Zai Lab Ltd. · HKEX:9688
Zai Lab — Technical Presentation (2020)
17 slides from Zai Lab's technical presentation, 2020
Slide 1: Niraparib versus Placebo as Maintenance Therapy in Extensive-stage SCLC
A Randomized Double-blind Phase III Study of Niraparib versus Placebo as Maintenance Therapy in Extensive-stage Small Cell Lung Cancer Xinghao Ai1, Yueyin Pan2, Jianhua Shi3, Nong Yang4, Chuanling Liu5, Jianying Zhou6, Xiaodong Zhang7, Xiaorong Dong8, Jianxing He9, Xiaoling Li10, Gongyan Chen11, Xin
Slide 2: Disclosure Information
DISCLOSURE INFORMATION Lead PI (Shun Lu) disclose the following conflict of interest: Received research support from AstraZeneca, Hutchison, BMS, Heng Rui, BeiGene and Roche Received speaker fees from AstraZeneca, Roche, Hansoh, Hengrui Therapeutics Being an advisor and consultant of AstraZeneca, Pf
Slide 3: Background
Background • Small cell lung cancer (SCLC) is characterized by early dissemination and rapid development of chemo- resistant disease after platinum response (60-80%)1,2. • The poly(ADP-ribose) polymerase-1 (PARP-1) is highly expressed in SCLC, and SCLC is initially sensitive to platinum-based chemot
Slide 4: Study Design
Study Design Niraparibb Randomization Key Eligibility Criteria (N=394) Treatment until • Patients with ES-SCLC Optional disease • CR or PR after 4 cycles of 1L EP PCI 2:1 progression or or EC unacceptable Placebo • ECOG PS 0 or 1 toxicity • No brain metastasis Patients will be stratified by • Gender
Slide 5: Study Conduct
Study Conduct 1. A futility analysis was planned to be performed after approximately 70 PFS events (30% of the total number of events assessed by BIRC) and iDMC recommended the study to continue. 2. Based on the positive results from the Phase III IMpower133 study of atezolizumab plus chemotherapy f
Slide 6: CONSORT Flow Diagram
CONSORT Flow Diagram 272 subjects screened First patient enrollment : Aug 27, 2018 Last patient enrollment : Feb 21, 2020 Data Cut-off : Mar 20, 2020 185 subjects enrolled Database Lock: May 28, 2020 125 subjects randomized to Niraparib 60 subjects randomized to Placebo 125 subjects dosed 60 subject
Slide 7: Demographics and Baseline Characteristics
Demographics and Baseline Characteristics Niraparib Placebo Total (N=125) (N=60) (N=185) Sex, n (%) Male 101 (80.8) 49 (81.7) 150 (81.1) Female 24 (19.2) 11 (18.3) 35 (18.9) Median age, years (range) 63.0 (33, 74) 62.0 (46, 72) 63.0 (33, 74) Age group (years), n (%) 18-64 71 (56.8) 36 (60.0) 107 (57
Slide 8: Primary Endpoint: PFS (BICR) in ITT Population
Primary Endpoint: PFS (BICR) in ITT Population 100 34% reduced risk of disease progression or death 90 in niraparib Niraparib Placebo Progression-free survival, % 80 Niraparib Placebo (N=125) (N=60) 70 Events, n(%) 91 (72.8) 47 (78.3) 60 Median PFS (95% CI), 1.54 1.36 50 months (1.41, 2.69) (1.31, 1
Slide 9: Primary Endpoint: OS in ITT Population
Primary Endpoint: OS in ITT Population 100 90 Niraparib Placebo (N=125) (N=60) 80 Overall survival, % 70 Events, n(%) 48 (38.4) 22 (36.7) 60 Median OS# (95% CI), 9.92 11.43 50 months (9.33, 13.54) (9.53, NE) 40 Stratified Log-rank 0.9052 p-value* 30 20 Niraparib Stratified HR (95% CI) 1.03 (0.62, 1.
Slide 10: Secondary Endpoint: PFS by Investigator
Secondary Endpoint: PFS by Investigator 100 90 Niraparib Niraparib Placebo Placebo (N=125) (N=60) 80 Progression-free survival, % 70 Events#, n(%) 105 (84.0) 44 (73.3) 60 Median PFS (95% CI), 1.48 1.41 50 months (1.41, 2.56) (1.31, 2.00) 40 Stratified Log-rank 0.4653 p-value* 30 20 Stratified HR (95
Slide 11: Subgroup Analysis: PFS (BICR) in ITT Population
Subgroup Analysis: PFS (BICR) in ITT Population Niraparib Placebo Subgroup Event/N Event/N HR and 95% CI Overall 91/125 47/60 0.66 (0.46, 0.95) Age Group 18-64 50/71 29/36 0.47 (0.29, 0.77) ≥65 41/54 18/24 1.13 (0.64, 2.01) Sex Group Male 75/101 38/49 0.70 (0.47, 1.04) Female 16/24 9/11 0.50 (0.21,
Slide 12: Subgroup Analysis: OS in ITT Population
Subgroup Analysis: OS in ITT Population Niraparib Placebo Subgroup Event/N Event/N HR and 95% CI Overall 48/125 22/60 1.03 (0.62, 1.73) Age Group 18-64 28/71 15/36 0.82 (0.42, 1.59) ≥65 20/54 7/24 1.28 (0.52, 3.14) Sex Group Male 39/101 18/49 0.93 (0.53, 1.64) Female 9/24 4/11 1.63 (0.48, 5.57) LDH
Slide 13: Summary of Adverse Events
Summary of Adverse Events Niraparib Placebo (n=125) (n=60) n (%) n (%) Any TEAE 125 (100.0) 57 (95.0) ≥Grade 3 43 (34.4) 15 (25.0) Any related TEAE 111 (88.8) 45 (75.0) ≥Grade 3 22 (17.6) 5 (8.3) Any serious TEAE 10 (8.0) 2 (3.3) Any related serious TEAE 5 (4.0) 2 (3.3) Any TEAE leading to dose inte
Slide 14: Summary of Adverse Events
Summary of Adverse Events Any grade TEAE，frequency ≥10% Niraparib (n=125) Placebo (n=60) N (%) N (%) Any grade Grade ≥3 Any grade Grade ≥3 Platelet count decreased 47 (37.6) 10 (8.0) 10 (16.7) 1 (1.7) Anemia 44 (35.2) 7 (5.6) 14 (23.3) 0 White blood cell count decreased 39 (31.2) 6 (4.8) 5 (8.3) 0 N
Slide 15: Conclusions
Conclusions • Niraparib demonstrated manageable and tolerable safety profile in patients with ES-SCLC. • Single-agent Niraparib was observed to have modest benefit in 1L ES-SCLC maintenance therapy: • PFS by BICR: HR 0.66 (95% CI: 0.46, 0.95). • OS: HR 1.03 (95% CI: 0.42, 1.73). (Data is immature) •
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 Shanghai Science and Technology Commission (18DZ1910700).
Slide 17: Bee e's'e
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