Slide 1: Efficacy of zipalertinib in NSCLC patients with EGFR exon 20 insertion mutations
Efficacy of zipalertinib in NSCLC patients with EGFR exon 20 insertion mutations who received prior platinum-based chemotherapy with or without amivantamab Helena Alexandra Yu,1 Danny Nguyen,2 Gerrina Ruiter,3 Victor Ho-Fun Lee,4 Ross A. Soo,5 Se Hyun Kim,6 Daniel Shao-Weng Tan,7 Se-Hoon Lee,8 Haruk
Slide 2: Disclosure
2 Disclosure • Consulting or Advisory Role: AbbVie, Amgen, AstraZeneca, Bayer, Black Diamond Therapeutics, BMS, Daiichi Sankyo, Pfizer, Orion, Janssen, Merck, Taiho, Takeda • Research Funding: AstraZeneca (Inst), Cullinan Therapeutics, Inc. (Inst), Daiichi Sankyo (Inst), Janssen (Inst), SystImmune (
Slide 3: Key Takeaways
3 Key Takeaways 1 2 3 Zipalertinib demonstrated Zipalertinib demonstrated a These findings support clinically meaningful manageable safety profile in zipalertinib as a potential efficacy in patients with this patient population, treatment option for patients EGFR ex20ins-mutant consistent with previ
Slide 4: Background
4 Background Unmet need Zipalertinib: a novel EGFR TKI Zipalertinib (CLN-081, TAS6417) is a Despite the approval of amivantamab for novel EGFR TKI that showed promising EGFR ex20ins-mutant NSCLC,1 an clinical activity and manageable safety in unmet need remains for well-tolerated a phase 1/2a study
Slide 5: REZILIENT1 Phase 2b study design
5 REZILIENT1 Phase 2b study design • REZILIENT1 is a phase 1/2, open-label, multicenter trial (NCT04036682) Primary endpoint: Key eligibility criteria • ORR and DOR as assessed by blinded ICR per RECIST v1.1 • Age ≥18 years Prior platinum-based chemotherapy without prior • Locally advanced or ex20in
Slide 6: Baseline demographic and disease characteristics
Baseline demographic and disease characteristics Platinum-based chemotherapy without Prior ex20ins-targeted ex20ins-targeted therapy therapy Safety population Characteristic (n=143) (n=101) (N=244) Age, y, median (range) 66 (36–86) 62 (31–85) 65 (31–86) Aged <65 y / ≥65 y, No. (%) 61 (43) / 82 (57)
Slide 7: Prior therapies
7 Prior therapies Platinum-based chemotherapy without ex20ins-targeted therapy Prior ex20ins-targeted therapy Safety population Characteristic (n=143) (n=101) (N=244) Median number of prior systemic 1 (0–6) 2 (1–7) 2 (0–7) regimens, No. (range) Prior chemotherapy, No. (%) 132 (92) 96 (95) 228 (93) P
Slide 8: Efficacy per ICR in all patients and subgroups
Efficacy per ICR in all patients and subgroups Median follow-up: 9.3 months Platinum-based Primary efficacy chemotherapy without Prior amivantamab ± other population ex20ins-targeted therapy ex20ins-target therapy Outcome (N=176) (n=125) (n=51)a BOR, No. (%)b CR 1 (1) 0 1 (2) PR 61 (35) 50 (40) 11 (
Slide 9: Efficacy per ICR in patients with prior amivantamab
Efficacy per ICR in patients with prior amivantamab ± other ex20ins-target therapy Prior amivantamab without Prior amivantamab and other ex20ins-targeted other ex20ins-targeted therapy therapy Total Outcome (n=30) (n=21) (n=51) BOR, No. (%)a CR 1 (3) 0 1 (2) PR 8 (27) 3 (14) 11 (22) Unconfirmed PRb
Slide 10: Efficacy per ICR in all patients and those with brain metastases
Efficacy per ICR in all patients and those with brain metastases Primary efficacy Patients with brain population metastasesa Outcome (N=176) (n=68) BOR, No. (%)b CR 1 (1) 1 (2) PR 61 (35) 20 (29) Unconfirmed PRc 7 (4) 2 (3) SD 88 (50) 37 (54) PD 11 (6) 5 (7) Not evaluabled 8 (5) 3 (4) Confirmed ORR,
Slide 11: Best change from baseline in target lesions (%)
11 Best change from baseline in target lesions 120 Platinum-based chemotherapy without ex20ins-targeted therapy (n=125) 100 Best change from baseline in target lesions (%) Platinum-based chemotherapy with amivantamab ± other ex20ins-target therapy (n=51) 80 60 40 20 0 –20 –40 –60 ORR, % (95% CI) Pri
Slide 12: Progression-free survival (%)
12 Progression-free survival per ICR 100 Kaplan-Meier estimates of progression-free survival 90 Platinum-based Prior amivantamab ± Primary efficacy chemotherapy without other ex20ins-target Progression-free survival (%) 68.0% 80 population ex20ins-targeted therapy 63.8% (N=176) therapy (n=125) (n=51
Slide 13: Overall survival (%)
13 Overall survival 6-month OS rate 100 85.8% 12-month OS rate Primary efficacy population (N=176) 84.1% 90 73.4% Platinum-based chemotherapy without 79.9% ex20ins-targeted therapy (n=125) 69.3% 80 Prior amivantamab ± other 59.8% Overall survival (%) ex20ins-target therapy (n=51) 70 60 59.1% 50 54.2
Slide 14: Summary of adverse events
14 Summary of adverse events Safety population • Median duration of treatment exposure was 6.4 months (range, 0.03–51.8) AE, No. (%) (N=244) • Median relative dose intensity was 94.1% TEAEs • TRAEs leading to treatment discontinuation Any TEAE 242 (99.2) was 8% Grade ≥3 TEAE 137 (56.1) • TRAEs that
Slide 15: Most common treatment-related adverse events
Most common treatment-related adverse events Any-grade TRAEs reported in Any grade Grade 3 • ≥10% of patients, No. (%) Anemia was the most common grade 3 TRAE Paronychia 94 (38.5) 0 • Other grade ≥3 TRAEs reported in Rash 74 (30.3) 6 (2.5) ≥5 patients included pneumonitis and rash (6 patients [2.5%]
Slide 16: Conclusions
16 Conclusions Efficacy Safety Summary Zipalertinib demonstrated Zipalertinib demonstrated a These findings support clinically meaningful efficacy manageable safety profile in zipalertinib as a potential in patients with EGFR this patient population, treatment option for patients with ex20ins-mutant
Slide 17: Acknowledgments
17 Acknowledgments • Patients and their families/caregivers • Investigators, nurses, and staff at all sites • The study was funded by Cullinan Therapeutics, Inc and Taiho Oncology, Inc The study has been simultaneously published in JCO with this presentation. “Zipalertinib in Patients With EGFR Exon