Data from 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

Dihong Tang,Hanmei Lou,Hongmin Chen,Jianjun Zou,Jifeng Feng,Jin Peng,Jing Wang,Junqin Yang,Linna Wang,Pan Liu,Qi Zhou,Yunlang Cai,Yuping Sun

doi:10.1158/1078-0432.c.6532929.v1

Abstract

<div>AbstractPurpose: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 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 3 weeks. Primary endpoint was objective response rate (ORR) per RECIST v1.1.Results: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.Conclusions: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.<a href="https://aacrjournals.org/clincancerres/article/doi/10.1158/1078-0432.CCR-22-1779" target="_blank">See related commentary by Miller and Friedman, p. 5238</a></div>

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