therascreen KRAS RGQ PCR Kit

• Health Canada-approved companion diagnostic (CDx) test
• Helps identify NSCLC patients with a G12C mutation for treatment with LUMAKRAS
• Helps identify CRC patients who may not benefit from anti-EGFR therapies
• Reliable detection of 7 mutations in the KRAS gene
• 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 seven somatic mutations in the KRAS oncogene using a sample of DNA extracted from formalin-fixed, paraffin-embedded (FPPE) non-small cell lung cancer (NSCLC) tissue and colorectal cancer (CRC) tissue.

The therascreen KRAS RGQ PCR Kit is a Health Canada-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. In addition, the kit can aid in the selection of patients with CRC who may not benefit from anti-EGFR therapies, such as cetuximab or panitumumab.

A clinical performance study was conducted to demonstrate the clinical validity of the therascreen KRAS RGQ PCR Kit as a companion diagnostic test that aids in the identification of NSCLC patients for treatment with 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 who will benefit from sotorasib treatment. The clinical trial 20170543 is an ongoing open-label, multicenter, phase 1/2 study designed to evaluate the efficacy and safety of 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 companion diagnostic 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 Response Evaluation Criteria in Solid Tumors (RECIST), version 1.1, of sotorasib as monotherapy in subjects with KRAS G12C-mutated advanced tumors.

Of a total of 126 subjects with NSCLC, 123 subjects were included in the full analysis set. Three subjects were excluded as they did not have ≥1 measurable lesion according to blinded independent centralized review (BICR). The primary endpoint of ORR (complete response + partial response) measured by computed tomography or magnetic resonance imaging and assessed per RECIST 1.1 by BICR laboratory for subjects with KRAS G12C-mutated NSCLC was 37.4% (46 of 123 subjects; 95% CI: 28.84, 46.58); two subjects (1.6%) achieved complete response and 44 subjects (35.8%) achieved partial response.

The therascreen KRAS RGQ PCR Kit is comprised of e separate PCR amplification reactions: seven mutation‑specific reactions in codons 12 and 13 of exon 2 of the KRAS oncogene and a wild‑type control in exon 4. Each 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 one or more mutations.

The simple and straightforward testing workflow begins with manual DNA extraction from either FFPE NSCLC or CRC tumor tissue using the QIAamp DSP 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 one or more of the seven mutations detected by the kit are present. The assay can be completed in ~8 hours, providing next-day results.

The therascreen KRAS RGQ PCR Kit enables qualitative detection of se mutations in codons 12 and 13 of the human KRAS gene (G12A, G12D, G12R, G12C, G12S, G12V, G13D) for in vitro diagnostic use. The kit is intended to discriminate between KRAS mutation-negative (wild-type) and KRAS mutant tumors.

The therascreen KRAS RGQ PCR Kit is a Health Canada-approved companion diagnostic (CDx) PCR test intended to aid in the identification of NSCLC patients for treatment with LUMAKRAS (sotorasib) and identification of patients with CRC who may not benefit from treatment with anti-EGFR therapies.