Avutometinib

GFH375 demonstrated an overall response rate (ORR) of 68.8% in non-small cell lung cancer (NSCLC) at the recommended Phase 2 dose of 600 mg QD GFH375 demonstrated an ORR of 57.7% in efficacy evaluable patients with NSCLC across all dose levels Mini oral presentation on Sunday, September 7, 2025 from 12:00 to 1:15 pm (CEST) BOSTON, MA, USA I August 13, 2025 I Verastem Oncology (Nasdaq: VSTM), a biopharmaceutical company committed to advancing new medicines for patients with RAS/MAPK-pathway-driven cancers, today announced positive, updated safety and efficacy data and late-breaking presentation details of partner GenFleet Therapeutics’ Phase 1/2 study in China of GFH375, an oral KRAS G12D (ON/OFF) inhibitor, known as VS-7375 outside of China, in advanced non-small cell lung cancer patients with a KRAS G12D mutation. The data will be presented in a mini oral presentation at the IASLC 2025 World Conference on Lung Cancer (WCLC) hosted by the International Association for the Study of Lung Cancer from September 6-9, in Barcelona, Spain. “These data at WCLC build on the encouraging data presented at ASCO earlier this year, where GenFleet initially reported an ORR of 42% in 12 patients with advanced non-small cell lung cancer harboring a KRAS G12D mutation,” said Dan Paterson, president and chief executive officer of Verastem Oncology. “The significant increase in patients with advanced lung cancer demonstrating a response, 68.8% ORR at the recommended Phase 2 dose, and 57.7% ORR across all dose levels, is impressive and continues to support the development and potential of VS-7375 in advanced lung cancer and across other advanced KRAS G12D solid tumors.” The late-breaking abstract was issued today by the WCLC. GenFleet reported cumulative safety data across the entire study population and preliminary efficacy data specific to patients with advanced NSCLC from the Phase 1/2 study in China. As of the data cutoff of July 15, 2025, the median follow-up time was 4.5 (range: 1.8-12.2) months. Tumor response was observed across the dose range tested. The study population includes 142 patients, including 28 with advanced NSCLC, 85 with advanced pancreatic ductal adenocarcinoma (PDAC) and 29 with other solid tumors. Amongst the patients with NSCLC, all had metastatic disease at baseline, 64.3% had received at least two prior lines of systemic therapies, and 96.4% had received an anti-PD1/PD-L1 therapy. At the recommended Phase 2 dose of 600 mg once daily (QD), the ORR was 68.8% (11/16) (both confirmed and unconfirmed) and the disease control rate (DCR) was 93.8% (15/16). Among the 26 evaluable patients with NSCLC treated across all dose levels, the ORR was 57.7% (15/26) (both confirmed and unconfirmed) and the DCR was 88.5% (23/26). Across all cancer types and dose levels evaluated, the most common treatment-related adverse events (TRAEs) occurring in at least 20% of patients were diarrhea, vomiting, nausea, anemia, decreased appetite, neutrophil count decreased, white blood cell count decreased, aspartate aminotransferase increased, asthenia, hypoalbuminemia, and alanine aminotransferase increased, predominately Grade 1 or 2 in severity. TRAEs and severe adverse events (SAEs), greater than Grade 3, occurred in 27.5% (39/142) and 7.7% (11/142) of patients, respectively. Of the 142 patients in the safety population, 11 patients had dose reduction, and six discontinued due to TRAEs. No TRAE-related deaths were reported. WCLC Details About KRAS G12D KRAS G12D represents 26% of all KRAS mutations, making it the most prevalent KRAS mutation in human cancers. The KRAS G12D mutation occurs most commonly in pancreatic (37%), colorectal (12.5%), endometrial (8%), and non-small cell lung (5%) cancers. Currently, no therapies are approved by the U.S. Food and Drug Administration (FDA) specifically targeting KRAS G12D mutations in cancer. About VS-7375, an Oral KRAS G12D (ON/OFF) Inhibitor VS-7375 is a potential best-in-class, potent, and selective oral KRAS G12D dual ON/OFF inhibitor. VS-7375 is the lead program from the Verastem Oncology discovery and development collaboration with GenFleet Therapeutics. Verastem announced in April 2025 that the U.S. Investigational New Drug (IND) application for VS-7375 was cleared and initiated a Phase 1/2a clinical trial in June 2025. GenFleet’s IND for VS-7375 (known as GFH375 in China) was approved in China in June 2024, and the first patient was dosed in a Phase 1/2 study in July 2024. About the GenFleet Therapeutics Collaboration The collaboration with GenFleet Therapeutics aims to advance three oncology discovery programs related to RAS/MAPK pathway-driven cancers. The collaboration provides Verastem with an exclusive option to obtain a license for each of the three compounds in the collaboration after the successful completion of pre-determined milestones in a Phase 1 trial. Verastem selected VS-7375 (also known as GFH375), an oral KRAS G12D (ON/OFF) inhibitor, as its lead program in December 2023 and the license for VS-7375 that was exercised in January 2025 is the first one from this collaboration. These licenses give Verastem development and commercialization rights outside the GenFleet markets of mainland China, Hong Kong, Macau, and Taiwan. About Verastem Oncology Verastem Oncology (Nasdaq: VSTM) is a biopharmaceutical company committed to developing and commercializing new medicines to improve the lives of patients diagnosed with RAS/MAPK pathway-driven cancers. Verastem markets AVMAPKI™ FAKZYNJA™ CO-PACK in the U.S. Our pipeline is focused on novel small molecule drugs that inhibit critical signaling pathways in cancer that promote cancer cell survival and tumor growth, including RAF/MEK inhibition, FAK inhibition, and KRAS G12D inhibition. For more information, please visit www.verastem.com and follow us on LinkedIn . SOURCE: Verastem Oncology

HOW TO USE THIS SNAPSHOT The information provided in Snapshots highlights who participated in the key clinical trials that supported the original FDA approval of this drug, and whether there were differences among sex, race, age, and ethnic groups. The “MORE INFO” bar shows more detailed, technical content for each section. The Snapshot is intended as one tool for consumers to use when discussing the risks and benefits of the drugs. LIMITATIONS OF THIS SNAPSHOT: Do not rely on Snapshots to make decisions regarding medical care. Always speak to your healthcare provider about the benefits and risks of a drug. Some of the information in this Snapshot is for presentation purposes and does not represent the approved conditions of use of this drug. Refer to the AVMAPKI FAKZYNJA CO-PACK Prescribing Information for all the approved conditions of use of this drug (e.g., indication(s), population(s), dosing regimen(s), safety information). Snapshots are limited to the information available at the time of the original approval of the drug and do not provide information on who participated in clinical trials that supported later approvals for additional uses of the drug (if applicable). AVMAPKI FAKZYNJA CO-PACK (avutometinib; defactinib) ave-MAP-kee Fak-zin-jah co-pac Verastem Inc. Original Approval date: April 28, 2025 DRUG TRIALS SNAPSHOT SUMMARY: What is the drug for? AVMAPKI FAKZYNJA CO-PACK, a combination of avutometinib and defactinib, each kinase inhibitors, is indicated for the treatment of adult patients with KRAS-mutated recurrent low-grade serous ovarian cancer (LGSOC) who have received prior systemic therapy. How is this drug used? AVMAPKI is administered as capsules taken by mouth two times a week (Day 1 and Day 4) with food for the first three weeks of each 4-week cycle. FAKZYNJA is administered as a tablet taken by mouth two times a day with food for the first three weeks of each 4-week cycle. Who participated in the clinical trials? The FDA approved AVMAPKI FAKZYNJA CO-PACK based on evidence from one clinical trial (RAMP-201/NCT04625270) using efficacy and safety data from 57 patients with KRAS-mutated recurrent LGSOC. The trial was conducted in seven countries including Belgium, Canada, France, Italy, Spain, the United Kingdom, and the United States. Of the 57 patients, 28 were enrolled at sites in the United States. Pooled safety data from two trials (RAMP-201; FRAME/NCT03875820), including 136 patients with recurrent LGSOC, also supported safety evaluation of AVMAPKI FAKZYNJA CO-PACK. How were the trials designed? The benefits and side effects of AVMAPKI FAKZYNJA CO-PACK were evaluated in one clinical trial using data from 57 patients with KRAS-mutated recurrent LGSOC. The RAMP-201 trial is an open-label, multicenter study. Patients received AVMAPKI 3.2 mg orally twice weekly for the first three weeks out of a 4-week cycle and FAKZYNJA 200 mg orally twice daily for the first three weeks out of a 4-week cycle until disease progression or unacceptable toxicity. The major efficacy outcome measure was overall response rate (ORR) assessed by blinded independent review committee) according to Response Evaluation Criteria in Solid Tumors (RECIST), version 1.1. An additional efficacy outcome measure was duration of response (DoR). Tumor response assessments occurred every 8 weeks for the first 72 weeks and every 12 weeks thereafter. DEMOGRAPHICS SNAPSHOT Figure 1 summarize the percentage of patients by sex enrolled in the clinical trial used to evaluate the safety and efficacy of AVMAPKI FAKZYNJA CO-PACK. Figure 1. Baseline Demographics by Sex Source: Adapted from FDA Review Figure 2 summarizes the percentage of patients by race enrolled in the clinical trial used to evaluate the safety and efficacy of AVMAPKI FAKZYNJA CO-PACK. Figure 2. Baseline Demographics by Race Source: Adapted from FDA Review Figure 3 summarizes the percentage of patients by age in the clinical trial used to evaluate the safety and efficacy of AVMAPKI FAKZYNJA CO-PACK. Figure 3. Baseline Demographics by Age Source: Adapted from FDA Review Figure 4 summarizes the percentage of patients by ethnicity in the clinical trial used to evaluate the safety and efficacy of AVMAPKI FAKZYNJA CO-PACK. Figure 4. Baseline Demographics by Ethnicity Source: Adapted from FDA Review Who participated in the trials? Table 1. Baseline Demographics Demographic All Patients N=57 n (%) Sex Female 57 (100) Age, years Mean (SD) 60 (12) Median (min, max) 60 (29, 87) Age group, years 18 to <65 34 (60) ≥65 23 (40) Race White 43 (75) Black or African American 2 (4) Asian 2 (4) Not reported 10 (18) Ethnicity Hispanic or Latino 2 (4) Not Hispanic or Latino 43 (75) Not reported 11 (19) Unknown 1 (2) Source: Adapted from FDA Review Abbreviations: SD, standard deviation What are the benefits of this drug? In the RAMP-201 trial, 44% of patients with previously treated KRAS-mutated LGSOC experienced complete or partial shrinkage of their tumor. For those patients whose tumors shrunk, the effect lasted for 3 to 31 months. What are the benefits of this drug (results of trials used to assess efficacy)? Table 2 shows efficacy results based on ORR and duration of response as determined by independent review according to RECIST v1.1. Table 2. Efficacy Results, Efficacy Population Endpoint AVMAPKI FAKZYNJA CO-PACK N=57 Confirmed ORR, % (95% CI) 44 (30.7,57.6) Complete response, % 3.5 Partial response, % 40 DoR Range (months) 3.3, 31.1 Patients with DoR ≥6 months, % 88 Source: AVMAPKI FAKZYNJA CO-PACK Prescribing Information Abbreviations: CI, confidence interval; DoR, duration of response; ORR, overall response rate Were there any differences in how well the drug worked in clinical trials among sex, race, age, and ethnicity? Sex: All the patients in the trial were female, therefore only race and age differences were evaluated. Race: The number of patients of races other than White was limited; therefore, differences in response among races could not be determined. Age: Clinical studies of AVMAPKI FAKZYNJA CO-PACK did not include a sufficient number of patients aged 65 and over to determine whether they respond differently from younger patients. Ethnicity: The majority of patients were not Hispanic or Latino. The number of patients of other ethnicities was limited; therefore, differences in response among ethnicities could not be determined. What are the possible side effects? AVMAPKI FAKZYNJA CO-PACK may cause eye problems, skin problems, liver problems, and muscle problems (rhabdomyolysis). The most common side effects of AVMAPKI FAKZYNJA CO-PACK include nausea; diarrhea; constipation; swelling in the face, legs, or arms; vomiting; acid reflux; tiredness; rash; dry or itchy skin; hair loss; infection around your fingernails or toenails; urinary tract infection; stomach-area (abdominal) pain; muscle spasms; pain in the joints; high blood pressure; blurry vision or impaired vision; dry eyes; headache; inflammation or soreness of the mouth; dry mouth; decreased appetite; loss of sense of taste; abnormal liver function tests; increase in an enzyme known as creatine phosphokinase; and decreased hemoglobin. What are the possible side effects (results of trials used to assess safety)? Table 3. Adverse Reactions (≥10%) in Patients With KRAS-Mutated Recurrent LGSOC Who Received AVMAPKI FAKZYNJA CO-PACK, Trial RAMP-2011 Adverse Reaction AVMAPKI FAKZYNJA CO-PACK, N=57 All Grades % Grade 3 or 4 7 % Gastrointestinal disorders Nausea 74 1.8 Diarrhea 68 7 Vomiting 49 3.5 Abdominal pain 2 39 1.8 Dyspepsia 2 37 0 Stomatitis 2 35 3.5 Constipation 30 0 Dry mouth 18 0 Decreased weight 11 0 General disorders and administration site condition Fatigue 2 72 3.5 Edema 2 67 1.8 Skin and subcutaneous tissue disorders Rash 3 72 3.5 Dermatitis acneiform 4 37 5.3 Pruritus 2 35 1.8 Dry skin 2 30 0 Alopecia 2 23 0 Photosensitivity 2 16 0 Musculoskeletal and connective tissue disorders Musculoskeletal pain 2 68 1.8 Joint swelling 11 0 Eye disorders Vitreoretinal disorders 5 37 3.5 Visual impairment 6 35 0 Dry eye 12 0 Respiratory disorders Dyspnea 2 26 5.3 Cough 25 0 Nervous system disorders Dizziness 23 1.8 Headache 16 0 Neuropathy peripheral 2 14 0 Dysgeusia 11 0 Vascular disorders Hemorrhage 2 23 0 Hypertension 16 5.3 Venous thromboembolism 2 14 5.3 Metabolism and nutrition disorders Decreased appetite 18 1.8 Infections and infestations Urinary tract infection 25 3.5 Paronychia 14 1.8 Upper respiratory tract infection 11 0 Source: AVMAPKI FAKZYNJA CO-PACK Prescribing Information 1 Severity as defined by National Center Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 5.0 2 Includes multiple terms 3 Includes: butterfly rash, dermatitis, drug eruption, erythema, rash, rash erythematous, rash macular, rash maculo-papular, rash papular, and rash pruritic 4 Includes: acne, dermatitis acneiform, folliculitis, perioral dermatitis, and rash pustular 5 Includes: chorioretinopathy, detachment of retinal pigment epithelium, macular fibrosis, macular hole, maculopathy, retinal detachment, retinal drusen, retinal vein occlusion, retinopathy, serous retinal detachment, serous retinopathy, subretinal fluid, vitreous detachment, and vitreous floaters 6 Includes: asthenopia, astigmatism, halo vision, metamorphopsia, photophobia, photopsia, vision blurred, visual field defect, and visual impairment 7 No Grade 4 treatment-emergent adverse events occurred Abbreviations: LGSOC, low-grade serous ovarian cancer Were there any differences in side effects among sex, race, and age? Sex: Everyone in the trial was female, therefore sex differences could not be determined. Race: The number of patients of races other than White was limited; therefore, differences in response among races could not be determined. Age: Clinical studies of AVMAPKI FAKZYNJA CO-PACK did not include a sufficient number of patients aged 65 and over to determine whether differences in safety were observed. Ethnicity: The majority of patients were not Hispanic or Latino. The number of patients of other ethnicities was limited; therefore, differences in safety among ethnicities could not be determined. GLOSSARY CLINICAL TRIAL: Voluntary research studies conducted in people and designed to answer specific questions about the safety or effectiveness of drugs, vaccines, other therapies, or new ways of using existing treatments. COMPARATOR: A previously available treatment or placebo used in clinical trials that is compared to the actual drug being tested. EFFICACY: How well the drug achieves the desired response when it is taken as described in a controlled clinical setting, such as during a clinical trial. PLACEBO: An inactive substance or “sugar pill” that looks the same as, and is given the same way as, an active drug or treatment being tested. The effects of the active drug or treatment are compared to the effects of the placebo. SUBGROUP: A subset of the population studied in a clinical trial. Demographic subsets include sex, race, and age groups. Back to Drug Trials Snapshots Legal Disclaimer: EIN Presswire provides this news content "as is" without warranty of any kind. We do not accept any responsibility or liability for the accuracy, content, images, videos, licenses, completeness, legality, or reliability of the information contained in this article. If you have any complaints or copyright issues related to this article, kindly contact the author above.