Avmapki (avutometinib) / Verastem, Roche - LARVOL DELTA

Verastem Oncology Announces Late-Breaking Oral Presentation of RAMP 201 Low-Grade Serous Ovarian Cancer Molecular Profiling and Tumor Biomarker Analysis at IGCS 2026 Annual Global Meeting (Businesswire) - "Additionally, previously reported results from the Phase 2 RAMP 201J study in Japanese patients with recurrent low-grade serous ovarian cancer has also been selected as a seminal oral presentation."

Late-breaking abstract • P2 data • Low Grade Serous Ovarian Cancer

Avutometinib plus defactinib (AvDf) with or without gemcitabine and nab-Paclitaxel (GnP) in previously treated patients with pancreatic ductal adenocarcinoma (PDAC) harboring KRAS mutations (ESMO 2026) - No abstract available

Clinical • Oncology • Pancreatic Ductal Adenocarcinoma • KRAS

Ligand-based pharmacophore modeling and molecular dynamics driven discovery of novel MEK1 inhibitors targeting KRAS signalling pathway. (PubMed, J Mol Graph Model) - "Molecular Docking studies identified three top ranked compounds, PubChem-125589749 (Rank 1), PubChem-122594448 (Rank 2) and PubChem-49842405 (Rank 3), with score -76.91, -75.54 and -75.3184 kcal/mol, respectively, whereas Avutometinib showed a score of -61.78 kcal/mol...Further extended MD simulations for 200 ns and MM-GBSA calculations confirmed the binding stability and binding energy over a longer time. The reproducibility of the MD simulations was assessed by performing an independent MD simulation of the complexes and analysing the results."

Journal • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Pancreatic Cancer • Solid Tumor • KRAS • MAP2K1 • MAPK1

Avutometinib, Abemaciclib, and Fulvestrant in Patients with HR+/HER2- Metastatic Breast Cancer Previously Treated with CDK4/6 Inhibitor: A Single-Arm Phase I Trial. (PubMed, Clin Cancer Res) - "The regimen was well tolerated at the RP2D, with no new safety signals, and showed preliminary clinical activity. A phase II trial is ongoing."

Journal • P1 data • Breast Cancer • Dermatology • Fibrosarcoma • Hematological Disorders • HER2 Breast Cancer • HER2 Negative Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Neutropenia • Oncology • Sarcoma • Solid Tumor • CDK4 • ER • HER-2

Panc 004: Neoadjuvant Avutometinib/Defactinib and mFOLFIRINOX Combination Therapy in Pancreatic Adenocarcinoma (clinicaltrials.gov) - P1/2 | N=31 | Not yet recruiting | Sponsor: University of Virginia

New P1/2 trial • Oncology • Pancreatic Adenocarcinoma • Pancreatic Cancer • Solid Tumor

RAMP 202: A phase 2 study of avutometinib (VS-6766) ± defactinib, in patients with advanced KRAS G12V mutant non–small cell lung cancer (NSCLC). (ASCO 2023) - P2 | "Patients received up to 5 lines of prior systemic therapy (median 2), including prior platinum-based chemotherapy, ICIs, and bevacizumab. In this heavily pretreated population of patients with KRAS G12V mt NSCLC, limited clinical activity was observed with combination therapy. While no new safety signals were identified, criteria to proceed to part B were not met, and further evaluation of avutometinib ± defactinib in KRAS G12V mt NSCLC will not be pursued. Additional trials evaluating rational avutometinib combinations (sotorasib, adagrasib, everolimus) are ongoing in patients with KRAS mt NSCLC."

Clinical • IO biomarker • Metastases • P2 data • Anemia • Hematological Disorders • Immune Modulation • Lung Adenocarcinoma • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • KRAS

Efficacy and Safety of Avutometinib ± Defactinib in Recurrent Low-Grade Serous Ovarian Cancer: Primary Analysis of ENGOT-OV60/GOG-3052/RAMP 201. (PubMed, J Clin Oncol) - P3 | "The efficacy and safety profile of avutometinib in combination with defactinib support this combination as a potential standard of care for recurrent LGSOC. A randomized phase 3 study of avutometinib and defactinib versus investigator's choice of therapy for women with recurrent LGSOC is currently enrolling (RAMP301; ClinicalTrials.gov identifier: NCT06072781)."

Journal • Fibrosarcoma • Hematological Disorders • Oncology • Ovarian Cancer • Ovarian Serous Adenocarcinoma • Sarcoma • Solid Tumor • KRAS

Avutometinib/defactinib and gemcitabine/nab-paclitaxel combination in first-line metastatic pancreatic ductal adenocarcinoma: Initial safety and efficacy of phase 1b/2 study (RAMP 205). (ASCO 2024) - P1/2 | "Avuto/defact and GnP are combinable and show notable preliminary efficacy in first-line metastatic PDAC based on RECIST v.1.1 criteria and CA19-9 levels. No DLTs were reported across the 4 dosing cohorts/schedules and safety signals were consistent with previous clinical data. Updated safety and efficacy will be reported."

Clinical • Metastases • P1/2 data • Alopecia • Anemia • Cardiovascular • Fatigue • Febrile Neutropenia • Gastrointestinal Cancer • Hematological Disorders • Hepatology • Immunology • Infectious Disease • Neutropenia • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • Pulmonary Embolism • Respiratory Diseases • Septic Shock • CA 19-9 • KRAS

Avutometinib/defactinib and gemcitabine/nab-paclitaxel combination in first-line metastatic pancreatic ductal adenocarcinoma: Updated safety and efficacy of a phase 1b/2 study (RAMP 205). (ASCO 2025) - P1/2 | "A/D + GnP have been combined in 5 dose cohorts. The MTD has not been reached. Enrollment and evaluation of mature data are ongoing to identify the recommended phase 2 dose."

Clinical • Metastases • P1/2 data • Alopecia • Anemia • Dermatitis • Dermatology • Fatigue • Febrile Neutropenia • Hematological Disorders • Hepatology • Immunology • Neutropenia • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • Thrombocytopenia • KRAS

A single-arm phase 1 trial of avutometinib (RAF/MEK inhibitor), abemaciclib (abema), and fulvestrant in CDK4/6 inhibitor (CDK4/6i)-pretreated patients (pts) with HR+ metastatic breast cancer (MBC) (AACR 2025) - "Pts had median age 61 yrs, 31% had visceral disease, all had received prior endocrine therapy for MBC (median 2 lines, range 1-5), all had received prior CDK4/6i (69% palbociclib, 19% ribociclib, 19% abema), 69% had spent >12 mos on a prior CDK4/6i for MBC, 44% received prior fulvestrant, 63% received any prior selective estrogen receptor degrader, and 25% received prior chemo for MBC. The combination of avutometinib, abema, and fulvestrant showed a manageable safety profile and preliminary efficacy in HR+/HER2- MBC resistant to CDK4/6i. A single-arm phase 2 trial is ongoing to further evaluate the clinical efficacy in this population."

Clinical • Metastases • P1 data • Breast Cancer • Oncology • Solid Tumor • CDK4 • ER • HER-2

Late-Breaking Abstract: EFFICACY AND SAFETY OF AVUTOMETINIB ± DEFACTINIB IN RECURRENT LOW GRADE SEROUS OVARIAN CANCER: PRIMARY ANALYSIS OF ENGOT-OV60/GOG-3052/RAMP 201 (IGCS 2024) - "Prior therapies included endocrine (86%), bevacizumab (51%), and MEK inhibitor (22%). Conclusion/Implications A+D was well tolerated allowing prolonged exposure to therapy. ORR and durable responses observed are clinically meaningful in this heavily pretreated population and support the potential of A+D as a new standard of care for recurrent LGSOC."

Clinical • Late-breaking abstract • Oncology • Ovarian Cancer • Ovarian Serous Adenocarcinoma • Solid Tumor • KRAS

Phase I trial of the RAF/MEK clamp VS-6766 in combination with everolimus using an intermittent schedule with expansion in NSCLC across multiple KRAS variants. (ASCO 2022) - P1 | "A tolerable intermittent dosing schedule targeting both the MAPK and PI3K pathways has been established. The combination of VS-6766 with everolimus has shown activity in patients with a variety of KRAS mutation variants including responses in KRAS mt NSCLC."

Combination therapy • P1 data • Dermatology • Endocrine Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Ovarian Cancer • Ovarian Serous Adenocarcinoma • Pruritus • Solid Tumor • Thyroid Gland Carcinoma • KRAS • NRAS

EFFICACY OF AVUTOMETINIB AND DEFACTINIB VS CONVENTIONAL CARE IN LOW-GRADE SEROUS OVARIAN CANCER: AN EXTERNAL CONTROL ARM ANALYSIS (IGCS 2026) - " Data from RAMP 201 (avutometinib 3.2 mg BIW and defactinib 200 mg BID) and GOG 281 (physician's choice CC: letrozole, tamoxifen, paclitaxel, pegylated liposomal doxorubicin, or topotecan) were included. 115 patients from RAMP 201 and 130 from GOG 281 CC were included. KRAS mutation status was captured for all patients in RAMP 201 and in 49% in GOG 281. Effective sample size after propensity score weighting was 64.5 for avutometinib + defactinib and 53.6 f or SOC."

Clinical • Oncology • Ovarian Cancer • Ovarian Serous Adenocarcinoma • Solid Tumor • KRAS

Long-Term Efficacy and Safety of Avutometinib + Defactinib in Patients with Recurrent Low-Grade Serous Ovarian Cancer: Results from ENGOT-OV60/GOG-3052/RAMP 201 (SGO 2026) - No abstract available

Clinical • Oncology • Ovarian Cancer • Ovarian Serous Adenocarcinoma • Solid Tumor

Initial Efficacy And Safety Results From ENGOT-Ov60/GOG-3052/RAMP 201: A Phase 2 Study Of Avutometinib (VS-6766) ± Defactinib In Recurrent Low-Grade Serous Ovarian Cancer (LGSOC) (ESGO 2023) - P2 | "Most treatment-related adverse events (AEs) for combo (n=81) were grade 1-2, with a low proportion of dose reductions (17%) and discontinuations due to AEs (12.3%) in the combo arm.Conclusion Interim data support avutometinib + defactinib as an active go-forward regimen in heavily-pretreated recurrent LGSOC, regardless of KRAS status. No new safety signals were observed; most AEs were mild to moderate."

Clinical • P2 data • Oncology • Ovarian Cancer • Ovarian Serous Adenocarcinoma • Solid Tumor • KRAS

Long-term efficacy and safety of avutometinib + defactinib in recurrent low-grade serous ovarian cancer: Results of a 2-year follow-up of ENGOT-OV60/GOG-3052/RAMP 201. (PubMed, Gynecol Oncol) - "With a median follow-up of approximately 2 years (about twice the duration of the primary analysis), the combination of avutometinib and defactinib demonstrated durable efficacy in patients with recurrent LGSOC and no new safety signals."

Journal • Hematological Disorders • Oncology • Ovarian Cancer • Ovarian Serous Adenocarcinoma • Solid Tumor • KRAS

Initial efficacy and safety results from ENGOT-ov60/GOG-3052/RAMP 201: A phase 2 study of avutometinib (VS-6766) ± defactinib in recurrent low-grade serous ovarian cancer (LGSOC). (ASCO 2023) - P2 | "The interim data support avutometinib + defactinib as an active go-forward regimen in heavily-pretreated recurrent LGSOC, regardless of KRAS status. No new safety signals were observed, and most AEs were mild to moderate. Enrollment continues in Part B for the combination of avutometinib and defactinib."

Clinical • P2 data • Dermatitis • Dermatology • Fatigue • Immunology • Oncology • Ovarian Cancer • Ovarian Serous Adenocarcinoma • Solid Tumor • KRAS

GOG-3097/ENGOT-ov81/GTG-UK/RAMP 301: a phase 3, randomized trial evaluating avutometinib plus defactinib compared with investigator's choice of treatment in patients with recurrent low grade serous ovarian cancer. (PubMed, Int J Gynecol Cancer) - P3 | "The estimated primary completion date of RAMP 301 is 2028, and the estimated study completion date is 2031. ClinicalTrials.gov NCT06072781."

Journal • P3 data • Oncology • Ovarian Cancer • Ovarian Serous Adenocarcinoma • Solid Tumor • KRAS

A PHASE II STUDY OF AVUTOMETINIB AND DEFACTINIB IN ADVANCED OR RECURRENT GYNECOLOGIC MESONEPHRIC CANCER: INTERIM RESULTS (SGO 2025) - No abstract available

Metastases • P2 data • Oncology

Defactinib with avutometinib in patients with solid tumors: the phase 1 FRAME trial. (PubMed, Nat Med) - P1 | "This study demonstrates the importance of intermittent dosing schedules in combined targeting of the mitogen-activated protein kinase and focal adhesion kinase pathways to improve tolerability, and has acquired proof of concept of anti-tumor activity against low-grade serous ovarian cancer, a tumor relatively resistant to chemotherapy. ClinicalTrials.gov identifier NCT03875820 ."

Journal • P1 data • Oncology • Ovarian Cancer • Ovarian Serous Adenocarcinoma • Solid Tumor

Avutometinib plus defactinib in recurrent low-grade serous ovarian cancer: A subgroup analysis of ENGOT-OV60/GOG-3052/RAMP 201 Part A (SGO 2024) - P1, P2 | "In RAMP 201 Part A, avutometinib + defactinib achieved high response rates in heavily pretreated recurrent LGSOC, regardless of previous line of therapy. Notably, tumor regression was observed in the majority of patients, including those with stable disease or progressive disease with last line of therapy including previous MEKi."

Late-breaking abstract • Oncology • Ovarian Cancer • Ovarian Serous Adenocarcinoma • Solid Tumor • ARAF • BRAF

ROBOTIC-ASSISTED MODIFIED LATERAL EXTENDED ENDOPELVIC RESECTION (IGCS 2026) - "The minimally invasive approach achieved oncologic resection with minimal morbidity and rapid recovery. The patient is currently enrolled in a phase II trial of avutometinib and defactinib, highlighting the importance of integrating surgical and systemic strategies in rare, aggressive histologies."

Gynecologic Cancers • Oncology

Progress with FAK inhibitors in the patent literature (2020-present). (PubMed, Expert Opin Ther Pat) - "Consequently, the recent U.S. FDA approval of the FAK inhibitor defactinib combined with avutometinib for recurrent KRAS-mutant low‑grade serous ovarian cancer (LGSOC) validates FAK as a clinically actionable anticancer target. The clinical success of defactinib-based combination therapy validates the therapeutic potential of FAK targeting, while emerging approaches offer opportunities to overcome resistance. Future progress will depend on biomarker-guided patient selection, rational combination regimens, and exploration of non-catalytic FAK functions to achieve more effective and durable therapies."

Journal • Review • Oncology • Ovarian Cancer • Ovarian Serous Adenocarcinoma • Solid Tumor • Targeted Protein Degradation • KRAS

Phase 2 trial of defactinib in combination with avutometinib in patients with advanced diffuse-type gastric cancer. (ASCO-GI 2025) - P2 | " This investigator-initiated, multicenter phase 2 trial will enroll 27 patients with metastatic/unresectable gastric or gastroesophageal junction carcinoma classified as diffuse, poorly cohesive, signet ring cell, or mixed type with progression on at least one line of therapy including platinum/fluorouracil chemotherapy. The trial was opened for enrollment in August 2024. Clinical trial information: NCT06487221."

Clinical • Combination therapy • Metastases • P2 data • Esophageal Cancer • Gastric Cancer • Gastroesophageal Junction Adenocarcinoma • Gastrointestinal Cancer • Oncology • Solid Tumor • CDH1 • HER-2 • RHOA

RAF/MEK Clamp Inhibition with Avutometinib and Cetuximab in RAF1 S257L-Mutated, Anti-EGFR-Refractory Metastatic Colorectal Cancer in Gaucher's disease. (PubMed, Oncologist) - "After progression on fluoropyrimidine-, oxaliplatin-, and irinotecan-based regimens (the latter with the anti-EGFR antibody panitumumab) complicated by recurrent neutropenic sepsis, he received off-label avutometinib and defactinib (an oral RAF/MEK clamp inhibitor plus a FAK inhibitor) combined with cetuximab. At progression, circulating tumor DNA revealed persistence of RAF1 S257L at high allele fraction with RAF1 amplification, together with newly acquired EGFR ectodomain mutations, KRAS alterations, and a MAP2K1 alteration-a polyclonal pattern of convergent MAPK/EGFR reactivation. This case illustrates how a molecular tumor board can translate a rare driver into a rational, individualized regimen, and how serial liquid biopsy informs resistance and next steps."

Journal • Colorectal Cancer • Gaucher Disease • Genetic Disorders • Hematological Disorders • Infectious Disease • Metabolic Disorders • Oncology • Septic Shock • Solid Tumor • Type 1 Gaucher Disease • KRAS • MAP2K1