Verastem, Inc. · NASDAQ:VSTM
Verastem — IGCS 2024 Annual Global Meeting
15 slides from Verastem's conference presentation, Oct 17, 2024
Slide 1: Efficacy and Safety of Avutometinib ± Defactinib in Recurrent LGSOC: Primary Analysis of RAMP 201
Efficacy and Safety of Avutometinib ± Defactinib in Recurrent Low-Grade Serous Ovarian Cancer: Primary Analysis of ENGOT-OV60/GOG-3052/RAMP 201 Susana N. Banerjee, Carol Aghajanian, Els Van Nieuwenhuysen, Alessandro D. Santin, Kari L. Ring, Nicoletta Colombo, Premal H. Thaker, Emily N. Prendergast,
Slide 2: Disclosure
Disclosure No, nothing to disclose x Yes, please specify: Honoraria/ Consulting/ Funded Royalties/ Ownership/ Other Company Name Stock Options Employee Expenses Advisory Board Research Patent Equity Position (please specify) AbbVie, AstraZeneca, BioNTech, Eisai, Gilead, GlaxoSmithKline, Immunogen, I
Slide 3: New Treatment Options Are Needed for Patients With LGSOC
New Treatment Options Are Needed for Patients With LGSOC • LGSOC is a rare, histopathologically, molecularly, and clinically distinct cancer accounting for <10% of new epithelial ovarian cancers1,2 • LGSOC is commonly driven by alterations in the RAS/MAPK pathway, including KRAS mutations, which occ
Slide 4: Avutometinib and Defactinib Mechanism of Action
Avutometinib and Defactinib Mechanism of Action • Avutometinib is a first-in-class oral RAF/MEK clamp that potently inhibits MEK while also blocking the compensatory reactivation of MEK by upstream RAF1,2 • Defactinib is a selective inhibitor of FAK, a key adaptive resistance mechanism to the RAS/MA
Slide 5: ENGOT-ov60/GOG-3052/RAMP 201: Registration-Directed Phase Trial
ENGOT-ov60/GOG-3052/RAMP 201: Registration-Directed Phase 2 Trial of Avutometinib ± Defactinib in Patients With Recurrent LGSOC Part A Part B Part C Part D Selection Phase Expansion Phase Expansion Phase Combination Lower Dose in Combination Go Forward Regimen Avutometinib + Defactinib Avutometinib
Slide 6: Baseline Characteristics: Parts A, B, and C
Baseline Characteristics: Parts A, B, and C Avutometinib + Defactinib Avutometinib Monotherapy 3.2 mg BIW + 200 mg BID 4.0 mg BIW 3 weeks on/1 week off 3 weeks on/1 week off All patients KRAS mt KRAS wt All patients KRAS mt KRAS wt N=115 N=58 N=57 N=70 N=31 N=39 Age, median (min, max), y 54 (21, 87)
Slide 7: Patient Disposition: Parts A, B, and C
Patient Disposition: Parts A, B, and C • Median follow-up in the combination group = 13.6 months (range, 1.4–39.5) • In the combination group, mean relative dose intensity of 0.84 for avutometinib and 0.77 for defactinib Avutometinib + Defactinib Avutometinib Monotherapy 3.2 mg BIW + 200 mg BID 4.0
Slide 8: Response Rate and Duration of Response: Parts A, B, and C
Response Rate and Duration of Response: Parts A, B, and C In the avutometinib + defactinib combination group • RECIST 1.1 Objective Response Rate by BICR (primary endpoint): • Median time to response: 3.7 months (range, 1.7 – 19.2) • 31% overall; 44% KRAS mt, 17% KRAS wt • Median duration of respons
Slide 9: Best Target Lesion Response Per IRC (% Change From Baseline)
125 Best Percentage Change From Baseline in Target Lesions Avutometinib + Defactinib: Parts A, B, and C Best Target Lesion Response Per IRC (% Change From Baseline) 75 ORR by Blinded Independent Central Review Total KRAS mt KRAS wt N=109 N=57 N=52 82% of patients had a reduction in target lesions 31
Slide 10: Progression-Free Survival: Avutometinib + Defactinib: Parts A, B, and C
Progression-Free Survival: Avutometinib + Defactinib: Parts A, B, and C PFS, median (95% CI) Total KRAS mt KRAS wt N=109 N=57 N=52 12.9 mo 22.0 mo 12.8 mo (10.9, 20.2) (11.1, 36.6) (7.4, 18.4) 10 KRAS, kirsten rat sarcoma virus; mt, mutant; PFS, progression-free survival; wt, wild type.
Slide 11: Adverse Events Profile for Avutometinib + Defactinib: Parts A, B, and C
Adverse Events Profile for Avutometinib + Defactinib: Parts A, B, and C Treatment-Related Adverse Events Avutometinib + Defactinib 3.2 mg BIW + 200 mg BID (>20% of patients)* 3 weeks on/1 week off n (%) N= 115 Preferred term All Grades Grade ≥3 • 80% (92/115) of patients had AEs leading to dose inte
Slide 12: Adverse Events Profile: Events of Interest Associated With MEK Inhibitors
Adverse Events Profile for Avutometinib + Defactinib: Parts A, B, and C Adverse events of interest that have been associated with MEK inhibitors Avutometinib + Defactinib 3.2 mg BIW + 200 mg BID Treatment-Related Adverse Events, n (%)* 3 weeks on/1 week off N=115 Preferred term All Grades Grade ≥3 O
Slide 13: Low-Dose Avutometinib Evaluation: Part D
Low-Dose Avutometinib Evaluation: Part D ➢ The low-dose regimen of avutometinib (1.6 mg BIW) + defactinib (200 mg BID) evaluated in Part D was determined to be suboptimal based on the predefined analysis • Suboptimal threshold: disease progression by second scheduled assessment (Cycle 5 Day 1) >50%
Slide 14: Summary and Conclusions
Summary and Conclusions • In women with recurrent LGSOC with few available treatment options, the combination of avutometinib 3.2 mg BIW + defactinib 200 mg BID resulted in clinically meaningful responses, duration of response, and progression-free survival • ORR: 31% overall; 44% in KRAS mt and 17%
Slide 15: We thank the patients and their families, the trial teams at the participating centers
We thank the patients and their families, the trial teams at the participating centers, ENGOT, and GOG for supporting this study United Kingdom (GTG-UK) Spain (GEICO) United States (GOG, continued) Royal Marsden NHS Foundation Trust (Susana Banerjee) Hospital Clínico Universitario de Valencia Sansum