Therascreen® KRAS RGQ PCR Kit

An interventional, prospective IVD device study for the testing of DNA extracted from tumor tissue biopsy samples from patients with Colorectal Cancer (CRC) who have previously tested positive for the KRAS G12C mutation for potential inclusion into the Amgen Phase III clinical trial (Protocol No 20190172) to demonstrate clinical performance of the therascreen® KRAS RGQ PCR Kit

This is an interventional, prospective clinical performance study protocol for the testing of DNA extracted from tumor tissue biopsy samples obtained from patients with CRC using the KRAS kit.

(RES, CNB are acceptable however (Fine needle aspiration (FNA), brushings, cell pellets from pleural effusion, bone biopsy and lavage samples are not acceptable.

Up to 200 patient tissue samples (from approximately 100 clinical trial sites), obtained in the Clinical Study (Protocol No. 20190172), will be tested using the KRAS Kit. The testing will be performed at the l device clinical testing sites, Q2 Solutions Laboratories in the two geographical locations: USA and UK.

The clinical study protocol (Protocol No. 20190172) requires an estimated total of 153 evaluable patient tissue biopsy samples to be tested. Approximately 200 patient biopsy samples are expected to be supplied to the test sites to reach this target.

The KRAS G12C mutation status of patients enrolling on the clinical trial is expected to be known prior to patient screening hence the relatively low estimate of screen failures. If existing local data are used for patient selection, the archival tumor sample is requested to be sent to the Test Site for confirmation of KRAS G12C status prior to enrollment. For the US (Site 001) and EU (Site 002) Test Sites a FFPE tissue block (preferred) and a copy of the de-identified pathology report is requested by the Test Site or a minimum of 9 - 20 unstained slides (4-5 µm) should be submitted during screening for prospective central confirmation.

If no remaining tumor tissue is available from the biopsy used for determining KRAS G12C status then an alternative archival tumor sample may be submitted to the Test Site. If this is unavailable or if there is insufficient quality of tumor sample, a new biopsy will need to be provided for central KRAS G12C confirmation.

The primary objective of the Amgen Clinical Study is to evaluate the progression free survival assessed by MODIFIED RECIST 1.1 criteria of Sotorasib (AMG 510) at 2 different dose levels as a combination therapy with panitumumab, compared to patients treated with investigators choice comparator (trifluridine and tipiracil or regorafenib) in patients using the Clinical Study Assay, therascreen®KRAS Kit to assess the presence of the KRAS G12C mutation in CRC, a key eligibility criteria.

The clinical data from the study will be used to determine the drug-device efficacy to support future regulatory submissions for the device-drug combination.

Eligibility Criteria:
Inclusion Criteria:

1. Patients with pathologically documented metastatic colorectal cancer (CRC).
2. Patients identified for inclusion in the Amgen Clinical Study (Protocol No. 20190172) who have signed and dated a valid informed consent form.
3. Patients must provide an archival tumor sample or a fresh tumor biopsy at baseline if an appropriate archival sample is unavailable.
4. Local KRAS data must be available for patient selection.
5. An archival tumor sample or fresh tumor biopsy is required for central confirmation of KRAS G12C status prior to enrollment.
6. Patient samples must meet the following criteria:

   1. A formalin-fixed paraffin-embedded (FFPE) tissue block (preferred) along with a de-identified pathology report.
   2. If an FFPE tissue block is unavailable, a minimum of 9-20 unstained slides (4-5 μm) must be submitted during screening for prospective central confirmation.
   3. If remaining tumor tissue from the KRAS status biopsy is unavailable, an alternative archival tumor sample may be submitted.
   4. If an alternative archival sample is unavailable or of insufficient quality, a new biopsy must be provided for central KRAS G12C confirmation.

   Submitted slides must be prepared using positively charged glass slides and cut within the past five years.
7. Patient samples must have been collected using one of the following methods:

   1. Core needle biopsy (CNB)
   2. Surgical resection (RES)
   3. Lavage samples

Exclusion Criteria:

1. Patients who do not meet all eligibility criteria for the Amgen Clinical Study (Protocol No. 20190172).
2. Patients with samples collected using one of the following methods:

   1. Fine needle aspiration (FNA)
   2. Brushings
   3. Cell pellets from pleural effusion
   4. Bone biopsy