SHR-1701, a Bifunctional Fusion Protein Targeting PD-L1 and TGFβ, for Recurrent or Metastatic Cervical Cancer: A Clinical Expansion Cohort of a Phase I Study.

Abstract

Patients with recurrent or metastatic cervical cancer have limited treatment options after platinum-containing treatment. We initiated a phase I study to assess SHR-1701, a novel bifunctional fusion protein composed of a mAb against programmed death ligand 1 (PD-L1) fused with the extracellular domain of TGFβ receptor II, in solid tumors (NCT03774979). Here, results from the cervical cancer cohort are presented. Patients with recurrent or metastatic cervical cancer who progressed during or after platinum-based therapy were enrolled to receive SHR-1701 at 30 mg/kg every 3 weeks. Primary endpoint was objective response rate (ORR) per RECIST v1.1. In total, 32 patients were recruited. ORR was 15.6% [95% confidence interval (CI), 5.3-32.8], and disease control rate was 50.0% (95% CI, 31.9-68.1). Responses were still ongoing in 80.0% of the responders; 6-month duration of response rate was 80.0% (95% CI, 20.4-96.9). Median progression-free survival (PFS) was 2.7 months (95% CI, 1.4-4.1). Of note, as assessed by immune-modified RECIST, median PFS was 4.1 months (95% CI, 1.6-4.3). Overall survival rate at 12 months was 54.6% (95% CI, 31.8-72.7). Treatment-related adverse events of grade 3 or 4 were reported in 11 (34.4%) patients. No treatment-related deaths occurred. No difference in ORR was found between patients with PD-L1 combined positive score ≥1 or <1; patients with high phosphorylated SMAD2 level in immune cells or tumor cells had numerically higher ORR. SHR-1701 exhibits encouraging antitumor activity and controllable safety in patients with recurrent or metastatic cervical cancer after platinum-based regimens, and therefore might provide another treatment option for this population. See related commentary by Miller and Friedman, p. 5238.