– A multicenter, randomized, open-label phase 3 study to assess the efficacy of the combination of Sotorasib with a platinum doublet compared to the combination of Pembrolizumab with a platinum doublet as first-line therapy in participants with non-squamous, non-small cell lung cancer stage IV or advanced stage IIIB/C, PD-L1-negative and KRAS-p.G12C-positive (CodeBreak 202) Short title: A phase 3 study of first-line therapy with a platinum doublet in combination with Sotorasib versus Pembrolizumab in PD-L1-negative KRAS p.G12C-positive advanced/metastatic NSCLC (CodeBreaK 202)
Descrizione riassuntiva dello studio
This is an international, multicenter, randomized, open-label phase 3 study to evaluate the efficacy and safety of Sotorasib in combination with Carboplatin and Pemetrexed compared to Pembrolizumab in combination with Carboplatin and Pemetrexed in patients with stage IV or advanced stage IIIB/C NSCLC that is PD-L1 negative and KRAS p.G12C mutation positive. The study consists of a pre-treatment phase (pre-screening phase for patients with available molecular data and a screening phase), a treatment phase (4 platinum-containing cycles followed by a maintenance therapy), and a post-treatment phase (safety follow-up period [SFU] and long-term follow-up period [LTFU]). The target population of the study consists of patients with non-squamous NSCLC who are PD-L1 immunohistochemically (IHC) negative (TC or TPS<1%) and KRAS p.G12C mutation positive. Participants in the treatment group receiving Sotorasib (investigational product) will receive 960 mg of Sotorasib orally once daily in combination with Carboplatin under the concentration-time curve of 5 mg/ml/min and Pemetrexed 500 mg/m2, intravenously every 21 days for 4 cycles, followed by maintenance therapy (cycle 5 and beyond) with Sotorasib 960 mg PO and Pemetrexed 500 mg/m2 IV every 21 days. Patients in the Pembrolizumab treatment group (control) will receive Pembrolizumab 200 mg in combination with Carboplatin AUC5 and Pemetrexed 500 mg/m2, IV every 21 days for 4 cycles, followed by maintenance treatment (from cycle 5) with Pembrolizumab 200 mg IV (up to 35 cycles) and Pemetrexed 500 mg/m2 IV every 21 days. All participants will undergo an SFU assessment after the final discontinuation of the study treatment(s). After the SFU visit, long-term follow-up (LTFU) or the start of a new cancer therapy begins and lasts until the end of the study, until consent is withdrawn, or until death, whichever occurs first.
(BASEC)
Intervento studiato
Participants will receive either oral Sotorasib at a daily dose of 960 mg in combination with Carboplatin (AUC5) and Pemetrexed 500 mg/m2 IV, or Pembrolizumab (200 mg) in combination with Carboplatin (AUC5) and Pemetrexed (500 mg/m2 IV) randomly. In both cases, the treatment cycle lasts 21 days and continues until disease progression, treatment intolerance, initiation of another cancer therapy, withdrawal of consent, or death.
(BASEC)
Malattie studiate
PD-L1-negative KRAS p.G12C-positive advanced/metastatic NSCLC
(BASEC)
- histologically or cytologically confirmed diagnosis of NSCLC with non-squamous histology - stage IV or advanced stage IIIB/C NSCLC - no prior systemic cancer therapy for metastatic/unresectable disease - must provide a tumor tissue sample (or be willing to undergo a biopsy) for central molecular analysis - must be plasma-circulating tumor DNA (ctDNA) and/or tumor tissue positive for KRAS p.G12C mutation tested by the central laboratory (in selected cases local testing may be accepted) - must have measurable disease per RECIST v1.1 criteria - has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 (BASEC)
Criteri di esclusione
- NSCLC with mixed histology and either small cell or large cell neuroendocrine component or predominant squamous cell histology - tumors known to have molecular alterations for which a targeted therapy is locally approved (including, but not limited to, EGFR or ALK alterations), except KRAS p.G12C - active brain metastases, defined as symptomatic (treated or untreated) brain metastases; participants with asymptomatic untreated brain metastases are eligible if they meet all predefined criteria - active autoimmune disease - evidence of active hepatitis B or C - known uncontrolled infection with human immunodeficiency virus (HIV), defined by detectable HIV concentration in blood and/or CD4 count below 400; known controlled HIV allowed (BASEC)
Luogo dello studio
Aarau, Basilea, Zurigo
(BASEC)
Sponsor
Amgen Inc. Thousand Oaks, CA, USA Amgen Switzerland AG, Rotkreuz
(BASEC)
Contatto per ulteriori informazioni sullo studio
Persona di contatto in Svizzera
Prof. Dr. med. et Dr. phil. nat. Sacha Rothschild
+41 56 486 27 62
sacha.rothschild@clutterksb.chKantonsspital Baden
(BASEC)
Informazioni scientifiche
non disponibile
Nome del comitato etico approvante (per studi multicentrici solo il comitato principale)
Commissione d'etica svizzera nord-ovest/centrale EKNZ
(BASEC)
Data di approvazione del comitato etico
03.10.2023
(BASEC)
ID di studio ICTRP
non disponibile
Titolo ufficiale (approvato dal comitato etico)
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 Patients with Stage IV and Advanced Stage IIIB/C Nonsquamous Non-Small Cell Lung Cancers, Positive for KRAS G12C. (BASEC)
Titolo accademico
non disponibile
Titolo pubblico
non disponibile
Malattie studiate
non disponibile
Intervento studiato
non disponibile
Tipo di studio
non disponibile
Disegno dello studio
non disponibile
Criteri di inclusione/esclusione
non disponibile
non disponibile
Endpoint primari e secondari
non disponibile
non disponibile
Data di registrazione
non disponibile
Inclusione del primo partecipante
non disponibile
Sponsor secondari
non disponibile
Contatti aggiuntivi
non disponibile
ID secondari
non disponibile
Risultati-Dati individuali dei partecipanti
non disponibile
Ulteriori informazioni sullo studio
non disponibile
Risultati dello studio
Riepilogo dei risultati
non disponibile
Link ai risultati nel registro primario
non disponibile