Slide 1: Primary Results of the Phase 3 Peak Study of Bezuclastinib + Sunitinib vs Sunitinib in GIST
Primary Results of the Phase 3 Peak Study of Bezuclastinib + Sunitinib vs Sunitinib Monotherapy in Advanced Gastrointestinal Stromal Tumors (GIST) Andrew J. Wagner1, Jonathan C. Trent2, William D. Tap3, Robin L. Jones4, Sebastian Bauer5, Margaret von Mehren6, Michael C. Heinrich7, Min-Hee Ryu8, Bree
Slide 2: Key Takeaways and Conclusions
Key Takeaways and Conclusions 2 Current Unmet Need: Treatment of KIT-mutant GIST in 2L+ with TKI monotherapies is challenging because each only inhibits a subset of clonal resistance mutations. Combining approved KIT inhibitors has been limited by risk of overlapping toxicities. Combination of Bezuc
Slide 3: GIST Treatment Resistance is Due to Heterogeneous Secondary KIT Mutations
3 GIST Treatment Resistance is Due to Heterogeneous Secondary KIT Mutations GIST is driven by Extracellular activating KIT mutations, Heterogeneity of secondary typically exons 9 and 11, mutations makes treatment in up to 85% of patients1-5 of imatinib-resistant GIST challenging, as each ATP-binding
Slide 4: GIST Treatment Resistance is Due to Heterogeneous Secondary KIT Mutations
4 GIST Treatment Resistance is Due to Heterogeneous Secondary KIT Mutations GIST is driven by Extracellular activating KIT mutations, Heterogeneity of secondary typically exons 9 and 11, mutations makes treatment in up to 85% of patients1-5 of imatinib-resistant GIST challenging, as each ATP-binding
Slide 5: Combination of Bezuclastinib + Sunitinib Inhibits Broad Spectrum of KIT Mutations
Combination of Bezuclastinib + Sunitinib Inhibits the Broad Spectrum of Primary and Secondary KIT Mutations Bezuclastinib: Next-generation oral KIT inhibitor Bezuclastinib Regorafenib + Sunitinib Ripretinib Sunitinib Imatinib • Highly active against resistance mutations in KIT exons 17 Exon and 181-
Slide 6: Peak Is a Global, Randomized, Open-label, Phase 3 Study
6 Peak Is a Global, Randomized, Open-label, Phase 3 Study Evaluating the efficacy and safety of bezuclastinib + sunitinib vs sunitinib as 2L treatment (NCT05208047) Bezuclastinib 600 mg QD + Sunitinib 37.5 mg QD (n = 204) Patients 1:1 Randomized Sunitinib 37.5 mg QD Crossover allowed following BICR-
Slide 7: Peak Part 2 Population Is Representative of Patients With Imatinib-treated GIST
7 Peak Part 2 Population Is Representative of Patients With Imatinib-treated GIST Bezuclastinib Baseline Bezuclastinib Patient Demographics Sunitinib Overall Sunitinib Overall + Sunitinib Characteristics + Sunitinib Patients, n 204 209 413 KIT mutations per molecular pathology report, n (%) Male, n
Slide 8: Extended PFS With 50% Reduction in Risk of Progression or Death
8 Bezuclastinib + Sunitinib Extended PFS With 50% Reduction in Risk of Progression or Death 100% Median PFS 90% Bezuclastinib 16.5 months + Sunitinib 95% CI (13.8 to 19.2) Progression-Free Survival (%) 80% 9.2 months 70% Sunitinib 95% CI (7.2 to 11.0) 60% Hazard Ratio = 0.50 50% 95% CI (0.39 to 0.65
Slide 9: PFS Benefit vs Sunitinib Across Subgroups and Baseline Mutation Profiles
Bezuclastinib + Sunitinib Demonstrated PFS Benefit vs 9 Sunitinib Monotherapy Across Subgroups and Baseline Mutation Profiles Bezuclastinib + Subgroup Sunitinib Hazard Ratio (95% CI) Median, mos Sunitinib Patients with primary outcomes, n/N (%) Bezu + Sun vs Sun Bezu + Sun Sun <65 69/113 (61.1) 82/1
Slide 10: Combination Significantly Improved ORR vs Sunitinib Monotherapy
10 Bezuclastinib + Sunitinib Combination Significantly Improved ORR vs Sunitinib Monotherapy Bezuclastinib + Bezuclastinib + Sunitinib Sunitinib Objective Response Sunitinib Additional End Points Sunitinib (n=204) (n=209) (n=209) (n=204) 45.6 (38.6- 52.7) 25.8 (20.0- 32.3) Disease control rate,%b (9
Slide 11: PFS2 Results Support the Durability of Response to Combination
11 PFS2 Results Support the Durability of Response to Combination vs Sunitinib Monotherapy Progression-Free Survival 2 (%) Median PFS2 100 Bezuclastinib Not yet reached + Sunitinib Sunitinib 21.0 months Hazard Ratio = 0.57 50 • PFS2 = time from Sunitinib Bezuclastinib + Sunitinib randomization to pr
Slide 12: Bezuclastinib + Sunitinib Is Generally Well-Tolerated With a Favorable Safety Profile
12 Bezuclastinib + Sunitinib Is Generally Well-Tolerated With a Favorable Safety Profile Bezuclastinib + Sunitinib Sunitinib (n=208)a (n=204) • The incidence of TEAEs and TRAEs was TEAEs, n (%) 204 (100) 207 (99.5) similar between treatment arms TRAEs, n (%) 202 (99.0) 204 (98.1) Gr3+ TRAEs, n (%) 1
Slide 13: All Grade TEAEs ≥ 20% Demonstrate Balance Between Arms
All Grade TEAEs ≥ 20% Demonstrate Balance Between 13 Arms All grade TEAEs ≥ 20% in either treatment arm Bezuclastinib + Sunitinib (n=204) Sunitinib (n=208)a • TEAEs reported at a higher frequency Preferred term, n (%) All Grade Grade 3+ All Grade Grade 3+ (>15%) in combination arm: ALT/AST Diarrhea
Slide 14: Incidence of Grade 3+ TEAEs (≥2%) Balanced Across Arms
14 Incidence of Grade 3+ TEAEs (≥2%) Balanced Across Arms Hypertension 29.4 27.4 • Majority of the Gr 3+ TEAEs were reported Neutropenia* 15.2 15.4 at a similar rate between combination and ALT/AST increased* 10.8 1.4 monotherapy arms; ALT/AST increase and anemia reported at higher incidence in the
Slide 15: Conclusions
15 Conclusions The Peak study represents the first time a combination of inhibitors targeting the same kinase in KIT-mutant GIST has delivered a significant efficacy benefit, balanced with a manageable safety profile. Bezuclastinib + sunitinib demonstrated No new safety risks were identified with th
Slide 16: Acknowledgements
16 Acknowledgements • The authors would like to thank the patients who participated in the study and those who support them, including family, caregivers, and patient advocates. • The authors would also like to acknowledge the additional investigators and study site staff. PRESENTED BY: Andrew J. Wa