PA-FORE-BIO
FORE Biotherapeutics today announced new clinical data from the Phase 1/2a clinical trial for plixorafenib (FORE8394), a novel, investigational, small-molecule, next-generation, orally available selective inhibitor of BRAF alterations. The results demonstrate promising single-agent activity against BRAF-altered tumors, including primary central nervous system (CNS) tumors, and will be featured in presentations at the 2023 American Society of Clinical Oncology (ASCO) Annual Meeting, being held June 2-6, 2023, in Chicago, IL.
“The updated data from our Phase 1/2a study further reinforces plixorafenib’s differentiated clinical profile,” said Stacie Shepherd, MD, PhD, and Chief Medical Officer of FORE. “Plixorafenib has demonstrated both promising antitumor activity with durable responses and favorable tolerability as a single agent in patients with advanced BRAF-altered tumors. Notably, plixorafenib has a striking safety profile as compared to the currently approved BRAF/MEK and investigational pan-raf inhibitors.”
“In addition, our results demonstrate that targeted efficacious exposures are achieved at the recommended Phase 2 dose of 900mg a day with cobicistat in patients greater than 10 years of age, and that this dose provides the most favorable efficacy and safety profile,” continued Shepherd. “We look forward to advancing plixorafenib in our ongoing, global FORTE Phase 2 clinical basket study in patients with V600E-mutated primary recurrent CNS malignancies and in patients with advanced solid and CNS tumors with non-V600 alterations.”
Updated safety and efficacy data from the Phase 1/2a study will be highlighted during an oral presentation, with dose optimization results presented in a poster session. As of the data cutoff date of March 31, 2023, 113 adults and children have received ≥1 dose of plixorafenib under continuous dosing and fasting conditions on 28-day cycles until disease progression and are included in the safety population. Forty-two adults (≥18 years) met the criteria for the V600+ efficacy analysis with an ORR of 28.6%, based upon confirmed responses, and a mDOR of 17.8 months. An additional analysis was conducted in the MAPKi-naïve subset (N=24). Both analyses excluded patients with colorectal cancer, due to known intrinsic resistance pathways. A wide range of doses (900–3600 mg/d) and schedules with and without cobicistat, a novel CYP3A inhibitor, were explored.
Key Findings from the Ongoing Phase 1/2a Study
Efficacy Highlights:
-
MAPKi-naïve adult V600+ population (N=24, excluding CRC):
- Confirmed and durable responses and disease control were seen across multiple tumor types.
-
Clinical activity observed in this population includes nine confirmed partial responses (PR) for a 37.5% ORR, mDOR was 32.2 months and mPFS was 28.6 months.
-
In primary CNS tumors, six of ten efficacy-evaluable patients experienced a PR, with durable responses in both high grade and low grade glioma
-
-
Patients experienced long term benefit and tolerability:
- Three V600+ patients with papillary thyroid cancer are ongoing after more than six years of treatment
- Four of the ten with primary CNS tumor have remained on treatment for over a year, including a patient with glioblastoma on treatment for 34 months
-
MAPKi pre-treated adult V600+ population (N=18, excluding CRC):
- Clinical activity observed in this population includes three confirmed PRs for a 16.7% ORR, mDOR was 12.9 months
- Responses were observed in two of two patients with V600+ ovarian cancer, both of whom had prior MAPKi treatment and one with multiple regimens and documented progression of disease (PD)
-
BRAF fusion population (N=14):
- Clinical activity continued to be observed in patients with tumors harboring BRAF non-V600 alterations, including a patient with metastatic melanoma with complete response who continues on plixorafenib after five years of treatment with a DOR of 55+ months
- Eight patients experienced stable disease (up to 9.2+ months)
- Four patients are ongoing with plixorafenib treatment
Safety and Tolerability Highlights
-
Plixorafenib demonstrated a favorable safety profile with a low frequency and grade of treatment-emergent adverse events (TEAEs) that are frequently seen with MAPKi therapies, including approved BRAF/MEK inhibitor combinations
- Only one participant discontinued treatment due to treatment-related adverse event
- Symptomatic adverse events (AEs) were predominantly low grade (Grade 1 or 2) and included fatigue, nausea, diarrhea & vomiting
- No secondary cutaneous skin malignancies occurred, in contrast to the early single agent data with the approved BRAF inhibitors
“These results demonstrate that plixorafenib has promising activity against V600 & non-V600 BRAF mutant tumors, and in particular, primary CNS tumors,” shared Macarena de la Fuente, MD, Associate Professor and Chief of Neuro-oncology at the University of Miami Sylvester Comprehensive Cancer Center. “With no signs of paradoxical activation of the MAPK pathway and plixorafenib’s long term tolerability, this investigational agent is ideally suited for continued investigation in recurrent primary CNS tumors harboring BRAF V600E mutations and unresectable, locally advanced/metastatic solid tumors/primary CNS tumors harboring BRAF fusions.”
Dose Optimization Results
- Twelve patients (10.6%) are still on treatment as of the data cutoff; overall experience with plixorafenib represents 80 patient-years of exposure, including patients with over seven years of treatment.
- The most common reasons for discontinuation are progressive disease (n=65 [57.5%]) and clinical progression (n=18 [15.9%]); one discontinuation due to plixorafenib treatment-related AE occurred with 3600 mg/day + cobicistat.
- Measurable clinical responses were observed across all doses, with a wide therapeutic window
- ORR was greatest with total daily doses of plixorafenib 900 mg + cobicistat, with three of four V600+ MAPKi-naïve patients having confirmed PR at this dose once daily; no increase in efficacy was observed at higher doses or exposures
- This dose provided favorable tolerability, maximizing dose intensity, with pharmacodynamically active exposures. As such plixorafenib 900 mg QD + cobicistat was declared the optimal dose and RP2D for further development
“The plixorafenib Phase 1/2a trial results demonstrate that the 900mg QD with cobicistat is the optimal monotherapy dose and schedule for this novel inhibitor of mutated BRAF,” added Eric Sherman, MD, Associate Attending Physician at Memorial Sloan Kettering Cancer Center. “With responses observed in both MAP-kinase naïve treated and previously treated patients and its depth of durable remissions, plixorafenib has shown both promising tolerability as a single agent and has achieved durable responses and long-term benefit across a variety of patients harboring both V600 and nonV600 alterations. I look forward to the further study of plixorafenib to address patients where high unmet needs remain.”
Plixorafenib was granted Orphan Drug Designation by the U.S. Food and Drug Administration in March 2023 for the treatment of primary CNS malignancies. In September 2022, the Agency granted plixorafenib Fast Track Designation for the treatment of patients with cancers harboring BRAF Class 1 (V600) and Class 2 alterations (including fusions) who have exhausted prior therapies.
Details for the ASCO 2023 presentations are as follows:
Oral Presentation
Title: Safety and efficacy of the novel BRAF inhibitor FORE8394 in patients with advanced solid and CNS tumors: Results from a phase 1/2a study
Presenter: Macarena de la Fuente, MD, University of Miami Sylvester Comprehensive Cancer Center
Session Title: Developmental Therapeutics – Molecularly Targeted Agents and Tumor Biology
Presentation Date and Time: Monday, June 5, 2023, 8:00a.m. – 11:00 a.m. CDT
Abstract Number: 3006
Poster Presentation
Title: Dose optimization of novel BRAF inhibitor FORE8394 based on PK and efficacy results
Presenter: Eric Sherman, MD, Memorial Sloan-Kettering Cancer Center
Session Title: Developmental Therapeutics – Molecularly Targeted Agents and Tumor Biology
Presentation Date and Time: Saturday, June 3, 2023, from 8:00a.m. – 11:00 a.m. CDT
Abstract Number: 3106
About Plixorafenib (FORE8394)
Plixorafenib is an investigational, novel, small-molecule, next-generation, orally available selective inhibitor of mutated BRAF. It was designed to target a wide range of BRAF mutations while sparing wild-type forms of RAF. Preclinical studies and clinical trials have shown that its unique mechanism of action effectively inhibits not only the constitutively active BRAFV600 monomers targeted by first-generation RAF inhibitors but also disrupts constitutively active dimeric BRAF class 2 mutants, fusions, splice variants and others. Unlike first-generation RAF inhibitors, plixorafenib does not induce paradoxical activation of the RAF/MEK/ERK pathway. As a “paradox breaker,” plixorafenib could therefore treat acquired resistance to current RAF inhibitors and, more generally, yield improved safety and more durable efficacy than first-generation RAF inhibitors.
About FORE Biotherapeutics
FORE Bio is a precision oncology company dedicated to developing innovative treatments that provide a better outcome for cancer patients. Its lead asset plixorafenib is a Class 1/V600 and 2 BRAF inhibitor with demonstrated clinical safety and early efficacy signals in an ongoing Phase 1/2a clinical trial. Leveraging a proprietary functional genomics platform that can screen a wide range of known mutations for cancer-driving genes, the Fore R&D team is optimizing drug development by identifying existing compounds with known clinical profiles and a clear path through clinical development to advance new medicines for patients without treatment options. For more information, please visit www.fore.bio or follow us on Twitter and LinkedIn.
To view this piece of content from cts.businesswire.com, please give your consent at the top of this page.
View source version on businesswire.com: https://www.businesswire.com/news/home/20230526005057/en/
About Business Wire
Subscribe to releases from Business Wire
Subscribe to all the latest releases from Business Wire by registering your e-mail address below. You can unsubscribe at any time.
Latest releases from Business Wire
Year-old European startup Maisa named alongside Google and Amazon in elite list of leading AI agent vendors in top global US research reports by Gartner3.7.2025 01:01:00 CEST | Press release
- First time a Spanish startup has made the list, thanks to its industry-first hallucination resistant ‘digital workers’ - AI startup is one of two European AI agent vendors in Gartner’s Hype Cycle report for Artificial Intelligence and Hype Cycle for the Future of Work lists Maisa, a rising star of enterprise AI, has been named by leading global research and advisory firm Gartner in its list of leading vendors for developing reliable AI agents. This press release features multimedia. View the full release here: https://www.businesswire.com/news/home/20250702640749/en/ Maisa founders David Villalón and Manuel Romero Inclusion in Gartner’s 2025 Hype Cycle for AI and Hype Cycle for the Future of Work marks the first time a Spanish startup has been mentioned in these influential reports. The company, which is barely a year old and made its first raise of $5m+ from leading US investors last year, now finds itself named alongside global giants Amazon Web Services, Google, Salesforce and Lan
Hoffmann Green Announces a Historic Increase in Production Over the First Half of 2025, Already Outperforming the Annual Volumes Realized in 20242.7.2025 19:05:00 CEST | Press release
Record activity levels: +151% increase in production volumes in H1 2025 vs. H1 2024More than 130 construction sites supplied with more than 60,000 m³ of 0% clinker concrete delivered by 10,000 truck mixers across the countryAcceleration driven by a strengthened partnership network and the successful diversification of targeted marketsSolid outlook for the second half of 2025, in line with the strategic roadmap Hoffmann Green Cement Technologies (ISIN: FR0013451044, Ticker: ALHGR) (“Hoffmann Green Cement” or the “Company”), an industrial player committed to the decarbonation of the construction sector that designs and markets innovative clinker-free cements, today announces a strong acceleration of production over the first half of 2025, validating the relevance of its industrial and commercial business model. Production volumes reached 19,640 tonnes over the first half of 2025, compared with 7,833 tonnes in the first half of 2024, representing a 2.5-fold increase. This very strong leve
Institutional Real Estate, Inc. Announces Acquisition of U.K.-based Lyndon Publishing 2 Limited2.7.2025 18:44:00 CEST | Press release
Institutional Real Estate, Inc. (“IREI”) has completed its acquisition of the assets of London-based Lyndon Publishing 2 Ltd (“Lyndon Publishing”), which include The Property ChronicleandThe Green Chronicle.The former Lyndon Publishing 2 will now operate as a division of IREI. The Property Chronicle reaches a global audience of real estate investment professionals, researchers, and academics. Its sister publication, The Green Chronicle, is edited to address the interests and concerns of emerging young talent in these real estate professions. Both publications are produced as weekly news briefings filled with original content and contributed feature articles from industry thought and opinion leaders. In addition, The Property Chronicle is also published as a quarterly, illustrated full-color magazine available in both digital and print formats, while The Green Chronicleis published exclusively in digital format. Together, the two publications reach approximately 50,000 professionals acr
Sinopec Wins Technological Innovation Award at 2nd Sino-European Corporate ESG Best Practice Conference2.7.2025 18:21:00 CEST | Press release
China Petroleum & Chemical Corporation ("Sinopec", HKG: 0386) has won the "Best Scientific and Technological Innovation Practice" award at the 2nd Sino-European Corporate ESG Best Practice Conference (the "Conference") on June 26 in Stuttgart. Sinopec’s case submission of Breakthrough in Depth, Climb to New Heights — Empowering the Energy and Chemical Industry with Technological Innovation stood out among numerous entries. This press release features multimedia. View the full release here: https://www.businesswire.com/news/home/20250702387465/en/ Wang Tao, Sinopec representative, delivered a speech at the conference. The Conference reviews and awards the best ESG application cases in six areas of environmental protection, social responsibility, corporate management, scientific and technological innovation, education, and training to further enhance mutual understanding between Chinese and European businesses, facilitate bilateral economic and trade exchanges, and showcase China’s open,
Xsolla Releases Their Q2 2025 The State of Play Report: Mobile Gaming Is Projected to Hit $126B in 2025 Amid Global App Boom With In-Depth Analysis of Trends, Genres, and Monetization Strategies2.7.2025 18:00:00 CEST | Press release
Key Topics Include In-App Purchase Trends, Genre Performance, Player Demographics, D2C Strategy Adoption, and Hybrid Monetization Models Xsolla, a leading global video game commerce company, proudly announces the release of the Q2 2025 Edition of “The Xsolla Report: The State of Play.” This detailed report provides crucial insights, trends, and opportunities shaping the gaming landscape, empowering industry professionals to adapt and thrive in today’s rapidly changing market. This press release features multimedia. View the full release here: https://www.businesswire.com/news/home/20250702208715/en/ Graphic: Xsolla In 2024, global mobile app usage soared to an astonishing 4.2 trillion hours, an all-time high that powered a massive $150 billion consumer spending across mobile platforms. Mobile gaming is leading this charge, which accounted for more than half of that total. Despite a 6% dip in overall game downloads, falling to 49.6 billion, in-app purchase (IAP) revenue surged, indicati
In our pressroom you can read all our latest releases, find our press contacts, images, documents and other relevant information about us.
Visit our pressroom