Resumen

Este estudio está diseñado para evaluar la eficacia y seguridad de datopotamab deruxtecan (Dato-DXd) en combinación con pembrolizumab versus pembrolizumab en combinación con pemetrexed y quimioterapia con platino, en participantes sin terapia previa para el cáncer de pulmón de células no pequeñas (CPCNP) no escamoso avanzado o metastásico.

Descripción detallada

Los objetivos primarios del estudio son la Supervivencia Libre de Progresión (SLP) y la Supervivencia Global (SG) como terapia de primera línea en participantes con ligando de muerte programada 1 (PD-L1) TPS \<50% y CPCNP avanzado o metastásico sin alteraciones genómicas susceptibles de tratamiento, así como en participantes TROP2 NMR+ en la línea de base. La NMR de TROP2 se evaluará de forma retrospectiva. Los participantes elegibles serán aleatorizados en proporción 1:1:1 a: a) Dato-DXd más pembrolizumab más platino; b) Dato-DXd más pembrolizumab; o c) pembrolizumab más pemetrexed más platino. La terapia con platino será carboplatino o cisplatino a criterio del investigador. El estudio se dividirá en tres períodos: Período de Selección (incluida la selección de tejidos), Período de Tratamiento y Período de Seguimiento.

Elegibilidad

Edad mínima: 18 YearsSexo: ALL

Criterios de inclusión

Sign and date the Main ICF, prior to the start of any study- specific qualification procedures. Is willing and able to comply with scheduled visits, drug administration plan, laboratory tests, other study procedures, and study restrictions.
Adults ≥18 at the time the Main ICF is signed. (Follow local regulatory requirements if the legal age of adult voluntary consent for study participation is \>18 years old).
Has tumor with PD-L1 TPS \<50% as determined by PD-L1 IHC 22C3 pharmDx assay by central testing (minimum of 6 slides). PD-L1 expression results available at the same central laboratory from screening for the purpose of entry into another Dato-DXd study may be used for tissue screening purposes in this study as long as the subject has not been randomized/enrolled in the other study.
Has provided a formalin-fixed tumor tissue sample (minimum of 4 × 4-micron sections or block equivalent) for the measurement of TROP2 protein expression and for the assessment of other exploratory biomarkers. This tissue requirement is in addition to the tissue required for PD-L1 testing for tissue screening purposes. If a documented law or regulation prohibits (or does not approve) sample collection, then such sample will not be collected, and the subject is still eligible for the study.

Criterios de exclusión

Has measurable disease based on local imaging assessment using RECIST v1.1; radiographic tumor assessment must be performed within 28 days before randomization.
Has received prior systemic treatment for advanced/metastatic NSCLC.
Has received prior treatment with any of the following, including in the adjuvant/neoadjuvant setting (for NSCLC):
Any agent, including an ADC, containing a chemotherapeutic agent targeting topoisomerase I
TROP2-targeted therapy
Any anti-PD-1, anti-PD-L1, or anti-programmed death-ligand 2 (PD-L2) agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (eg, CTLA-4, OX40, CD137)
Any other ICIs Subjects who received adjuvant or neoadjuvant therapy other than those listed above are eligible if the adjuvant/neoadjuvant therapy was completed at least 6 months prior to the diagnosis of advanced or metastatic disease.
Has received a live vaccine within 30 days prior to the first dose of study treatment.
Examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, varicella/zoster (chicken pox), yellow fever, rabies, Bacillus Calmette-Guérin (BCG), and typhoid vaccine. Seasonal influenza vaccines for injection are generally killed virus vaccines and are allowed; however, intranasal influenza vaccines (eg, FluMist®) are live attenuated vaccines and are not allowed. For any subject receiving an approved severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) vaccine, please follow the vaccine label and/or local guidance. The vaccine manufacturer and the date of administration should be recorded on the electronic case report form (Concomitant Medications page), as should any AEs relating to the vaccine (including hypersensitivity or allergies). Note: Any licensed SARS-CoV2 vaccine (including those authorized for emergency use) in a particular country is allowed in the study as long as the vaccine is an mRNA vaccine, replication-incompetent adenoviral vaccine, or inactivated vaccine. Such vaccines will be treated just as any other concomitant therapy.
Investigational vaccines (ie, those not licensed or authorized for emergency use) are not allowed.
Has spinal cord compression or clinically active untreated CNS metastases and/or carcinomatous meningitis. Subjects with previously treated brain metastases may participate provided they are radiologically stable (ie, without evidence of progression) for at least 2 weeks by repeat imaging (Note: Repeat imaging should be performed during study screening), clinically stable, and without requirement of steroid treatment for at least 7 days before the first dose of study drug. Note: A contrasted computed tomography (CT) scan or magnetic resonance imaging (MRI) scan of the brain at baseline (MRI with contrast preferred) is required for all subjects. For those subjects in whom CNS metastases are first discovered at the time of screening, the treating investigator must delay of study treatment to document stability of CNS metastases with repeat imaging at least 2 weeks later (in which case, repeat of all screening activity may be required).
Has uncontrolled or significant cardiovascular disease not controlled by maximal medical therapy, including:
Mean QT interval corrected for heart rate using Fridericia's formula (QTcF) interval \>470 msec regardless of sex (based on the 12-lead electrocardiogram \[ECG\] performed at screening).
Myocardial infarction within 6 months prior to Cycle 1 Day 1.
History of a serious cardiac arrhythmia requiring treatment
Uncontrolled angina pectoris within 6 months prior to Cycle 1 Day 1.
Left ventricular ejection fraction (LVEF) \<50% by echocardiogram (ECHO) or multigated acquisition (MUGA) scan within 28 days before randomization.
New York Heart Association (NYHA) Class II-IV congestive heart failure (CHF) at screening. Subjects 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 randomization) in order to be eligible.
Uncontrolled hypertension (resting systolic blood pressure \>180 mmHg or diastolic blood pressure \>110 mmHg within 28 days before randomization that is not resolved despite maximal medical therapy).
Clinically severe pulmonary compromise as judged by the investigator resulting from intercurrent pulmonary illnesses including, but not limited to, any underlying pulmonary disorder (eg, pulmonary emboli diagnosed within 3 months of 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 (eg, rheumatoid arthritis, Sjögren's syndrome, sarcoidosis, etc), or prior complete pneumonectomy.

Intervenciones

drug

Datopotamab Deruxtecan

Dato-DXd will be administered as an intravenous (IV) infusion every 3 weeks on Day 1 of each 21-day cycle.

drug

Pembrolizumab

Pembrolizumab will be administered as an intravenous (IV) infusion every 3 weeks on Day 1 of each 21-day cycle.

drug

Pemetrexed

Pemetrexed will be administered as an intravenous (IV) infusion every 3 weeks on Day 1 of each 21-day cycle.

drug

Carboplatin

Carboplatin will be administered an intravenous (IV) infusion every 3 weeks on Day 1 of each 21-day cycle for up to 4 cycles.

drug

Cisplatin

Cisplatin will be administered an intravenous (IV) infusion every 3 weeks on Day 1 of each 21-day cycle for up to 4 cycles.

Ubicaciones

Centro de Investigaciones Medicas y Desarrollo LC SRL

Buenos Aires, Argentina

Instituto Alexander Fleming

Buenos Aires, Argentina

Fundacion CENIT para la investigacion en Neurociencias

Ciudad Autonoma de Buenos Aire, Argentina

Hospital de La Comunidad

Mar del Plata, Argentina

Centro de Investigacion Pergamino Sa

Pergamino, Argentina

Instituto de Oncologia de Rosario

Rosario, Argentina

Sanatorio Parque

Rosario, Argentina

Sanatorio Britanico

Rosario, Argentina

Centro Polivalente de Asistencia E Investigacion Clinica Cer San Juan

San Juan, Argentina

Centro de Investigaciones Clinicas. Clinica Viedma S.A.

Viedma, Argentina

Resumen

Descripción detallada

Elegibilidad

Criterios de inclusión

Criterios de exclusión

Intervenciones

Datopotamab Deruxtecan

Pembrolizumab

Pemetrexed

Carboplatin

Cisplatin

Ubicaciones

Centro de Investigaciones Medicas y Desarrollo LC SRL

Instituto Alexander Fleming

Fundacion CENIT para la investigacion en Neurociencias

Hospital de La Comunidad

Centro de Investigacion Pergamino Sa

Instituto de Oncologia de Rosario

Sanatorio Parque

Sanatorio Britanico

Centro Polivalente de Asistencia E Investigacion Clinica Cer San Juan

Centro de Investigaciones Clinicas. Clinica Viedma S.A.

Patrocinadores