PDGFR inhibitors(Platelet-derived growth factor receptor inhibitors), RTK inhibitors(Receptor protein-tyrosine kinase inhibitors), VEGFR antagonists(Vascular endothelial growth factor receptor antagonists)

Therapeutic Areas

NeoplasmsDigestive System DisordersEndocrinology and Metabolic Disease+ [5]

Active Indication

Malignant Gastric Gastrointestinal Stromal TumorIslet Cell AdenomaIslet Cell Carcinoma+ [14]

Inactive Indication

Adenocarcinoma of prostateAdrenocortical CarcinomaAdvanced breast cancer+ [69]

Originator Organization

Pfizer Inc.

Active Organization

Accord Healthcare SLUPfizer Ltd.

National Cancer Institute

+ [4]

Inactive Organization

Novartis Pharmaceuticals Corp.

The General Hospital Corp.

Huizhi Pharmaceutical (Dalian) Co., Ltd.

+ [7]

Drug Highest PhaseApproved

First Approval Date

US (26 Jan 2006),

Advanced Renal Cell CarcinomaGastrointestinal Stromal Tumors

RegulationAccelerated Approval (US), Orphan Drug (JP)

Structure

Molecular FormulaC26H33FN4O7

InChIKeyLBWFXVZLPYTWQI-IPOVEDGCSA-N

CAS Registry341031-54-7

508

Clinical Trials associated with Sunitinib Malate

NCT05687123 / RecruitingPhase 1IIT

A Phase I Dose Escalation-Expansion Trial of Sunitinib Malate Plus Lutetium Lu 177 Dotatate (Lutathera) in Somatostatin Receptor Positive Pancreatic Neuroendocrine Tumors

This phase I trial tests the safety, side effects, and best dose of sunitinib malate in combination with lutetium Lu 177 dotatate in treating patients with pancreatic neuroendocrine tumors. Sunitinib malate is in a class of medications called kinase inhibitors and a form of targeted therapy that blocks the action of abnormal proteins called VEGFRs that signal tumor cells to multiply. This helps stop or slow the spread of tumor cells. Radioactive drugs, such as lutetium Lu 177 dotatate, may carry radiation directly to tumor cells and not harm normal cells. It is also a form of targeted therapy because it works by attaching itself to specific molecules (receptors) on the surface of tumor cells, known as somatostatin receptors, so that radiation can be delivered directly to the tumor cells and kill them. Giving sunitinib malate and lutetium Lu 177 dotatate in combination may be safer and more effective in treating pancreatic neuroendocrine tumors than giving either drug alone.

Start Date04 Jul 2024

Sponsor / Collaborator

National Cancer Institute

NCT06222593 / Not yet recruitingPhase 1/2IIT

A Phase I/II Study to Evaluate the Safety and Efficacy of Bicalutamide in Combination With Sunitinib in Patients With Receptor Tyrosine Kinase Inhibitor Resistant Renal Cell Carcinoma

This is a Phase I/II open-label, efficacy and safety study of bicalutamide in combination with sunitinib in patients with advanced renal cell carcinoma (RCC) who have been treated with a receptor tyrosine kinase inhibitor (RTKI) and experienced disease progression.

Start Date01 Jun 2024

Sponsor / Collaborator

State University of New York at Buffalo

NCT06208748 / Not yet recruitingPhase 2IIT

A Phase II Trial of Bezuclastinib in Combination With Sunitinib in Patients With GIST Who Progressed on Sunitinib Monotherapy

This is an open label, single arm, phase 2 trial investigating bezuclastinib plus sunitinib in patients with GIST who have previously progressed on sunitinib.

Start Date01 Jun 2024

Sponsor / Collaborator

Sarcoma Alliance for Research through Collaboration

[+3]

100 Clinical Results associated with Sunitinib Malate

100 Translational Medicine associated with Sunitinib Malate

100 Patents (Medical) associated with Sunitinib Malate

494

Literatures (Medical) associated with Sunitinib Malate

01 Nov 2023·Future oncology (London, England)

Ripretinib versus sunitinib in patients with advanced gastrointestinal stromal tumor after treatment with imatinib: a plain language summary of the phase 3 INTRIGUE trial.

Review

Author: Symcox, Marina ; Jones, Robin L

WHAT IS THIS SUMMARY ABOUT?:

This document presents a patient-friendly summary of the phase 3 INTRIGUE clinical trial results, which were published in the Journal of Clinical Oncology in August 2022. A phase 3 trial is a study that tests the safety of a proposed treatment and how well it works compared with a standard treatment or a treatment with no active ingredient (also called a placebo). The aim of the INTRIGUE trial was to understand whether treatment with a drug called ripretinib (brand nameQINLOCK^®) was superior to treatment with sunitinib (brand name SUTENT^®) in participants with advanced gastrointestinal stromal tumor (also known as GIST) who cannot tolerate or whose disease progressed beyond first-line treatment with imatinib (brand name GLEEVEC^®). The INTRIGUE trial included 453 participants with advanced GIST who had previously been treated with a tyrosine kinase inhibitor (also known as a TKI) medicine called imatinib. For patients with advanced GIST who cannot tolerate or whose disease progresses while taking imatinib, the recommended second-line TKI medicine is sunitinib. The recommended third-line TKI medicine is called regorafenib (brand name STIVARGA^®). Ripretinib is currently the only medication approved for adults with advanced GIST who have previously been treated with 3 or more TKIs (fourth-line).

WHAT WERE THE RESULTS?:

The trial showed that ripretinib did not significantly increase the time that participants survived without their cancer getting worse (progression-free survival or PFS) over sunitinib. However, participants treated with ripretinib had similar PFS to those treated with sunitinib. Importantly, treatment with ripretinib resulted in fewer severe adverse events, or side effects, compared with sunitinib, and participants reported better quality of life with ripretinib compared with sunitinib.

WHAT DO THE RESULTS MEAN?:

Treatment with ripretinib, after imatinib stops working or can no longer be tolerated, provided similar PFS for participants with advanced GIST and had fewer severe adverse events compared with sunitinib. Sunitinib is the only medication currently approved for use as a second-line treatment in patients with advanced GIST previously treated with imatinib. With more investigation, ripretinib could be a treatment option for these patients. Patients should always talk to their medical team before making any decisions about their treatment.

27 Sep 2023·ACS central science

Molecular Editing of Pyrroles via a Skeletal Recasting Strategy.

Article

Author: Zhou, Xueting ; Lu, Yixin ; Guo, Jiami ; Dai, Lei ; Huang, Qingqin

Heterocyclic scaffolds are commonly found in numerous biologically active molecules, therapeutic agents, and agrochemicals. To probe chemical space around heterocycles, many powerful molecular editing strategies have been devised. Versatile C-H functionalization strategies allow for peripheral modifications of heterocyclic motifs, often being specific and taking place at multiple sites. The past few years have seen the quick emergence of exciting "single-atom skeletal editing" strategies, through one-atom deletion or addition, enabling ring contraction/expansion and structural diversification, as well as scaffold hopping. The construction of heterocycles via deconstruction of simple heterocycles is unknown. Herein, we disclose a new molecular editing method which we name the skeletal recasting strategy. Specifically, by tapping on the 1,3-dipolar property of azoalkenes, we recast simple pyrroles to fully substituted pyrroles, through a simple phosphoric acid-promoted one-pot reaction consisting of dearomative deconstruction and rearomative reconstruction steps. The reaction allows for easy access to synthetically challenging tetra-substituted pyrroles which are otherwise difficult to synthesize. Furthermore, we construct N-N axial chirality on our pyrrole products, as well as accomplish a facile synthesis of the anticancer drug, Sutent. The potential application of this method to other heterocycles has also been demonstrated.

01 Jul 2023·European journal of cancer (Oxford, England : 1990)

Sex differences on multikinase inhibitors toxicity in patients with advanced gastroenteropancreatic neuroendocrine tumours.

Article

Author: Ibrahim, Toni ; Hernando, Jorge ; Roca-Herrera, Maria ; Garcia-Alvarez, Alejandro ; Garcia-Carbonero, Rocio ; Valle, Juan W. ; Tafuto, Salvatore ; Salazar, Ramon ; Ruszniewski, Philippe ; Alonso, Vicente ; Navarro, Victor ; Capdevila, Jaume ; Teule, Alex ; Fazio, Nicola ; Carmona, Ana ; Grande, Enrique ; Kulke, Matthew H. ; Castellano, Daniel ; Raymond, Eric

PURPOSE:

There is an increasing interest in the role of sex and gender in cancer patients. The impact of sex differences in oncological systemic therapies is still unknown, and there is a lack of evidence specially in uncommon neoplasms like neuroendocrine tumours (NET). In the present study, we combine the differential toxicities by sex in five published clinical trials with multikinase inhibitors (MKI) in gastroenteropancreatic (GEP) NET.

METHODS:

We performed a pooled univariate analysis of reported toxicity in patients treated in five phase 2 and phase 3 clinical trials with MKI in the GEP NET setting: sunitinib (SU11248, SUN1111), Pazopanib (PAZONET), sorafenib-bevacizumab (GETNE0801) and Lenvatinib (TALENT). Differential toxicities between male and female patients were evaluated considering relationship with study drug and different weights of each trial by random effect adjustment.

RESULTS:

We found nine toxicities which were more frequent in female patients (leukopenia, alopecia, vomiting, headache, bleeding, nausea, dysgeusia, neutrophil count decreased and dry mouth) and two toxicities being more frequent in male patients (Anal Symptoms and Insomnia). Asthenia and diarrhoea were the only severe (Grade 3-4) toxicities more frequent in female patients.

CONCLUSIONS:

Sex-related differences in toxicity with the MKI treatment require targeted information and individualised management of patients with NET. Differential reporting of toxicity should be promoted when clinical trials are published.

151

News (Medical) associated with Sunitinib Malate

03 Jun 2024

·www.biospace.com

IDRx Reports Updated Preliminary Phase 1 Data from Ongoing Phase 1/1b StrateGIST 1 Trial Supporting Best-in-Class Potential for IDRX-42 in Patients with GIST

Encouraging signs of activity were observed, including a 23% objective response rate (ORR) across all patients (median four prior lines of therapy) and a 43% ORR across second-line patients Favorable tolerability pro observed, consistent with use in front-line and second-line settings Data to be highlighted in an oral presentation today at the 2024 American Society of Clinical Oncology (ASCO) Annual Meeting PLYMOUTH, Mass.--(BUSINESS WIRE)-- IDRx, Inc., a clinical-stage biopharmaceutical company dedicated to transforming cancer treatment with purpose-built precision therapies, today announced updated preliminary clinical data from the Phase 1 portion of the company’s ongoing StrateGIST 1 study of IDRX-42 in patients with advanced gastrointestinal stromal tumors (GIST). These data will be highlighted today in an oral presentation at the 2024 American Society of Clinical Oncology (ASCO) Annual Meeting. IDRX-42 is a novel, KIT mutant-selective, tyrosine kinase inhibitor (TKI) that has potent activity against both the key activating mutations and broad coverage of the clinically relevant resistance mutations in KIT-driven GIST. IDRX-42 was designed to overcome the twin challenges of on-target treatment resistance and off-target driven adverse events, which limit the clinical benefit of currently available TKIs. “There is a significant unmet medical need for next-generation therapies for GIST patients. Current standards of care either lack the breadth of resistance mutation coverage necessary for patients to realize long durations of response or disease stabilization, or they lack selectivity, resulting in unwanted side effects, or both,” said Professor Patrick Schöffski, M.D., M.P.H., Head of the Department of General Medical Oncology at the University Hospitals Leuven. “These promising Phase 1 data support the potential of IDRX-42 to provide meaningful clinical benefit for GIST patients, with encouraging evidence of clinical activity in patients with activating KIT mutations in exons 9 and 11, as well as in patients with clinically relevant resistance mutations in KIT, importantly those in exons 13 and 17.” Updated Preliminary Clinical Data Summary As of the data cut-off date of April 28, 2024, 73 patients have been treated with IDRX-42 in the Phase 1 portion of the ongoing StrateGIST 1 trial across dose cohorts ranging from 120 mg once daily (QD) to 600 mg twice daily (BID). All 73 patients had KIT-mutant GIST. 66 patients were evaluable for efficacy as of the time of the data cut-off. Patients who were efficacy evaluable must have had at least 1 post-baseline tumor assessment or had clinical progression or death before the first post-baseline tumor assessment. While a maximum tolerated dose was not reached, dose escalation in the Phase 1 portion of the trial has completed, and the Phase 1b dose confirmation portion of the trial has been initiated utilizing a dose of 300mg tablet formulation, which is equivalent to the 400mg capsule formulation. Patients were heavily pretreated, with a median of four prior lines of therapy. 19% (14/73) patients had received one prior line of therapy. 11% (8/73) patients had received two prior lines of therapy. 70% (51/73) patients had received three or more prior lines of therapy. 74% of patients remained on study treatment, and the median duration of treatment was 16 weeks as of the data cut-off. 100% of second line patients remained on treatment as of the data cut-off. The objective response rate (ORR) by modified RECIST v1.1 in the efficacy evaluable population was 23% (15/66) treated across all lines of therapy, of which all were partial responses (12 confirmed PRs, 3 pending confirmation). The ORR across second line patients was 43% (6/14; 4 confirmed PRs, 2 pending confirmation). In analyses of circulating tumor DNA (ctDNA), reductions in mutant allele fraction were observed consistently across KIT mutations detected in baseline samples. Reductions in mutant allele fraction, including to undetectable levels, as best response were observed in exon 9 and 11 activating mutations, and in resistance mutations exon 13, 14, and 17. IDRX-42 exhibited a favorable safety pro treatment-related adverse events (TRAEs) were mainly low grade. The most frequently reported TRAEs (≥20%) were gastrointestinal symptoms (diarrhea, nausea, decreased appetite, vomiting, dysgeusia) and fatigue. Gastrointestinal adverse events were Grade 1 in most patients, when they occurred. A low rate of dose modifications due to TRAEs was observed at the 400mg QD dose level, with only 6% dose reductions, 9% dose interruptions, and 0% discontinuations due to TRAEs. Dose-limiting toxicities (DLTs) were observed in 3/73 patients at doses of 600 mg, 800 mg and 1200 mg, respectively. All 3 patients elected to reduce dose and remained on study as of the data cut-off (range: >3 to >11 months); 2 of these patients have achieved a confirmed PR at a reduced dose of 400 mg QD. A flat and dose-linear pharmacokinetic pro observed. “In this dataset, IDRx has presented preliminary proof-of-concept of IDRX-42 supporting its potentially best-in-class pro patients with GIST,” said Tim Clackson, Ph.D., Chief Executive Officer of IDRx. “Importantly, we believe these efficacy and safety data support our plan to move IDRX-42 rapidly into early lines of therapy, including second-line and front-line, where patients haven’t seen a new treatment option in over 15 years.” “We are excited for these data to be presented today, as they support all aspects of our target product profile, including evidence of potent activity against relevant activating and resistance mutations in KIT, combined with a favorable safety profile,” said David Kerstein, M.D., Chief Medical Officer of IDRx. “Across a wide dose range and in this heavily pre-treated patient population, promising signs of clinical activity have been observed, and the initial data compares favorably against approved therapies and those in clinical development. We are encouraged by the emerging safety and tolerability profile, characterized mainly by low grade, manageable gastrointestinal adverse events with a notable lack of adverse events generally associated with off-target activity, such as hand-foot skin reaction and hypertension, supporting the overall selectivity of the molecule. We would like to express our gratitude to the patients and investigators for their participation in the ongoing StrateGIST 1 study.” The Data Will be Highlighted in an Oral Presentation at the 2024 American Society of Clinical Oncology (ASCO) Annual Meeting: Title: StrateGIST 1: A first-in-human (FIH), phase 1 study of IDRX-42 in patients with metastatic gastrointestinal stromal tumors resistant to prior treatment with tyrosine kinase inhibitors (TKIs) Presenter: Patrick Schöffski, M.D., M.P.H. Abstract Number: 11501 Presentation Type: Oral Abstract Session Session Title: Sarcoma (Sub Track Gastrointestinal Stromal Tumors) Time: 3:12 P.M. CDT About GIST Gastrointestinal stromal tumors (GIST) are the most common subtype of soft tissue sarcoma. Approximately 80% of cases arise from gain of function mutations in the KIT receptor tyrosine kinase, driving the malignancy through constitutive activation of aberrant signaling. Resistance mutations in KIT emerge in ~90% of patients treated with imatinib, the current standard of care for GIST. In unresectable or metastatic GIST, clinical benefits from existing treatments can vary by mutation type. About the StrateGIST 1 Study StrateGIST 1 is an ongoing, open-label, first-in-human Phase 1/1b study designed to evaluate the safety, tolerability, pharmacokinetics, and preliminary antitumor activity of IDRX-42 in patients with metastatic and/or surgically unresectable GIST after failure of imatinib and other approved drugs. The study is currently enrolling patients with documented pathogenic mutation in KIT or any platelet-derived growth factor receptor alpha (PDGFRA) mutation (other than PDGFRA exon 18) at sites in the U.S., Belgium, Germany and Spain. The Phase 1b portion will include expanded exploratory cohorts based on defined lines of prior TKI therapy. About IDRX-42 IDRX-42 is a potent, oral, highly selective KIT inhibitor targeting all major categories of activating and resistance mutations in patients with KIT-mutant GIST (including variants in exons 9, 11, 13 and 17). In preclinical studies, IDRX-42 demonstrated superior antitumor activity compared to imatinib, the current first-line of therapy, in GIST human xenograft models expressing mutations in KIT exons 9 and 11. In xenograft models expressing secondary resistance mutations in KIT exon 13 or 17, IDRX-42 treatment resulted in potent and dose-dependent antitumor activity superior to the second-line standard of care agent, sunitinib. IDRX-42 is currently being evaluated in a first-in-human Phase 1/1b study. About IDRx IDRx is a clinical-stage biopharmaceutical company dedicated to transforming cancer care with intelligently designed precision therapies. IDRx aims to address the limitations of today’s precision cancer medicines with highly potent and selective targeted therapies to stop key tumor escape mechanisms and prolong response to therapy. IDRx’s lead program is IDRX-42, designed to inhibit key genetic drivers and drug-resistant mutations of KIT in gastrointestinal stromal tumor (GIST). IDRx's pipeline also includes a second KIT inhibitor, IDRX-73. Founded in 2021, IDRx’s leadership team has extensive experience in drug development and collectively has been involved in the discovery, development, and commercialization of more than 10 approved medicines. To learn more, please visit and follow us on LinkedIn. View source version on businesswire.com: Contacts 1AB Katie Engleman katie@1abmedia.com Source: IDRx, Inc. View this news release online at:

Phase 1ASCOClinical Result

23 May 2024

·www.globenewswire.com

Cogent Biosciences Announces Positive Updated Lead-In Data from Ongoing Phase 3 PEAK Trial Evaluating Bezuclastinib in Combination with Sunitinib in Patients with Gastrointestinal Stromal Tumors (GIST) at ASCO Annual Meeting

Bezuclastinib + sunitinib combination therapy reached median progression free survival (mPFS) of 19.4-months and 33% ORR in subset of advanced GIST patients with one prior treatment Encouraging long-term safety and tolerability with combination bezuclastinib and sunitinib therapy in Part 1 PEAK Phase 3 guidance accelerated with enrollment completion now expected in 3Q 2024 Company announces new advanced GIST clinical trial sponsored by the Sarcoma Alliance for Research through Collaboration (SARC) and in collaboration with The Life Raft Group and Dana-Farber Cancer Institute WALTHAM, Mass. and BOULDER, Colo., May 23, 2024 (GLOBE NEWSWIRE) -- Cogent Biosciences, Inc. (Nasdaq: COGT), a biotechnology company focused on developing precision therapies for genetically defined diseases, today announced positive updated lead-in data from the company’s ongoing Phase 3 PEAK trial evaluating the selective and potent KIT mutant inhibitor, bezuclastinib, in combination with sunitinib, in patients with Gastrointestinal Stromal Tumors (GIST). The data will be presented in a poster presentation at the American Society of Clinical Oncology (ASCO) Annual Meeting in Chicago, IL on June 1. Cogent also announced today a new Phase 2 clinical trial of bezuclastinib plus sunitinib in later line GIST patients, sponsored by the Sarcoma Alliance for Research through Collaboration (SARC) and in collaboration with The Life Raft Group and Dana-Farber Cancer Institute. “These data presented today reinforce our excitement that the combination of bezuclastinib and sunitinib has the potential to become a new standard of care for advanced GIST patients,” said Andrew Robbins, President and Chief Executive Officer at Cogent Biosciences. “Coupled with the impressive clinical activity demonstrated by the combination, the addition of bezuclastinib to sunitinib continues to be generally well-tolerated with an encouraging safety profile. We are pleased to report that the pace of enrollment in PEAK is significantly ahead of schedule, and we now expect enrollment to complete in the third quarter of 2024.” “We are also excited today to announce a collaboration with SARC, The Life Raft Group and Dana-Farber on a new Phase 2 clinical trial assessing the potential benefit of bezuclastinib with sunitinib in later line GIST patients who are not eligible for the PEAK study and currently have very limited treatment options,” continued Mr. Robbins. “There is tremendous need for additional treatment options for GIST patients,” said Andrew Wagner M.D., Ph.D., Senior Physician, Center for Sarcoma and Bone Oncology, Dana-Farber Cancer Institute, and Associate Professor of Medicine, Harvard Medical School. “Today’s updated lead-in data from the bezuclastinib combination are very promising, and I remain excited about the ongoing PEAK trial. Additionally, with the announcement of this new study today, we have a clinical trial which allows us to explore the use of bezuclastinib with sunitinib in patients who are not eligible for the PEAK study.” PEAK Trial UpdatePEAK is a randomized, open-label, global, Phase 3 clinical trial evaluating bezuclastinib in combination with sunitinib vs sunitinib alone in GIST patients previously treated with imatinib. In the updated lead-in data being presented at ASCO, as of the cutoff date, April 1, 2024, the 42 patients in Part 1 have been on study for a median of 15.3 months. The median progression-free survival (mPFS) during treatment with bezuclastinib and sunitinib was 10.2 months in all patients. In a subset of second-line GIST patients with only prior imatinib, which most closely resembles patients currently enrolling in Part 2 of PEAK, the data demonstrate a mPFS of 19.4 months. In addition, the objective response rate (ORR) in all patients treated with bezuclastinib and sunitinib was 27.5% and in the subset of second-line patients the ORR was 33.3%, per investigator assessment. Combination treatment resulted in a disease control rate of 80% in all patients and 100% in patients with prior imatinib only. Safety DataAs of the data cutoff, the combination of bezuclastinib and sunitinib does not appear to add to the severity of adverse events known to be associated with sunitinib monotherapy and is well-tolerated. The majority of treatment-emergent adverse events (TEAEs) were low-grade and reversible. No additional serious adverse reactions or discontinuations due to TEAEs have been reported since the last presentation of data in November 2023. ASCO Poster DetailsTitle: Peak part 1 summary: A phase 3, randomized, open-label multicenter clinical study of bezuclastinib (CGT9486) and sunitinib combination versus sunitinib in patients with gastrointestinal stromal tumors (GIST)Session Type and Title: Poster Session – SarcomaSession Date and Time: June 1, 2024, 1:30 PM-4:30 PM CDT The poster will be available in the Posters and Publications portion of the Cogent website at approximately 8:00 AM ET on June 1. Phase 2 SARC TrialThe open label, single arm Phase 2 trial sponsored by SARC and in collaboration with The Life Raft Group and Dana-Farber Cancer Institute is designed to evaluate the mPFS as well as the safety and tolerability of bezuclastinib plus sunitinib in 40 patients with GIST who have previously progressed on sunitinib. This trial will focus on later line patients, where limited treatment options are available. Additional details can be found on clinicaltrials.gov; Identifier NCT06208748. For more information about SARC or The Life Raft Group, please visit www.sarctrials.org or www.liferaftgroup.org. Bezuclastinib Clinical DevelopmentEnrollment continues in the Phase 3 registration-enabling PEAK study, which will include approximately 388 second-line, post imatinib GIST patients. Due to rapid enrollment, the Company now expects PEAK enrollment to be completed in the third quarter of 2024 with top-line results still expected by the end of 2025. Cogent remains on-track to complete enrollment in APEX in patients with advanced systemic mastocytosis (AdvSM) by the end of 2024 and report top-line results mid-2025 and complete enrollment in SUMMIT Part 2 in the second quarter of 2025 and report top-line results by the end of 2025. Upcoming Investor ConferenceCogent will participate in the Jefferies Global Healthcare Conference on Wednesday, June 5 at 2:30 p.m. ET. A live webcast will be available on the Investors & Media page of Cogent’s website at investors.cogentbio.com/events. A replay will be available approximately two hours after completion of the event and will be archived for up to 30 days. 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 and PI3Kα. 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 long-term safety and tolerability profile of the combination of bezuclastinib and sunitinib therapy, the potential for the combination of bezuclastinib and sunitinib to become a new standard of care for advanced GIST patients, the updated guidance that the Company now expects PEAK enrollment to be completed in the third quarter of 2024 with top-line results still expected by the end of 2025, the expectation that PEAK will include approximately 388 second-line post imatinib GIST patients, the expectation to complete enrollment in APEX by the end of 2024 and to report top-line results mid-2025 and the expectation to complete enrollment in SUMMIT Part 2 in the second quarter of 2025 and to report top-line results by the end of 2025. 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

Phase 3Phase 2Clinical ResultASCO

23 May 2024

·www.fiercepharma.com

ASCO: Merck KGaA, Pfizer's Bavencio combo misses survival mark in crowded kidney cancer space

For Bavencio, Merck KGaA has had a “limited focus” in kidney cancer and is instead focusing on the drug's bladder cancer use, a spokesperson said. Five years after scoring an FDA approval to treat newly diagnosed advanced kidney cancer, the combination of Merck KGaA’s Bavencio and Pfizer’s Inlyta has failed on the overall survival endpoint of a phase 3 trial. The Bavencio-Inlyta combo showed a favorable trend, reducing the risk of death by 14% compared with Pfizer’s Sutent as a first-line treatment in renal cell carcinoma with PD-L1 expression, the final overall survival (OS) analysis from the JAVELIN Renal 101 trial showed. But the number, gleaned after a median follow-up of more than six years, missed statistical significance. The study has therefore missed one of its two independent primary endpoints. In the overall trial population, the death-risk reduction was smaller at 12%. The results were shared in an abstract Thursday and will be presented in detail at the upcoming American Society of Clinical Oncology 2024 annual meeting. The Bavencio regimen won’t lose its FDA approval, and the trial is still considered positive because the PD-L1/TKI combo previously showed it can significantly stall tumor progression or death versus Sutent. But missing the overall survival mark won’t be helpful to Bavencio in its competition with PD-1/TKI rivals from Merck & Co. and Bristol Myers Squibb. Longer trial follow-ups are typically unfavorable for OS readouts for immunotherapy-based regimens in first-line kidney cancer, a spokesperson for Merck KGaA’s EMD Serono biopharma arm told Fierce Pharma, citing external factors that can affect the analyses. Previously, in the phase 3 CheckMate-9ER trial, BMS’ Opdivo and Exelixis’ Cabometyx significantly reduced the risk of death by 30% compared with Sutent in the preplanned final OS analysis after a median follow-up of about 33 months. But the showing shrank to 23% during a longer follow-up of about 56 months. Similarly, in its own combination with Inlyta, Merck’s Keytruda significantly slashed the risk of death by 47% against Sutent in the KEYNOTE-426 trial after a short follow-up of nearly 13 months. Then, after about 30 months of median follow-up, the figure decreased to 32%. While the Bavencio combo missed the OS mark in the overall population, EMD Serono pointed to a subgroup of patients who had a favorable risk profile under the International Metastatic RCC Database Consortium. In these roughly 200 patients of the nearly 900-strong trial, Bavencio and Inlyta showed a 27% reduction in the risk of death, which is the biggest benefit seen so far among existing therapies. The regimen also boasts a low discontinuation rate: Only 4.8% of patients permanently stopped both Bavencio and Inlyta due to treatment-related adverse events versus 9.3% for Sutent. “We continue to believe in the value of Bavencio + [Inlyta] as the data, both clinical and real-world, clearly show the benefit of this treatment combination by balancing efficacy and [quality of life] for patients in the [first-line kidney cancer] setting, especially in favorable-risk group and older patients where maintained QoL is a key goal,” the company spokesperson said in a statement. Nevertheless, as the combo has failed to register a significant OS benefit since its approval, the Bavencio-Inlyta regimen has largely come to be viewed as inferior to PD-1/TKI combos, including Keytruda’s Lenvima pairing. Merck KGaA, recognizing the competition, only has had a “limited focus” in kidney cancer, according to the spokesperson. Instead, the company is directing its Bavencio efforts toward first-line maintenance use in advanced bladder cancer, which represents the drug’s largest indication in the U.S. But it faces a new threat in that indication in the form of Keytruda’s combination with Pfizer and Astellas’ antibody-drug conjugate Padcev, which entered first-line bladder cancer treatment last year to much fanfare. Earlier this month, Peter Guenter, who leads Merck KGaA’s pharma business, said the company had not yet seen a significant effect from the Keytruda-Padcev launch in the U.S. But he noted a decrease of platinum-based chemotherapy in the first three months of 2024. That means Bavencio might see a bigger impact starting in the second quarter, because the PD-L1 drug is approved as a maintenance therapy in patients who’ve responded to a round of chemo. In the first quarter, Bavencio’s sales increased 14% year over year at constant exchange rate to 186 million euros. Because only about 30% of the drug’s sales come from the U.S., Merck KGaA still expects the drug to continue to grow in 2024. Merck KGaA had previously shared Bavencio rights with Pfizer until the New York pharma returned its stake last year to win antitrust clearance for its $43 billion acquisition of Seagen, which co-developed Padcev.

Clinical ResultPhase 3AcquisitionDrug ApprovalASCO

100 Deals associated with Sunitinib Malate

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KEGG	Wiki	ATC	Drug Bank
D06402	Sunitinib Malate	L01XE04	DB01268

R&D Status

Approved

10 top approved records.

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Indication	Country/Location	Organization	Date
Malignant Gastric Gastrointestinal Stromal Tumor	EU	Accord Healthcare SLU	11 Feb 2021
Malignant Gastric Gastrointestinal Stromal Tumor	IS	Accord Healthcare SLU	11 Feb 2021
Malignant Gastric Gastrointestinal Stromal Tumor	LI	Accord Healthcare SLU	11 Feb 2021
Malignant Gastric Gastrointestinal Stromal Tumor	NO	Accord Healthcare SLU	11 Feb 2021
Islet Cell Adenoma	JP	Pfizer Japan, Inc.	10 Aug 2012
Islet Cell Carcinoma	US	C.P. Pharmaceuticals International CV	20 May 2011
Renal Cell Carcinoma	JP	Pfizer Japan, Inc.	16 Apr 2008
Metastatic Renal Cell Carcinoma	EU	Pfizer Ltd.	19 Jul 2006
Metastatic Renal Cell Carcinoma	IS	Pfizer Ltd.	19 Jul 2006
Metastatic Renal Cell Carcinoma	LI	Pfizer Ltd.	19 Jul 2006
Metastatic Renal Cell Carcinoma	NO	Pfizer Ltd.	19 Jul 2006
Neuroendocrine tumor of pancreas	EU	Pfizer Ltd.	19 Jul 2006
Neuroendocrine tumor of pancreas	IS	Pfizer Ltd.	19 Jul 2006
Neuroendocrine tumor of pancreas	LI	Pfizer Ltd.	19 Jul 2006
Neuroendocrine tumor of pancreas	NO	Pfizer Ltd.	19 Jul 2006
Pancreatic neuroendocrine tumour metastatic	EU	Pfizer Ltd.	19 Jul 2006
Pancreatic neuroendocrine tumour metastatic	IS	Pfizer Ltd.	19 Jul 2006
Pancreatic neuroendocrine tumour metastatic	LI	Pfizer Ltd.	19 Jul 2006
Pancreatic neuroendocrine tumour metastatic	NO	Pfizer Ltd.	19 Jul 2006
Well Differentiated Pancreatic Endocrine Tumor	EU	Pfizer Ltd.	19 Jul 2006

Developing

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Indication	Highest Phase	Country/Location	Organization	Date
Advanced Hepatocellular Carcinoma	Phase 3	US	Pfizer Inc.	01 Jul 2008
Advanced Hepatocellular Carcinoma	Phase 3	CN	Pfizer Inc.	01 Jul 2008
Advanced Hepatocellular Carcinoma	Phase 3	JP	Pfizer Inc.	01 Jul 2008
Advanced Hepatocellular Carcinoma	Phase 3	AU	Pfizer Inc.	01 Jul 2008
Advanced Hepatocellular Carcinoma	Phase 3	BE	Pfizer Inc.	01 Jul 2008
Advanced Hepatocellular Carcinoma	Phase 3	CA	Pfizer Inc.	01 Jul 2008
Advanced Hepatocellular Carcinoma	Phase 3	FR	Pfizer Inc.	01 Jul 2008
Advanced Hepatocellular Carcinoma	Phase 3	DE	Pfizer Inc.	01 Jul 2008
Advanced Hepatocellular Carcinoma	Phase 3	HK	Pfizer Inc.	01 Jul 2008
Advanced Hepatocellular Carcinoma	Phase 3	IT	Pfizer Inc.	01 Jul 2008

Clinical Result

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT01371201 (FIRSTMAPPP, Pubmed)	Phase 2	Paraganglioma \| Pheochromocytoma SDHB status (mutation present vs wild type) \| number of previous systemic therapies (0 vs ≥1)	78	Sunitinib	yojgxonjuq(pdvvrjfzdg) = Two deaths occurred in the placebo group due to aspiration pneumonia and septic shock. uxidswyuim (idjdrythfu ) View more	Positive	22 Feb 2024
				Placebo
NCT03277924 (Immunosarc II, ESMO2023) Manual	Phase 2	Sarcoma	23	Sunitinib + nivolumab	smvahxuczg(utrsbbairq) = fhpaueluet cuydxbffso (yjbuuoihas )	Positive	23 Oct 2023
				Sunitinib + nivolumab (angiosarcoma)	smvahxuczg(utrsbbairq) = vyptuvhvky cuydxbffso (yjbuuoihas ) View more
NCT01517243 (CTgov)	Phase 2	Metastatic Renal Cell Carcinoma	37	Sunitinib+Temsirolimus	gowvcuqjzy(nkydpstjwd) = lerzgndich fmhtaywdny (dacqcobxie, tvlyfjpitv - srbtnhnyin) View more	-	21 Sep 2023
ESC2023	Not Applicable	Renal Cell Carcinoma	-	Patients with RCC treated with sunitinib or pazopanib	zrctndfkye(mqwsgtajwp) = mowfxjthtu nvefaqmqrf (jgqmgbobhw ) View more	-	25 Aug 2023
NCT05461664 (ASCO2023) Manual	Not Applicable	Gastrointestinal Stromal Tumors	11	Sunitinib Malate+Avapritinib	hbbwzxgtzg(ggbmsphztp) = anemia, leukopenia, diarrhea, fatigue, periorbital and face oedema, and memory impairment sqlczmujzh (tipxpcmmjr ) View more	Positive	31 May 2023
NCT03541902 (CABOSUN II, ASCO2023) Manual	Phase 2	Renal Cell Carcinoma	32	cabozantinib	nssqelxagd(nchigrrovk) = qxjducbhmo rdjeprnblv (mpthcrbpwy, 4.3 - NR) View more	Non-superior	31 May 2023
				sunitinib	nssqelxagd(nchigrrovk) = juzcuvmzdt rdjeprnblv (mpthcrbpwy, 11 - NR) View more
ChiCTR1800017136 (ASCO2023) Manual	Phase 2	Renal Cell Carcinoma First line	42	Sunitinib	ukjhqjxekn(twcjibnqmh) = butvzguryr acvofxsxod (wgjgqsmdrd ) View more	Positive	31 May 2023
				Sunitinib + SBRT	ukjhqjxekn(twcjibnqmh) = niewaahkix acvofxsxod (wgjgqsmdrd ) View more
NCT03025893 (STELLAR, AACR2023) Manual	Phase 2/3	Recurrent Glioblastoma	-	Sunitinib 300mg/700mg (Sunitinib 300mg + part 1)	isqazhonqu(ytjsuyjmmq) = mutcegieyc bkdzssuuje (fcgcqlppwv, 1.4 - 1.7) View more	Negative	14 Apr 2023
				Sunitinib 300mg/700mg (Sunitinib 700mg + part 2)	isqazhonqu(ytjsuyjmmq) = qaqutaqapy bkdzssuuje (fcgcqlppwv, 1.3 - 1.5) View more
NCT01306045 (CTgov)	Phase 2	Thymoma, Familial \| Small Cell Lung Cancer \| Advanced Lung Non-Small Cell Carcinoma ... View more	647	Selumetinib (AZD6244)+Erlotinib+Lapatinib+MK-2206+Sunitinib (Non-Small Cell Lung Cancer (NSCLC))	dhjfeikqof(qijpvutjxx) = jpqgynxokh dgvswhznhd (ogeorvdato, tiieogxidf - fnyojxllze) View more	-	11 Apr 2023
				Selumetinib (AZD6244)+Erlotinib+Lapatinib+MK-2206+Sunitinib (Small Cell Lung Cancer (SCLC))	dhjfeikqof(qijpvutjxx) = htauwepoyh dgvswhznhd (ogeorvdato, zzitauvskw - ccjpdpiaij) View more
NCT02919371 (ASCO_GU2023) Manual	Phase 1/2	Advanced Renal Cell Carcinoma	25	Sunitinib+Bevacizumab	prtxtbhxyu(qdetitmkon) = tunsjmbhfn eipjmxvesj (oscbzvyzcl, 4.1 - 28.8) View more	Positive	21 Feb 2023

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