(P 97) AN EXPLORATORY STUDY OF AN ANTI-PD-L1/TGF-β ANTIBODY, TQB2858, IN PATIENTS WITH REFRACTORY OR RECURRENT OSTEOSARCOMA AND ALVEOLAR SOFT PART SARCOMA: A REPORT FROM CHINESE SARCOMA STUDY GROUP

Objective: Novel effective immune-therapies are urgently needed in refractory or recurrent sarcoma. Transforming Growth Factor-Beta (TGF-β) is a diverse regulatory and fibrogenic protein expressed in multiple sarcoma tumors, which promotes epithelial-mesenchymal transition and excessive deposition of extracellular matrix. This study evaluated efficacy and safety of anti-PD-L1/TGF-β antibody TQB2858 in patients with refractory osteosarcoma or alveolar soft part sarcoma (ASPS).

Methods: In this single-arm Phase 1b exploratory study, we included patients with refractory osteosarcoma with progressive disease who had received at least 2 lines of systemic therapy previously or ASPS at least one line of systemic therapy. Patients were administered with 1200mg TQB2858 on day 1 every 3 weeks. The primary endpoint was Objective Response Rate (ORR), with null and alternative hypotheses of ORR≤5% and ≥20%, respectively. Exploratory biomarker analyses with immunohistochemistry (IHC) staining (PD-L1 and TGF-β) were performed on pre-treatment tumor samples.

Results: Eleven eligible patients were included in the outcome analysis. TQB2858 did not demonstrate evidence of efficacy as 0/5 osteosarcoma had any objective response while 2/6 ASPS showed partial response, of whom the median progression free survival were respectively 1.51 (1.38, NE) and 2.86 (1.38, NE) months for osteosarcoma group and ASPS group. None of the administered therapy cycles met criteria for unacceptable toxicity. Other Grade 3 toxicities included abnormal liver function and elevation of γ-glutamyltransferase. IHC analysis revealed that functional enrichment neither in the TGF-β pathway or in PD-L1 was not associated with treatment outcome.

Conclusion: The combination of PD-L1 and TGF-β antibody TQB2858 did not significantly improve ORR in recurrent osteosarcoma. However, it did improve the immunogenic responses in ASPS even after progression upon anti-PD-1/PD-L1 therapy with an acceptable safety profile. IHC profiling with pathway enrichment analysis would have possibilities to have predictive value for survival outcome, necessitating further investigation to confirm.