– 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)

Zusammenfassung der Studie

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follow-up (LTFU) or the start of a new cancer therapy begins and lasts until the end of the study, until consent is withdrawn, or until death, whichever occurs first.

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Untersuchte Intervention

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.

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Untersuchte Krankheit(en)

PD-L1-negative KRAS p.G12C-positive advanced/metastatic NSCLC

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Sponsor

Amgen Inc. Thousand Oaks, CA, USA Amgen Switzerland AG, Rotkreuz

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Name der bewilligenden Ethikkommission (bei multizentrischen Studien nur die Leitkommission)

Ethikkommission Nordwest- und Zentralschweiz EKNZ

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Datum der Bewilligung durch die Ethikkommission

03.10.2023

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Ergebnisse der Studie