Abstract 1501P
Background
Undifferentiated pleomorphic sarcoma (UPS) is one of the common subtypes of soft tissue sarcoma (STS). Alternative therapy is needed for patients who are not suitable for chemotherapy. Antiangiogenic agents are approved for the treatment of advanced STS. In the SARC028 study, PD-1 inhibitor showed initial efficacy on UPS. The combination of antiangiogenic agent and PD-1 inhibitor may have synergistic effects. This single-arm phase II study aims to evaluate the efficacy and safety of anlotinib combined with toripalimab in the first-line treatment of patients with unresectable or metastatic UPS.
Methods
This study planned to recruit 25 eligible patients who refused chemotherapy in the first line of treatment. All patients would receive anlotinib (12 mg/d, PO, d1-14) combined with toripalimab (240mg, IV, d8) on the first 28-day cycle. From the second cycle, anlotinib (d1-14) and toripalimab (d1) would be administered every 3 weeks. The primary endpoint was progression-free rate (PFR) on 3 months (PFR3m). The secondary endpoints include ORR, DCR，DOR，OS, and safety. The correlation between tumor immune microenvironment and clinical efficacy would be explored simultaneously.
Results
From November 2019 to December 2021, 7 patients were recruited. The median follow-up time was 5.32 m (range from 1.53 to 15.2 m), and the PFR3m is 85.7%. ORR is 28.6% (2 PR). The overall incidence of adverse events (AEs) was 100%. All patients experienced grade 1-2 AEs. Highly expressed PD-L1 (>50%) and T cells and monocyte/macrophage infiltrating was found in a PR patient. Activated CD8+ T cells and PD-L1 high-expressing cells also showed co-localization. (Detailed result in the table). Table: 1501P
| Study number | Age (gender) | Primary site (metastasis) | TNM staging | Treatment cycle | Best curative effect | Main AEs |
| 1 | 72(F) | the left thigh (both lungs) | T1N0M1 G3, Stage Ⅳ | 4 | SD | Oral pain (G2), allergic dermatitis (G2) |
| 2 | 62(M) | the right shoulder (both lungs) | T2N0M1 G3 Stage Ⅳ | 21 | PR | Hypertension (G2) |
| 3 | 42(M) | the left leg (both lungs) | T3N0M1 G3 Stage Ⅳ | 2 | PD | Proteinuria (G2) |
| 4 | 65(M) | the left hip (both lungs) | T2N0M1 G3 Stage Ⅳ | 6 | SD | HFS reaction (G2), pneumothorax (G2) |
| 5 | 74(M) | the left shoulder and back | T4N0MxG3 Stage Ⅳ | 11 | SD | Triglyceride elevation (G2) |
| 6 | 64(F) | the left thigh (both lungs) | T1N0M1G3 Stage Ⅳ | 5 | PR | Hypothyroidism (G2) |
| 7 | 74(M) | the left hip recurred (both lungs) | TxN0M1 G3 Stage Ⅳ | 4 | SD | Hypertension (G2) |
Conclusions
Anlotinib combined with toripalimab showed good anti-tumor activity in unresectable or metastatic UPS patients, with acceptable toxicity, and the correlation between the efficacy and the tumor microenvironment is still under exploration.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.