Zai Lab Ltd. · HKEX:9688
Zai Lab — Technical Presentation (November 2021)
16 slides from Zai Lab's technical presentation, November 2021
Slide 1: Efficacy and Safety of Niraparib in Platinum-Sensitive Recurrent Ovarian Cancer (NORA) with Individualized Starting Dose
Efficacy and Safety of Niraparib in Patients with Platinum-Sensitive Recurrent Ovarian Cancer (NORA) with Individualized Starting Dose A Subgroup Analysis of a Randomized, Double-Blind, Placebo-Controlled, Phase 3 Trial Jianqing Zhu1, Xiaohua Wu2, Rutie Yin3, Jiaxin Yang4, Jihong Liu5, Jing Wang6, L
Slide 2: Disclosure Information
DISCLOSURE INFORMATION The authors have no conflict of interest to declare. 1.wmf
Slide 3: Background of ISD population analysis
Background of ISD population analysis • NORA was initially designed to evaluate the efficacy and safety profile of niraparib in Chinese patients with platinum-sensitive recurrent (PSR) ovarian cancer using fixed starting dose (FSD) 300mg orally daily. • After the first 16 patients treated with FSD,
Slide 4: NORA 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 grade • Time to progression after penul
Slide 5: Subgroup CONSORT flow diagram
Subgroup CONSORT flow diagram ITT 265 randomized 16 patients with fixed starting dose of 300mg 249 patients with individualized starting dose After protocol amendment: After protocol amendment: ▪ 155 patients at 200mg 166 received niraparib 83 received placebo ▪ 80 patients at 200mg ▪ 11 patients at
Slide 6: ISD population demographics and baseline characteristics
ISD population demographics and baseline characteristics Niraparib Placebo Total Characteristic (N=166) (N=83) (N=249) Median age, years (range) 54.0 (37, 78) 55.0 (38, 71) 54.0 (37, 78) Median weight, kg (range) 60.0 (39, 93) 61.0 (42, 88) 61.0 (39, 93) ECOG performance status, n (%) 0 64 (38.6) 33
Slide 7: Primary endpoint: PFS (BICR) of ISD population
Primary endpoint: PFS (BICR) of ISD population 100 70% reduction of hazard for relapse or Progression-free survival, % 80 death with niraparib 60 Niraparib Placebo (n=166) (n=83) 40 Median PFS 20 Niraparib Months 18.3 5.4 Placebo (95% CI) (11.0–NE) (3.7–5.7) 0 Hazard ratio 0.30 0 2 4 6 8 10 12 14 16
Slide 8: PFS (BICR) in pre-specified subgroups
PFS (BICR) in pre-specified subgroups in ISD population Niraparib Placebo Subgroup Events/n Events/n HR (95% CI) Overall 73/166 64/83 0.30 (0.21, 0.43) Age, year 18-64 56/141 55/73 0.29 (0.20, 0.43) >=65 17/25 9/10 0.41 (0.18, 0.93) Time to progression after penultimate therapy 6-12 month 29/55 25/2
Slide 9: PFS (BICR) of biomarker subgroups
PFS (BICR) of biomarker subgroups in ISD population gBRCAmut subgroup non-gBRCAmut subgroup Niraparib Placebo (n=60) (n=32) Niraparib Placebo (n=106) (n=51) NR 5.5 mPFS, mo (95% CI) 11.1 3.8 (13.1-NE) (3.7-5.7) mPFS, mo (95% CI) 100 (7.5-NE) (3.7-7.4) HR (95% CI) 0.18 (0.10-0.34) 100 HR (95% CI) 0.3
Slide 10: Secondary efficacy endpoints
Secondary efficacy endpoints in ISD population Chemo-free interval (CFI) Time to first subsequent therapy (TFST) Niraparib Placebo Niraparib Placebo (n=166) (n=83) (n=166) (n=83) 19.4 9.7 16.7 7.7 Median, mo (95% CI) 100 Median, mo (95% CI) (13.0-NE) (6.8-9.0) 100 (15.3-NE) (8.0-10.8) HR (95% CI) 0.
Slide 11: Secondary endpoint: OS
Secondary endpoint: OS in ISD population 100 90 Niraparib Placebo 80 (n=166) (n=83) Niraparib Overall survival, % 70 Placebo Events, n (%) 15 (9.0%) 10 (12.0%) 60 50 Data is immature Median OS 40 Months NR NR 30 (95% CI) (NE–NE) (NE–NE) 20 Hazard ratio 0.61 10 (95% CI) （0.27-1.36） 0 p-value* 0.2176
Slide 12: ISD population showed consistent efficacy with ITT group
ISD population showed consistent efficacy with ITT group NORA ISD population NORA ITT population Niraparib Placebo Niraparib Placebo (n=166) (n=83) (n=177) (n=88) PFS, months (95% CI) 18.3 (11.0, NE) 5.4 (3.7, 5.7) 18.3 (10.9–NE) 5.4 (3.7–5.7) HR (95% CI) 0.30 (0.21, 0.43) 0.32 (0.23-0.45) PFS in gB
Slide 13: Overall summary of TEAE
Overall summary of TEAE in ISD population Niraparib Placebo (n=166) (n=83) N (%) N (%) Any TEAE 166 (100.0) 80 (96.4) Any Related TEAE 165 (99.4) 74 (89.2) Any CTCAE Grade ≥ 3 TEAE 81 (48.8) 17 (20.5) Any Related CTCAE Grade ≥ 3 TEAE 70 (42.2) 10 (12.0) Any Serious TEAE 27 (16.3) 10 (12.0) Any Relat
Slide 14: Grade 3/4 hematological TEAE
Grade 3/4 hematological TEAE in ISD population Niraparib Placebo (n=166) (n=83) N (%) N (%) Any grade Grade ≥3 Any grade Grade ≥3 White blood cell count decreaseda,c 99 (59.6) 12 (7.2) 36 (43.4) 2 (2.4) Neutrophil count decreasedb,c 97 (58.4) 34 (20.5) 36 (43.4) 7 (8.4) Platelet count decreasedd 89
Slide 15: Conclusions
Conclusions • This is the first RCT study to demonstrate the efficacy and safety of niraparib in Chinese patients with platinum-sensitive recurrent (PSR) ovarian cancer. • 94% (235/249) patients received niraparib 200 mg or matched placebo based on baseline body weight and platelet count. • Consiste
Slide 16: 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