A multicenter, single-arm clinical study of evaluate the efficacy and safety of avapritinib as maintenance therapy following allogeneic hematopoietic stem cell transplantation for acute myeloid leukemia patients with KIT mutation.

Start Date01 Feb 2025

Sponsor / Collaborator

Ruijin Hospital, Shanghai Jiaotong University School of Medicine

NCT06748001

/ RecruitingPhase 4

An Open-label, Multicenter, Rollover Study in Patients Who Participated in an Avapritinib Clinical Study

The primary objective of the rollover study is to evaluate the long-term safety of avapritinib in participants who have completed a Blueprint Medicines sponsored study (parent study) and continued to benefit from avapritinib.

Start Date28 Nov 2024

Sponsor / Collaborator

Blueprint Medicines Corp.

NCT06327685

/ RecruitingPhase 1IIT

A Phase 1 Study of Avapritinib in Combination With Decitabine in Patients With Systemic Mastocytosis With an Associated Hematologic Neoplasm (SM-AHN)

Systemic mastocytosis with an associated hematologic neoplasm (SM-AHN) is a challenging disease to treat. Targeted KIT inhibitors have been approved for this indication based on their ability to control the mastocytosis portion of the disease, but patients frequently experience progression of the concomitant myeloid malignancy (i.e. the AHN). Using a combination approach to treat both aspects of the disease has the potential to provide enhanced disease control; however, overlapping toxicity is a concern. In this study, investigators aim to study the safety and tolerability of combined avapritinib and decitabine for the treatment of SM-AHN.

Start Date13 Mar 2024

Sponsor / Collaborator

H. Lee Moffitt Cancer Center & Research Institute, Inc.

[+1]

100 Clinical Results associated with Avapritinib

100 Translational Medicine associated with Avapritinib

100 Patents (Medical) associated with Avapritinib

179

Literatures (Medical) associated with Avapritinib

02 Jan 2025·Journal of Biomolecular Structure and Dynamics

Drug repurposing for targeting fibronectin in treatment of endometriosis and cancers

Article

Author: Shahhoseini, Maryam ; Moini, Ashraf ; Esfandiari, Fereshteh ; Mahdian, Soodeh

Increased concentrations of the fibronectin glycoprotein can cause ectopic tissue growth patients with endometriosis and the formation of various cancerous tumors. Furthermore, fibronectin binding to its receptors from the EDA (Extra Domain A) region contributes to promote tumorigenesis, metastasis and vasculogenesis. Thus, the EDA region can be considered a unique target for therapeutic intervention. Therefore, the present study used computational methods to identify the best fibronectin inhibitor(s) among FDA-approved drugs. First, docking-based virtual screening was performed using PyRx 0.8. Next, FDA-approved drugs that obtained favorable results in the docking phase were selected for further studies and analysis using molecular dynamics (MD) simulation. The preliminary findings of the virtual screening showed that 17 FDA-approved drugs (from 2471) had more favorable energy with their binding energy less than -9 kcal/mol. The MD simulation results of these 17 drugs showed that Avapritinib had a lower RMSD value and higher binding energy and hydrogen bonding than the other complexes in the EDA domain. Also, analyses related to the second structure changes displayed that Avapritinib in the EDA domain led to more changes in the second structure. According to the results, the anticancer drug Avapritinib forms a more stable complex with fibronectin than other FDA-approved drugs. Furthermore, this drug leads to more changes in the second EDA structure, which may have more serious potential for inhibiting EDA fibronectin.Communicated by Ramaswamy H. Sarma.

01 Dec 2024·Biochemical and Biophysical Research Communications

Avapritinib efficacy in primary hepatic neuroendocrine carcinoma with elevated PDGFRA expression: Insights from a PDX model study

Article

Author: Wang, Ying-Chao ; Yu, Xiao-Ruo ; Song, Xiang-Lin ; Guo, Luo-Bin ; Zhou, Yang

BACKGROUND & AIMSPrimary Hepatic Neuroendocrine Carcinoma (PHNEC) is a rare and aggressive tumor with high recurrence rates. Surgical resection remains the only therapeutic strategy. The effectiveness of tyrosine kinase inhibitors (TKIs) for PHNEC remains unclear due to limited research.METHODSWe employed immunohistochemical staining to diagnose PHNEC and assess the expression of eight tyrosine kinase receptors in tumor tissues, including VEGFRs, PDGFRA, EGFR, FGFRs et al. A patient-derived xenograft (PDX) model was established using PHNEC tumor tissues to test the efficacy of TKIs. PDX mice bearing tumors were treated with Avapritinib, an FDA-approved PDGFRA-targeting drug, at a daily oral dose of 10 mg/kg for 2 weeks.RESULTSPathological analysis confirmed the diagnosis of PHNEC with positive expression of Neural cell adhesion molecule (NCAM/CD56), Synaptophysin (Syn), and Somatostatin receptor 2 (SSTR-2), and negative expression of Hep (Hepatocyte Paraffin 1), a biomarker for Hepatocellular carcinoma. Notably, PDGFRA was significantly overexpressed in PHNEC tumor tissues compared to other tyrosine kinases. Avapritinib treatment significantly reduced tumor growth in PDX mice by 73.9 % (p = 0.008). Additionally, Avapritinib treatment led to a marked decrease in PDGFRA and Ki-67 expression, suggesting that it inhibits tumor cell proliferation by suppressing PDGFRA.CONCLUSIONOur findings suggest that PDGFRA is a potential therapeutic target for PHNEC, and its inhibition with Avapritinib may offer clinical benefits to patients with this rare malignancy.

01 Sep 2024·Annals of Hematology

Pediatric acute myeloid leukemia with t(8;21) and KIT mutation treatment with avapritinib post-stem cell transplantation: a report of four cases

Article

Author: Li, Bohan ; Hu, Yixin ; Zhang, Senlin ; Xiao, Peifang ; Wang, Qingwei ; Cheng, Shengqin ; Gao, Li ; Yao, Yanhua ; Hu, Shaoyan ; Lu, Jun ; Li, Jie

AbstractAcute myeloid leukemia (AML) with t(8;21) (q22;q22), which forms RUNX1::RUNX1T1 fusion gene, is classified as a favorable-risk group. However, the presence of mutations in KIT exon 17 results in an adverse prognosis in this group. Avapritinib, a novel tyrosine kinase inhibitor, was designed to target KIT mutation. We report a retrospective study of four pediatric patients with AML with t(8:21) and KIT exon 17 mutation who were treated with avapritinib, three of them failed to demethylate drugs and donor lymphocyte infusion targeting RUNX1::RUNX1T1-positivity after allogeneic hematopoietic stem cell transplantation (allo-HSCT). So far, all patients with RUNX1::RUNX1T1 positivity had turned negative after 1, 9, 7, 2 months of avapritinib treatment. The common adverse effect of avapritinib is neutropenia, which is well-tolerated. This case series indicates that avapritinib may be effective and safe for preemptive treatment of children with AML with t(8;21) and KIT mutation after allo-HSCT, providing a treatment option for preventing relapse after allo-HSCT.

News (Medical) associated with Avapritinib

12 Jan 2025

·ir.blueprintmedicines.com

Blueprint Medicines Provides 2025 Outlook and Highlights Strategy for Continued Growth

-- Updating peak systemic mastocytosis franchise revenue opportunity to $4 billion , catalyzed by strong AYVAKIT® (avapritinib) launch and evolving SM prevalence estimates -- -- Expect to achieve $2 billion in AYVAKIT revenue by 2030 -- -- BLU-808 demonstrates wide therapeutic window with rapid, robust and sustained tryptase reductions exceeding 80% in Phase 1 healthy volunteer study -- -- Kate Haviland , CEO, to present at J.P. Morgan conference on Monday, January 13 at 9:00 a.m. PT ( 12:00 p.m. ET ) -- CAMBRIDGE, Mass. , Jan. 12, 2025 /PRNewswire/ -- Blueprint Medicines Corporation (Nasdaq: BPMC) today provided a 2025 corporate outlook and strategy for continued growth leveraging the company's proven R&D and commercial capabilities. "With AYVAKIT growing towards a multibillion-dollar opportunity, anchoring our SM franchise, and with BLU-808, our next program with blockbuster potential coming into focus, we enter 2025 in the strongest position we have ever been in as a company. We have a number of commercial and clinical catalysts that we expect to deliver significant near- and long-term value to both patients and shareholders," said Kate Haviland , Chief Executive Officer of Blueprint Medicines . "Driven by scalable innovation and operational excellence, we aspire to fundamentally shift the way many allergic and inflammatory diseases are treated by targeting the mast cell. We have built a high-performing commercial engine that enables a truly integrated approach from research to development to commercialization, allowing us to realize operational efficiencies and resulting in a durable financial profile." Systemic Mastocytosis (SM): A Large and Growing Opportunity Based on the strength of the global AYVAKIT launch to date, significant sustained growth in diagnosed SM patients, and new epidemiology data suggesting SM prevalence is greater than previously thought, Blueprint now estimates the peak revenue opportunity for the company's SM franchise is $4 billion , with $2 billion in annual revenues expected to be achieved by AYVAKIT by 2030. Blueprint plans to report financial results for the fourth quarter and full-year 2024 in February 2025 . The company previously provided guidance in October 2024 for AYVAKIT product revenue of $475 to $480 million for full-year 2024, representing an increase of more than 130 percent over 2023. Positive Data from BLU-808 Healthy Volunteer Trial Blueprint today announced results from the Phase 1 single-ascending dose (SAD; n=56) and multiple-ascending dose (MAD; n=31, 14-day dosing) trial of BLU-808, a highly potent and selective oral wild type KIT inhibitor, in healthy volunteers. Detailed data will be presented at the J.P. Morgan conference. Safety: BLU-808 was well-tolerated at all doses tested. All treatment-emergent adverse events (AEs) in the MAD cohorts [1-12 mg once daily (QD)] in those who received BLU-808 were Grade 1. There were no serious AEs, no discontinuations or dose modifications due to AEs, and no significant changes in laboratory measures. Pharmacokinetics: BLU-808 showed a half-life of approximately 40 hours, enabling once-daily dosing, and consistent, dose-dependent increases in drug exposure. In the MAD cohorts, all BLU-808 doses led to sustained target coverage, with mean plasma concentrations exceeding predicted KIT IC50 levels at ≥1 mg QD and IC90 levels at ≥3 mg QD. Pharmacodynamics: BLU-808 showed dose-dependent serum tryptase responses, reflecting evidence of mast cell target engagement across multiple dose levels. In the SAD cohorts, reductions in tryptase were observed after a single dose of BLU-808. In the MAD cohorts, rapid, robust and sustained reductions in tryptase were observed, with reductions below the lower limit of quantification (LLOQ) at multiple dose levels. Change in Serum Tryptase (MAD) Dose Tryptase reduction at Day 15 Participants reaching LLOQ Placebo (n=8) -4 % 0 1 mg (n=6) -23 % 1/6 3 mg (n=6) -41 % 1/6 6 mg (n=6) -66 % 3/6 12 mg (n=4) a -87 % 3/4 a One participant in the 12 mg cohort had undetectable tryptase levels at baseline and was not included in the tryptase analysis. "These Phase 1 data support the best-in-class potential of BLU-808, which was designed to achieve unique potency and selectivity enabling a tunable treatment approach and optimization of benefit-risk across a diverse set of mast cell-driven diseases," said Percy Carter , Ph.D., Chief Scientific Officer at Blueprint Medicines . "The results show that BLU-808 performed consistently, with dose-dependent outcomes, including rapid, robust and sustained reductions in serum tryptase across a range of doses, which reinforce the potential for tunable treatment. Based on these positive data, we are initiating proof-of-concept studies in chronic urticaria, allergic asthma, allergic rhinitis, allergic conjunctivitis and mast cell activation syndrome to characterize BLU-808's broad therapeutic potential across multiple diseases where mast cells play a core role in the disease biology." Additional Pipeline Updates Blueprint continues to evaluate programs across the company's diverse pipeline and prioritize investments in the most compelling programs with first- or best-in-class potential. Blueprint today announced the following updates: With a focus driving continued innovation and extending the longer-term lifecycle of the company's SM franchise, Blueprint has initiated the registration-enabling Phase 3 HARBOR trial of elenestinib, a next-generation KIT D816V inhibitor, in patients with indolent systemic mastocytosis (ISM). Blueprint is advancing CDK2 and CDK4 targeted protein degraders, which have progressed faster than expected in preclinical development toward potentially best-in-class profiles and is prioritizing further investment in its CDK franchise for breast cancer and other solid tumors to these programs. Blueprint is completing the Phase 1 dose escalation study of its CDK2 inhibitor BLU-222 and plans to de-prioritize further investment in this program. The company continues to engage strategic partners on potential opportunities to broadly advance its franchise of CDK programs. 2025 Corporate Goals Grow franchise leadership in SM Deliver continued strong and steady AYVAKIT revenue growth in 2025 Present additional long-term data from the PIONEER trial of AYVAKIT in ISM in the first half of 2025 Achieve reimbursement of AYVAKYT in ≥20 countries overall by the end of 2025 Activate sites and drive patient enrollment of the Phase 3 HARBOR trial of elenestinib in ISM throughout 2025 Achieve BLU-808 clinical proof-of-concept in allergic and inflammatory diseases Present topline results from the Phase 1 healthy volunteer trial at the J.P. Morgan conference on January 13, 2025 Initiate proof-of-concept trials in chronic spontaneous urticaria, chronic inducible urticaria, allergic rhinitis and allergic conjunctivitis in the first half of 2025 Initiate proof-of-concept trials in allergic asthma and mast cell activation syndrome in the second half of 2025 Drive research innovation in allergy/inflammation and oncology/hematology Nominate two development candidates, including the company's first targeted protein degrader, in the second half of 2025 J.P. Morgan Healthcare Conference Presentation Information Kate Haviland , Chief Executive Officer of Blueprint Medicines, will present a company overview and 2025 outlook at the 43rd Annual J.P. Morgan Healthcare Conference on Monday, January 13 at 9:00 a.m. PT ( 12:00 p.m. ET ). A live webcast of the presentation and Q&A session will be available by visiting the "Events and Presentations" section of Blueprint Medicines' website at http://ir.blueprintmedicines.com. A replay of the webcast will be archived on Blueprint Medicines' website for 30 days following the presentation. About Blueprint Medicines Blueprint Medicines is a global, fully integrated biopharmaceutical company that invents life-changing medicines. We seek to alleviate human suffering by solving important medical problems in two core focus areas: allergy/inflammation and oncology/hematology. Our approach begins by targeting the root causes of disease, using deep scientific knowledge in our core focus areas and drug discovery expertise across multiple therapeutic modalities. We have a track record of success with two approved medicines, including AYVAKIT®/AYVAKYT® (avapritinib) which we are bringing to patients with systemic mastocytosis (SM) in the U.S. and Europe . Leveraging our established research, development, and commercial capability and infrastructure, we now aim to significantly scale our impact by advancing a broad pipeline of programs ranging from early science to advanced clinical trials in mast cell diseases including SM and chronic urticaria, breast cancer and other solid tumors. For more information, visit www.BlueprintMedicines.com and follow us on X (formerly Twitter; @BlueprintMeds) and LinkedIn. Cautionary Note Regarding Forward-Looking Statements This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995, as amended, including, without limitation, statements regarding Blueprint Medicines' views with respect to the peak systemic mastocytosis franchise and AYVAKIT revenue opportunities; the continued growth of the AYVAKIT launch in the U.S. and in other countries; the expansion of Blueprint Medicines' mast cell disease franchise with the development of elenestinib and BLU-808; the advancement of BLU-808 and targeted protein degrader research programs for CDK2; the potential for BLU-808 to address allergic and inflammatory diseases; plans to continue the Phase 3 portion of the HARBOR trial of elenestinib; plans, strategies, timelines, expectations and potential benefits for Blueprint Medicines' current or future approved drugs and drug candidates and in treating patients; and Blueprint Medicines' financial performance, strategy, including the prioritization of its capital resources, goals and anticipated 2025 corporate milestones, business plans, outlook and focus. The words "aim," "goals" "may," "will," "could," "would," "should," "expect," "plan," "anticipate," "intend," "believe," "estimate," "predict," "project," "potential," "continue," "target" and similar expressions are intended to identify forward-looking statements, although not all forward-looking statements contain these identifying words. Any forward-looking statements in this press release are based on management's current expectations and beliefs and are subject to a number of risks, uncertainties and important factors that may cause actual events or results to differ materially from those expressed or implied by any forward-looking statements contained in this press release, including, the risk that the market opportunities for systemic mastocytosis, including AYVAKIT (avapritinib), or other Blueprint Medicines drug candidates are smaller than the company estimates or that any approval it obtains may be based on a narrower definition of the patient population than it anticipates; the marketing and sale of AYVAKIT (avapritinib) or any future approved drugs may be unsuccessful or less successful than anticipated, or that AYVAKIT (avapritinib) may not gain market acceptance by physicians, patients, third-party payors and others in the medical community; the risk of delay of any current or planned clinical trials or the development of Blueprint Medicines' current or future drug candidates; risks related to Blueprint Medicines' ability to successfully demonstrate the safety and efficacy of its drug candidates and gain approval of its drug candidates on a timely basis, if at all; preclinical and clinical results for Blueprint Medicines' drug candidates may not support further development of such drug candidates either as monotherapies or in combination with other agents or may impact the anticipated timing of data or regulatory submissions; the timing of the initiation of clinical trials and trial cohorts at clinical trial sites and patient enrollment rates may be delayed or slower than anticipated; actions of regulatory agencies may affect its approved drugs or its current or future drug candidates, including affecting the initiation, timing and progress of clinical trials; risks related to Blueprint Medicines' ability to obtain, maintain and enforce patent and other intellectual property protection for its products and current or future drug candidates it is developing; the success of Blueprint Medicines' current and future collaborations, financing arrangements, partnerships or licensing and other arrangements; risks related to its liquidity and financial position, including the risk that Blueprint Medicines may be unable to generate sufficient future product revenues to achieve and maintain a self-sustainable financial profile; and the accuracy of its estimates of revenues, expenses and capital requirements. These and other risks and uncertainties are described in greater detail in the section entitled "Risk Factors" in Blueprint Medicines' filings with the Securities and Exchange Commission (SEC), including Blueprint Medicines' most recent Annual Report on Form 10-K, as supplemented by its most recent Quarterly Report on Form 10-Q and any other filings that Blueprint Medicines has made or may make with the SEC in the future. Any forward-looking statements contained in this press release represent Blueprint Medicines' views only as of the date hereof and should not be relied upon as representing its views as of any subsequent date. Except as required by law, Blueprint Medicines explicitly disclaims any obligation to update any forward-looking statements. Trademarks Blueprint Medicines , AYVAKIT, AYVAKYT and associated logos are trademarks of Blueprint Medicines Corporation. View original content to download multimedia:https://www.prnewswire.com/news-releases/blueprint-medicines-provides-2025-outlook-and-highlights-strategy-for-continued-growth-302348688.html SOURCE Blueprint Medicines Corporation Media Contact: Andrew Law, +1 (617) 844-8205, media@blueprintmedicines.com Investor Contact: Cassie Saitow, +1 (617) 909-3127, ir@blueprintmedicines.com

Phase 1Clinical ResultFinancial Statement

12 Dec 2024

·www.globenewswire.com

Cogent Biosciences Announces Positive Updated Data from Ongoing Phase 2 APEX Trial Evaluating Bezuclastinib in Patients with Advanced Systemic Mastocytosis (AdvSM)

52% ORR per mIWG criteria, including 83% ORR for patients receiving 100 mg BID 88% ORR per PPR criteria, including 100% ORR for patients receiving 100 mg BID Median time to response 2.2 months with median duration of response and median PFS not yet reached Top-line data from APEX Part 2 on-track for mid-2025 Cogent to host investor webcast on Monday, December 9 at 8:00 a.m. ET Dec. 08, 2024 -- Cogent Biosciences, Inc. (Nasdaq: COGT), a biotechnology company focused on developing precision therapies for genetically defined diseases, today reported positive updated data from Part 1 of the Company’s ongoing Phase 2 APEX clinical trial evaluating bezuclastinib in patients with advanced systemic mastocytosis (AdvSM) at the 66th American Society of Hematology (ASH 2024) Annual Meeting & Exposition taking place December 7-10, 2024 in San Diego, CA. “Bezuclastinib has the potential to transform the treatment landscape for people living with advanced systemic mastocytosis,” said Daniel J. DeAngelo, M.D., Ph.D., Chief of the Division of Leukemia at the Dana-Farber Cancer Institute and Professor of Medicine, Harvard Medical School. “The impressive clinical data presented today from APEX Part 1 demonstrates a combination of rapid and deep clinical responses, with a safety profile that avoids several of the most concerning side effects for AdvSM patients today.” “We are excited to share today the updated clinical data from APEX Part 1 studying bezuclastinib in patients with advanced systemic mastocytosis,” said Andrew Robbins, Cogent’s President and Chief Executive Officer. “These results show the enormous promise that a highly potent, highly selective, non-brain penetrant KIT inhibitor may provide to this patient population. We look forward to completing enrollment in APEX Part 2 and sharing the results from that study in mid-2025.” APEX is a global, open-label, multi-center, two-part Phase 2 clinical trial in patients with AdvSM evaluating the safety, efficacy, pharmacokinetic, and pharmacodynamic profiles of bezuclastinib. Thirty-two patients were treated in Part 1 at one of four dose levels (50 mg BID, 100 mg BID, 200 mg BID or 400 mg QD). Earlier this year, Cogent announced APEX Part 2 would be conducted at the optimized 150mg QD dose, which closely matches the exposure from 100 mg BID dose in APEX Part 1. The median age of patients at study entry was 68 years (ranging from 33-87 years). Patients were enrolled with the following sub-types: seven patients with aggressive systemic mastocytosis (ASM), 23 patients with systemic mastocytosis with associated hematologic neoplasm (SM-AHN), and two patients with mast cell leukemia (MCL). Five patients had received prior avapritinib and 10 patients had received prior midostaurin treatment. As of the data cutoff date of October 11, 2024, 32 patients enrolled were evaluated for signs of clinical activity, 27 of whom were mIWG-MRT-ECNM evaluable. Clinical activity analyzed across dose levels and focused on 100 mg BID cohort showed: 52% ORR (CR+CRh+PR+CI) per mIWG-MRT-ECNM criteria, including 61% ORR for TKI-treatment-naïve patients 83% ORR for patients treated at 100 mg BID dose cohort 88% ORR (CR+PR) per pure pathological response (PPR) criteria 100% ORR for patients treated at 100 mg BID dose cohort Median time to achieve response was 2.2 months and median duration of response has not yet been reached Median PFS was not yet reached at median follow-up of 20 months; PFS rate at 24 months was 82% Nearly all patients demonstrated a significant improvement in biomarkers associated with disease burden. Patients without post baseline biomarker data were excluded from relevant analyses. 94% of patients achieved ≥50% reduction in serum tryptase levels 100% of patients receiving ≥2 cycles achieved ≥50% reduction 66% of patients achieved reduction of serum tryptase below 20 ng/mL 93% of KITD816V-positive patients achieved ≥50% reduction in KIT D816V variant allele fraction (VAF) 100% of evaluable patients achieved a ≥50% reduction in bone marrow mast cell burden 83% achieved complete clearance of mast cell aggregates by central review Cogent is actively enrolling patients into APEX Part 2 which is anticipated to complete enrollment in Q1 2025 with top-line results expected in mid-2025. Cogent will present 24-week follow-up data from patients who participated in the Open Label Extension portion of the ongoing SUMMIT trial on Monday, December 9, 2024 at ASH. SUMMIT is a randomized, double-blind, placebo-controlled, global, multicenter Phase 2 trial evaluating bezuclastinib in patients with Nonadvanced Systemic Mastocytosis (NonAdvSM). Cogent Biosciences is a biotechnology company focused on developing precision therapies for genetically defined diseases. The most advanced clinical program, bezuclastinib, is a selective tyrosine kinase inhibitor that is designed to potently inhibit the KIT D816V mutation as well as other mutations in KIT exon 17. KIT D816V is responsible for driving systemic mastocytosis, a serious disease caused by unchecked proliferation of mast cells. Exon 17 mutations are also found in patients with advanced gastrointestinal stromal tumors (GIST), a type of cancer with strong dependence on oncogenic KIT signaling. In addition to bezuclastinib, the Cogent Research Team is developing a portfolio of novel targeted therapies to help patients fighting serious, genetically driven diseases initially targeting mutations in FGFR2, ErbB2, PI3Kα and KRAS. Cogent Biosciences is based in Waltham, MA and Boulder, CO. Visit our website for more information at www.cogentbio.com. Follow Cogent Biosciences on social media: X (formerly known as Twitter) and LinkedIn. Information that may be important to investors will be routinely posted on our website and X. The content above comes from the network. if any infringement, please contact us to modify.

Clinical ResultASH

09 Dec 2024

·www.globenewswire.com

Cogent Biosciences Announces Updated Clinical Results from SUMMIT, Showcasing Powerful Symptomatic Improvement in NonAdvanced Systemic Mastocytosis Patients

56% mean improvement in Total Symptom Score (TSS) at 24 weeks with 76% of patients achieving at least a 50% reduction in TSS 89% of patients had >50% decrease in serum tryptase by four weeks of treatment and 95% of patients with elevated baseline tryptase achieved serum tryptase levels <20 ng/ml by week 24 SUMMIT Part 2 enrollment completed early; surpassing original enrollment target with 179 patients enrolled, top-line results now expected in July 2025 Cogent to host investor webcast today, Monday, December 9 at 8:00 a.m. ET WALTHAM, Mass. and BOULDER, Colo., Dec. 09, 2024 (GLOBE NEWSWIRE) -- Cogent Biosciences, Inc. (Nasdaq: COGT), a biotechnology company focused on developing precision therapies for genetically defined diseases, today announced updated clinical results from the Open Label Extension (OLE) portion of SUMMIT, a clinical trial evaluating bezuclastinib in patients with nonadvanced systemic mastocytosis (NonAdvSM). The OLE data are being presented at the 66th American Society of Hematology (ASH 2024) Annual Meeting & Exposition taking place December 7-10, 2024 in San Diego, CA. “The rapid, deep, and sustained symptomatic improvement reported by SUMMIT patients receiving bezuclastinib is very impressive,” said Daniel J. DeAngelo, M.D., Ph.D., Chief of the Division of Leukemia at the Dana-Farber Cancer Institute and Professor of Medicine, Harvard Medical School. “Coupled with its favorable tolerability profile, bezuclastinib has clear potential to establish itself as the best-in-class KIT inhibitor for systemic mastocytosis patients.” “The SUMMIT data reported today are encouraging to thousands of NonAdvSM patients around the world who are waiting for a novel treatment that can rapidly and meaningfully improve a wide variety of symptoms that impact their daily lives,” said Andrew Robbins, Cogent’s President and Chief Executive Officer. “We set out earlier this year to enroll our registration-directed SUMMIT Part 2 trial, and I’m excited to announce that based on the overwhelming demand from investigators and patients around the world, we’ve completed enrollment in the study with 179 patients more than six months ahead of schedule. Top-line results are now expected in July 2025, meaning we have dramatically accelerated our timeline as we aim to make bezuclastinib available to all NonAdvSM patients.” Patient DemographicsSUMMIT is a registration-directed, randomized, double-blind, placebo-controlled, global, multicenter, clinical trial of bezuclastinib in patients with NonAdvSM. In SUMMIT Part 1, patients received bezuclastinib or placebo for a 12-week period to determine the recommended dose for use in the pivotal portion of the trial, SUMMIT Part 2. Earlier this year, Cogent announced that the recommended go-forward dose was selected at once-daily 100 mg. After the initial 12-week period, all patients were given the opportunity to receive bezuclastinib in the SUMMIT Open Label Extension (OLE). The clinical results presented today focus on 27 patients in the OLE who were treated with the once-daily 100 mg dose of bezuclastinib. The median age of patients at study entry was 52 years (ranging from 36-76 years). One patient had received prior avapritinib. Patient Reported Outcomes (PRO) DataSUMMIT patients were evaluated for signs of clinical activity over 24 weeks using multiple PRO measures, including the Mastocytosis Symptom Severity Daily Diary (MS2D2) and the Mastocytosis Quality-of-Life (MC-QoL) scale. Updated clinical data presented today show: 56% mean improvement in Total Symptom Score (TSS) at 24 weeks76% of patients demonstrated >50% reduction from baseline in MS2D2 Total Symptom Score (TSS) with 88% of patients exceeding 30% reduction from baseline after 24 weeks49% mean improvement in MC-QoL Total Score at 24 weeks At 24 weeks of treatment, 31% of patients have already reduced or discontinued best supportive care (BSC) medications. Pharmacodynamic DataBezuclastinib showed rapid, deep, and sustained reductions in serum tryptase over the course of 24 weeks of treatment including: 89% of patients had >50% decrease in serum tryptase levels by four weeks of treatment95% of patients with baseline tryptase ≥20ng/mL achieved <20ng/mL by week 2484% of patients with baseline serum tryptase >11.4ng/ml achieved <11.4ng/mL by week 24 Safety DataAs of the data cutoff, August 29, 2024, the median duration of bezuclastinib treatment was 56 weeks for patients in the active arm and 40 weeks for placebo patients who crossed over to the OLE. The majority of treatment emergent adverse events were low grade and reversible with no treatment-related bleeding or cognitive impairment events reported. The most common treatment related adverse events were hair discoloration and transaminase elevations. All patients experiencing elevated transaminases were asymptomatic and reversible: five patients resolved without any dose modifications and remain on study; two patients resolved with dose reduction and remain on study, one of whom re-escalated to original dose; and two patients resolved following discontinuation, one of whom was presented previously at ASH 2023. There were no other discontinuations due to adverse events. SUMMIT Enrollment UpdateCogent also announced today that enrollment in the registration-directed SUMMIT Part 2 study is now complete. In the nine months between February and October 2024, 265 NonAdvSM patients were screened for SUMMIT Part 2 at 70 clinical sites, concentrated predominantly in the U.S. and Western Europe. More than 90% of these patients were naïve to KIT inhibitor therapy. A total of 179 patients were enrolled and top-line results from the trial are expected in July 2025. Webcast Information and ASH PosterCogent will host a webcast today, Monday, December 9, 2024, at 8:00 a.m. ET to discuss these updated SUMMIT clinical results. The live event will be available on the Investors & Media page of Cogent’s website at investors.cogentbio.com. A replay of the webcast will be available approximately two hours after the completion of the event and will be archived for up to 30 days. The ASH poster is available to registered conference attendees and is also in the Posters and Publications section of Cogent’s website at www.cogentbio.com/research. About Cogent Biosciences, Inc. Cogent Biosciences is a biotechnology company focused on developing precision therapies for genetically defined diseases. The most advanced clinical program, bezuclastinib, is a selective tyrosine kinase inhibitor that is designed to potently inhibit the KIT D816V mutation as well as other mutations in KIT exon 17. KIT D816V is responsible for driving systemic mastocytosis, a serious disease caused by unchecked proliferation of mast cells. Exon 17 mutations are also found in patients with advanced gastrointestinal stromal tumors (GIST), a type of cancer with strong dependence on oncogenic KIT signaling. In addition to bezuclastinib, the Cogent Research Team is developing a portfolio of novel targeted therapies to help patients fighting serious, genetically driven diseases initially targeting mutations in FGFR2, ErbB2, PI3Kα and KRAS. Cogent Biosciences is based in Waltham, MA and Boulder, CO. Visit our website for more information at www.cogentbio.com. Follow Cogent Biosciences on social media: X (formerly known as Twitter) and LinkedIn. Information that may be important to investors will be routinely posted on our website and X. Forward Looking StatementsThis press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995, including, but not limited to, statements regarding: the company’s expectation to present top-line results from SUMMIT Part 2 in July 2025; the potential for bezuclastinib to establish itself as the best-in-class KIT inhibitor for systemic mastocytosis patients; and the company’s goal of making bezuclastinib available to all NonAdvSM patients. The use of words such as, but not limited to, "anticipate," "believe," "continue," "could," "estimate," "expect," "intend," "may," "might," "plan," "potential," "predict," "project," "should," "target," "will," or "would" and similar words expressions are intended to identify forward-looking statements. Forward-looking statements are neither historical facts nor assurances of future performance. Instead, they are based on our current beliefs, expectations and assumptions regarding the future of our business, future plans and strategies, our clinical results, the rate of enrollment in our clinical trials and other future conditions. New risks and uncertainties may emerge from time to time, and it is not possible to predict all risks and uncertainties. No representations or warranties (expressed or implied) are made about the accuracy of any such forward-looking statements. We may not actually achieve the forecasts or milestones disclosed in our forward-looking statements, and you should not place undue reliance on our forward-looking statements. Such forward-looking statements are subject to a number of material risks and uncertainties including but not limited to those set forth under the caption "Risk Factors" in Cogent's most recent Quarterly Report on Form 10-Q filed with the SEC. Any forward-looking statement speaks only as of the date on which it was made. Neither we, nor our affiliates, advisors or representatives, undertake any obligation to publicly update or revise any forward-looking statement, whether as result of new information, future events or otherwise, except as required by law. These forward-looking statements should not be relied upon as representing our views as of any date subsequent to the date hereof. Contact:Christi WaarichSenior Director, Investor Relationschristi.waarich@cogentbio.com617-830-1653

Clinical ResultClinical StudyASH

100 Deals associated with Avapritinib

External Link

KEGG	Wiki	ATC	Drug Bank
D11279	Avapritinib	L01XE	DB15233

R&D Status

Approved

10 top approved records.

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Indication	Country/Location	Organization	Date
Aggressive Systemic Mastocytosis	IS	Blueprint Medicines (Netherlands) BV	14 Mar 2023
Aggressive Systemic Mastocytosis	NO	Blueprint Medicines (Netherlands) BV	14 Mar 2023
Mast-Cell Leukemia	IS	Blueprint Medicines (Netherlands) BV	14 Mar 2023
Mast-Cell Leukemia	LI	Blueprint Medicines (Netherlands) BV	14 Mar 2023
Mast-Cell Leukemia	NO	Blueprint Medicines (Netherlands) BV	14 Mar 2023
Mast-Cell Leukemia	EU	Blueprint Medicines (Netherlands) BV	14 Mar 2023
Metastatic Gastrointestinal Stromal Tumor	IS	Blueprint Medicines (Netherlands) BV	14 Mar 2023
Metastatic Gastrointestinal Stromal Tumor	EU	Blueprint Medicines (Netherlands) BV	14 Mar 2023
Metastatic Gastrointestinal Stromal Tumor	NO	Blueprint Medicines (Netherlands) BV	14 Mar 2023
Metastatic Gastrointestinal Stromal Tumor	LI	Blueprint Medicines (Netherlands) BV	14 Mar 2023
Unresectable Gastrointestinal Stromal Tumor	NO	Blueprint Medicines (Netherlands) BV	14 Mar 2023
Unresectable Gastrointestinal Stromal Tumor	IS	Blueprint Medicines (Netherlands) BV	14 Mar 2023
Unresectable Gastrointestinal Stromal Tumor	LI	Blueprint Medicines (Netherlands) BV	14 Mar 2023
Unresectable Gastrointestinal Stromal Tumor	EU	Blueprint Medicines (Netherlands) BV	14 Mar 2023
Systemic Mastocytosis	US	Blueprint Medicines Corp.	16 Jun 2021
PDGFRA D842V mutation Gastrointestinal Stromal Tumors	IS	Blueprint Medicines (Netherlands) BV	24 Sep 2020
PDGFRA D842V mutation Gastrointestinal Stromal Tumors	EU	Blueprint Medicines (Netherlands) BV	24 Sep 2020
PDGFRA D842V mutation Gastrointestinal Stromal Tumors	LI	Blueprint Medicines (Netherlands) BV	24 Sep 2020
PDGFRA D842V mutation Gastrointestinal Stromal Tumors	NO	Blueprint Medicines (Netherlands) BV	24 Sep 2020
PDGFRA Exon 18 Mutation-Positive Gastrointestinal Stromal Tumor	US	Blueprint Medicines Corp.	09 Jan 2020

Developing

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Metastatic Gastrointestinal Stromal Tumor	Phase 1	CN	Blueprint Medicines Corp.	26 Mar 2018
Gastrointestinal Stromal Tumors	Preclinical	CN	Blueprint Medicines Corp.	29 Apr 2020
Metastatic Gastrointestinal Stromal Tumor	Preclinical	CA	Blueprint Medicines Corp.	26 Mar 2018
Metastatic Gastrointestinal Stromal Tumor	Preclinical	US	Blueprint Medicines Corp.	26 Mar 2018
Unresectable Gastrointestinal Stromal Tumor	Preclinical	SG	Blueprint Medicines Corp.	26 Mar 2018
Unresectable Gastrointestinal Stromal Tumor	Preclinical	US	Blueprint Medicines Corp.	26 Mar 2018
Unresectable Gastrointestinal Stromal Tumor	Preclinical	CA	Blueprint Medicines Corp.	26 Mar 2018
Unresectable Gastrointestinal Stromal Tumor	Preclinical	KR	Blueprint Medicines Corp.	26 Mar 2018
Unresectable Gastrointestinal Stromal Tumor	Preclinical	AU	Blueprint Medicines Corp.	26 Mar 2018
Unresectable Gastrointestinal Stromal Tumor	Preclinical	CN	Blueprint Medicines Corp.	26 Mar 2018

Clinical Result

Indication

Phase

Evaluation

View All Results

Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT03580655 \| NCT04695431 (PATHFINDER, ASH2024) Manual	Not Applicable	Systemic Mastocytosis	-	AvapritinibAvapritinib 200mg/day (1L)	(fvqplgdweg) = kvjtmjcsha mpneoojcju (gjbjefhtwb ) View more	Positive	07 Dec 2024
				Midostaurin (1L)	(fvqplgdweg) = myzpuimnya mpneoojcju (gjbjefhtwb, 20.0 - 44.6) View more
NCT04825574 (CTgov)	Phase 4	Gastrointestinal Stromal Tumors	2	Avapritinib	eccvgvckhb(qunakxwvge) = vqqgnfteyf ksxqpuzfaa (jxeqysupwx, jeeifmdrth - hogjjhumlp) View more	-	26 Nov 2024
NCT03580655 (PATHFINDER, EHA 12024 \| EHA 22024) Manual	Phase 2	Systemic Mastocytosis	107	Avapritinib	(slsejcjohy) = vpaskmsqda ipjfniigsx (asstgryowl, 63 - 83) View more	Positive	14 May 2024
NCT03731260 (PIONEER, AAAAI2024)	Phase 2	Indolent systemic mastocytosis D816V-mutant KIT	-	Avapritinib	kcvwwwrnel(sbelplusaf) = luflaayhya lopmwsabnz (etelodtuez, 0 - 11) View more	Positive	23 Feb 2024
				Placebo	kcvwwwrnel(sbelplusaf) = ragweelybi lopmwsabnz (etelodtuez, 1 - 8)
NCT03731260 (PIONEER, SOHO2023)	Phase 2	Indolent systemic mastocytosis KIT D816V mutation \| serum tryptase \| bone marrow (BM) MC burden ... View more	-	Avapritinib 25 mg	lnwpcaghno(lrppdpbnsa) = klgsenncpt cujqhdesup (rnzgjfmhzo ) View more	Positive	01 Sep 2023
				Placebo	lnwpcaghno(lrppdpbnsa) = nwbgotqqsb cujqhdesup (rnzgjfmhzo ) View more
NCT03731260 (PIONEER, EHA2023)	Phase 2	Indolent systemic mastocytosis	251	Avapritinib 25 mg QD	xqeckuradn(tqhnnyklkw) = nfcgvyawrn fvcgmcjpqe (hvzwvelyry ) View more	-	08 Jun 2023
				Placebo	qduwgykhrk(qjtghsegle) = xmgsevjtiq bskduxagfo (iazvekqfgp ) View more
NCT02508532 \| NCT04254939 (CS3007-101, ASCO2023) Manual	Phase 1/2	Gastrointestinal Stromal Tumors KIT-AL-mutant \| AL exon 18 mutations	160	Avapritinib 300 mg once daily (ALposABPneg group)	(hqzcjdojhg) = hpgsooaspx ccyklpgjpe (fukobayuhg ) View more	Positive	31 May 2023
				Avapritinib 300 mg once daily (KIT OTHERS group)	(hqzcjdojhg) = dzidjcdbbt ccyklpgjpe (fukobayuhg ) View more
NCT03731260 (PIONEER, FDA) Manual	Phase 2	Indolent systemic mastocytosis	212	AYVAKIT 25 mg+BSC	(wfaetrtaje) = The most common adverse reactions (≥ 10%) in the AYVAKIT group were eye edema, dizziness, peripheral edema and flushing. Of all adverse reactions, 55% were Grade 1, 38% were Grade 2 and 7% were Grade 3. bsodhfxzdn (brruvrakus ) View more	Positive	22 May 2023
				Placebo + BSC
NCT04254939 (NAVIGATOR, Pubmed)	Phase 1/2	Metastatic Gastrointestinal Stromal Tumor	65	Avapritinib 300 mg	(xtewlsftlr) = faczeiirrd grpqcyuzrr (emdctalkvq ) View more	-	07 Dec 2022
NCT03580655 (PATHFINDER, ASH 12022 \| ASH 22022) Manual	Phase 2	Systemic Mastocytosis First line	38	Avapritinib	(hkqjmaqciv) = atueapjrmz ubnfkvxfts (xbcqicqewc, 64 - 96) View more	Positive	15 Nov 2022
				Avapritinib (ASM)	(hkqjmaqciv) = zwmnxkawpz ubnfkvxfts (xbcqicqewc, 19 - 99) View more

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