Final overall survival analysis from the Sotorasib compassionate use program in Germany for patients with metastatic non-small cell lung cancer harboring KRAS p.G12c alteration.

Background: Sotorasib is a first-in-class targeted therapy for non-small cell lung cancer (NSCLC) harboring the KRAS p.G12C mutation. It has been approved by the EMA for use in the second-line setting and beyond, following the pivotal CodeBreaK 200 trial. Real-world data were collected from the German compassionate use program between Jul 2020 and Dec 2022. Here, we present the final overall survival (OS) data after a median follow-up of 14.7 months. Methods: We conducted a multicenter, retrospective cohort study across 127 sites in Germany. Patient characteristics and treatment details were collected from electronic hospital registry databases and merged into a combined dataset after strict de-identification. The data cut-off for the final follow-up was Nov 2024; 58 sites were re-contacted to provide an updated dataset. Results: Fourteen sites (24.1%) reported follow-up data, resulting in a data maturity of 59.2%. In total, 141 patients participated in the follow-up analysis of the German CUP program. Median progression-free survival (PFS) and OS were 4.8 months (95% CI, 4.0–5.8) and 11.2 months (95% CI, 8.2–13.9), respectively. Patients with bone metastases (26% of the patients) had significantly shorter OS (median 5.0 vs. 27.7 months, p=0.001), whereas liver metastases (18% of the patients) or brain metastases (24% of the patients) had no significant impact. The absence of KEAP1 (KEAP1 Mutation was seen in 42% of the patients) co-alterations was associated with improved OS (median 10.1 vs. 4.76 months, p=0.0002). A considerable subset of 17 patients (12%) derived long-term benefit from Sotorasib, defined as PFS>1 year; all were classified as KEAP1 wild-type. Discussion/Conclusion: Sotorasib demonstrated consistent efficacy and safety compared with pivotal clinical trials. This study confirms that Sotorasib provides meaningful clinical benefit outside of a prospective trial setting, including those with multiple prior treatment lines and in patients with poor performance status. Metastatic sites and molecular co-alterations may influence prognosis and treatment outcomes with Sotorasib. Publication History Article published online: 04 March 2026 © 2026. Thieme. All rights reserved. Georg Thieme Verlag KG Oswald-Hesse-Straße 50, 70469 Stuttgart, Germany