Background: Distant metastasis is the main cause of nasopharyngeal carcinoma (NPC) related death while there are few treatment options for it. How to further improve the survival of NPC patients with distant metastases is an urgent problem to be solved in clinical practice. This study investigated the efficacy and safety of chemotherapy in combination with anlotinib (a multi-target tyrosine kinase inhibitor), toripalimab, and stereotactic radiotherapy(SBRT) in treatment of metastatic NPC. Methods: This is a prospective, multi-centered, single-arm, phase II trial (ChiECRCT20210147). Patients with histologically confirmed non-keratinous carcinoma and post-treatment metastatic NPC (stage IVb, AJCC 8th) who had no local recurrence and received no systemic antitumor therapy for metastatic lesions previously were enrolled. No more than 5 metastatic lesions (metastatic sites include lung, liver, bone, etc.), and with at least one measurable target lesion according to RECIST1.1. Other inclusion criteria included 18-65 years old and ECOG 0-1. All patients received gemcitabine (1000 mg/m², ivgtt, d1/8), cisplatin (80 mg/m², ivgtt, d1), toripalimab (240mg, ivgtt, d1) and anlotinib (12mg, oral, qd, d1-14) every 3 weeks for 6 cycles, then followed by toripalimab (240mg, ivgtt, d1) and anlotinib (12mg, oral, qd, d1-14) every 3 weeks for 11 cycles. The SBRT was initiated after 2 cycles of chemotherapy (bone GTV 30-45Gy/3-5f, liver and lung GTV 45-60Gy/4-6f). The primary endpoint was objective response rate (ORR). Here we report the results of a preliminary analysis. Results: Between January 2022 and January 2023, a total of 19 patients were enrolled (13 males and 6 females), the median age was 46 years old. At the data cutoff date on January 31, 2023, 15 patients were eligible for the evaluation of tumor response with metastatic lesions. 100% of the patients (15 of 15) had a response and the confirmed ORR was 100% (complete response, n = 4; partial response, n = 11) for metastatic lesions. The most common treatment-related adverse events (TRAE) of any grade were leukopenia (15 of 15,100%), anaemia(13 of 15, 93.3%), decreased appetite (10 of 15, 66.7%), hypothyroidism (6 of 15, 40.0%), rash(5 of 15, 33.3%) and pneumonitis (5 of 15, 33.3%). Grade 3-4 TRAE included leukopenia (3 of 15, 20.0%) and no fatal adverse events occurred. Conclusions: This preliminary analysis indicated that chemotherapy combined with anlotinib, toripalimab, and stereotactic radiotherapy had promising efficacy and favorable tolerance as treatment of oligo-metastatic NPC. Clinical trial information: ChiECRCT20210147.