– 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)
Summary description of the study
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follow-up (LTFU) or the start of a new cancer therapy begins and lasts until the end of the study, until consent is withdrawn, or until death, whichever occurs first.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)
Intervention under investigation
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)
Disease under investigation
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)
Exclusion criteria
- 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)
Trial sites
Aarau, Basel, Zurich
(BASEC)
Sponsor
Amgen Inc. Thousand Oaks, CA, USA Amgen Switzerland AG, Rotkreuz
(BASEC)
Contact
Contact Person Switzerland
Prof. Dr. med. et Dr. phil. nat. Sacha Rothschild
+41 56 486 27 62
sacha.rothschild@clutterksb.chKantonsspital Baden
(BASEC)
Scientific Information
not available
Name of the authorising ethics committee (for multicentre studies, only the lead committee)
Ethics Committee northwest/central Switzerland EKNZ
(BASEC)
Date of authorisation
03.10.2023
(BASEC)
ICTRP Trial ID
not available
Official title (approved by ethics committee)
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)
Academic title
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Public title
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Disease under investigation
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Intervention under investigation
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Type of trial
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Trial design
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Inclusion/Exclusion criteria
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Primary and secondary end points
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Registration date
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Incorporation of the first participant
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Secondary sponsors
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Additional contacts
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Secondary trial IDs
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Results-Individual Participant Data (IPD)
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Further information on the trial
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Results of the trial
Results summary
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Link to the results in the primary register
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