SHR-1701, a bifunctional fusion protein targeting PD-L1 and TGF-β, for recurrent or metastatic cervical cancer: a clinical expansion cohort of phase 1 study

Abstract

Purpose: Recurrent or metastatic cervical cancer patients have limited treatment options after platinum-containing treatment. We initiated a phase 1 study to assess SHR-1701, a novel bifunctional fusion protein composed of a mAb against PD-L1 fused with the extracellular domain of TGF-β receptor II, in solid tumors (NCT03774979). Here, results from the cervical cancer cohort are presented. Patients and Methods: 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 three weeks. Primary endpoint was objective response rate (ORR) per RECIST v1.1. Results: Totally, 32 patients were recruited. ORR was 15.6% (95% 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 imRECIST, median PFS was 4.1 months (95% CI, 1.6–4.3). 12-month overall survival rate 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 CPS ≥1 or <1; patients with high pSMAD2 level in immune cells or tumor cells had numerically higher ORR. Conclusion: SHR-1701 exhibits encouraging antitumor activity and controllable safety in patients with recurrent or metastatic cervical cancer after platinum-based regimens, might providing another treatment option for this population.