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106 Background: Current first-line standard therapy (SOC) for R/M CC is platinum-based chemotherapy +/- bevacizumab (bev). AK104 monotherapy has shown promising efficacy and tolerable toxicity in pretreated R/M CC (NCT04380805). In this study, we report the efficacy and safety of AK104 combined with SOC for the first-line treatment of R/M CC (NCT04868708). Methods: The multicenter, open-label, phase II study enrolled R/M CC pts without previous systemic therapy. Eligible pathological types were squamous cell carcinoma, adenocarcinoma, or adenosquamous cell carcinoma. Pts were assigned to 3 cohorts (A-15/A-10: AK104 15/10 mg/kg + PTX 175mg/m2 + DDP 50 mg/m2/CBP AUC 5, q3w; B-10: AK104 10 mg/kg + PTX 175 mg/m2 + DDP 50 mg/m2/CBP AUC 5 + bev 15 mg/kg, q3w). All pts received AK104 until PD or unacceptable toxicity. The primary endpoint was safety. Secondary endpoints included ORR, PFS per RECIST1.1, and OS, etc. Results: 45 pts were enrolled at 6 centers from Jun 3, 2021, to Nov 5, 2021. As of Jan 10, 2022, we assessed safety in all pts and efficacy in pts with at least one tumor assessment result. TRAEs of any grade occurred in 43 (95.6%) pts. Grade ≥3 TRAEs occurred in 23 (51.1%) pts. The most common TRAEs were anemia (55.6%), white blood cell count decreased (46.7%), rash (24.4%), and hypoesthesia (24.4%). The most common grade ≥ 3 TRAEs were anemia (15.6%), white blood cell count decreased (11.1%), neutrophil count decreased (8.9%), and platelet count decreased (8.9%). TRSAE occurred in 17 (37.8%) pts. IrAEs of any grade, assessed by INV, occurred in 24 (53.3%) pts. Grade ≥ 3 irAE occurred in 8 (17.8%) pts. One death due to hemorrhagic shock occurred in cohort B-10 and was judged as treatment-related. ORR were 73.3% (11/15) for A-15, 68.8% (11/16) for A-10, 92.3% (12/13) for B-10, respectively. The response to the treatment was favorable regardless of CPS (Table). PFS or OS data are not mature by cut-off date. Conclusions: AK104 combined with standard therapy was well tolerated, with encouraging antitumor activity in pts with R/M CC. Meanwhile, long-term safety evaluation still needs following up. A phase III trial is ongoing to evaluate the efficacy of AK104 plus standard therapy in first-line treatment for R/M CC (NCT04982237). Clinical trial information: NCT04868708. [Table: see text]

5534 Background: NORA is the first, phase III, randomized controlled trial (RCT) that demonstrated individualized starting dose regimen of niraparib, which significantly improved PFS in Chinese patients with platinum-sensitive recurrent ovarian cancer (PSROC). This sub-group analysis evaluated the efficacy of niraparib maintenance therapy with and without secondary cytoreductive surgery (SCS) in PSROC. Methods: The NORA phase III RCT included adult (≥18 years) Chinese women with PSROC who were randomized in a 2:1 ratio to receive oral niraparib (n = 177) or matched placebo (n = 88). This retrospective subgroup analysis was based on the progression-free survival (PFS) of niraparib maintenance therapy in these two groups of patients with PSROC, patients with SCS, and patients without SCS. The PFS was assessed by blinded independent central review. The Kaplan-Meier (KM) estimator and log-rank test were performed to calculate the median PFS time. Results: Of the 265 evaluable patients, 69 (26.0%) patients received the SCS (niraparib, n = 48; placebo, n = 21), and 196 (74.0%) patients were without SCS (niraparib, n = 129; placebo, n = 67). Among patients with and without SCS, baseline characteristics for BRCA mutation were 26.1% vs 41.8%, complete response to last platinum-based chemotherapy were 68.1% vs 43.9%, time (6-12 months) to progression after penultimate therapy were 23.2% vs 34.7%, respectively. Treatment with niraparib led to a significant reduction of risk to disease progression compared with placebo in patients with SCS (Hazard ratio [95% CI]: 0.32 [0.13–0.78]; P = 0.0102) and without SCS (0.34 [0.23–0.50]; P< 0.001). Moreover, in the subgroups of patients who received SCS, niraparib maintenance therapy had a significantly longer PFS compared with placebo (Median [95% CI]: not reached [18.33 – not estimable] vs 5.75 months [3.68 – not estimable]; P = 0.0102). This trend was also similar in the subgroup of patients who did not receive SCS (Median [95% CI]: 10.28 months [7.49 – 18.37] vs 4.90 months [3.71 – 5.52]; P < 0.0001). Conclusions: The results from this retrospective sub-group analysis revealed that niraparib maintenance therapy provided significant clinical efficacy in patients with PSROC, irrespective of SCS. Clinical trial information: NCT03705156.

5535 Background: To present the safety profile of niraparib maintenance therapy in patients with platinum-sensitive recurrent ovarian cancer (PSROC) included in the NORA trial. Methods: The double-blind, randomized, placebo-controlled, multicenter, phase III NORA trial (NCT03705156) included adult (≥18 years) Chinese women with PSROC who received ≥2 prior lines of platinum-based chemotherapy. Post ≤8 weeks of the last chemotherapy, patients were randomized (2:1) to receive oral niraparib (300 mg/day or 200 mg/day for patients with bodyweight 3/µL) or matched placebo. The primary endpoint was progression free survival, reported previously. Safety was assessed in terms of treatment emergent adverse events (TEAEs) related to hematologic toxicity (anemia/platelet count decreased and neutrophil count decreased) and non-hematologic toxicity (nausea/vomiting/constipation/insomnia/palpitations/hypertension). Adverse events (AEs) were graded using the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) v4.03. The data cutoff was February 1, 2020. Results: Of 265 patients included, the first 16 patients were given oral niraparib or matched placebo at a fixed starting dose of 300mg while 249 patients received individualized starting dose of niraparib (n = 166) or matched placebo (n = 83) based on baseline bodyweight and platelet count. The incidence of any TEAEs and grade ≥3 TEAEs was 100% and 50.8%, respectively in niraparib group, while 95.5% and 19.3%, respectively in placebo. Incidence of all grades of hematologic toxicity, gastrointestinal adverse events (nausea, constipation and vomiting), insomnia, palpitation and hypertension were highest in the first month after treatment with a gradual decrease in the further months. The median time to onset of grade ≥3 anemia, decreased neutrophil count and decreased platelet count were 87, 28, and 22 days, respectively, in the niraparib group. In niraparib group, any TEAEs that lead to dose reduction was observed in 59.9% of patients. Only 2 (1.1%) patients discontinued the treatment due to platelet count decreased and no patients discontinued niraparib treatment due to anemia or neutrophil count decreased. Overall, only 4% of patients in the niraparib group and 5.7% in the placebo group discontinued the treatment due to TEAEs. Conclusions: The lower incidence of TEAEs and the discontinuation rates indicate improved safety profile of niraparib with individualized starting dose in PSROC. Clinical trial information: NCT03705156.

e17510 Background: Limited effective treatments are available for advanced cervical cancer patients who progress after first-line chemotherapy. Historic data indicate PD-1 antibodies have significant activity in advanced cervical cancer patients. This study was designed to determine the efficacy and safety of HLX10 (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, multicenter, two-stage phase 2 study (NCT04150575). 143 eligible patients aged between 18 and 75, 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 infusion of HLX10 (4.5 mg/kg) plus albumin-bound paclitaxel (260 mg/m2) every 3 weeks. Stage one (N = 20) was a safety run-in and preliminary efficacy exploration study with primary endpoints of adverse events, serious adverse events and objective response rate (ORR, assessed by IRRC per RECIST v1.1). In this stage, after all patients completed two tumor evaluations (every 6 weeks), a safety evaluation and a preliminary evaluation of anti-tumor efficacy were conducted to determine whether to proceed to the second stage (N = 123). Stage two is a single-arm, open-label, multicenter, phase 2 study with primary endpoint of ORR assessed by IRRC per RECIST v1.1. Results: Here we report the stage one results (safety and preliminary efficacy) of HLX10 in advanced cervical cancer patients. By cut-off date Oct 14, 2020, 21 eligible patients with median age of 50 (range: 31–65) and average CPS of 39.33 were enrolled; the median follow-up duration was 4.34 months. 71.4% patients had ECOG PS 1. The ORR assessed by IRRC and investigators were 52.4% (95% CI: 29.8%, 74.3%) and 42.9% (95% CI: 21.8%, 66.0%), respectively. The most common grade 3 or worse treatment-emergent adverse events (TEAEs) were decreased neutrophil counts (n = 7, 33.3%), decreased white blood cell count (n = 6, 28.6%) and anemia (n = 4, 19.0%). No TEAEs leading to drug discontinuation were observed. One death (multiple organ dysfunction syndrome) possibly related to treatment was reported. Conclusions: Stage one results demonstrated a manageable safety profile and encouraging efficacy (ORR 52.4%) of HLX10 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. Clinical trial information: NCT04150575.