >110 mmHg) within 28 days before Cycle 1 Day 1

- 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

including, but not limited to, any underlying pulmonary disorder (ie, pulmonary emboli

within 3 months of study Cycle 1 Day 1, severe asthma, severe chronic obstructive

pulmonary disease, restrictive lung disease, pleural effusion, etc.), or any

autoimmune, connective tissue or inflammatory disorders with pulmonary involvement

(ie, rheumatoid arthritis, Sjogren's syndrome, sarcoidosis, etc.), or prior

pneumonectomy.

- Significant third-space fluid retention (for example ascites or pleural effusion) and

is not amenable for required repeated drainage.

- Clinically significant corneal disease

- Uncontrolled infection requiring IV antibiotics, antivirals, or antifungals; suspected

infections (eg, prodromal symptoms); or inability to rule out infections

- Has known human immunodeficiency virus (HIV) infection that is not well controlled

- Active hepatitis B and/or hepatitis C infection, such as those with serologic evidence

of viral infection within 28 days of Cycle 1 Day 1

- 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.

- Toxicities from previous anticancer therapy, defined as toxicities (other than

alopecia) not yet improved to NCI-CTCAE version 5.0 Grade ≤1 or baseline

- 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

- Has a history of severe hypersensitivity reactions to either the drug substances,

inactive ingredients (including but not limited to polysorbate 80) of DS-1062a or

docetaxel, or monoclonal antibodies

- Pregnant or breastfeeding

- Have substance abuse or any other medical conditions such as clinically significant

cardiac or psychological conditions

Studien-Rationale

Primary outcome:

1. Progression-free Survival (PFS) As Assessed by Blinded Independent Central Review (BICR) Per RECIST v1.1 Following DS-1062a Versus Docetaxel (Time Frame - From randomization until disease progression or death (whichever occurs first), up to approximately 43 months):
PFS is defined as the time from randomization to the earlier of the dates of the first documentation of radiographic progressive disease or death due to any cause.

2. Overall Survival (OS) Following DS-1062a Versus Docetaxel (Time Frame - From randomization until date of death due to any cause, up to approximately 43 months):
OS is defined as the time from randomization to the date of death due to any cause.

Secondary outcome:

1. Progression-free Survival (PFS) As Assessed by Investigator Per RECIST v1.1 Following DS-1062a Versus Docetaxel (Time Frame - From randomization until disease progression or death (whichever occurs first), up to approximately 43 months):
PFS is defined as the time from randomization to the earlier of the dates of the first documentation of radiographic progressive disease or death due to any cause.

2. Objective Response Rate (ORR) As Assessed by Blinded Independent Central Review (BICR) and Investigator As Per RECIST v1.1 Following DS-1062a Versus Docetaxel (Time Frame - From randomization until disease progression or death (whichever occurs first), up to approximately 43 months):
ORR is defined as the proportion of participants with a best overall response of complete response (CR) or partial response (PR).

3. Duration of Response (DOR) As Assessed by Blinded Independent Central Review (BICR) and Investigator As Per RECIST v1.1 Following DS-1062a Versus Docetaxel (Time Frame - From date of first objective response (CR or PR) to date of first radiographic disease progression or death due to any cause (whichever occurs first), up to approximately 43 months):
DOR is defined as the time from the date of the first documentation of objective response (confirmed CR or confirmed PR) to the date of the first documentation of radiographic PD or death due to any cause, whichever occurs first.

4. Disease Control Rate (DCR) As Assessed by Blinded Independent Central Review (BICR) and Investigator As Per RECIST v1.1 Following DS-1062a Versus Docetaxel (Time Frame - From randomization until disease progression or death (whichever occurs first), up to approximately 43 months):
DCR is defined as the proportion of participants who achieved a best overall response (BOR) of CR, PR, or stable disease (SD).

5. Time to Response (TTR) As Assessed by Blinded Independent Central Review (BICR) and Investigator As Per RECIST v1.1 Following DS-1062a Versus Docetaxel (Time Frame - From randomization to date of first objective response (CR or PR), up to approximately 43 months):
TTR is defined as the time from randomization to the date of the first documentation of objective response (CR or PR) in responding participants.

6. European Organization for Research and Treatment of Cancer (EORTC) Core Quality of Life Questionnaire (QLQ) and EORTC Quality of Life Questionnaire (QLQ) for Lung Cancer Trials Scores (Except Questions 36 and 37) Following DS-1062a Versus Docetaxel (Time Frame - Baseline and assessed on Day 15 of each cycle (only odd cycles after Cycle 4 for QLQ-C30) until disease progression or end of treatment (each cycle is 21 days) and then every 3 months until end of study, up to approximately 43 months)

7. Percentage of Participants Who Reported Treatment-emergent Adverse Events Following DS-1062a Versus Docetaxel (Time Frame - Baseline up to 35 days after last study dose, up to approximately 43 months):
Reported treatment-emergent adverse events, serious adverse events, adverse events of special interest, and those considered related to the study drug or study procedures, or that are associated with study treatment reduction, interruption, or discontinuation.

8. Pharmacokinetic Parameter Maximum Plasma Concentration (Cmax) of DS-1062a, Total Anti-Trophoblast cell surface protein 2 (Anti-TROP2) Antibody, and Active Metabolite MAAA-1181a (Time Frame - Cycle 1, Day 1: predose and 30 minutes, 3 hours, 5 hours, and 7 hours postdose and Days 2, 4, 8, and 15; Cycles 2, 3, 4, 6, and 8, Day 1: predose and 1 hour postdose (each cycle is 21 days))

9. Pharmacokinetic Parameter Time to Maximum Plasma Concentration (Tmax) of DS-1062a, Total Anti-TROP2 Antibody, and Active Metabolite MAAA-1181a (Time Frame - Cycle 1, Day 1: predose and 30 minutes, 3 hours, 5 hours, and 7 hours postdose and Days 2, 4, 8, and 15; Cycles 2, 3, 4, 6, and 8, Day 1: predose and 1 hour postdose (each cycle is 21 days))

10. Pharmacokinetic Parameter Area Under the Plasma Concentration-Time Curve (AUC) of DS-1062a, Total Anti-TROP2 Antibody, and Active Metabolite MAAA-1181a (Time Frame - Cycle 1, Day 1: predose and 30 minutes, 3 hours, 5 hours, and 7 hours postdose and Days 2, 4, 8, and 15; Cycles 2, 3, 4, 6, and 8, Day 1: predose and 1 hour postdose (each cycle is 21 days)):
Area under the plasma concentration-time curve up to last quantifiable time (AUClast) and area under the plasma concentration-time curve during dosing interval (AUCtau) will be assessed.

11. Proportion of Participants Who Are Anti-Drug Antibody (ADA)-Positive (Baseline and Post-Baseline) and Proportion of Participants Who Have Treatment-emergent ADA (Time Frame - Cycle 1, Day 1 predose; Cycle 1, Day 8; Cycles 2, 4, and subsequent cycles, Day 1 predose; end of treatment; 28-day safety follow up; and long-term survival follow up every 3 months, up to approximately 43 months (each cycle is 21 days))

Studien-Arme

  • Experimental: DS-1062a 6.0 mg/kg
    Participants will be randomized to receive 6.0 mg/kg of DS-1062a.
  • Active Comparator: Docetaxel 75 mg/m^2
    Participants will be randomized to receive 75 mg/m^2 docetaxel.

Geprüfte Regime

  • DS-1062a (Datopotamab deruxtecan (Dato-DXd)):
    DS-1062a will be administered as an intravenous (IV) infusion on Day 1 of each 3-week cycle
  • Docetaxel:
    Docetaxel will be administered as an IV infusion on Day 1 of each 3-week cycle.

Quelle: ClinicalTrials.gov


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