Clinical study supporting use of LUMAKRAS (sotorasib)1
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 124 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 36% (45 of 124 subjects; 95% CI: 28-45%); 1.6% (two subjects) achieved complete response and 35.8% (43 subjects) achieved partial response.
Clinical study supporting use with Erbitux (cetuximab)1
A clinical performance study generated data supporting the clinical utility of the therascreen KRAS RGQ PCR Kit as a CDx test to enable selection of patients for treatment with Erbitux (cetuximab). Study CA225025 was a multicenter, open-label, randomized clinical trial conducted in 572 patients with EGFR-expressing, previously treated, metastatic CRC (mCRC). Patients were randomized (1:1) to receive either Erbitux (cetuximab) plus best supportive care (BSC) or BSC alone. Erbitux (cetuximab) was administered as a 400 mg/m2 initial dose, followed by 250 mg/m2 weekly until disease progression or unacceptable toxicity.
KRAS mutation status was available for 453 (79%) patients. 245 (54%) patients had KRAS mutation-negative tumors and 208 (46%) patients had KRAS mutation-positive tumors as assessed using the therascreen KRAS RGQ PCR Kit.
The main outcome measure of the study was overall survival (OS) (Table 1). For the KRAS mutation-negative (wild-type) population, median survival time was 8.6 months (95% CI: 7.0, 10.3) months in the Erbitux (cetuximab)+BSC group and 5.0 months (95% CI: 4.3, 5.7) in the BSC alone group. For the KRAS mutation-positive population, median survival time was 4.8 months (95% CI: 3.9, 5.6) in the Erbitux (cetuximab)+BSC group and 4.6 months (95% CI: 3.6, 4.9) in the BSC alone group.
Table 1. Overall survival in previously treated EGFR-expressing mCRC
|| All randomized
||Wild-type: KRAS mutation-negative
|| KRAS mutation-positive
|6.1 (5.4, 6.7)
||4.6 (4.2, 4.9)
||8.6 (7.0, 10.3)
||5.0 (4.3, 5.7)
||4.8 (3.9, 5.6)
||4.6 (3.6, 4.9)
|0.77 (0.64, 0.92)
||0.63 (0.47, 0.84)
||0.91 (0.67, 1.24)
Overall survival rates based on Kaplan-Meier estimates at months 6 and 12 were higher for the Erbitux (cetuximab)+BSC group than the BSC group for the KRAS wild-type subset. This advantage was not observed in the KRAS mutant subset.
Clinical study supporting use with Vectibix (panitumumab)1
A clinical performance study generated data supporting the clinical utility of the therascreen KRAS RGQ PCR Kit as a CDx test to enable selection of patients for treatment with Vectibix (panitumumab). The objective of the study was to assess whether KRAS mutation status as determined by the therascreen KRAS RGQ PCR Kit can be used to select patients with mCRC who will benefit from Vectibix (panitumumab) treatment. Clinical trial 20050203 was a multicenter, prospective, open‐label, randomized phase 3 study to assess the efficacy of panitumumab in combination with oxaliplatin, 5‐fluorouracil (5‑FU) and leucovorin (FOLFOX4) vs. FOLFOX4 alone in patients with previously untreated mCRC.
Banked tumor samples from patients in study 20050203 were tested using the therascreen KRAS RGQ PCR Kit to identify two subgroups: KRAS mutation-positive (mutant KRAS) and KRAS mutation-negative (wild-type KRAS), according to whether at least one or none of 7 KRAS mutations in codons 12 and 13 of exon 2 in the KRAS gene was detected. In retrospective analyses, efficacy data from study 20050203 were stratified by KRAS subgroup. The primary objective of the KRAS analysis was to assess whether an overall improvement in progression-free survival (PFS) for Vectibix (panitumumab) plus FOLFOX4 relative to FOLFOX4 alone was significantly greater among subjects with KRAS wild‐type tumors compared to subjects with KRAS mutant tumors.
The prespecified primary efficacy endpoint was PFS in the group of patients (n = 656) with wild-type KRAS mCRC as assessed by blinded independent central review (BICR) of imaging (Table 2). Other key efficacy endpoints included OS and ORR.
Table 2. Efficacy results in patients with wild-type KRAS mCRC
||Wild-type KRAS population
||Median (months) (95% CI)
||Hazard ratio (95% CI)
||ORR (95% CI)
|Panitumumab plus FOLFOX4*
||9.6 (9.2, 11.1)
||0.80 (0.66, 0.97)
||54% (48%, 59%)
||8.0 (7.5, 9.3)
||47% (41%, 52%)