Efficacy and Safety of Olomorasib with Pembrolizumab+Chemotherapy as First Line Treatment in Patients with KRAS G12C-Mutant Advanced NSCLC
Bibliographic record
Abstract
Olomorasib, a potent, second-generation KRAS G12C inhibitor has demonstrated promising activity in KRAS G12C-mutant non-small cell lung cancer (NSCLC) as monotherapy and in combination with pembrolizumab. Here, we report the first clinical data describing olomorasib in combination with chemo-immunotherapy (chemo – IO). The phase 1 trial (NCT04956640) enrolled patients (pts) with advanced KRAS G12C-mutant NSCLC into multiple cohorts. Two doses of olomorasib (50 mg and 100 mg, orally BID) in combination with standard chemotherapy (CT) platinum/pemetrexed and pembrolizumab were studied. Of the 89 pts who received olomorasib+pembrolizumab, a subset of 20 pts received CT. Median age was 68 years; PD-L1 was negative in 11 pts, low in 7, high in 1 and unknown in 1. Prior to enrollment 8 pts received 1 cycle of SOC therapy. Median duration of therapy was 4.2 months and 16 pts remained on study therapy at time of data-cut. All grade TRAEs in>20% of pts were anemia, nausea, decreased appetite, fatigue, and neutrophil count decreased; grade≥3 TRAEs in≥10% of pts were diarrhea and decrease in neutrophil count, WBC count, and platelet count. Grade 3 immune-related AEs included elevated ALT/AST and pneumonitis. TRAEs resulted in olomorasib dose reduction in 2 pts. Hematologic toxicity delayed subsequent cycle of chemo in 3 pts. Among the 18 efficacy-evaluable pts, ORR was 44% (95% CI, 22-69) and disease control rate was 83% (95% CI, 59-96). Olomorasib in combination with chemo-IO demonstrated a favorable safety profile, consistent with the safety profiles observed with other combinations of CT and targeted therapy. The ORR was lower in this first-line cohort compared to the prior report with olomorasib+pembrolizumab, representative of the higher risk, PD-L1 negative pts enrolled to chemo-IO backbone. A global, registrational study investigating this combination in first-line NSCLC is currently enrolling (SUNRAY-01, NCT06119581). Publication History Article published online: 18 March 2025 © 2025. Thieme. All rights reserved. Georg Thieme Verlag KG Oswald-Hesse-Straße 50, 70469 Stuttgart, Germany
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.001 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".