Slide 1: Gedatolisib Plus Fulvestrant, With & Without Palbociclib, vs Fulvestrant: First Results from VIKTORIA-1
Gedatolisib Plus Fulvestrant, With & Without Palbociclib, vs Fulvestrant in Patients With HR+/HER2-/PIK3CA Wild-Type Advanced Breast Cancer: First Results from VIKTORIA-1 Sara A. Hurvitz, Rachel M. Layman, Giuseppe Curigliano, Fabrice André, Massimo Cristofanilli, Sung-Bae Kim, Martin Richardet, Jor
Slide 2: Declaration of Interests Sara A. Hurvitz, MD, FACP
Declaration of Interests Sara A. Hurvitz, MD, FACP Advisory/Consulting (paid to institution): BeOne, BriaCell, BridgeBio Oncology Therapeutics, Bristol Myers Squibb, Daiichi Sankyo Inc, Genentech, a member of the Roche Group, Gilead Sciences Inc, Jazz Pharmaceuticals Inc, Luminate, Mersana Therapeut
Slide 3: Background
Background • The PI3K/AKT/mTOR (PAM) pathway drives breast cancer growth and contributes to endocrine and CDK4/6i resistance – Most available therapies are indicated only for patients with PI3K-pathway activation1,2 – There remains a need for safe and effective therapies for those with PIK3CA-WT dis
Slide 4: VIKTORIA-1 Study Design
VIKTORIA-1 Study Design HR+/HER2- Arm A† 180 mg IV once weekly, Advanced Breast Cancer Gedatolisib 3 weeks on, 1 week off Primary Endpoints 125 mg daily, Eligibility Criteria Palbociclib 21 days on, 7 days off PFS (BICR) 500 mg; cycle 1, days 1 & 15, then Arm A vs. Arm C • Pre- & postmenopausal wome
Slide 5: Statistical Considerations
Statistical Considerations • Co-primary endpoints (PFS by blinded independent central review [BICR]), tested hierarchically − One-sided overall alpha of 0.025 − PFS for Arm A vs. Arm C per BICR, with 98% power to detect HR ≤0.50 − PFS for Arm B vs. Arm C per BICR, with 75% power to detect HR ≤0.65 •
Slide 6: Patient Disposition
Patient Disposition Randomized (N=392) Gedatolisib + palbociclib + Gedatolisib + fulvestrant fulvestrant Fulvestrant (n=131) (n=130) (n=131) Received allocated treatment, n=130 Received allocated treatment, n=130 Received allocated treatment, n=123 Discontinued treatment, n=97 Discontinued treatment
Slide 7: Baseline Demographics and Disease Characteristics
Baseline Demographics and Disease Characteristics Gedatolisib + Palbo Gedatolisib + Gedatolisib + Palbo + Gedatolisib + Fulvestrant Fulvestrant Characteristic + Fulvestrant Fulvestrant Characteristic Fulvestrant Fulvestrant (n=131) (n=131) (n=131) (n=130) (n=131) (n=130) Age, yr, median (range) 57 (
Slide 8: 1st Co-Primary Endpoint: Progression-Free Survival
1st Co-Primary Endpoint: Progression-Free Survival Gedatolisib Triplet vs. Fulvestrant, BICR Assessment 100 Geda + Palbo + Fulvestrant Fulvestrant (n=131) 90 (n=131) 80 9.3 2.0 Median PFS, months (95% CI) (7.2-16.6) (1.8-2.3) Progression-free Survival (%) 70 Adjusted HR (95% CI) 0.24 (0.17-0.35); P
Slide 9: 2nd Co-Primary Endpoint: Progression-Free Survival
2nd Co-Primary Endpoint: Progression-Free Survival Gedatolisib Doublet vs. Fulvestrant, BICR Assessment 100 Gedatolisib + Fulvestrant Fulvestrant (n=130) (n=131) 90 7.4 2.0 80 Median PFS, months (95% CI) (5.5-9.9) (1.8-2.3) Progression-free Survival (%) 70 Adjusted HR (95% CI) 0.33 (0.24-0.48); P <
Slide 10: PFS in Key Subgroups: Gedatolisib Triplet vs. Fulvestrant
PFS in Key Subgroups: Gedatolisib Triplet vs. Fulvestrant Gedatolisib + Palbociclib + Fulvestrant Fulvestrant Subgroup n/N mPFS, mo. n/N mPFS, mo. Hazard Ratio (90% CI) Age <65 years 39/93 9.3 74/108 1.9 0.23 (0.17-0.35) ≥65 years 20/38 9.7 15/23 2.1 0.28 (0.16-0.55) Menopause status Pre/perimenopau
Slide 11: PFS in Key Subgroups: Gedatolisib Doublet vs. Fulvestrant
PFS in Key Subgroups: Gedatolisib Doublet vs. Fulvestrant Gedatolisib + Fulvestrant Fulvestrant Subgroup n/N mPFS, mo. n/N mPFS, mo. Hazard Ratio (90% CI) Age <65 years 52/96 5.6 74/108 1.9 0.31 (0.25-0.46) ≥65 years 17/34 7.7 15/23 2.1 0.53 (0.29-1.10) Menopause status Pre/perimenopause 19/37 5.6 2
Slide 12: PFS in Key Subgroups: Gedatolisib Triplet vs. Doublet
PFS in Key Subgroups: Gedatolisib Triplet vs. Doublet Gedatolisib + Palbociclib + Fulvestrant Gedatolisib + Fulvestrant Subgroup n/N mPFS, mo. n/N mPFS, mo. Age <65 years 39/93 9.3 52/96 5.6 ≥65 years 20/38 9.7 17/34 7.7 Menopause status Pre/perimenopause 9/28 11.1 19/37 5.6 Postmenopause 50/101 8.9
Slide 13: Key Secondary Endpoint: Overall Survival (Interim Analysis)
Key Secondary Endpoint: Overall Survival (Interim Analysis) Geda + Palbo Geda + + Fulvestrant Fulvestrant Fulvestrant Fulvestrant (n=131) (n=131) (n=130) (n=131) 23.7 18.5 NR 18.5 Median OS, months (95% CI) (21.4-NE) (15.8-NE) Median OS, months (95% CI) 100 100 (NE-NE) (15.8-NE) Adjusted HR (95% CI)
Slide 14: Sensitivity Analysis: Interim OS Censored at Cross-Over
Sensitivity Analysis: Interim OS Censored at Cross-Over Geda + Palbo Geda + + Fulvestrant Fulvestrant Fulvestrant Fulvestrant (n=131) (n=131) (n=130) (n=131) 23.7 15.8 NR 15.8 Median OS, months (95% CI) (21.4-NE) (11.7-NE) Median OS, months (95% CI) 100 (NE-NE) (11.7-NE) 100 Adjusted HR (95% CI) 0.6
Slide 15: Secondary Endpoint: Tumor Response (BICR Assessment)
Secondary Endpoint: Tumor Response (BICR Assessment) Patients With Evaluable Disease Duration of Response Geda + P a l b o + Fulv Geda + Palbo + Gedatolisib + (n=124) Fulvestrant Endpoint, n (%) Fulvestrant Fulvestrant 100 (n=105) Median DOR, months (95% CI) 17.5 (8.8-NE) Duration of Response (%) 90
Slide 16: Safety and Tolerability
Safety and Tolerability Treatment-Related Adverse Events (Safety Population)* SAE and Gedatolisib + palbociclib + fulvestrant Gedatolisib + fulvestrant Fulvestrant discontinuation, (n=130) (n=130) (n=123) n (%) Pts with ≥1 SAE 14 (10.8) 12 (9.2) 1 (0.8) Study treatment D/C 3 (2.3) 4 (3.1) 0 due to T
Slide 17: Conclusions
Conclusions • VIKTORIA-1 is the first study to demonstrate a statistically significant and clinically meaningful improvement in PFS with PAM inhibition in patients with PIK3CA-WT disease, all of whom received prior CDK4/6i − Gedatolisib triplet, mPFS 9.3 months (HR, 0.24; 95% CI, 0.17-0.35; P < 0.00
Slide 18: Acknowledgments
Acknowledgments • We thank the 392 clinical trial participants and their families/caregivers from the 147 sites in 23 countries for participating in this trial • We thank the VIKTORIA-1 investigators and their staff who participated in this work • We are grateful for the participation and insights o