Verastem, Inc. · NASDAQ:VSTM
Verastem — Technical Presentation (March 2025)
18 slides from Verastem's technical presentation, Mar 17, 2025
Slide 1: Multiply Your Impact: SGO Annual Meeting on Women's Cancer 2025
MULTIPLY YOUR IMPACT ANNUAL MEETING ON WOMEN’S CANCER SEATTLE, WA - 2025
Slide 2: Avutometinib + Defactinib in Recurrent Low-Grade Serous Ovarian Cancer: Dose Intensity and Subgroup Analysis
Avutometinib + Defactinib in Recurrent Low-Grade Serous Ovarian Cancer (ENGOT-ov60/GOG-3052/RAMP 201): Dose Intensity and Subgroup Analysis Rachel N. Grisham, Els Van Nieuwenhuysen, Carol Aghajanian, Veronique D’Hondt, Bradley J. Monk, Andrew R. Clamp, Emily N. Prendergast, Ana Oaknin, Kari L. Ring,
Slide 3: Financial Disclosure for Rachel N. Grisham
Financial Disclosure for: Rachel N. Grisham I have the following financial relationships with ACCME defined ineligible companies to report over the past 24 months: • AZ (ended), GSK (ended), Verastem (ended), Cardinal Health (ended), Genmab (ended), Incyte (ended), Incyclix (ended)
Slide 4: Unlabeled/Investigational Uses
Unlabeled/Investigational Uses Avutometinib and defactinib are investigational drugs and have not been approved for use by the FDA or any other regulatory health authority. Safety and efficacy have not been established. This presentation includes data from a phase 2 trial (ENGOT-ov60/GOG-3052/RAMP 2
Slide 5: 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 6: 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 7: ENGOT-ov60/GOG-3052/RAMP 201: Registration-Directed Phase 2 Trial Design
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 Avutometinib + Defactinib Avutometinib + Defact
Slide 8: Baseline Characteristics
Baseline Characteristics Avutometinib 3.2 mg BIW and Defactinib 200 mg BID All patients KRAS mt KRAS wt Baseline characteristic (N=115) (n=58) (n=57) Age, median (min, max), y 54 (21, 87) 60 (29, 87) 45 (21, 80) ECOG PS, n (%) 0 78 (68) 42 (72) 36 (63) 1 37 (32) 16 (28) 21 (37) Number of prior syste
Slide 9: Patient Disposition
Patient Disposition Avutometinib 3.2 mg BIW and Defactinib 200 mg BID Median follow-up was 13.6 months (range, 1.4-39.5) All patients treated KRAS mt treated KRAS wt treated (N=115) (n=58) (n=57) Discontinued treatment Discontinued treatment Discontinued treatment (n=83; 72%) (n=34; 59%) (n=49; 86%)
Slide 10: Best Percentage Change From Baseline in Target Lesions
Best Percentage Change From Baseline in Target Lesions Avutometinib 3.2 mg BIW and Defactinib 200 mg BID 82% of patients had a reduction in target lesions aAccording to RECIST v1.1 as assessed by BICR. bIncludes unconfirmed partial response; stable disease (or unconfirmed partial response) must occu
Slide 11: Duration of Response
Duration of Response: Avutometinib 3.2 mg BIW and Defactinib 200 mg BID Avutometinib and defactinib dosing was 3 weeks on and 1 week off. DOR as assessed by the BICR was calculated for patients with a complete response or partial response from the time of first response to progressive disease using
Slide 12: Progression-Free Survival
Progression-Free Survival Avutometinib 3.2 mg BIW and Defactinib 200 mg BID Avutometinib and defactinib dosing was 3 weeks on and 1 week off. BID, twice daily; BIW, twice weekly; CI, confidence interval; KRAS, Kirsten rat sarcoma virus; mo, months; mt, mutant; No, number; PFS, progression-free survi
Slide 13: Confirmed ORR in Subgroups by Prior Therapies and KRAS Status
Confirmed ORR in Subgroups by Prior Therapies and KRAS Status Avutometinib 3.2 mg BIW and Defactinib 200 mg BID 80 Prior MEKi Prior Bevacizumab Prior Lines of Therapy 70 60 53% 47% 49% Confirmed ORR, % 50 40 33% 36% 30% 30 25% 21% 20 15% 18% 13% 13% 10 0 Yes No Yes No Yes No Yes No >3 1–3 >3 1–3 (n=
Slide 14: Adverse Event Profile
Adverse Event Profile Treatment-Related AEs (>20% of patients)a, n (%) All patients (N=115) Avutometinib 3.2 mg BIW and Defactinib 200 mg BID Preferred term All grades Grade ≥3 Non-laboratory AEs Mean relative dose intensity: Nausea 77 (67) 3 (3) 0.84 for avutometinib and 0.77 for defactinib Diarrhe
Slide 15: Adverse Events of Interest
Adverse Events of Interest Avutometinib 3.2 mg BIW and Defactinib 200 mg BID Ocular AEs – Blurred Vision Skin and Subcutaneous Tissue AEs • Treatment-related skin reactions included • Blurred vision was the most common rash (50%), dermatitis acneiform (34%), and treatment-related ocular event (41% o
Slide 16: Low Starting Dose of Avutometinib
Low Starting Dose of Avutometinib Avutometinib 1.6 mg BIW and Defactinib 200 mg BID Parts A, B, and C Part D BICR Assessment, Avutometinib 3.2 mg BIW Avutometinib 1.6 mg BIW Efficacy n (%) and Defactinib 200 mg BID and Defactinib 200 mg BID • Low-dose regimen was suboptimala (N=109) (N=23) based on
Slide 17: Summary and Conclusions
Summary and Conclusions • In women with recurrent LGSOC with few available treatment options, the combination of avutometinib 3.2 mg BIW and defactinib 200 mg BID resulted in clinically meaningful ORR, DOR, and PFS • Confirmeda ORR: 31% overall; 44% in KRAS mt and 17% in KRAS wt • Median DOR: 31 mon
Slide 18: Acknowledgments: Patients, Trial Teams and 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