238P Neoadjuvant divarasib shows manageable safety and promising activity in patients with resectable, early-stage, KRAS G12C+ NSCLC: First results from the NAUTIKA1 KRAS G12C+ cohort
lymph node evaluation not measurable per RECIST.PERCIST response can complement early efficacy endpoints like MPR.Methods: Adults w resectable, EGFRm, stage II-IIIB NSCLC were randomised 1:1:1 to osi (80 mg QD; 9 wks) CTx (Q3W, 3 cycles [C]) or PBO (QD; 9 wks) + CTx (Q3W, 3C), followed by surgery and optional adjuvant tx. 18F-FDG-PET-CT scans were performed at baseline and before surgery.Exploratory endpoint: BICR-assessed PERCIST response and correlation w pathological response.PERCIST response was categorised as complete (CMR) or partial metabolic response (PMR), stable or progressive metabolic disease, or not evaluable and was compared to pathologic response and molecular residual disease (MRD).Results: There were more PERCIST responders (CMR + PMR) w osi + CTx (76%) and osi mono (68%) vs PBO + CTx (37%; table).The proportion of pts w CMR trended higher w osi + CTx vs osi mono (27% vs 20%).Overall, 87% (54/62) of pts w MPR were PERCIST responders; PERCIST responses were more common in pts w presurgical MRD clearance vs non clearance (74/93 [80%] vs 10/30 [33%]).Associations between pathological nodal staging at surgery, presurgical PERCIST staging and MRD will be shown. Conclusions:PERCIST results reinforce the clinical benefit of neoadj osi CTx vs PBO + CTx, complementing previously reported improvements in MPR and surgical outcomes.Observed trends between PERCIST and MPR or MRD results may support their use as a prognostic assessment.Table: 237P PERCIST analysis set: N349* PERCIST metabolic response, n (%) Osi + CTx (n=115) Osi mono (n=117) PBO + CTx (n=117) Complete metabolic response 31 (27) 23 (20) 8 (7) Partial metabolic response 56 (49) 57 (49) 35 (30) Stable metabolic disease 19 (17) 26 (22) 56 (48) Progressive metabolic disease 6 (5) 8 (7) 16 (14) Missing/NE 3 (3) 3 (3) 2 (2) *Clinical data cut-off: 15 Oct 2024. Percentages are based on the number of pts who completed 18 F-FDG-PET-CT scans at baseline and presurgical visit. Pts who had 18 F-FDG-PET-CT scans, but whose PERCIST response was NE. 18 F-FDG-PET-CT, 18 Ffluorodeoxyglucose-positron emission tomography-computed tomography; NE, not evaluable.
Authors
- A.L. Cummings
- Andreas Saltos (ORCID: https://orcid.org/0000-0003-3622-026X)
- S.Y. Kim
- Elaine Shum (ORCID: https://orcid.org/0000-0002-0390-5716)
- Philip E. Lammers (ORCID: https://orcid.org/0000-0002-6023-9342)
- Jamie E. Chaft (ORCID: https://orcid.org/0000-0002-5838-9982)
- J. Jack Lee (ORCID: https://orcid.org/0000-0001-5469-9214)
- M.V. Negrao
- E. Brandao
- J. Schutzman
- K. He
- N. Mohindra
- K. Schulze
- Q. Zhu
- C. Ngiam
- T. Patil
- I. Bara
Institutions
- Northwestern University (US)
- Memorial Sloan Kettering Cancer Center (US)
- The University of Texas MD Anderson Cancer Center (US)
- University of California, Los Angeles (US)
- The Ohio State University Comprehensive Cancer Center – Arthur G. James Cancer Hospital and Richard J. Solove Research Institute (US)
- Moffitt Cancer Center (US)
- Yale University (US)
- NYU Langone Health (US)
- Baptist Cancer Center (US)
- University of Colorado Cancer Center (US)
- University of Colorado Denver (US)
Publication Details
- Journal
- ESMO Open
- Published
- 2026-03-17
- DOI
- https://doi.org/10.1016/j.esmoop.2026.106546
- Primary Topic
- Melanoma and MAPK Pathways
- Type
- article
- Field-Weighted Citation Impact
- 0.00