2321 - SATURN-STS: Phase II Study of Neoadjuvant Atezolizumab with Doxorubicin, Concurrent Atezolizumab with Preoperative Radiotherapy, and Adjuvant Atezolizumab in Patients with High-Risk Surgically Resectable Extremity and Truncal Soft Tissue Sarcoma
Presenter(s)
A. Farooqi1, N. Somaiah2, C. L. Roland3, H. Y. Lin4, D. Mitra1, A. K. Yoder1, A. P. Conley2, R. Ratan2, R. Denu2, J. A. Livingston2, M. A. Zarzour2, M. Nakazawa2, P. Lin5, E. Z. Keung3, H. Lillemoe3, H. Lyu3, B. Moon5, B. A. Guadagnolo1, A. J. Bishop1, and E. F. Nassif Haddad2; 1Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, 2Department of Sarcoma Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, 3Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, 4Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, TX, 5Department of Orthopedic Oncology, Division of Surgery, The University of Texas MD Anderson Cancer Center, Houston, TX
Purpose/Objective(s): High-risk localized soft tissue sarcoma (STS) continues to carry a substantial risk of relapse despite contemporary multimodality therapy. While radiotherapy (RT) is essential for optimizing local control, distant metastasis remains the dominant cause of treatment failure. Novel systemic strategies capable of improving relapse outcomes are urgently needed. Immune checkpoint inhibition (ICI) has demonstrated activity in select metastatic STS subtypes, with emerging evidence suggesting enhanced responses when combined with anthracycline-based chemotherapy. RT may further potentiate antitumor immunity through immunogenic tumor cell death and remodeling of the tumor microenvironment. However, the optimal sequencing and integration of chemotherapy, ICI, and RT in resectable STS remain undefined. SATURN-STS evaluates an intensified combined-modality approach incorporating neoadjuvant atezolizumab with doxorubicin followed by concurrent atezolizumab with preoperative RT and additional adjuvant atezolizumab. Correlative studies will characterize immune and molecular determinants of response.
Materials/Methods: SATURN-STS is an investigator-initiated, single-arm phase II study enrolling 50 adults with treatment-naïve, localized, intermediate- to high-grade STS >5 cm of the extremity or trunk. Eligible histologies include undifferentiated pleomorphic sarcoma, myxofibrosarcoma, dedifferentiated/pleomorphic liposarcoma, leiomyosarcoma, and unclassified sarcoma. Neoadjuvant therapy consists of 4–6 cycles of doxorubicin (60–75 mg/m²) plus atezolizumab (1200 mg IV) every 3 weeks, followed by atezolizumab administered concurrently with preoperative RT (50 Gy in 25 fractions or 42.75 Gy in 15 fractions), surgical resection, and up to 16 cycles of adjuvant atezolizumab. The primary endpoint is time-to-relapse (TTR), defined from surgical resection to documented recurrence. Secondary endpoints include radiographic response (RECIST 1.1), pathologic response, local recurrence-free survival, distant metastasis-free survival, progression-free survival, overall survival, and safety (CTCAE v5.0). The primary analysis employs a Bayesian time-to-event design comparing relapse dynamics with historical benchmarks. Posterior probability monitoring is conducted at prespecified interim analyses, enabling adaptive early stopping for futility. Radiographic imaging is obtained at baseline, during systemic therapy, post-RT prior to surgery, and throughout follow-up. Longitudinal tumor tissue is collected prior to systemic therapy, prior to RT/atezolizumab, and at surgery. Enrollment has begun, and accrual is ongoing, with a total of 7 patients enrolled as of February 2026. Clinical trial registry number: NCT07049848
Results: TBD
Conclusion: TBD