CodeBreaK 202

A Phase 3 Study of Front-Line Platinum Doublet Therapy With Sotorasib Versus Pembrolizumab in PD-L1 Negative KRAS p.G12C Positive Advanced/Metastatic NSCLC

Subjects ages ≥ 18 years (or legal adult age within country, whichever is older) who have provided informed consent before initiation of any study-specific activities/procedures will be eligible if they satisfy these key inclusion criteria:
• histologically or cytologically confirmed diagnosis of nonsquamous histology NSCLC (adenosquamous histology allowed if nonsquamous histology is  50 of the tumor); presence of small cell or large cell neuroendocrine component is an exclusion criterion
• Stage IV or advanced Stage IIIB/C NSCLC (not a candidate for definitive multimodality therapy due to the extent of disease)
• no history of systemic anticancer therapy in metastatic/incurable settings
• must provide tumor tissue sample (or be willing to undergo biopsy) for central molecular analysis
• must be tumor tissue negative for PD-L1 expression (TC  1), tested using SP263
• IHC assay in the central laboratory (in selected cases, local laboratory results can be used for study entry and randomization while central laboratory results are pending;
• must be plasma circulating tumor DNA (ctDNA) and/or tumor tissue positive for KRAS p.G12C mutation tested by central laboratory (in selected cases, local laboratory results can be used for study entry and randomization while central laboratory results are pending)
• must have measurable disease as defined by RECIST v1.1 criteria
• has Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1

• mixed histology NSCLC with either small-cell or large-cell neuroendocrinecomponent (any percentage) or predominant squamous cell histology (more than 50% of the available tumor)
• tumors known to harbor molecular alterations for which targeted therapy is approved (including but not limited to EGFR or ALK alteration) other than KRAS p.G12C
• active brain metastases, defined as symptomatic (treated or untreated) brain metastases; subjects with asymptomatic untreated metastases or asymptomatic treated brain metastases are eligible if they meet all prespecified criteria
• active autoimmune disease
• evidence of active hepatitis B or C (hepatitis panel test performed during screenin
• known uncontrolled human immunodeficiency virus (HIV) infection, defined by detectable level of HIV in the blood and/or CD4 level below 400; known controlled HIV allowed