Durvalumab plus pazopanib combination in patients with advanced soft tissue sarcomas: a phase II trial

Area of Science:

• Oncology
• Immunotherapy
• Pharmacology

Background:

• Metastatic and/or recurrent soft tissue sarcoma (STS) remains a challenging clinical problem with limited effective treatment options.
• VEGF receptor tyrosine-kinase inhibitors and PD-L1 inhibitors are emerging as promising therapeutic agents in various cancers.

Purpose of the Study:

• To evaluate the efficacy and safety of combining pazopanib (anti-VEGF receptor tyrosine-kinase inhibitor) with durvalumab (anti-PD-L1 inhibitor) in patients with metastatic/recurrent STS.
• To identify potential biomarkers predictive of treatment response.

Main Methods:

• A single-arm, phase 2 clinical trial (NCT03798106) was conducted.
• Patients received pazopanib 800 mg once daily and durvalumab 1500 mg every 3 weeks.
• Primary endpoint was overall response rate (ORR); secondary endpoints included progression-free survival (PFS) and safety.

Main Results:

• The study met its primary endpoint, achieving an ORR of 30.4%.
• Median PFS was 7.7 months. Common grade 3-4 adverse events included neutropenia, elevated liver enzymes, and thrombocytopenia.
• Transcriptomic analysis revealed a B lineage signature as a key determinant of response (P=0.014).
• High CD20+ B cell infiltration and vessel density correlated with longer PFS (P=6.5 × 10-4) and better response rates (50% vs 12%, P=0.019).
• CD20+ B cell infiltration was the sole independent predictor of PFS in multivariate analysis.

Conclusions:

• The combination of durvalumab and pazopanib demonstrates promising efficacy in an unselected cohort of STS patients.
• The treatment regimen exhibited a manageable toxicity profile.
• CD20+ B cell infiltration serves as a significant predictive biomarker for treatment response and survival in STS patients receiving this combination therapy.