Avutometinib

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.

BOSTON--(BUSINESS WIRE)--Verastem Oncology (Nasdaq: VSTM), a biopharmaceutical company committed to advancing new medicines for patients with RAS/MAPK pathway-driven cancers, today announced the U.S. Food and Drug Administration (FDA) has granted Fast Track Designation (FTD) to VS-7375, an oral KRAS G12D (ON/OFF) inhibitor, for the first-line treatment of patients with KRAS G12D-mutated locally advanced or metastatic adenocarcinoma of the pancreas (PDAC) and for the treatment of patients with KRAS G12D-mutated locally advanced or metastatic PDAC who have received at least one prior line of standard systemic therapy. Fast Track is a process designed to facilitate the development and expedite the review of new drugs intended to treat or prevent serious conditions and address unmet medical needs. “The Fast Track Designation for VS-7375 underscores the importance of our potential best-in-class KRAS G12D (ON/OFF) inhibitor. As we continue enrollment in our U.S. Phase 1/2a clinical trial, our goal is to accelerate the program’s development given the lack of FDA-approved, KRAS G12D-targeted treatments for people living with KRAS G12D cancers,” said Dan Paterson, president and chief executive officer of Verastem Oncology. “Given the encouraging initial safety and efficacy results in China reported by our partner, GenFleet Therapeutics, at ASCO this year, we are excited to be advancing VS-7375 in the U.S. to evaluate it in advanced pancreatic cancer and non-small cell lung cancer and in combination with cetuximab in advanced solid tumors, including colorectal cancer.” VS-7375-101 is a Phase 1/2a study being conducted in the U.S., with plans to expand globally, and will evaluate the safety and efficacy of VS-7375 in patients with advanced KRAS G12D mutant solid tumors, including PDAC. The monotherapy dose escalation phase of the study started at a 400mg QD dose based on an efficacious dose identified in the Phase 1/2 study conducted in China by the Company’s partner, GenFleet Therapeutics. GenFleet announced encouraging initial safety and efficacy results from its Phase 1 dose-escalation phase of its study of VS-7375 (known as GFH375 in China) at the 2025 American Society of Clinical Oncology (ASCO) Annual Meeting. Verastem plans to dose-escalate across dose levels where encouraging initial safety and efficacy were observed in patients with advanced KRAS G12D mutant solid tumor cancers in GenFleet’s study. Upon successful completion of the dose-escalation phase, the Company will select a recommended Phase 2 dose and assess the efficacy and safety of monotherapy VS-7375 in expansion cohorts of patients with advanced pancreatic cancer and non-small cell lung cancer. In parallel with the monotherapy dose escalation, Verastem will evaluate VS-7375 in combination with cetuximab in advanced solid tumors. Subject to the results of the Phase 1 dose escalation combination of VS-7375 and cetuximab, Verastem plans to initiate a combination expansion cohort in colorectal cancer. 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. Forward-Looking Statements Notice This press release includes forward-looking statements. These forward-looking statements generally can be identified by the use of words such as “anticipate,” “expect,” “plan,” “could,” “may,” “believe,” “estimate,” “forecast,” “goal,” “project,” and other words of similar meaning. Such forward-looking statements address various matters about, among other things, Verastem Oncology’s programs and product candidates, strategy, future plans and prospects, including statements related to the potential for and timing of commercialization of product candidates, the expected outcome and benefits of the Company’s collaboration with GenFleet Therapeutics (Shanghai), Inc., the timing of commencing and completing trials and compiling data, the expected timing of the presentation of data by the Company and the potential clinical value of various of the Company’s clinical trials. Each forward-looking statement contained in this press release is subject to risks and uncertainties that could cause actual results to differ materially from those expressed or implied by such statement. Applicable risks and uncertainties include, among others: the uncertainties inherent in research and development, such as the possibility of negative or unexpected results of clinical trials; that we may not see a return on investment on the payments we have and may continue to make pursuant to the collaboration and option agreement with GenFleet, or that GenFleet may fail to fully perform under the agreement; that the development and commercialization of our product candidates may take longer or cost more than planned, including as a result of conducting additional studies or our decisions regarding execution of such commercialization; that data may not be available when expected; the risk that our preliminary and interim data may not be representative of more mature data; uncertainties related to the recent change in the U.S. presidential administration, including regulatory and policy changes that may adversely affect our business; that our product candidates may not receive regulatory approval, become commercially successful products, or result in new treatment options being offered to patients; and the risks identified under the heading "Risk Factors" as detailed in the Company’s Annual Report on Form 10-K for the year ended December 31, 2024, as filed with the Securities and Exchange Commission (SEC) on March 20, 2025, as well as the other information we file with the SEC, are possibly realized. We caution investors not to place considerable reliance on the forward-looking statements contained in this press release. You are encouraged to read our filings with the SEC, available at www.sec.gov, for a discussion of these and other risks and uncertainties. The forward-looking statements in this press release speak only as of the date of this press release, and we undertake no obligation to update or revise any of these statements. Our business is subject to substantial risks and uncertainties, including those referenced above. Investors, potential investors, and others should give careful consideration to these risks and uncertainties.