Background: Salivary gland carcinomas (SGCs) are rare entities that contribute to approximately 5% of head and neck malignancies. The current standard therapy for resectable SGC is complete surgical resection with adjuvant radiotherapy or chemoradiotherapy. However, the patients with high-grade histological subgroup tumors have the highest risk of regional and distant metastasis as the primary cause of treatment failure.. The previous evidence demonstrates that neoadjuvant chemotherapy showed a statistically significant advantage in survival for patients with head and neck cancer. Based on the success of neoadjuvant immune checkpoint inhibitors (ICI) in preventing disease recurrence and achieving pathologic complete response (pCR) in different types of cancer, we designed this study by incorporating nivolumab combined with neoadjuvant cytotoxic chemotherapy in patients with potentially resectable high-grade SGCs. Methods: This study is the phase II, open-label, single-center study of nivolumab in combination with docetaxel, and cisplatin as a neoadjuvant therapy in high-grade resectable SGCs. All the patients must be confirmed with pre-defined high-grade histology and clinically node-positive. As the representative inclusion/exclusion criteria, all the patients must not receive prior cancer therapy in advance to study enrollment, including another kind of immunotherapy, cytotoxic chemotherapy, or radiotherapy. Three cycles of nivolumab (360mg), docetaxel (60mg per m²), and cisplatin (60mg per m²) are applied every three weeks. Three weeks after the last treatment, the patient is re-evaluated for the surgery and will undergo surgery within seven weeks after the last treatment. Based on the surgical pathologic outcome, additional radiotherapy will be initiated between 4 to 8 weeks after the surgery per the following guidance; R0: 59.4Gy/25fx; R1 or R2: 59.4Gy/25fx with optional boost 6.6Gy/3fx. The primary objective is the major pathologic response rate defined by ≤ 10% of tumors composed of viable tumors. Complete resection rate, response rate, downstaging at pathologic staging, two-year distant metastasis free-survival, disease-free survival, overall survival, safety results, surgical outcomes of facial nerve function, completeness of post-neoadjuvant surgery will be analyzed as the secondary objectives. The sample size was calculated using H₀ of mPR ≤25% and H₁ of mPR ≥50%, according to the one-arm binomial model (power of 90% and one-sided alpha of 0.05). A total of 50 patients will be recruited, include 40 evaluable patients. This study is currently recruiting patients at Samsung Medical Center, South Korea. The first subject received treatment in Nov. 2022 and three patients received the treatment. The time point for the primary analyses is Q3.2025. (ONO-4538-X78). Clinical trial information: NCT05727410.