Background: Presently osimertinib is used as first-line therapy in stage IV EGFR mutation NSCLC patients. Unfortunately, acquired resistance gradually develops, resulting in disease progression in most patients after 1 to 2 years. A retrospective study demonstrates that similar to the first- and second-generation EGFR-TKIs, half of the patients experienced failure within the residual disease. Consolidative local therapy had been evaluated as a promising strategy to improve PFS and delayed the appearance of new metastatic lesions in the pre-osimertinib era. It is intriguing to hypothesize that new distant metastases may arise from drug-resistant tumor cells at the residual tumor lesions. Therefore, compared to the salvage SBRT, preemptive consolidative SBRT to all oligo-residual tumor sites could potentially prevent recurrence and improve survival. Of note, this proposal is challenging because both EGFR-TKI and thoracic radiation have a detrimental effect on pulmonary interstitial tissue. Two retrospective studies had reported severe pneumonitis with radiotherapy plus osimertinib. Therefore, the potential toxicity profile needs to evaluate prospectively. Therefore, we performed this preliminary trial (ChiCTR2100053807) to evaluate the safety of consolidation SBRT at maximal osimertinib response. Methods: Patients were enrolled if residual metastasis was limited to five sites. Consolidative SBRT was initiated to all residual sites with different doses (30–50Gy) and fractions (3-10) when maximal tumor shrinkage was achieved with osimertinib. The primary endpoint was an adverse reaction defined by the Common Terminology Criteria for Adverse Events, version 4.0. Results: 5 consecutive patients were enrolled between December 2021 and December 2022. 80% of their residual disease was located in the lungs and lymph nodes, which constituted targets for thoracic SBRT. The median time to maximal response was 3 months (range, 2-6). The median follow-up time from consolidative SBRT was 6 months（range,6-12）. The most common grade 1-2 adverse events included leukopenia (60%, n = 3), anorexia (40%, n = 2), lymphopenia (40%, n = 2), paronychia (40%, n = 2), rash (40%, n = 2), which were thought to be likely related to osimertinib. One patient suffered from grade 1 pulmonary fibrosis at 16 months after SBRT. There was no Grade 3/4 acute and late radiation toxicity. So far, no disease progression occur with a median follow-up time of 18 months（range, 13-19）. Conclusions: This pilot studydemonstrated concurrent treatment with osimertinib and SBRT for the oligo-residue disease at TKI maximum response was well tolerated. Future prospective, randomized studies are desirable to confirm these preliminary findings. Clinical trial information: ChiCTR2100053807.