Trial results for the Phase 1/2 study (NCT05313009) investigating the combination of sotorasib and tarloxotinib in patients with KRAS G12C-mutated Non-Small Cell Lung Cancer were posted on ClinicalTrials.gov on 2025-12-16. The trial was terminated and showed 0 participants achieving objective response or progression-free survival in either stage.
Background
Sotorasib (Lumakras) is an oral small molecule inhibitor specifically targeting the KRAS G12C mutation, which is found in various cancers, including a subset of Non-Small Cell Lung Cancer (NSCLC). It is approved for the treatment of adult patients with KRAS G12C-mutated locally advanced or metastatic NSCLC, as determined by an FDA-approved test, who have received at least one prior systemic therapy. This trial investigated sotorasib in combination with tarloxotinib in patients who had already progressed on a prior KRAS G12C small molecule inhibitor.
Trial design
The Phase 1/2 study (NCT05313009), titled "Tarlox and Sotorasib in Patients With KRAS G12C Mutations," was designed as a Phase 1B dose expansion trial with a safety lead-in. It aimed to evaluate the safety and clinical activity/efficacy of combining tarloxotinib and sotorasib. The trial enrolled 5 participants with KRAS G12C-mutated Non-Small Cell Lung Cancer who had progressed on any prior small molecule targeting KRAS G12C. The study was ultimately terminated.
Key results
Results from the terminated trial indicated a lack of objective response and progression-free survival in the enrolled patient population. For the outcome of "Objective Response":
- In STAGE 1: SAFETY LEAD IN, 0 Participants achieved an objective response.
- In STAGE 2: EFFICACY, 0 Participants achieved an objective response.
Similarly, for "Best Overall Response":
- In STAGE 1: SAFETY LEAD IN, 0 Participants achieved the best overall response.
- In STAGE 2: EFFICACY, 0 Participants achieved the best overall response.
For "Progression Free Survival":
- In STAGE 1: SAFETY LEAD IN, 0 Participants achieved progression-free survival.
- In STAGE 2: EFFICACY, 0 Participants achieved progression-free survival.
Regarding "Overall Survival":
- In STAGE 1: SAFETY LEAD IN, the median overall survival was 0.75 years.
What this means
The termination of this Phase 1/2 trial and the reported results, showing 0 objective responses and 0 progression-free survival in patients with KRAS G12C-mutated Non-Small Cell Lung Cancer who had progressed on prior KRAS G12C inhibitors, suggest that the combination of sotorasib and tarloxotinib did not demonstrate clinical activity in this challenging patient population. The median overall survival of 0.75 years in the safety lead-in stage further underscores the limited benefit observed. These findings indicate that this particular combination may not be a viable treatment strategy for patients with advanced KRAS G12C-mutated NSCLC who have developed resistance to existing KRAS G12C inhibitors.
Source
The information regarding these trial results was obtained from ClinicalTrials.gov, a public database of clinical studies. The results for study NCT05313009, titled "Tarlox and Sotorasib in Patients With KRAS G12C Mutations," were posted on 2025-12-16 on clinicaltrials.gov.