MEK1 inhibitors(Dual specificity mitogen-activated protein kinase kinase 1 inhibitors), MEK2 inhibitors(Dual specificity mitogen-activated protein kinase kinase 2 inhibitors)

Therapeutic Areas

NeoplasmsHemic and Lymphatic DiseasesSkin and Musculoskeletal Diseases+ [11]

Active Indication

Histiocytic SarcomaBRAF V600 mutation-positive MelanomaMelanoma+ [42]

Inactive Indication

Adenocarcinoma of large intestineAdvanced breast cancerAdvanced Colorectal Adenocarcinoma+ [35]

Originator Organization

Exelixis, Inc.

Active Organization

Hoffmann-La Roche, Inc.

Genentech, Inc.

Exelixis, Inc.

+ [3]

Inactive Organization

Roche Farma SARoche Pharma AG

Drug Highest PhaseApproved

First Approval Date

United States (10 Nov 2015),

Melanoma

RegulationFast Track (United States), Orphan Drug (United States), Breakthrough Therapy (United States)

Structure/Sequence

Molecular FormulaC46H46F6I2N6O8

InChIKeyRESIMIUSNACMNW-BXRWSSRYSA-N

CAS Registry1369665-02-0

123

Clinical Trials associated with Cobimetinib Fumarate

NCT06813079

/ Not yet recruitingPhase 2IIT

ADOPT: Adaptive Organoid-Based Precision Therapy Study in Pancreatic Cancer - A Prospective Single-Arm Phase II Trial

The purpose of this study is to see if using Patient Derived Organoids (PDO) to choose a drug for the treatment of pancreatic cancer individually for each patient is useful. The study will look at the number of participants who have a response to their assigned drug.

Start Date17 Feb 2025

Sponsor / Collaborator

University Health Network

NCT06440850

/ RecruitingPhase 2IIT

A Pilot Clinical Trial of Vemurafenib and Cobimetinib as a Redifferentiation Strategy in High-Risk, Radioactive Iodine (RAI) Naïve, BRAFV600E Mutated Differentiated Thyroid Carcinoma Patients Undergoing Initial RAI Therapy

This phase II trial tests how well vemurafenib and cobimetinib work in treating patients with high risk differentiated thyroid carcinoma with BRAFV600E mutation, in preparation for radioactive iodine therapy. Vemurafenib and cobimetinib are used in patients whose cancer has a mutated (changed) form of a gene called BRAF. They are in a class of medications called kinase inhibitors. They work by blocking the action of an abnormal protein that signals cancer cells to multiply. This helps slow or stop the spread of cancer cells. Giving vemurafenib and cobimetinib may work better to treat patients with high risk differentiated thyroid carcinoma with BRAFV600E mutation, in preparation for radioactive iodine therapy.

Start Date15 Jul 2024

Sponsor / Collaborator

City of Hope National Medical Center

[+1]

NCT05756556

/ SuspendedPhase 2

A Phase 2a, Open-label Study of T3011 in Combination With Cobimetinib in Patients With Advanced Melanoma

This study will evaluate the efficacy and safety of T3011 in combination with Cobimetinib in patients with advanced melanoma.

Start Date30 Jun 2024

Sponsor / Collaborator

Shenzhen Yinuowei Medical Technology Co., Ltd.Startup

100 Clinical Results associated with Cobimetinib Fumarate

100 Translational Medicine associated with Cobimetinib Fumarate

100 Patents (Medical) associated with Cobimetinib Fumarate

807

Literatures (Medical) associated with Cobimetinib Fumarate

01 May 2025·INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES

Effects of F53 hotspot mutations on the molecular dynamics of MEK1 protein and the binding of its FDA-approved inhibitors

Article

Author: Vural, Berkin Ersin ; Yandım, Cihangir

MEK1 (MAP2K1) could emerge as an oncogenic protein in the presence of certain mutations, and could be inhibited by FDA-approved drugs (trametinib, cobimetinib, binimetinib and selumetinib). However, how the mutations on MEK1's hotspot residue F53 affect the bindings of these therapeutic molecules remained largely unexplored. We performed molecular dynamics (MD) simulations with wild-type and mutated (F53L/V/C/I/Y) MEK1 structures in the presence and absence of these drugs and observed changes on the motion of MEK1. A longer duration in the lowest energy state conformation was observed during the simulations in the presence of F53 mutations. This was complemented by cross-correlated motions of amino acids of MEK1. More importantly, the binding affinities of inhibitors were affected. There was a marked reduction in the calculated binding affinity of trametinib in the presence of F53C mutation. On the other hand, the binding affinities of cobimetinib and selumetinib could overcome F53 mutations on MEK1. Binimetinib interestingly exhibited an increased binding affinity when F53C/I mutations were present. Taken together, our results provide a comprehensive perspective on the structural and drug-binding effects of observed mutations on the hotspot residue F53 within MEK1; warranting further research in stratifying F53 hotspot mutations for effective drug binding.

01 Apr 2025·LUNG CANCER

Letter: Alectinib combined with cobimetinib in ALK-rearranged lung cancer: A phase IB study

Letter

Author: Khan, Saad ; Khan, Ayesha ; Naveed, Fatima ; Arshad, Faraz ; Ahmad, Rizwan

01 Apr 2025·MOLECULAR DIVERSITY

Targeting AFP-RARβ complex formation: a potential strategy for treating AFP-positive hepatocellular carcinoma

Article

Author: Dev, Radul R ; Soman, Sowmya ; Banjan, Bhavya ; Raju, Rajesh ; Vishwakarma, Riya ; Rehman, Niyas ; Kalath, Haritha ; Kumar, Pankaj ; Revikumar, Amjesh ; Abhinand, Chandran S ; Ramakrishnan, Krishnapriya

Alpha-fetoprotein (AFP) is a glycoprotein primarily expressed during embryogenesis, with declining levels postnatally. Elevated AFP levels correlate with pathological conditions such as liver fibrosis, cirrhosis, and hepatocellular carcinoma (HCC). Recent investigations underscore AFP's intracellular role in HCC progression, wherein it forms complexes with proteins like Phosphatase and tensin homolog (PTEN), Caspase 3 (CASP3), and Retinoic acid receptors and Retinoid X receptors (RAR/RXR). RAR and RXR regulate gene expression linked to cell death and tumorigenesis in normal physiology. AFP impedes RAR/RXR dimerization, nuclear translocation, and function, promoting gene expression favoring cancer progression in HCC that provoked us to target AFP as a drug candidate. Despite extensive studies, inhibitors targeting AFP to disrupt complex formation and activities remain scarce. In this study, employing protein-protein docking, amino acid residues involved in AFP-RARβ interaction were identified, guiding the definition of AFP's active site for potential inhibitor screening. Currently, kinase inhibitors play a significant role in cancer treatment and, the present study explores the potential of repurposing FDA-approved protein kinase inhibitors to target AFP. Molecular docking with kinase inhibitors revealed Lapatinib as a candidate drug of the AFP-RARβ complex. Molecular dynamics simulations and binding energy calculations, employing Mechanic/Poisson-Boltzmann Surface Area (MM-PBSA), confirmed Lapatinib's stability with AFP. The study suggests Lapatinib's potential in disrupting the AFP-RARβ complex, providing a promising avenue for treating molecularly stratified AFP-positive HCC or its early stages.

106

News (Medical) associated with Cobimetinib Fumarate

12 Sep 2024

·www.biospace.com

FDA Approves Genentech’s Tecentriq Hybreza, the First and Only Subcutaneous Anti-PD-(L)1 Cancer Immunotherapy

– Tecentriq Hybreza provides patients and physicians with greater flexibility of treatment options while showing safety and efficacy consistent with intravenous (IV) Tecentriq – – New subcutaneous (SC) option reduces treatment time to approximately 7 minutes, compared with 30-60 minutes for IV infusion – SOUTH SAN FRANCISCO, Calif.--(BUSINESS WIRE)--Genentech, a member of the Roche Group (SIX: RO, ROG; OTCQX: RHHBY), announced today that the U.S. Food and Drug Administration (FDA) has approved Tecentriq Hybreza™ (atezolizumab and hyaluronidase-tqjs), the first and only PD-(L)1 inhibitor for subcutaneous (SC), under the skin injection for patients in the United States. Tecentriq Hybreza can be injected subcutaneously over approximately seven minutes, compared with 30-60 minutes for standard IV infusion of Tecentriq (atezolizumab). It will be available for all IV indications of Tecentriq approved for adults in the U.S., including certain types of lung, liver, skin and soft tissue cancer. “By enabling subcutaneous administration for a cancer immunotherapy, Tecentriq Hybreza now offers patients with multiple cancer types and their physicians greater flexibility and choice of treatment administration,” said Levi Garraway, M.D., Ph.D., chief medical officer and head of Global Product Development. “We are pleased to introduce this new subcutaneous formulation that builds on the established safety and efficacy pro intravenous Tecentriq and can treat patients faster and in more accessible settings.” “This approval represents a significant option to improve the patient experience,” said Ann Fish-Steagall, RN, senior vice president of Patient Services at the LUNGevity Foundation. “When patients have options, they feel empowered to be vital participants in their own care and choose their preferred treatment option.” The FDA approval is based on pivotal data from the Phase IB/III IMscin001 study, which showed comparable levels of Tecentriq in the blood, when administered subcutaneously, and a safety and efficacy pro with the IV formulation. The Phase II IMscin002 study showed that 71% of patients preferred Tecentriq Hybreza over intravenous atezolizumab, and the most common reasons were less time in the clinic, increased comfort during treatment and reduced emotional distress. 4 out of 5 patients (79%) chose Tecentriq Hybreza to continue their treatment, after experiencing both formulations. Developing new formulations of our medicines is part of our commitment to improve the patient experience and support people living with different illnesses at every step of their treatment journey. With Tecentriq Hybreza and Roche/Genentech’s 13 other subcutaneous therapies – available across various diseases – we offer additional administration options to meet the diverse preferences of patients. The subcutaneous formulation of Tecentriq received its first worldwide approval in Great Britain in August 2023 and is now approved in over 50 countries (outside the U.S. marketed as Tecentriq SC). Regulatory reviews in other countries and regions are ongoing. Genentech is committed to helping people access the medicines they are prescribed and offers comprehensive services for people prescribed Tecentriq Hybreza to help minimize barriers to access and reimbursement. For people who qualify, Genentech offers patient assistance programs through Genentech Access Solutions. More information is also available at 866-4ACCESS/866-422-2377 or . Visit for additional information. About the IMscin001 study IMscin001 is a Phase IB/III, global, multicenter, randomized study evaluating the pharmacokinetics, safety and efficacy of Tecentriq Hybreza, compared with IV Tecentriq, in patients with previously treated locally advanced or metastatic non-small cell lung cancer (NSCLC) for whom prior platinum therapy has failed. The study enrolled 371 patients. The study met its primary endpoints, demonstrating comparable levels of Tecentriq in the blood during a given dosing interval on the basis of established pharmacokinetic measurements; observed serum C trough and model-predicted area under the curve. Observed efficacy, as measured by the overall response rate, progression-free survival, overall survival and duration of response, was similar between the SC and IV treatment arms and consistent with the known pro IV Tecentriq. The safety pro Tecentriq Hybreza was also consistent with that of IV Tecentriq. About the IMscin002 study IMscin002 is a Phase II, global crossover study evaluating patient preference between the SC and IV formulations of Tecentriq. The study enrolled 179 patients, including people with PD-L1-positive resected Stage II-IIIB NSCLC who have completed adjuvant platinum-based chemotherapy without evidence of disease recurrence, and untreated patients with PD-L1-high Stage IV NSCLC. The study met its primary endpoint, showing that 71% of participants preferred the SC formulation (21% preferred IV and 8% stated no preference); 79% opted for Tecentriq Hybreza to complete their treatment, after experiencing both formulations of Tecentriq. The study confirmed that switching between Tecentriq Hybreza and IV Tecentriq was well tolerated, with no new safety signals. About Tecentriq Hybreza Tecentriq Hybreza combines Tecentriq with Halozyme Therapeutics’ Enhanze ® drug delivery technology. Tecentriq is a monoclonal antibody designed to bind with a protein called PD-L1. Tecentriq is designed to bind to PD-L1 expressed on tumor cells and tumor-infiltrating immune cells, blocking its interactions with both PD-1 and B7.1 receptors. By inhibiting PD-L1, Tecentriq may enable the re-activation of T cells. Tecentriq may also affect normal cells. The Enhanze drug delivery technology is based on a proprietary recombinant human hyaluronidase PH20 (rHuPH20), an enzyme that locally and temporarily degrades hyaluronan – a glycosaminoglycan or chain of natural sugars in the body – in the subcutaneous space. This increases the permeability of the tissue under the skin, allowing space for Tecentriq to enter, enabling it to be rapidly dispersed and absorbed into the bloodstream. Tecentriq is approved for some of the most aggressive and difficult-to-treat forms of cancer. Tecentriq was the first cancer immunotherapy approved for the treatment of a certain type of early-stage (adjuvant) NSCLC, small cell lung cancer (SCLC) and hepatocellular carcinoma (HCC). Tecentriq is also approved in countries around the world, either alone or in combination with targeted therapies and/or chemotherapies, for various forms of metastatic NSCLC, certain types of metastatic urothelial cancer (mUC), PD-L1-positive metastatic triple-negative breast cancer (TNBC), BRAF V600 mutation-positive advanced melanoma and alveolar soft part sarcoma (ASPS). In addition to intravenous infusion, Tecentriq has been approved as a subcutaneous formulation in over 50 countries (outside the U.S. marketed as Tecentriq SC). The approved indications for Tecentriq Hybreza and Tecentriq SC mirror those of IV Tecentriq. What is Tecentriq Hybreza? Tecentriq Hybreza is a prescription medicine used to treat: Adults with a type of lung cancer called non-small cell lung cancer (NSCLC). Tecentriq Hybreza may be used alone as a treatment for their lung cancer: to help prevent their lung cancer from coming back after their tumor(s) has been removed by surgery and they have received platinum-based chemotherapy, and they have stage 2 to 3A NSCLC (patients should talk to their healthcare provider about what these stages mean), and their cancer tests positive for “PD-L1”. Tecentriq Hybreza may be used alone as their first treatment when their lung cancer: has spread or grown, and their cancer tests positive for “high PD-L1”, and their tumor does not have an abnormal “EGFR” or “ALK” gene. Tecentriq Hybreza may be used with the medicines bevacizumab, paclitaxel, and carboplatin as their first treatment when their lung cancer: has spread or grown, and is a type called “non-squamous NSCLC,” and their tumor does not have an abnormal “EGFR” or “ALK” gene. Tecentriq Hybreza may be used with the medicines paclitaxel protein-bound and carboplatin as their first treatment when their lung cancer: has spread or grown, and is a type called “non-squamous NSCLC,” and their tumor does not have an abnormal “EGFR” or “ALK” gene. Tecentriq Hybreza may be used alone when their lung cancer: has spread or grown, and if they have tried chemotherapy that contains platinum, and it did not work or is no longer working. if their tumor has an abnormal “EGFR” or “ALK” gene, they should have also tried an FDA-approved therapy for tumors with these abnormal genes, and it did not work or is no longer working. Adults with a type of lung cancer called small cell lung cancer (SCLC). Tecentriq Hybreza may be used with the chemotherapy medicines carboplatin and etoposide as their first treatment when their lung cancer: is a type called “extensive-stage small cell lung cancer,” which means that it has spread or grown. Adults with a type of liver cancer called hepatocellular carcinoma (HCC). Tecentriq Hybreza may be used with the medicine bevacizumab when their liver cancer: has spread or cannot be removed by surgery, and they have not received other medicines by mouth or injection through their vein (IV) to treat their cancer. Adults with a type of skin cancer called melanoma. Tecentriq Hybreza may be used with the medicines cobimetinib and vemurafenib in patients with melanoma when their skin cancer: has spread to other parts of the body or cannot be removed by surgery, and has a certain type of abnormal “BRAF” gene. Healthcare providers will perform a test to make sure this Tecentriq Hybreza combination is right for the patient. Adults with a type of soft tissue tumor (cancer) called alveolar soft part sarcoma (ASPS). Tecentriq Hybreza may be used when their sarcoma: has spread to other parts of the body or cannot be removed by surgery. It is not known if Tecentriq Hybreza is safe and effective in children. Important Safety Information Who should not receive TECENTRIQ HYBREZA? Patients should not receive TECENTRIQ HYBREZA if they are allergic to hyaluronidase or any of the ingredients in TECENTRIQ HYBREZA. What is the most important information about Tecentriq Hybreza? Tecentriq Hybreza can cause the immune system to attack normal organs and tissues in any area of the body and can affect the way they work. These problems can sometimes become severe or life threatening and can lead to death. Patients can have more than one of these problems at the same time. These problems may happen anytime during their treatment or even after their treatment has ended. Patients should call or see their healthcare provider right away if they develop any new or worse signs or symptoms, including: Lung problems cough shortness of breath chest pain Intestinal problems diarrhea (loose stools) or more frequent bowel movements than usual stools that are black, tarry, sticky, or have blood or mucus severe stomach-area (abdomen) pain or tenderness Liver problems yellowing of the skin or the whites of the eyes severe nausea or vomiting pain on the right side of their stomach area (abdomen) dark urine (tea colored) bleeding or bruising more easily than normal Hormone gland problems headaches that will not go away or unusual headaches eye sensitivity to light eye problems rapid heartbeat increased sweating extreme tiredness weight gain or weight loss feeling more hungry or thirsty than usual urinating more often than usual hair loss feeling cold constipation their voice gets deeper dizziness or fainting changes in mood or behavior, such as decreased sex drive, irritability, or forgetfulness Kidney problems decrease in their amount of urine blood in their urine swelling of their ankles loss of appetite Skin problems rash itching skin blistering or peeling painful sores or ulcers in mouth or nose, throat, or genital area fever or flu-like symptoms swollen lymph nodes Problems can also happen in other organs. These are not all of the signs and symptoms of immune system problems that can happen with Tecentriq Hybreza. Patients should call or see their healthcare provider right away for any new or worse signs or symptoms, including: Chest pain, irregular heartbeat, shortness of breath, or swelling of ankles Confusion, sleepiness, memory problems, changes in mood or behavior, stiff neck, balance problems, tingling or numbness of the arms or legs Double vision, blurry vision, sensitivity to light, eye pain, changes in eyesight Persistent or severe muscle pain or weakness, muscle cramps Low red blood cells, bruising Infusion reactions that can sometimes be severe or life-threatening. Signs and symptoms of infusion reactions may include: chills or shaking itching or rash flushing shortness of breath or wheezing dizziness feeling like passing out fever back or neck pain Complications, including graft-versus-host disease (GVHD), in people who have received a bone marrow (stem cell) transplant that uses donor stem cells (allogeneic). These complications can be serious and can lead to death. These complications may happen if patients undergo transplantation either before or after being treated with Tecentriq Hybreza. A healthcare provider will monitor for these complications. Getting medical treatment right away may help keep these problems from becoming more serious. A healthcare provider will check patients for these problems during their treatment with Tecentriq Hybreza. A healthcare provider may treat patients with corticosteroid or hormone replacement medicines. A healthcare provider may also need to delay or completely stop treatment with Tecentriq Hybreza if patients have severe side effects. Before receiving Tecentriq Hybreza, patients should tell their healthcare provider about all of their medical conditions, including if they: have immune system problems such as Crohn’s disease, ulcerative colitis, or lupus have received an organ transplant have received or plan to receive a stem cell transplant that uses donor stem cells (allogeneic) have received radiation treatment to their chest area have a condition that affects their nervous system, such as myasthenia gravis or Guillain-Barré syndrome are pregnant or plan to become pregnant. Tecentriq Hybreza can harm an unborn baby. Patients should tell their healthcare provider right away if they become pregnant or think they may be pregnant during treatment with Tecentriq Hybreza. Females who are able to become pregnant: A healthcare provider should do a pregnancy test before they start treatment with Tecentriq Hybreza They should use an effective method of birth control during their treatment and for at least 5 months after the last dose of Tecentriq Hybreza are breastfeeding or plan to breastfeed. It is not known if Tecentriq Hybreza passes into the breast milk. Patients should not breastfeed during treatment and for at least 5 months after the last dose of Tecentriq Hybreza Patients should tell their healthcare provider about all the medicines they take, including prescription and over-the-counter medicines, vitamins, and herbal supplements. The most common side effects of Tecentriq Hybreza when used alone include: feeling tired or weak decreased appetite nausea cough shortness of breath The most common side effects observed with TECENTRIQ and may be experienced with TECENTRIQ HYBREZA are shown below The most common side effects of TECENTRIQ when used alone as the first treatment for NSCLC include: feeling tired or weak The most common side effects of TECENTRIQ when used alone in NSCLC that has spread or grown include: feeling tired or weak cough decreased appetite shortness of breath muscle or bone pain The most common side effects of TECENTRIQ when used in NSCLC with bevacizumab, paclitaxel, and carboplatin include: numbness, pain, tingling, or burning in your hands or feet feeling tired or weak hair loss muscle or bone pain nausea diarrhea constipation decreased appetite joint pain high blood pressure rash cough The most common side effects of TECENTRIQ when used in non-squamous NSCLC with paclitaxel protein-bound and carboplatin include: feeling tired or weak nausea diarrhea muscle or bone pain constipation numbness, pain, tingling, or burning in your hands or feet hair loss shortness of breath decreased appetite cough vomiting rash The most common side effects of TECENTRIQ when used in SCLC with carboplatin and etoposide include: feeling tired or weak nausea hair loss decreased appetite constipation vomiting The most common side effects of TECENTRIQ when used in HCC with bevacizumab include: high blood pressure feeling tired or weak too much protein in the urine The most common side effects of TECENTRIQ when used in melanoma with cobimetinib and vemurafenib include: skin rash joint, muscle, or bone pain feeling tired or weak liver injury fever nausea itching swelling of legs or arms mouth swelling (sometimes with sores) low thyroid hormone levels sunburn or sun sensitivity The most common side effects of TECENTRIQ when used alone in ASPS include: muscle or bone pain feeling tired or weak rash cough headache nausea high blood pressure vomiting constipation shortness of breath dizziness bleeding diarrhea trouble sleeping stomach-area (abdominal) pain low thyroid hormone levels fever anxiety irregular heartbeat (arrhythmia) decreased appetite Tecentriq Hybreza may cause fertility problems in females, which may affect the ability to have children. Patients should talk to their healthcare provider if they have concerns about fertility. These are not all the possible side effects of Tecentriq Hybreza. Patients should ask their healthcare provider or pharmacist for more information about the benefits and side effects of Tecentriq Hybreza. Report side effects to the FDA at 1-800-FDA-1088 or . Report side effects to Genentech at 1-888-835-2555. Please see for full Prescribing Information and additional Important Safety Information. About Genentech in lung cancer Lung cancer is a major area of focus and investment for Genentech, and we are committed to developing new approaches, medicines and tests that can help people with this deadly disease. Our goal is to provide an effective treatment option for every person diagnosed with lung cancer. We currently have six approved medicines to treat certain kinds of lung cancer and more than 10 medicines being developed to target the most common genetic drivers of lung cancer or to boost the immune system to combat the disease. Genentech is committed to improving treatment of early-stage lung cancers to help increase the chance of cure for more people. About Genentech Founded more than 40 years ago, Genentech is a leading biotechnology company that discovers, develops, manufactures and commercializes medicines to treat patients with serious and life-threatening medical conditions. The company, a member of the Roche Group, has headquarters in South San Francisco, California. For additional information about the company, please visit . Contacts Media Contact: Kendall Tich (650) 467-6800 Advocacy Contact: Meg Harrison (617) 694-7060 Investor Contacts: Loren Kalm (650) 225-3217 Bruno Eschli +41616875284

Clinical ResultImmunotherapyDrug ApprovalPhase 2

10 Sep 2024

·www.prnewswire.com

Adcentrx Therapeutics Announces Formation of Scientific Advisory Board

Company appoints Mike Varney, Ph.D. and Kerry Blanchard, M.D., Ph.D. as founding SAB members SAN DIEGO and SHANGHAI, Sept. 10, 2024 /PRNewswire/ -- Adcentrx Therapeutics ("Adcentrx"), a clinical-stage biotechnology company focused on accelerating breakthroughs in developing protein conjugate therapeutics for cancer and other life-threatening diseases, today announces the formation of its Scientific Advisory Board (SAB) to support the advancement of its innovative Antibody-Drug Conjugate (ADC) technology platform and pipeline, including ADRX-0706, a Nectin-4 targeting ADC therapeutic currently being evaluated in a Phase 1a/b clinical trial. Continue Reading The inaugural SAB will work closely with Adcentrx's executive team to provide strategic guidance and expert insights to advance its mission of creating the best therapies to treat serious and life-threatening diseases. Formation of SAB with founding members Dr. Varney and Dr. Blanchard represents significant advancement for Adcentrx. Post this "The establishment of our SAB represents a significant advancement for Adcentrx as we progress our ADC portfolio," said Hui Li, Ph.D., President and CEO of Adcentrx. "We are privileged to welcome these exceptional scientific leaders to the Adcentrx team, and their combined expertise and guidance will be instrumental in shaping our future research and clinical development." The Founding Members of the Adcentrx SAB are: Mike Varney, Ph.D. Dr. Varney brings extensive experience in drug discovery and development, having served as Executive Vice President, Head of Genentech Research and Early Development, where he was responsible for all research activities. During his tenure at Genentech, he oversaw the discovery and development of multiple innovative therapies, including the approved cancer treatments Erivedge® and Cotellic®. Earlier in his career, Dr. Varney pioneered the use of protein-structure based drug design at Agouron Pharmaceuticals. This innovative approach led to the discovery and market approval of HIV protease inhibitor, Viracept®. After Agouron's acquisition by Warner Lambert and subsequently by Pfizer, he served as Vice President of Drug Discovery at Pfizer Global Research & Development, leading research initiatives across oncology, virology, diabetes, and ophthalmology at the La Jolla site. Dr. Varney holds a Ph.D. in Organic Synthesis from the California Institute of Technology and a B.S. in Chemistry from the University of California, Los Angeles, and was an American Cancer Society Postdoctoral Research Fellow at Columbia University. Kerry Blanchard, M.D., Ph.D. Dr. Blanchard has been a drug hunter and entrepreneur for more than four decades in the US and Asia. He is currently cofounder, Chairman, and CEO of Perpetual Medicines, a peptide therapeutics/computational AI platform company. Previously, he was the CEO of Everest Medicines, Chief Science Officer at Innovent Biologics, Senior Vice President of Lilly China Drug Development and External Innovation, and a senior executive at Eli Lilly and Company. He was a member of the board for Lilly China and Zymeworks Inc., and was the co-chairman of the Lilly Asia Ventures Investment Committee. Prior to joining Lilly in 2000, he was a tenured Professor of Medicine and Biochemistry & Molecular Biology at Louisiana State University Health Sciences Center in Shreveport, LA. Dr. Blanchard has brought four medicines to the market from his own research including Verzenio®, a CDK 4/6 inhibitor, and, his development teams in China have had more than 30 approved medicines in Asia including Trodelvy®, Trulicity®, Byetta®, Forteo®, and Tyvyt®. At Innovent and Everest, Dr. Blanchard successfully raised over $2 billion to support and expand their pipelines. His track record in accelerating clinical development and navigating regulatory landscapes will significantly enhance Adcentrx's strategic initiatives and global expansion. Dr. Blanchard received his M.D. and Ph.D. in Biochemistry from Indiana University and completed his residency and fellowships at Brigham and Women's Hospital, Dana Farber Cancer Institute, and Harvard Medical School. About Adcentrx Therapeutics Adcentrx is a biotechnology company focused on accelerating breakthroughs in protein conjugate therapeutic development for cancer and other life-threatening diseases. Adcentrx has pioneered the development of i-Conjugation™, an ADC technology platform addressing key components of protein conjugate design to solve challenges typically seen in ADCs. In addition to ADRX-0706, Adcentrx is developing a robust pipeline of ADCs with first-in-class potential. For more information about Adcentrx and its innovative ADC technologies, please visit . Contact Information: Investor Relations [email protected] SOURCE Adcentrx Therapeutics

Executive ChangeAcquisitionADC

03 Jun 2024

·www.globenewswire.com

At ASCO 2024, Treos Bio Reports Key Survival Results for Chemo-Free Regimen of PolyPEPI1018 Peptide Immunotherapy and Roche’s PD-L1 Inhibitor in Late-Stage Colorectal Cancer

PolyPEPI1018 is the first cancer vaccine to demonstrate promising results when combined with a PD-(L)1 inhibitor in late-stage microsatellite stable colorectal cancer (MSS CRC), a form of cancer —representing 96% of all metastatic CRC — historically resistant to checkpoint inhibitor immunotherapy. LONDON and BOSTON, June 03, 2024 (GLOBE NEWSWIRE) -- Treos Bio Limited, a clinical-stage biotechnology company using data science and proprietary biomarkers to develop precision peptide immunotherapies, today announced the presentation of results from its phase 2 OBERTO-301 study of the company’s lead product candidate, PolyPEPI1018, in combination with atezolizumab in patients with late-stage microsatellite stable metastatic colorectal cancer (MSS mCRC) at the 2024 American Society of Clinical Oncology (ASCO) Annual Meeting. PolyPEPI1018 is an off-the-shelf, multi-peptide vaccine that has previously demonstrated the ability to induce immunological responses at both the peripheral and tumor levels, effectively turning immunologically ‘cold’ tumors into ‘hot’ ones. This was observed in first-line maintenance MSS mCRC (OBERTO-101) and late-stage MSS mCRC (OBERTO-201), providing a strong rationale for testing PolyPEPI1018 in combination with PD-(L)1 inhibitors in MSS mCRC. OBERTO-301 is a multicenter, open-label, phase 2 clinical trial, conducted at the Mayo Clinic in Minnesota, Florida and Arizona, evaluating the combination treatment of PolyPEPI1018 and atezolizumab in patients with MSS mCRC who have progressed on two or three prior treatment regimens. The primary endpoint of the study is the incidence and severity of treatment-related adverse events. Secondary endpoints include objective response rate, duration of response, progression-free survival, and overall survival. Key Study Findings: Patient Enrolment and Treatment: The study enrolled 18 patients with refractory non-MSI-H metastatic colorectal cancer who were administered PolyPEPI1018 (1.2 mg) and atezolizumab (1,200 mg) every three weeks. Of these, 67% had undergone three or more prior therapy lines, and 44% had active liver metastasis.Safety and Tolerability: PolyPEPI1018 in combination with atezolizumab was well tolerated, with no unexpected toxicities or serious adverse events related to treatment.Survival Benefits: The median overall survival (mOS) was 12.8 months (95% CI 8.8 - NE) and the 12-months survival was 60%; this compares favorably to the historical data of 7.1 months and 27% respectively for atezolizumab monotherapy in a similar patient population. Differences between the survival of patients with and without liver metastasis were not statistically significant (HR: 0.58 [95% CI 0.18 - 1.90]; P=0.36): Patients without active liver metastases (NLM) had a 12-month overall survival (OS) estimate of 67% and a median OS of 16.5 months.Patients with active liver metastases (LM) had a 12-month OS estimate of 50% and a median OS of 8.6 months. Progression-Free Survival (PFS) and Disease Control Rate (DCR): The median PFS was 2.7 months (95% CI 1.4-4.0), and the DCR was 61%. No tumor responses by RECIST 1.1 were observed.Immune Response and Tumor Microenvironment: PolyPEPI1018-specific CD8+ and/or CD4+ T cell responses were detected in 13 out of 16 subjects (ex vivo FluoroSpot), complemented by humoral responses against multiple PolyPEPI1018-antigens. Patients with available biopsy pairs (n=8) showed significant increases in average PD-L1 expression (IC%, p=0.029) and CD8+ tumor infiltrating lymphocytes (TILs, p=0.019) post-treatment, demonstrating an immune conversion from ‘cold’ to ‘hot’ tumor.Correlation with PFS and Immunological Markers: Patients with increased PFS (>12 weeks) showed significant increases in both post-treatment PD-L1 expression (p=0.007) and TILs (p=0.016) versus patients with PFS ≤ 12 weeks. Pre-treatment levels were not prognostic.T Cell Responses and Survival: Patients with robust CD8+ T cell responses had improved OS compared to patients with poor immunological responses (HR=0.13, p=0.022). Dr. Joleen Hubbard, Deputy Director for Clinical Research at Allina Health Cancer Institute and principal investigator of three clinical studies with PolyPEPI1018 at Mayo Clinic, commented, “MSS mCRC patients represent the largest population of mCRC, most of whom have poor-prognostic metastatic sites, where survival beyond one year with standard care is rare. In this latest study, I was particularly intrigued by the correlative data showing that the combination of PolyPEPI1018 and atezolizumab actually increased TILs and PD-L1 expression, which correlated with improved PFS. I am enthusiastic about the potential of PolyPEPI1018 in the development of new treatment alternatives for this challenging disease.” “We are highly encouraged by the consistency observed across three clinical trials in MSS mCRC in different settings. The survival and biomarker data from this study further highlight the potential benefit of PolyPEPI1018 either as an add-on to standard-of-care or as part of a chemo-free IO-IO combination for treating refractory MSS mCRC. We look forward to progressing PolyPEPI1018 to randomized, controlled trials in combination with chemotherapy, biologics, and PD-(L)1 inhibitor,” added Christopher C. Gallen, M.D., Ph.D., CEO of Treos Bio. The poster can be accessed at http://treosbio.com/index.php/publications-2/ References: Hubbard et al, Safety and Activity of PolyPEPI1018 Combined with Maintenance Therapy in Metastatic Colorectal Cancer: An Open-Label, Multicenter, Phase Ib Study. Clin Cancer Res 2022.Hubbard et al, PolyPEPI1018 Vaccine in Combination with TAS-102 in Participants with Late-Stage Microsatellite-Stable Metastatic Colorectal Cancer (MSS mCRC): A Phase Ib Study to Evaluate Safety, Tolerability, Immunogenicity, and Efficacy (OBERTO-201). ASCO2023.Eng et al, Atezolizumab with or without Cobimetinib versus Regorafenib in Previously Treated Metastatic Colorectal Cancer (IMblaze370): A Multicentre, Open-Label, Phase 3, Randomised, Controlled Trial. Lancet Oncol 2019. About Colorectal Cancer:Colorectal cancer (CRC) is the third most common cancer and cause of cancer-related deaths in the United States and worldwide. There are approximately 1.4 million people living with colorectal cancer in the United States. Current treatments for CRC include surgery and chemotherapy in early stages, and chemotherapy, biologics, and targeted therapies in later stages. Microsatellite stable (MSS) CRC accounts for approximately 85% of all colorectal cancers and approximately 96% of all metastatic CRC. Patients with MSS CRC do not benefit from available immunotherapies. About PolyPEPI1018:PolyPEPI1018, Treos’ lead product candidate, is an immunotherapy in clinical development for the treatment of metastatic colorectal cancer, with plans to incorporate a candidate companion diagnostic in future clinical trials. The therapy is in development as an add-on to first-line maintenance therapy and to third-line treatment. PolyPEPI1018 has been developed using Treos’ proprietary PASCal computational tool to identify Personal EPItopes (PEPIs) likely to induce multiple tumor-specific T cell responses in a patient. Prior to the OBERTO-301 clinical trial, PolyPEPI1018 was evaluated in two Phase Ib clinical trials: OBERTO-101 in the first-line maintenance setting and OBERTO-201 in the advanced, refractory setting of MSS mCRC. These trials explored treatment combinations that had not been previously tested. In the first-line maintenance setting, adding PolyPEPI1018 to fluoropyrimidine and bevacizumab led to unprecedented tumor responses according to RECIST v1.1 and dose-dependent improvements in progression-free survival (PFS). To explore the potential of PolyPEPI1018 in treating advanced, refractory MSS mCRC, Treos adopted a stepwise approach. This involved initially assessing the safety, immunogenicity, and preliminary efficacy of PolyPEPI1018 as an add-on to standard chemotherapy, TAS-102 (OBERTO-201). Following this, the effect of PolyPEPI1018 in combination with an experimental immunotherapy in MSS CRC, atezolizumab, was tested in a similar patient population (OBERTO-301). Treos now plans to advance the testing of PolyPEPI1018 in a randomized, controlled phase 2 study comparing a complex chemo-immunotherapeutic regimen to standard of care. About Treos Bio Limited:Treos Bio develops precision peptide cancer immunotherapies combined with novel biomarkers using proprietary computational data science integrating HLA genetics, tumor profile, and clinical outcome of thousands of real subjects. Treos has conducted three clinical trials in the United States and the European Union of its lead candidate, PolyPEPI1018, an off-the-shelf immunotherapy for the treatment of metastatic colorectal cancer. Treos has completed preclinical development of additional off-the-shelf immunotherapies for ovarian, breast, bladder, gastric, lung cancers, and melanoma. The Company is also developing off-the-shelf immunotherapies personalized to an individual patient’s HLA genotype for several types of solid tumors. Treos has raised $45 million to date. More information can be found at www.treosbio.com. Media Contact: Daniel LevineLevine Media Group+1 (510) 280-5405danny@levinemediagroup.com

Clinical ResultImmunotherapyPhase 2ASCOPhase 3

100 Deals associated with Cobimetinib Fumarate

External Link

KEGG	Wiki	ATC	Drug Bank
D10615	Cobimetinib Fumarate	L01XE38	DB05239

R&D Status

Approved

10 top approved records.

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Indication	Country/Location	Organization	Date
Histiocytic Sarcoma	United States	Genentech, Inc.	28 Oct 2022
BRAF V600 mutation-positive Melanoma	European Union	Roche Registration GmbH	20 Nov 2015
BRAF V600 mutation-positive Melanoma	Iceland	Roche Registration GmbH	20 Nov 2015
BRAF V600 mutation-positive Melanoma	Liechtenstein	Roche Registration GmbH	20 Nov 2015
BRAF V600 mutation-positive Melanoma	Norway	Roche Registration GmbH	20 Nov 2015
Melanoma	United States	Genentech, Inc.	10 Nov 2015

Developing

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Anaplastic Thyroid Carcinoma	Phase 3	United Kingdom	Hoffmann-La Roche, Inc.	01 Mar 2023
BRAF V600 mutation-positive Neoplasms	Phase 3	United Kingdom	Hoffmann-La Roche, Inc.	01 Mar 2023
Colorectal Cancer	Phase 3	United Kingdom	Hoffmann-La Roche, Inc.	01 Mar 2023
Erdheim-Chester Disease	Phase 3	United Kingdom	Hoffmann-La Roche, Inc.	01 Mar 2023
Glioma	Phase 3	United Kingdom	Hoffmann-La Roche, Inc.	01 Mar 2023
Laryngeal Neoplasms	Phase 3	United Kingdom	Hoffmann-La Roche, Inc.	01 Mar 2023
Multiple Myeloma	Phase 3	United Kingdom	Hoffmann-La Roche, Inc.	01 Mar 2023
Non-Small Cell Lung Cancer	Phase 3	United Kingdom	Hoffmann-La Roche, Inc.	01 Mar 2023
Ovarian Cancer	Phase 3	United Kingdom	Hoffmann-La Roche, Inc.	01 Mar 2023
Papillary thyroid cancer	Phase 3	United Kingdom	Hoffmann-La Roche, Inc.	01 Mar 2023

Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT04214418 (MEKiAUTO, CTgov)	Phase 1/2	Microsatellite instability-high colorectal cancer \| Duodenal Neoplasms \| Adenocarcinoma of large intestine ... View more	27	Cobimetinib+Hydroxychloroquine+atezolizumab (Phase 2: Cohort 1)	gvmfhzbdeh(xdnsvzdgra) = fvjkieypvl yglmtgheta (wdvxbbbjcd, zgmhuvmdbq - gqnyeglecz) View more	-	25 Mar 2025
				Cobimetinib+Hydroxychloroquine+atezolizumab (Phase 2: Cohort 2)	gvmfhzbdeh(xdnsvzdgra) = olmsfdeuyj yglmtgheta (wdvxbbbjcd, tbubanidct - gckxxuljjd) View more
ACTRN12620000861954 (MoST, ESMO2024) Manual	Phase 2	BRAF mutation Solid Tumors \| BRAF V600 Mutation-Positive Non-small Cell Lung Cancer First line BRAF V600M	64	vemurafenib cobimetinib	zmpzmnynfe(hahnvzalbh) = vaupqesyvn rvwecugely (bxjynestip ) View more	Positive	14 Sep 2024
				vemurafenib cobimetinib	zmpzmnynfe(hahnvzalbh) = kuyjrkezqi rvwecugely (bxjynestip ) View more
NCT02091141 (MyPathway, CTgov)	Phase 2	Advanced Malignant Solid Neoplasm \| Bladder Cancer \| Biliary Tract Neoplasms ... View more	673	Trastuzumab+Pertuzumab (Trastuzumab Plus Pertuzumab)	udhotfczqo = uqczujqeve vwqlmkulnb (qxcrhjaqok, lzghyoxbou - spedizikgp) View more	-	23 Jul 2024
				atezolizumab (Atezolizumab)	udhotfczqo = bgfgosvfet vwqlmkulnb (qxcrhjaqok, xqrsqrgjid - tktjlvosyo) View more
NCT03695380 (Pubmed) Manual	Phase 1	Ovarian Cancer Second line BRCA Gene Mutation Negative	74	Cobimetinib 60 mg daily + Niraparib 200 mg daily	rcrdxhjwlz(ncpydwaics) = sealnyaqvg wpdtguvszb (nqlxfyvpcg, 20 - 53) View more	Positive	01 Jun 2024
				Cobimetinib 60 mg daily + Niraparib 200 mg daily + Atezolizumab 840 mg	rcrdxhjwlz(ncpydwaics) = skadnnhdou wpdtguvszb (nqlxfyvpcg, 14 - 44) View more
NCT03625141 (TRICOTEL, ASCO2024) Manual	Phase 2	BRAF V600 mutation-positive Melanoma BRAF V600 mutation	65	Atezolizumab (A) + cobimetinib (C) + vemurafenib (V)	hcetiosxas(lvcnaonmkr) = vrjsfihtyj fhuohekbaw (zcxbpajxqi, 27 - 51) View more	Positive	24 May 2024
NCT03363867 (BEACON, ASCO2024) Manual	Phase 2	-	29	Cobimetinibbevacizumabatezolizumab	hijgmccpvk(jtolljxsak) = dxcwxtiprc nfqsraafyr (jxblvuyblz, 8 - 40) View more	Positive	24 May 2024
NCT03181100 (ASCO2024)	Phase 2	thyroid gland poorly differentiated carcinoma RASmutation \| NF1 \| NF2	8	Atezolizumab plus cobimetinib	huzjfauuoh(atllqlkwiw) = hwaffmdtrs lsawbhewty (kfquqabmwb, 12.8 - 33.2) View more	Positive	24 May 2024
				Lenvatinib	huzjfauuoh(atllqlkwiw) = zflfelgosb lsawbhewty (kfquqabmwb )
ASCO2024	Not Applicable	Metastatic Pancreatic Cancer G12D \| G12V	12	Nab-paclitaxel and Gemcitabine	cnzhkfnmsy(pisxitmziq) = neutropenia and neutrophil support was needed in 6 out of 12 patients kirmpwnkza (bonokasnis )	Positive	24 May 2024
NCT04941287 \| NCT03201458 (ASCO2024)	Phase 2	Unresectable Biliary Tract Carcinoma	57	Atezolizumab + Varlilumab	bnrcblrxrz(gbnjogpayo) = sjmoimosbm ezrxobenlw (wbcnhalyld ) View more	Negative	24 May 2024
				Cobimetinib + Atezolizumab + Varlilumab	htlnjzfkan(vgcvxowksl) = umwuatavyt uquryfifiw (vuqczpcloc ) View more
NCT03554083 (NeoACTIVATE, Pubmed) Manual	Phase 2	Melanoma Neoadjuvant	30	vemurafenib + cobimetinib + atezolizumab (BRAF-mutated)	sosynrlngx(jjmorfqihb) = ryfsvbkmsj khkrypqipq (ibchjrwmxd ) View more	Positive	16 Feb 2024
				Cobimetinib + atezolizumab (BRAF-wild-type)	sosynrlngx(jjmorfqihb) = riiynptqyr khkrypqipq (ibchjrwmxd ) View more

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