Avmapki (avutometinib) / Verastem, Roche - LARVOL DELTA

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: 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

Properties of FDA-approved small molecule protein kinase inhibitors: a 2026 update. (PubMed, Pharmacol Res) - "The following ten drugs received FDA approval in 2025 - avutometinib (inhibiting MEK1/2 in serous ovarian carcinomas), defactinib (blocking FAK in low grade serous ovarian carcinomas), delgocitinib (antagonizing the JAK family in hand eczema), mirdametinib (inhibiting MEK1/2 in type I neurofibromatosis), remibrutinib (blocking BTK in chronic spontaneous urticaria), rilzabrutinib (antagonizing BTK in chronic immune thrombocytopenia), sunvozertinib (blocking mutant exon 21 insertion EGFR NSCLC), taletrectinib (inhibiting mutant ROS1 in NSCLC), vimseltinib (blocking CSF1R in tenosynovial giant cell tumors), and zongertinib (antagonizing mutant HER2 in NSCLC). This article summarizes the physicochemical properties of all 94 FDA-approved small molecule protein kinase inhibitors including the molecular weight, number of hydrogen bond donors/acceptors, ligand efficiency, lipophilic efficiency, polar surface area, and solubility. A total of 45 of the 94 FDA-approved drugs have a..."

FDA event • Journal • Review • Atopic Dermatitis • Chronic Spontaneous Urticaria • Contact Dermatitis • Dermatology • Genetic Disorders • Giant Cell Tumor of Bone • Hematological Disorders • Immune Thrombocytopenic Purpura • Immunology • Lung Cancer • Neurofibromatosis • Non Small Cell Lung Cancer • Oncology • Ovarian Cancer • Ovarian Serous Adenocarcinoma • Solid Tumor • Tenosynovial Giant Cell Tumor • Thrombocytopenia • Thrombocytopenic Purpura • Urticaria • CSF1R • EGFR • HER-2 • ROS1

Financial Update (Businesswire) - "Based on preliminary, unaudited results, Verastem expects AVMAPKI FAKZYNJA CO-PACK net product revenues of approximately $17.5 million for the fourth quarter of 2025 and approximately $30.9 million for the full year 2025. Full year 2025 net product revenue reflects the launch period of May, following U.S. Food and Drug Administration (FDA) approval, through December 2025."

Sales • Low Grade Serous Ovarian Cancer

Verastem expects to Report an update on the safety and efficacy of the RAMP 205 expansion cohort with at least six months of follow-up on all patients in Q2 2026 (Businesswire)

P1/2 data • Pancreatic Ductal Adenocarcinoma

2026 Priorities:…AVMAPKI FAKZYNJA CO-PACK (avutometinib; defactinib) (Businesswire) - "Verastem expects to: (i) Maximize adoption of AVMAPKI FAKZYNJA CO-PACK in the U.S. as the treatment of choice at the earliest recurrence, leveraging its robust clinical data; (ii) Report a topline readout of the primary endpoint in the RAMP 301 trial in mid-2027; (iii) Continue to pursue regulatory paths for potential expansion of the product launch into Europe and Japan."

Commercial • Launch • P3 data: top line • Low Grade Serous Ovarian Cancer

…Updated data from the ongoing RAMP201J Phase 2 clinical trial in Japan evaluating the combination in patients with LGSOC with or without a KRAS mutation (Businesswire) - "As of the data cutoff on January 30, 2026, 16 patients were efficacy evaluable by investigator assessment, having at least one post-baseline assessment with a median follow-up of 10 months. Of the 16 total patients, a confirmed overall response rate (ORR) of 38% (6/16) was achieved. Among patients with KRAS-mutated recurrent LGSOC, the confirmed ORR was 57% (4/7) and the disease control rate (DCR) was 100% (7/7). Among patients with KRAS wild-type recurrent LGSOC, the confirmed ORR was 22% (2/9) and the DCR was 89% (8/9). Of the 16 patients enrolled, 11 patients remain on treatment."

P2 data • Low Grade Serous Ovarian Cancer

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

DDU RAF/MEK: Phase I Trial of VS-6766 Alone and in Combination With Everolimus (clinicaltrials.gov) - P1 | N=104 | Completed | Sponsor: Royal Marsden NHS Foundation Trust | Active, not recruiting ➔ Completed | Trial completion date: Jun 2025 ➔ Oct 2025 | Trial primary completion date: Jun 2025 ➔ Oct 2025

Trial completion • Trial completion date • Trial primary completion date • Hematological Malignancies • Lung Cancer • Multiple Myeloma • Oncology • Ovarian Cancer • Ovarian Serous Adenocarcinoma • Solid Tumor • BRAF • KRAS • NRAS

Recent FDA-approved kinase inhibitors for cancer therapy in 2025: A comprehensive review and perspectives. (PubMed, EXCLI J) - "The present review paper aims to provide a summary and a critical synthesis of the development, therapeutic potential, and clinical performance of novel of kinase inhibitors in oncology (i.e. zongeritinib, sunvozertinib, vimseltinib, mirdametinib, avutometinib and defactinib), authorized by the US Food and Drug Administration (FDA) in 2025, aiming to highlight both their transformative role and their inherent limitations. See also the graphical abstract(Fig. 1)."

FDA event • Journal • Review • Hematological Disorders • Hematological Malignancies • Lung Cancer • Non Small Cell Lung Cancer • Oncology • 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

Long lasting response to the combination of Avutometinib and Defactinib after progression on Binimetinib in a patient with recurrent low grade serous ovarian carcinoma - A case report. (PubMed, Gynecol Oncol Rep) - "The oral drug combination was well tolerated with no dose-limiting toxicity or need for dose reduction over the 4 year period. The Avutometinib and Defactinib combination may represent a new standard treatment option for platinum-resistant and AI-resistant/recurrent LGSOC who have failed other MEKi."

Journal • Platinum resistant • Oncology • Ovarian Cancer • Ovarian Serous Adenocarcinoma • Solid Tumor • KRAS • MUC16

A Study of Avutometinib (VS-6766) and Defactinib in People With Mesonephric Gynecologic Cancer (clinicaltrials.gov) - P2 | N=40 | Recruiting | Sponsor: Memorial Sloan Kettering Cancer Center | Trial completion date: Mar 2026 ➔ Mar 2027 | Trial primary completion date: Mar 2026 ➔ Mar 2027

Trial completion date • Trial primary completion date • Gynecologic Cancers • Oncology

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

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

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

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

Exposure-Response Analysis for Avutometinib in Combination with Defactinib in Low-Grade Serous Ovarian Cancer (SGO 2026) - No abstract available

Combination therapy • Oncology • Ovarian Cancer • Ovarian Serous Adenocarcinoma • Solid Tumor

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

RAMP 203: Phase 1/2 Study of Avutometinib (VS-6766) + Sotorasib With or Without Defactinib in KRAS G12C NSCLC Patients (clinicaltrials.gov) - P1/2 | N=153 | Active, not recruiting | Sponsor: Verastem, Inc. | Recruiting ➔ Active, not recruiting | Trial primary completion date: Sep 2025 ➔ Jun 2026

Enrollment closed • Trial primary completion date • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • KRAS