CodeBreaK 202 - A Phase 3, Multicenter, Randomized, Open-label Study Evaluating Efficacy of Sotorasib Platinum Doublet Combination Versus Pembrolizumab Platinum Doublet Combination as a Front-Line Therapy in Subjects With Stage IV or Advanced Stage IIIB/C Nonsquamous Non-Small Cell Lung Cancers, Negative for PD-L1, and Positive for KRAS p.G12C

Studio Clinico

Patologia: Neoplasie del polmone

Osservazionale-Sperimentale: Sperimentale

Monocentrico-Multicentrico: Multicentrico

Randomizzato: Sì

Fase di studio: III

Linee di trattamento: Prima linea

Criteri di inclusione: 

- Histologically or cytologically confirmed diagnosis of nonsquamous stage IV or advanced Stage IIIB or IIIC NSCLC with KRAS p. G12C mutation and negative for PD-L1 expression by central testing or local laboratory testing confirmed through central testing
- No history of systemic anticancer therapy in metastatic/non-curable settings
- Eastern Cooperative Oncology Group (ECOG) ≤ 1.

Criteri di esclusione: 

- Mixed histology NSCLC with either small-cell or large-cell neuroendocrine cell component or predominant squamous cell histology
- Participants with tumors known to harbor molecular alterations for which targeted therapy is locally approved
- Symptomatic (treated or untreated) brain metastases
- Gastrointestinal (GI) tract disease causing the inability to take oral medication
- Myocardial infarction within 6 months of randomization, unstable arrhythmias, or unstable angina
- Prior therapy with a KRAS G12C inhibitor.

Schema di trattamento: 

Sotorasib - Oral administration;
Pembrolizumab - Intravenous administration;

Trattamento sperimentale: 

Sotorasib administered in combination with carboplatin and pemetrexed

Trattamento di controllo: 

Pembrolizumab administered in combination with carboplatin and pemetrexed

Obiettivi primari dello studio: 

Progression-free Survival (PFS) [ Time Frame: From Baseline up to end of study (EOS) (approximately 5.5 years) ]
PFS is defined as the time from randomization until the first documentation of radiologic disease progression or death due to any cause, whichever occurs first. Progression will be based on Response Evaluation Criteria in Solid Tumors (RECIST) v1.1, per Blinded Independent Central Review (BICR).

Obiettivi secondari dello studio: 

- Objective Response Rate (ORR) [ Time Frame: From Baseline up to EOS (approximately 5.5 years) ]
    Objective response is defined as the best overall response of complete response (CR) or partial response (PR), based on RECIST v1.1, per BICR.
- Overall Survival (OS) [ Time Frame: From Baseline up to EOS (approximately 5.5 years) ]
    OS is defined as the time from randomization until death due to any cause.
- Change in Quality-of-Life Questionnaire Core 30 (QLQ-C30) Dyspnea Domain Score [ Time Frame: From Baseline to Week 12 ]
- Change in Quality-of-Life Questionnaire Lung Cancer 13 (QLQ-LC13) Symptoms of Dyspnea Subscale [ Time Frame: From Baseline to Week 12 ]
- Change in QLQ-LC13 Symptoms of Cough Subscale [ Time Frame: From Baseline to Week 12 ]
- Change in QLQ-LC13 Symptoms of Chest Pain Subscale [ Time Frame: From Baseline to Week 12 ]
- Change in Physical Function as Measured by QLQ-C30 [ Time Frame: From Baseline to Week 12 ]
- Change in Global Health Status as Measured by QLQ-C30 [ Time Frame: From Baseline to Week 12 ]
- Progression-free Survival 2 (PFS2) [ Time Frame: From Baseline up to EOS (approximately 5.5 years) ]
    PFS2 is defined as the time from randomization to progression per investigator after initiation of new anticancer therapy or treatment beyond progression (ie, second progression) or death from any cause, whichever occurs first.
- Change in QLQ-LC13 Subscale Scores [ Time Frame: From Baseline up to EOS (approximately 5.5 years) ]
- Change in QLQ-C30 Subscale Scores [ Time Frame: From Baseline up to EOS (approximately 5.5 years) ]
- Time to Deterioration in QLC-LC13 Subscale Scores [ Time Frame: From Baseline to Week 12 ]
- Time to Deterioration in QLC-C30 Subscale Scores [ Time Frame: From Baseline to Week 12 ]
- Change in Summary Scores and Visual Analogue Scale (VAS) Scores [ Time Frame: From Baseline up to EOS (approximately 5.5 years) ]
    Measured by EuroQol-5 Dimension (EQ-5D-5L).
- Duration of Response [ Time Frame: From Baseline up to EOS (approximately 5.5 years) ]
    Duration of response is defined as the time from the first documentation of objective response until the first documentation of disease progression per BICR or death due to any cause, whichever occurs first.
- Time to Response [ Time Frame: From Baseline up to EOS (approximately 5.5 years) ]
    Defined as the time from randomization to first evidence of PR or CR per BICR.
- Disease Control [ Time Frame: From Baseline up to EOS (approximately 5.5 years) ]
    Defined as CR plus PR plus stable disease based on RECIST v1.1 per BICR.
- PFS [ Time Frame: From Baseline up to EOS (approximately 5.5 years) ]
    Based on investigator tumor assessments per RECIST v1.1.
- Objective Response [ Time Frame: From Baseline up to EOS (approximately 5.5 years) ]
    Based on investigator tumor assessments per RECIST v1.1.
- Number of Participants With Treatment-Emergent Adverse Events [ Time Frame: From Baseline up to EOS (approximately 5.5 years) ]
- Number of Participants With Clinically Significant Changes in Vital Signs [ Time Frame: From Baseline up to EOS (approximately 5.5 years) ]
- Number of Participants With Clinically Significant Changes in Clinical Laboratory Tests [ Time Frame: From Baseline up to EOS (approximately 5.5 years) ]
- Maximum Plasma Concentration (Cmax) of Sotorasib [ Time Frame: Pre-dose Day 1 up to Day 64 ]
- Minimum Plasma Concentration (Cmin) of Sotorasib [ Time Frame: Pre-dose Day 1 up to Day 64 ]
- Area Under The Curve (AUC) of Sotorasib [ Time Frame: Pre-dose Day 1 up to Day 64 ].

Centri partecipanti

Nord Italia

Centro Italia

Sud Italia e isole

Informazioni Generali

Protocollo

Numero di iscrizione a registro: 2022-501863-41 - NCT05920356

Data di inserimento: 16.04.2024

Promotore

Amgen

Principal Investigator ITALIA

Riferimento: Dr. NA na

Telefono: 00000

Email: na@ns.it

Localita: na