Efficacy and safety of serplulimab (an anti-PD-1 antibody) combined with albumin-bound paclitaxel in patients with advanced cervical cancer who have progressive disease or intolerable toxicity after first-line standard chemotherapy (074)

Objectives: Limited effective treatments are available for advanced cervical cancer patients who have failed first-line chemotherapy. Historical data indicate that PD-1 antibodies and albumin-bound paclitaxel monotherapy have certain antitumor activity (ORR: 14.3% for pembrolizumab and 28.6% for albumin-bound paclitaxel) in recurrent/advanced cervical cancer patients. This study aimed to determine the efficacy and safety of serplulimab (a recombinant humanized anti-PD-1 monoclonal antibody) plus albumin-bound paclitaxel in patients with advanced cervical cancer who have progressed on or are intolerant to first-line standard chemotherapy. Methods: This is an ongoing, single-arm, open-label, multi-center phase II study (NCT04150575). Twenty eligible patients aged between 18 and 75 years, who had ECGO PS 0 or 1, with histologically or cytologically diagnosed cervical cancer and positive PD-L1 expression (combined positive score [CPS] ≥1) were planned to be enrolled and given intravenous infusions of serplulimab (4.5 mg/kg) plus albumin-bound paclitaxel (260 mg/m2) every three weeks. The primary endpoints of this study were the adverse events, serious adverse events, and ORR (assessed by independent radiological review committee [IRRC] per RECIST v1.1). After all patients completed two tumor evaluations (every six weeks), a safety evaluation and a preliminary evaluation of antitumor efficacy were conducted. Results: By cut-off date July 15, 2021, 21 eligible patients were enrolled with a median age of 50.8 years (range: 31-64) and an average CPS of 39.3 (1 ≤CPS <20: n=7 [33.3%], CPS ≥20: n=14 [66.7%]). The median follow-up duration was 12.5 months; 71.4% patients had ECOG PS 1. The ORR assessed by IRRC and investigators were 57.1% (n=12; 95% CI: 34.0%-78.2%) and 47.6% (n=10; 95% CI: 25.7%-70.2%), respectively. The disease control rate (DCR) assessed by IRRC and investigators were both 76.2% (n=16; 95% CI: 52.8%-91.8%). The median PFS assessed by IRRC was 5.7 months (95% CI: 3.0-not reached). The median OS was not reached (95% CI: 10.5 months-not reached). The most common grade 3 or worse treatment-emergent adverse events (TEAEs) were decreased neutrophil count (n=7, 33.3%), decreased white blood cell count (n=6, 28.6%) and anemia (n=5, 23.8%). The most common immune-related adverse events (irAEs) were hypothyroidism (n=6, 28.6%), hyperthyroidism (n=3, 14.3%) and pruritus (n=3, 14.3%), all of which were grade 1 to 2. No TEAEs leading to drug discontinuation were observed. Conclusions: The results demonstrated a manageable safety profile and encouraging efficacy (IRRC-ORR: 57.1%) of serplulimab plus albumin-bound paclitaxel in advanced cervical cancer patients who have progressive disease or intolerable toxicity to first-line standard chemotherapy, representing a novel potential treatment option that warranted further investigation. Objectives: Limited effective treatments are available for advanced cervical cancer patients who have failed first-line chemotherapy. Historical data indicate that PD-1 antibodies and albumin-bound paclitaxel monotherapy have certain antitumor activity (ORR: 14.3% for pembrolizumab and 28.6% for albumin-bound paclitaxel) in recurrent/advanced cervical cancer patients. This study aimed to determine the efficacy and safety of serplulimab (a recombinant humanized anti-PD-1 monoclonal antibody) plus albumin-bound paclitaxel in patients with advanced cervical cancer who have progressed on or are intolerant to first-line standard chemotherapy. Methods: This is an ongoing, single-arm, open-label, multi-center phase II study (NCT04150575). Twenty eligible patients aged between 18 and 75 years, who had ECGO PS 0 or 1, with histologically or cytologically diagnosed cervical cancer and positive PD-L1 expression (combined positive score [CPS] ≥1) were planned to be enrolled and given intravenous infusions of serplulimab (4.5 mg/kg) plus albumin-bound paclitaxel (260 mg/m2) every three weeks. The primary endpoints of this study were the adverse events, serious adverse events, and ORR (assessed by independent radiological review committee [IRRC] per RECIST v1.1). After all patients completed two tumor evaluations (every six weeks), a safety evaluation and a preliminary evaluation of antitumor efficacy were conducted. Results: By cut-off date July 15, 2021, 21 eligible patients were enrolled with a median age of 50.8 years (range: 31-64) and an average CPS of 39.3 (1 ≤CPS <20: n=7 [33.3%], CPS ≥20: n=14 [66.7%]). The median follow-up duration was 12.5 months; 71.4% patients had ECOG PS 1. The ORR assessed by IRRC and investigators were 57.1% (n=12; 95% CI: 34.0%-78.2%) and 47.6% (n=10; 95% CI: 25.7%-70.2%), respectively. The disease control rate (DCR) assessed by IRRC and investigators were both 76.2% (n=16; 95% CI: 52.8%-91.8%). The median PFS assessed by IRRC was 5.7 months (95% CI: 3.0-not reached). The median OS was not reached (95% CI: 10.5 months-not reached). The most common grade 3 or worse treatment-emergent adverse events (TEAEs) were decreased neutrophil count (n=7, 33.3%), decreased white blood cell count (n=6, 28.6%) and anemia (n=5, 23.8%). The most common immune-related adverse events (irAEs) were hypothyroidism (n=6, 28.6%), hyperthyroidism (n=3, 14.3%) and pruritus (n=3, 14.3%), all of which were grade 1 to 2. No TEAEs leading to drug discontinuation were observed. Conclusions: The results demonstrated a manageable safety profile and encouraging efficacy (IRRC-ORR: 57.1%) of serplulimab plus albumin-bound paclitaxel in advanced cervical cancer patients who have progressive disease or intolerable toxicity to first-line standard chemotherapy, representing a novel potential treatment option that warranted further investigation.