Anlotinib Plus Toripalimab Yields Antitumor Activity in Advanced Soft Tissue Sarcoma and Bone Sarcoma

Combination therapy with anlotinib and toripalimab led to durable efficacy in patients with advanced soft tissue sarcoma and bone sarcoma, according to data from a phase 2 trial (NCT04172805) conducted in China.

Findings presented at the 2025 ASCO Annual Meeting showed that all efficacy-evaluable patients (n = 68) achieved an overall response rate (ORR) of 27.9% and a disease control rate (DCR) of 86.8%. Among those with soft tissue sarcoma (n = 64), the ORR was 29.7%.

In the overall cohort, the median progression-free survival (PFS) was 7.0 months (95% CI, 4.2-9.8), and the median overall survival (OS) was 23.5 months (95% CI, 9.2-37.8). In the soft tissue sarcoma subgroup, the median PFS was 8.1 months (95% CI, 4.7-11.5).

“A randomized controlled trial may be conducted to further verify [these results], especially in several treatment-sensitive histologic subtypes,” lead study author Xing Zhang, MD, PhD, of the Melanoma and Sarcoma Medical Oncology Unit, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center in Guangzhou, and colleagues wrote in a poster presentation of the data.

Phase 2 Trial Overview

Because anlotinib has been associated with lower ORRs as monotherapy, investigators sought to evaluate the efficacy and safety of the TKI given in combination with toripalimab, an immune checkpoint inhibitor.

The study enrolled patients aged 14 to 70 years with histologically confirmed advanced or unresectable bone or soft tissue sarcoma who progressed on or were intolerant to standard therapy or had no standard therapy available. Notably, patients younger than 18 years were required to have a body surface area of at least 1.5 m2. Patients with alveolar soft-part sarcoma or clear cell sarcoma were allowed to receive the combination as first-line therapy. Other key inclusion criteria comprised at least 1 measurable lesion per RECIST 1.1 criteria and an ECOG performance status of 0 to 2.

All patients (n = 70) received anlotinib at 12 mg once per day on days 1 to 14 in combination with toripalimab at 240 mg on day 1 of each 3-week cycle. Treatment continued until disease progression or unacceptable toxicity.

ORR served as the trial’s primary end point. Secondary end points included DCR, PFS, OS, and safety.

Among the safety population, the median age was 37 years (range, 15-69), 50% were female, and 85.7% had an ECOG performance status of 1. Histologic subtypes comprised synovial sarcoma (15.7%), rhabdomyosarcoma (8.6%), extraskeletal Ewing sarcoma (7.1%), epithelioid sarcoma (7.1%), leiomyosarcoma (7.1%), alveolar soft-part sarcoma (5.7%), liposarcoma (5.7%), undifferentiated sarcoma (5.7%), clear cell sarcoma (4.3%), osteosarcoma (2.9%), chondrosarcoma (2.9%), CIC-rearranged sarcoma (2.9%), desmoplastic small round cell tumor (2.9%), fibrosarcoma (2.9%), inflammatory myoblastic tumor (2.9%), malignant peripheral nerve sheath tumor (2.9%), malignant solitary fibrous tumor (2.9%), and other (10%). Most patients had FNCLCC (French Federation of Cancer Centers Sarcoma Group) grade 3 disease (54.3%) and a primary tumor site in the trunk or an extremity (51.4%).

Number of metastatic sites included 0 (4.3%), 1 (32.9%), 2 (34.3%), and 3 or more (28.6%). Additionally, 84.6% of patients underwent prior surgery, and all but 8.6% received at least 1 prior line of systemic therapy. Only 15.7% received prior antiangiogenic therapy.

Safety Findings

The most any-grade common treatment-related adverse effects included hypertriglyceridemia (68.6%), proteinuria (67.1%), hypertension (65.7%), hypothyroidism (65.7%), hand-foot syndrome (65.7%), hypercholesterolemia (61.4%), lymphocytopenia (54.3%), hyperuricemia (47.1%), increased alanine aminotransferase levels (44.3%), anemia (38.6%), increased γ-glutamyl transferase (35.7%), and diarrhea (35.7%).

Reference

Zhang X, Pan Q, Zhang P, et al. Multicenter phase II study of anlotinib and toripalimab in patients with advanced soft tissue sarcoma (STS) and bone sarcoma (BS). J Clin Oncol. 2025;43(suppl 16):11556. doi:10.1200/JCO.2025.43.16_suppl.11556