therascreen KRAS RGQ PCR Kit

• PMDA-approved CDx for LUMAKRAS in NSCLC
• Reliable detection of the KRAS G12C mutation
• Ready-to-use system with simple workflow and next-day results
• Automated data analysis using Rotor-Gene Q software

The therascreen KRAS RGQ PCR Kit is a real-time, qualitative in vitro diagnostic test for the detection of the G12C somatic mutation in the KRAS oncogene using a sample of DNA extracted from formalin-fixed, paraffin-embedded (FPPE) non-small cell lung cancer (NSCLC) tissue.

The therascreen KRAS RGQ PCR Kit is a PMDA-approved companion diagnostic (CDx) PCR test intended to aid in the identification of NSCLC patients for treatment with LUMAKRAS (sotorasib) based on a KRAS G12C Mutation Detected result.

A clinical performance study demonstrated the clinical validity of the therascreen KRAS RGQ PCR Kit as a CDx test to aid the identification of NSCLC patients for treatment with LUMAKRAS (sotorasib). The objective of the study was to assess whether G12C mutation status, as determined by the therascreen KRAS RGQ PCR Kit, can be used to select patients with advanced NSCLC that will benefit from LUMAKRAS (sotorasib) treatment. Clinical trial 20170543 is an ongoing open-label, multicenter, phase 1/2 study designed to evaluate the efficacy and safety of LUMAKRAS (sotorasib) in adult subjects with advanced solid tumors that harbor the KRAS G12C mutation. Data from the primary analysis of the NSCLC phase 2 portion of this study has been used to support the clinical validity of the therascreen KRAS RGQ PCR Kit as a CDx test. Enrollment was restricted to subjects with KRAS G12C-mutated NSCLC as assessed by a local laboratory result, which was confirmed by central testing using the therascreen KRAS RGQ PCR Kit.

The primary endpoint of the NSCLC phase 2 portion of this study was to evaluate tumor objective response rate (ORR) assessed by RECIST 1.1 criteria of LUMAKRAS (sotorasib) as monotherapy in subjects with KRAS G12C-mutated advanced tumors.

Analysis was performed on 123 patients. The primary endpoint of ORR (complete response + partial response) was assessed by blinded independent centralized review (BICR) using RECIST 1.1. For subjects with KRAS G12C-mutated NSCLC ORR was 37.4% (46 of 123 subjects; 95% CI: 28.8-46.6%); 1.6% (two subjects) achieved complete response and 35.8% (44 subjects) achieved partial response.

The therascreen KRAS RGQ PCR Kit utilizes specific PCR reaction mixes and a wild‑type control. The mutation-specific reaction mix uses an amplification refractory mutation system (ARMS) primer to selectively amplify mutated DNA and then a Scorpions primer to detect the amplification product. If both the run controls and the sample results are valid, the therascreen KRAS RGQ PCR Kit qualitatively determines the mutation status of the DNA samples and reports if the sample contains the G12C mutation.

The simple and straightforward testing workflow begins with manual DNA extraction from FFPE NSCLC tumor tissue using the QIAamp DNA FFPE Tissue Kit, followed by sensitive real-time PCR on the Rotor-Gene Q MDx 5plex HRM instrument. Rotor-Gene Q software rapidly and accurately determines mutations and reports results, informing the system operator if the KRAS G12C mutation is present. The assay can be completed in ~8 hours, providing next-day results.

The therascreen KRAS RGQ PCR Kit enables qualitative detection of the G12C mutation in codon 12 of the human KRAS gene for in vitro diagnostic use. The kit is intended to discriminate between KRAS G12C mutation-negative (wild-type) and KRAS G12C mutant tumors.