Verastem, Inc. · NASDAQ:VSTM
Verastem — Technical Presentation (March 2025)
17 slides from Verastem's technical presentation, March 2025
Slide 1: Annual Meeting on Women's Cancer, Seattle 2025
MULTIPLY YOUR IMPACT ANNUAL MEETING ON WOMEN’S CANCER SEATTLE, WA - 2025
Slide 2: Single Arm Phase II Study of Avutometinib and Defactinib in Mesonephric/MLA Gynecologic Cancer: Interim Results
Single Arm Phase II Study of Avutometinib and Defactinib in Advanced or Recurrent Mesonephric or Mesonephric-like (MLA) Gynecologic Cancer: Interim Results Rachel N. Grisham, Aaron Praiss, Alexia Iasonos, Britta Weigelt, Pier Selenica, Angela Green, Robin Guo, Seth Cohen, Salvador Alonso, Maria Rubi
Slide 3: Financial Disclosure
Financial Disclosure for: [Insert Name] 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 I will be discussing unlabeled or investigational uses of pharmaceutical products or medical devices. Avutometinib and defactinib are not currently FDA approved for any indication
Slide 5: Mesonephric and Mesonephric-like Adenocarcinomas Can Arise From Multiple Gyn Sources
Mesonephric and Mesonephric-like Adenocarcinomas Can Arise From Multiple Gyn Sources Often GATA3 +, TTF1 +, ER-, PR- MA arises from Wolffian duct remnant within deep cervical walls (not HPV associated) MLA typically not associated with Wolffian remnant, thought to arise from trans-differentiat
Slide 6: Mesonephric and MLA Cancers Commonly Harbor Somatic KRAS mutations
Mesonephric and MLA Cancers Commonly Harbor Somatic KRAS mutations 96% of Patients Harbored MAP Kinase Pathway Alterations KRAS * (n = 20, 77%) NRAS * (n = 3, 11%) HRAS amplification (n = 1, 4%) NF1 truncating mutation (n = 1, 4%) *Hotspot missense mutation Praiss, White, Iasonos, Selenica, Zivanovi
Slide 7: Avutometinib and Defactinib
Avutometinib and Defactinib • Avutometinib is a first-in-class oral RAF/MEK clamp that potently inhibits MEK kinase activity, while also blocking the compensatory reactivation of MEK by upstream RAF1-4 • Defactinib is a selective inhibitor of FAK, a signaling target that has been shown to mediate re
Slide 8: RAMP 201 Study in LGSOC: Highest Response Rates in KRAS Mutation
RAMP 201 Phase 2 Study in Low Grade Serous Ovarian Cancer: Highest Response Rates Seen in Patients with KRAS Mutation 125 ORR by Blinded Independent Central Review Best Target Lesion Response Per IRC (% Change 75 82% of patients had a reduction in target lesions From Baseline) 25 * -25 * ** * ** * *
Slide 9: Study Schema
Study Schema Primary Endpoint: Confirmed Response Stage 1 Rate (complete or partial Stage 2 response), as determined Accrue 13 patients with by RECIST 1.1 response, measurable, advanced or Accrue an additional 7 in patients with advanced or recurrent mesonephric recurrent MC eligible patients or mes
Slide 10: Key Eligibility Criteria
Key Eligibility Criteria Inclusion Criteria Exclusion Criteria • Female patients ≥ 18 years of age • Systemic anti-cancer therapy (other than endocrine therapy) within 4 weeks, 1 cycle, or 5 half-lives • Histologic confirmation of Mesonephric or (whichever is shortest) of the first dose of study Mes
Slide 11: Interim Results For Stage I Patients: Baseline Characteristics
Interim Results For Stage I Patients: Baseline Characteristics Patient Characteristics (n=13) Median Age (range) 66 years (53-85) Site of Origin : Cervix 5 (38.5 %) Ovary 5 (38.5 %) Endometrium 3 (23 %) Median Prior Lines of Therapy 3 (0-7) (range) Prior Radiation 10 (77 %)
Slide 12: All Patients Had Reduction in Target Lesions
All Patients Had Reduction in Target Lesions Maximum Percent Reduction In Target Lesions 0 -10 = Cervix -20 = Endometrium -30 = Ovary = Confirmed Partial -40 Response = Remains on Treatment -50 Reasons For Discontinuation (n=12) RECIST POD 9 -60 Withdrawal of 1 Consent (travel logistics) -70 Clinica
Slide 13: Molecular Results and Clinical Features
Molecular Results and Clinical Features Figure Courtesy of Britta Weigelt and Pier Selenica
Slide 14: Interim Results: Adverse Laboratory Events Related to Treatment
Laboratory Toxicities Interim Results Grade 1 Grade 2 Grade 3 For Stage I Alkaline phosphatase 1 (8%) 0 1 (8%) elevation Patients: Adverse Anemia Aspartate 0 1 (8%) 0 0 0 0 Laboratory aminotransferase elevation Events Related to Bilirubin increased 6 (46%) 3 (23%) 1 (8%) Treatment CPK increased Lymp
Slide 15: Interim Results: Adverse Events Related to Treatment
Interim Results Grade 1 Grade 2 Grade 3 Rash Maculopapular 4 (31%) 1 (8%) 1 (8%) Diarrhea 8 (62%) 2 (15%) 1 (8%) For Stage I Edema limb Fatigue 7 (54%) 8 (63%) 3 (23%) 3 (23%) 1 (8%) 1 (8%) Patients: Adverse Pruritis GERD 5 (38%) 1 (8%) 2 (15%) 3 (23%) Events Related to Nausea Rash Acneiform 2 (15%)
Slide 16: Conclusions
Conclusions • Mesonephric and Mesonephric-like Gynecologic Cancers are rare cancers that commonly recur and frequently metastasize to the lung • Most cases (96%) will harbor a MAPK alteration, usually KRAS • Avutometinib in combination with defactinib has previously shown activity in patients with L
Slide 17: Thank You to our Patients and Their Supporters
Thank You to our Patients and Their Supporters Who Make This Research Possible This study was funded by Verastem Oncology