Verastem, Inc. · NASDAQ:VSTM
Verastem — ESMO Gynaecological Cancers Congress 2025
17 slides from Verastem's conference presentation, Jun 19, 2025
Slide 1: Blood ctDNA vs Tumor Tissue Screening for Detection of KRAS Mutations in LGSOC
BLOOD ctDNA VS TUMOR TISSUE SCREENING FOR THE DETECTION OF KRAS MUTATIONS IN LOW-GRADE SEROUS OVARIAN CANCER ENGOT-OV60/GOG-3052/RAMP 201 Els Van Nieuwenhuysen, MD1; Rachel N. Grisham, MD2,3; Isabelle Ray-Coquard, MD, PhD4,5; Charles K. Anderson, MD6; Andrew Clamp, BMBCh, MSc Oncology, MRCP, PhD7; C
Slide 2: Declaration of Interests
DECLARATION OF INTERESTS Els Van Nieuwenhuysen, MD Financial Interests Non-Financial Interests • AstraZeneca, Advisory Board, Institutional • Eli Lilly, Product Samples • GSK, Expert Testimony, Institutional • MSD, Expert Testimony, Institutional Other • Oncoinvent, Advisory Board, Institutional • G
Slide 3: Low Grade Serous Ovarian Cancer (LGSOC)
Low Grade Serous Ovarian Cancer (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 occur in approximate
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: Responses Observed in both KRAS Mutant and KRAS Wild-Type Recurrent LGSOC
Responses Observed in both KRAS Mutant and KRAS Wild-Type Recurrent LGSOC with Avutometinib 3.2 mg BIW + Defactinib 200 mg BID ORR by Blinded Independent Central Review Study ENGOT-OV60/GOG-3052/RAMP 201 Total KRAS mt KRAS wt Avutometinib With or Without Defactinib N=109 N=57 N=52 Go-forward regimen
Slide 6: Background and Objective
Background and Objective • Molecular profiling is becoming standard practice for patients with ovarian cancer – US guidelines, including ASCO, NCCN and SGO, recommend germline/somatic tumor testing for all patients with ovarian cancer – In Europe, there is no standardized guidance for germline/somat
Slide 7: Circulating Tumor DNA (ctDNA)
Circulating Tumor DNA (ctDNA) • Tumor cells release/shed ctDNA into the bloodstream by apoptosis, necrosis and secretion • ctDNA can be differentiated based on shorter length relative to cell-free DNA (cfDNA), which comes from normal cells • ctDNA tumor fraction measures the % of ctDNA relative to t
Slide 8: Methods
Methods Patients from Sample type Assay Analysis ENGOT-OV60/GOG- 3052/RAMP 201 • 65 selected based on KRAS • KRAS status in tumor samples status in tumor samples Archival tumor tissue sample (range, 0 to 17 years old; Local testing – KRAS mutant (50 patients) – 40 patients enrolled in median, 2 year
Slide 9: 32% of Patients With LGSOC Have Detectable ctDNA in Blood Samples
32% (21/65) of Patients With LGSOC Have Detectable ctDNA in Blood Samples Collected at Study Entry "! • Out of 65 patients with LGSOC included in the analysis D()G+,(-.L0,N0OD(PL4 C! % – 21 patients (32%) showed ctDNA tumor fraction above the limit of detection of 0.25% (ranging from A 5S7 0.4% to 1
Slide 10: No Correlation Seen Between Tumor Burden at Baseline and ctDNA Tumor Fraction
No Correlation Seen Between Tumor Burden at Baseline and ctDNA Tumor Fraction ?4@AB.4*+I-.C-3?4TI2.8a> A>> #! /0*+/N-2P.-*4DDR*6T89: A>> /0*+/N-2P.-*4DDR*6T89 "( BCD()*+C)I-. %CD()*+C)I-. D #>> #>> C ">> B ">> # > ! > ;/0P-.0N*<P0=*>0?@A ;/0P-.0N*<P0=*>0?@A ! "!! #!! A!! 0CD()*B)/>0P(.*C>a#bc 0CD()*
Slide 11: Similar ctDNA Tumor Fraction Between Patients With Different KRAS Mutation Variants
Similar ctDNA Tumor Fraction Between Patients With Different KRAS Mutation Variants Detected in Tumor Samples ()*+,-)K/0N-2NP()40R-S78 T8AVW%8X<=>%?>@T8A=D%CB) "! #+ &D "Q % 6 A N # R " # ! + ") ) ) +) ) ) Q) 9P)4:R);-<4)= 9P)4:R);-<4)= (# (- (- (" (# (# (" CD CD %CD %CD >?,@-/K)P)40R; >?,@-<4BaE)cA
Slide 12: 44% (22/50) Concordance Between KRAS Detection in Tumor vs Blood Samples
In Patients With KRAS Mutations Detectable in Tumor Samples, 44% (22/50) Concordance Between KRAS Detection in Tumor vs Blood Samples 22 patients with • 44% (22/50) concordance between tumor vs KRAS mutations blood samples 50 patients with detected in blood – For these 22, the same KRAS variant was
Slide 13: No Correlation Between KRAS VAF in Tumor and KRAS VAF in Blood
In Patients With KRAS Mutations Detectable in Tumor Samples, No Correlation Between KRAS VAF in Tumor and KRAS VAF in Blood &!! &!! 12+=;SS>+8VR:;<8 12+P4RS7+8VR:;<8 %! %! '(F*+,F-+K/0 '(F*+,F-+K/0 A! &! % #! A # "! " ! ! ! "! #! A! %! &!! '(F*+R4PV2P '(F*+?1;>@PA:< '(F*+,F-+K/0 12+=;SS> 12+=;SS> 12
Slide 14: Correlation Between ctDNA Tumor Fraction and KRAS VAF in Blood
In Patients With KRAS Mutations Detectable in Tumor Samples, Correlation Between ctDNA Tumor Fraction and KRAS VAF in Blood D()*+,(-K/0,N02D(P/4,RS7 "! &! 34,=>//?,@2KA>B@ !"#$%& 8V+:,;+<,RS7 &! % % A A # # " " ! ! ! " # A % 89+:,K-(24( 89+:,>P<=?(@AB P4,;<//= P4,;<//= D(F*+,(-K/0,N02D(3/4,RS7 6 pat
Slide 15: Conclusions
Conclusions • In the ENGOT-OV60/GOG-3052/RAMP 201 study, only 32% (21/65) of patients with LGSOC exhibited a ctDNA tumor fraction above the limit of detection, suggesting that LGSOC is a low shedding tumor • In patients with KRAS mutations detectable in tumor samples (N=50/65), – 44% (22/50) concord
Slide 16: Acknowledgments
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
Slide 17: European Society for Medical Oncology (ESMO)
European Society for Medical Oncology (ESMO) Via Ginevra 4, CH-6900 Lugano T. +41 (0)91 973 19 00 esmo@esmo.org esmo.org