Zai Lab Ltd. · HKEX:9688
Zai Lab — Technical Presentation (November 2021)
17 slides from Zai Lab's technical presentation, November 2021
Slide 1: Individualized Starting Dose of Niraparib in Platinum-Sensitive Recurrent Ovarian Cancer (NORA)
Individualized Starting Dose of Niraparib in Patients with Platinum-Sensitive Recurrent Ovarian Cancer (NORA) : A Randomized, Double-Blind, Placebo- Controlled, Phase III Trial Xiaohua Wu1, Jianqing Zhu2, Rutie Yin3, Jiaxin Yang4, Jihong Liu5, Jing Wang6, Lingying Wu7, Ziling Liu8, Yunong Gao9, Danb
Slide 2: Disclosure Information
DISCLOSURE INFORMATION • The authors have no conflict of interest to declare.
Slide 3: Background
Background • FDA has approved niraparib as maintenance treatment for platinum-sensitive recurrent (PSR) ovarian cancer based on results of the NOVA trial1. • The starting dose in the NOVA trial was 300 mg orally daily. A retrospective analysis indicated that an individualized starting dose (ISD) bas
Slide 4: Study Design
NORA Study Design Main Inclusion Criteria Stratification Factor Primary Endpoint • Platinum-sensitive, recurrent • gBRCA mutation: Yes or No • Progression-free ovarian cancer; • Response to last chemotherapy: CR or PR survival (PFS) • High grade serous or high • Time to progression after penultimate
Slide 5: NORA CONSORT Flow Diagram
NORA CONSORT Flow Diagram 265 randomized First patient enrollment : Sep 26, 2017 Last patient enrollment : Feb 2, 2019 Data Cut-off : Feb 1, 2020 Database Lock : May 22, 2020 Starting Dose: Starting Dose Before protocol amendment: Before protocol amendment: ▪ 11 patients at 300mg ▪ 5 patients at 300
Slide 6: Baseline Demographic and Disease Characteristics
NORA Baseline Demographic and Disease Characteristics Niraparib Placebo Total Characteristic (N=177) (N=88) (N=265) Median age, years (range) 53.0 (35.0, 78.0) 55.0 (38.0,72.0) 54.0 (35.0,78.0) Median weight, kg (range) 61.0 (39.0, 93.0) 60.5 (40.0, 88.0) 61.0 (39.0,93.0) Mean body mass index, kg/m2
Slide 7: Primary Endpoint: PFS (BICR) in ITT Population
NORA Primary Endpoint: PFS (BICR) in ITT Population 1.0 68% reduction of hazard for relapse or death with niraparib Cumulative probability of progression-free 0.8 Niraparib Placebo 0.6 (n=177) (n=88) survival,% 0.4 Median PFS 0.2 Months 18.3 5.4 Niraparib Placebo (95% CI) (10.9–NE) (3.7–5.7) Censore
Slide 8: PFS (BICR) in Pre-specified Subgroups
PFS (BICR) in Pre-specified Subgroups Niraparib Placebo Hazard Ratio (95% Cl) Events/n Events/n Subgroup Overall 80/177 66/88 0.32 (0.23,0.46) Age, year 18-64 63/152 57/76 0.30 (0.21,0.44) ≥65 17/25 9/12 0.65 (0.29,1.46) Time to progression after penultimate therapy, months 6-12 29/56 25/28 0.31 (0.
Slide 9: PFS (BICR) in Biomarker Subgroups
PFS (BICR) in Biomarker Subgroups gBRCAmut subgroups Non-gBRCAmut subgroups Niraparib Placebo Niraparib Placebo (n=65) (n=35) (n=112) (n=53) NR 5.5 11.1 3.9 mPFS, mo (95% CI) mPFS, mo (95% CI) 1.0 (11.0-NE) (3.7-6.9) 1.0 (7.5-NE) (3.7-6.9) Cumulative probability of progression-free Cumulative probab
Slide 10: Secondary Efficacy Endpoints: CFI and TFST
NORA Secondary Efficacy Endpoints: CFI and TFST Chemo-free interval (CFI) Time to first subsequent therapy (TFST) Niraparib Placebo Niraparib Placebo (n=177) (n=88) (n=177) (n=88) 18.5 9.7 16.7 7.7 1.0 mPFS, mo (95% CI) 1.0 mPFS, mo (95% CI) (15.3-NE) (7.9-10.8) (12.7-NE) (6.6-9.0) Cumulative probab
Slide 11: Secondary Efficacy Endpoint: OS
NORA Secondary Efficacy Endpoint: OS 1.0 0.8 Cumulative probability of survival,% Niraparib Placebo Niraparib Placebo (n=177) (n=88) 0.6 (N=177) (N=88) mOS, months NR(NE-NE) NR(NE-NE) (95%CI) 0.4 Hazard ratio (95%CI) 0.64(0.29-1.42) Events, n (%) 16 (9.0) 10 (11.4) 0.2 p-value* p=0.267 Censored, n (
Slide 12: Summary of the Efficacy (PFS) of NORA vs NOVA
Summary of the Efficacy (PFS) of NORA vs NOVA NORA NOVA 1 Number of Patients 265 553 Overall Population, HR (95% CI) 0.32 (0.23 to 0.45) NA gBRCAmut, HR (95% CI） 0.22 (0.12 to 0.39) 0.27 (0.17 to 0.41) Non-gBRCAmut, HR (95% CI) 0.40 (0.26 to 0.61) 0.45 (0.34 to 0.61) HR, hazard ratio; CI, confidence
Slide 13: Summary of Adverse Events in NORA
Summary of Adverse Events in NORA Niraparib Placebo (n=177) (n=88) n (%) n (%) Any TEAE 177 (100.0) 84 (95.5) ≥Grade 3 90 (50.8) 17 (19.3) Any treatment-related TEAE 176 (99.4) 77 (87.5) ≥Grade 3 79 (44.6) 10 (11.4) Any serious TEAE 31 (17.5) 10 (11.4) Any related Serious TEAEs 23 (13.0) 4 (4.5) Any
Slide 14: Summary of Adverse Events
Summary of Adverse Events Any grade in >10% of patients in either arm and/or grade ≥3 in patients overall Any Grade Any Grade Grade ≥3 Grade ≥3 White blood cell count decreased* 59.3% 7.3% 43.2% 2.3% Neutrophil count decreased* 58.8% 20.3% 42.0% 8.0% Platelet count decreased 54.8% 11.3% 25.0% 1.1% A
Slide 15: Selective Grade 3/4 TEAEs by PT in NORA and NOVA
Selective Grade 3/4 TEAEs by PT in NORA and NOVA NORA NOVA Niraparib Placebo Niraparib Placebo (N=177) (N=88) (N=367) (N=179) n (%) n (%) n (%) n (%) Neutrophil count decreaseda 36 (20.3) 7 (8.0) Thrombocytopeniad 124 (33.8) 1 (0.6) Anaemiab 26 (14.7) 2 (2.3) Anaemiab 93 (25.3) 0 Platelet count decr
Slide 16: Conclusions
Conclusions • NORA is the first fully powered phase III RCT evaluating a PARP inhibitor in Chinese patients with ovarian cancer. • NORA met its primary endpoint, demonstrating that niraparib administered with an ISD regimen significantly improves the outcome in the patients with recurrent epithelial
Slide 17: Acknowledgements
Acknowledgements • We sincerely thank all the patients, their families, the investigators, the staff for their involvement and support. • This study was funded by Zai Lab. The study was also partially supported by the National Major Scientific and Technological Special Project for “Significant New D