SATURN-STS: Phase II study of neoadjuvant atezolizumab with doxorubicin, concurrent atezolizumab with pre-operative radiation therapy and adjuvant atezolizumab in patients with high-risk surgically resectable extremity and truncal soft tissue sarcoma.

Abstract

TPS11595 Background: High-risk, localized soft tissue sarcoma (STS) remains associated with high rates of distant relapse despite modern multimodality therapy. Immune checkpoint inhibition (ICI) has demonstrated activity in certain metastatic STS subtypes with signals of enhanced response when combined with doxorubicin in the advanced/metastatic setting, as well as improved disease-free survival when combined with radiotherapy (RT) in the neoadjuvant setting; however, the optimal integration of neoadjuvant chemotherapy, immunotherapy, and RT in resectable disease is unknown. This single-arm phase II trial evaluates whether neoadjuvant atezolizumab combined with doxorubicin, followed by concurrent atezolizumab with preoperative RT and adjuvant atezolizumab, can improve relapse outcomes in patients with resectable, high-risk STS of the extremity and trunk. Methods: SATURN-STS is an investigator-initiated phase II study enrolling 50 adults with treatment-naïve, localized, intermediate- to high-grade STS >5 cm, including undifferentiated pleomorphic sarcoma, myxofibrosarcoma, de-differentiated/pleomorphic liposarcoma, leiomyosarcoma, and unclassified sarcoma. Neoadjuvant treatment includes 4–6 cycles of doxorubicin (60–75 mg/m²) plus atezolizumab (1200 mg IV q3w), followed by atezolizumab 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. Radiographic imaging is performed at baseline, during neoadjuvant therapy, post-RT prior to surgery, and throughout follow-up. Longitudinal tissue is acquired for translational analyses with biopsy prior to initiation of chemoimmunotherapy and prior to RT/immunotherapy combination, followed by collection at the time of surgery. The primary endpoint is time-to-relapse (TTR), defined from time of surgical resection to the date of documented disease recurrence, compared to a historical control using a single-arm, time-to-event Bayesian monitoring approach. Secondary endpoints include objective response (RECIST 1.1), pathologic response, local recurrence-free survival, distant metastasis-free survival, progression-free survival, overall survival, and safety (CTCAE v5.0). Exploratory objectives include profiling immune microenvironment changes, genomic correlatives, circulating tumor DNA, and spatial analyses. As of January 2026, 6 patients have initiated treatment at an accrual rate of 1-2 patients per month. Clinical trial registration: NCT07049848. Support: The University of Texas MD Anderson Cancer Center and Genentech Strategic Alliance Grant. Clinical trial information: NCT07049848 .