Slide 1: Zipalertinib Plus Chemotherapy for 1st Line NSCLC With EGFR Exon 20 Insertions: REZILIENT 3
Zipalertinib Plus Chemotherapy for 1st Line NSCLC With EGFR Exon 20 Insertions: Results From the Phase 3 Trial (REZILIENT 3) Dr. Daniel SW Tan, P. Danchaivijitr, Y. Shinno, C. Ho, J. Zugazagoitia, T. Inoue, G-W. Lee, A.J. de Langen, A. Sezer, A. Pender, C. Dooms, F. Cappuzzo, Y. Fujiwara, Y. Runglod
Slide 2: Disclosures
Disclosures • Consultant: Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, DKSH, GlaxoSmithKline, Merck, Novartis, Pfizer, Roche, Beigene, Zymeworks, Genmab, Astellas, and Takeda • Grant/Research support: ACM Biolabs, Amgen, AstraZeneca, and Pfizer • Advisor/Stock options: PRISM.AI and T-Knife Thera
Slide 3: Background
Background • NSCLC with EGFR exon 20 insertions (ex20ins) comprise 5–10% of EGFR mutations and represents a heterogeneous molecular subgroup with variable responses to EGFR-directed therapies1 • Amivantamab (1L in combination with platinum-based chemotherapy) and sunvozertinib have shown improved PF
Slide 4: REZILIENT 3: 1L Zipalertinib + Chemotherapy vs Chemotherapy
REZILIENT 3: 1L Zipalertinib + Chemotherapy vs Chemotherapy REZILIENT :Researching Zipalertinib in EGFRmt Non–Small Cell Lung Cancer Tumors Eligibility criteria: Safety Lead-in Randomized Phase 3 Study (NCT05973773) (N=6) (N=280) Primary: • 1L metastatic NSCLC • PFS by BICR • Local testing of Zipale
Slide 5: Baseline Characteristics
REZILIENT 3: Baseline Characteristics Zipalertinib + Chemotherapy Chemotherapy Characteristics (n=140) (n=139) Median Age (min–max) 66.5 (30–89) 64.0 (27–82) Female, n (%) 92 (65.7) 88 (63.3) Never Smoker 83 (59.3) 85 (61.2) Region per IVRS, n (%) Asia 56 (40.0) 56 (40.3) Rest of world 84 (60.0) 83
Slide 6: Primary Endpoint PFS by BICR
REZILIENT 3: Primary Endpoint PFS by BICR Total Failed Censored Median 95% CI 100 Zipalertinib + Chemotherapy: 140 50 90 14.5 months (12.9, 21.4) 90 Chemotherapy: 139 72 67 8.5 months (7.0, 10.9) 80 Hazard Ratio: 0.50 (95% CI 0.34, 0.73) P=0.00015 70 Probability of PFS 60 50 40 30 20 Censor Z+C (64.
Slide 7: BICR PFS by Subgroups
REZILIENT 3: BICR PFS by Subgroups Zipalertinib + Chemotherapy Chemotherapy Subgroup Event n/N (%) Event n/N (%) Hazard Ratio HR (95% CI) Baseline ECOG PS 0 18/58 (31.0) 24/56 (42.9) 0.56 (0.30, 1.04) 1 32/82 (39.0) 48/83 (57.8) 0.54 (0.34, 0.85) Brain Metastases Yes 21/44 (47.7) 30/44 (68.2) 0.38 (
Slide 8: Tumor Response by BICR
REZILIENT 3: Tumor Response by BICR Zipalertinib + Chemotherapy Chemotherapy Response (RECIST v1.1) (n=140) (n=139) Best Overall Response, n (%) Complete response 9 (6.4) 3 (2.2) Partial response 82 (58.6) 53 (38.1) Stable disease 29 (20.7) 55 (39.6) Progressive disease 4 (2.9) 12 (8.6) Objective Re
Slide 9: Overall Survival
REZILIENT 3: Overall Survival Total Failed Censored Median 95% CI Zipalertinib + chemotherapy: 140 24 116 NE (NE, NE) 100 Chemotherapy: 139 31 108 NE (18.4, NE) Hazard Ratio: 0.72 (95% CI, 0.42–1.23) P=0.11082 90 Overall survival probability (%) 80 70 60 50 40 30 • 64.2 % crossover to zipalertiniba
Slide 10: Safety Summary
REZILIENT 3: Safety Summary Zipalertinib + Chemotherapy Chemotherapy (n=140), n (%) (n=136), n (%) Treatment-Related Adverse Events 138 (98.6) 120 (88.2) Grade ≥3 treatment-related adverse events 113 (80.7) 55 (40.4) Serious Adverse Events 71 (50.7) 45 (33.1) Treatment-related serious adverse events
Slide 11: Summary of Adverse Events
REZILIENT 3: Summary of Adverse Events Zipalertinib + Chemotherapy Chemotherapy (n=140) (n=136) Adverse Event in ≥25%a, % Any Grade Grade ≥3 Any Grade Grade ≥3 Anemiaa 80.7 48.6 50.0 12.5 Neutropeniab 50.7 33.6 40.4 22.1 Thrombocytopeniac 56.4 30.0 19.9 8.1 Rash 45.7 10.7 6.6 0 Nausea 44.3 3.6 41.9
Slide 12: Cytopenias Observed With Combination
REZILIENT 3: Cytopenias Observed With Combination All-Treated Population for Zipalertinib + Chemotherapy arm 100 70 First 4 Cycles Grade 4 60 Percentage of patients Grade 3 Grade 2 50 Grade 1 40 After 4 Cycles 30 Grade 4 Grade 3 20 Platinum Grade 2 Grade 1 10 0 First 4 Cycles (n=140) After 4 Cycles
Slide 13: Conclusions
Conclusions • REZILIENT-3 met its primary endpoint, with Zipalertinib and chemotherapy demonstrating statistically significant improvement in PFS compared to chemotherapy alone • 6-month improvement in median PFS (14.5 months vs 8.5 months, HR of 0.5, P=0.00015) • Increased ORR (65% vs 40.3%, P<0.00
Slide 14: Acknowledgments
Acknowledgments • Trial participants, their families, and caregivers • Investigators, team members and site staff (represents 122 sites across 24 countries in Asia, North America, South America, and Europe) • Steering committee 14
Slide 15: Thank You
wclc.iasIc.org CO@OOO #WCLC26 Thank Youe Science Without Boundaries: Uniting the World Against Thoracic Cancer