Afatinib Dimaleate

- Preclinical data demonstrates synergy of QTX3544 with EGFR inhibitors, broadly enhancing anti-tumor activity - - Data supports ongoing Phase 1 clinical trial for QTX3544 as monotherapy and in combination with cetuximab in patients with KRASG12V mutations - SOUTH SAN FRANCISCO, Calif., April 28, 2025 (GLOBE NEWSWIRE) -- Quanta Therapeutics, a privately-held clinical-stage biopharmaceutical company leading the development of innovative, oral therapeutics for RAS-driven cancers, today announced late-breaking preclinical data for QTX3544, an oral, G12V-preferring, dual ON/OFF state, multi-KRAS inhibitor currently being evaluated in a Phase 1 clinical trial in patients with KRASG12V mutation. Data are being presented at the American Association for Cancer Research (AACR) Annual Meeting 2025 being held April 25-30, 2025, in Chicago, Illinois. “There is a high unmet need for effective treatments in KRASG12V-mutated cancers, the second most prevalent in KRAS-driven cancers, for which there are no current targeted treatments, including colorectal and pancreatic cancers. Using a clinically validated approach against G12C mutations, we aim to combine allosteric KRAS inhibition and EGFR blockade to enhance the depth and durability of tumor response against G12V,” said Leonardo Faoro, MD, MBA, Chief Medical Officer of Quanta Therapeutics. “QTX3544 has shown high potency against multiple KRAS variants, particularly G12V. These preclinical data support the clinical strategy to combine QTX3544 and cetuximab to enhance the therapeutic activity against KRASG12V-driven cancers. We look forward to evaluating this combination in the ongoing Phase 1 clinical trial.” “We continue to generate promising data supporting our unique pipeline of KRAS-directed agents, as we advance three distinct candidates in the clinic targeting high prevalence KRAS mutations across solid tumors with major unmet need. QTX3034 and QTX3046 are being developed for G12D-mutant and QTX3544 for G12V-mutant KRAS-driven cancers,” said Perry Nisen, MD, PhD, Chief Executive Officer of Quanta. “We are building a compelling clinical package across our three lead programs and are on track to share proof-of-concept data later this year as our pipeline continues to progress.” Studies evaluating the potential synergy between QTX3544 and EGFR inhibitors (afatinib and cetuximab) in KRASG12V-driven cancer cell lines and tumor models demonstrated: QTX3544 synergized with EGFR inhibitors and potently inhibited KRASG12V-mutant cell proliferation in cell viability assays.Combined treatment of QTX3544 with afatinib led to a deeper suppression of MAPK signaling and enhanced inhibition of KRASG12V-driven cancer cell survival in colony formation assays.Combination treatment of QTX3544 with cetuximab significantly enhanced anti-tumor efficacy and elicited greater tumor regressions in pancreatic and colorectal KRASG12V-mutant cell line-derived xenograft models, as well as in a patient-derived colorectal tumor xenograft model. AACR presentation information:Title: QTX3544, a potent and selective G12V-preferring KRAS inhibitor, synergizes with EGFR inhibitors for enhanced anti-tumor activityDate and Time: Wednesday, April 30, 2025; 9:00 AM - 12:00 PMSession Name: Late-Breaking Research: Experimental and Molecular Therapeutics 4Abstract Number: LB430 Location: Poster Section 51 About QTX3544QTX3544 is an allosteric, G12V-preferring multi-KRAS inhibitor. The QTX3544 Phase 1 clinical trial is initially enrolling patients with KRASG12V mutation in dose escalation cohorts as monotherapy and in combination with cetuximab. The Phase 1 clinical endpoints include safety and tolerability, determination of the maximum tolerated dose/recommended Phase 2 dose, pharmacokinetic properties, anti-tumor activity, and molecular markers. The clinical trial is being conducted at clinical sites in the US. More information about the QTX3544 clinical trial (NCT06715124) can be found on https://clinicaltrials.gov/. About RAS and the MAPK PathwayThe mitogen-activated protein kinase (MAPK) pathway is a central signaling cascade that regulates cellular growth, proliferation, differentiation, and survival. When one of the proteins in the pathway is mutationally activated, it can drive tumor development and growth. RAS is the most frequently mutated oncogene in cancer, with KRAS mutations occurring in nearly one-quarter of all human cancers. RAS mutations impair the ability of RAS to convert from its active GTP-bound “ON” form into its inactive GDP-bound “OFF” state, leading to the sustained activation of the MAPK signaling pathway and ultimately driving tumorigenesis. KRAS mutations, especially G12D, G12V, and G12C, are highly prevalent in pancreatic, colorectal, and lung cancers. First-generation KRAS inhibitors have demonstrated clinical benefit, but their impact is limited to a subset of patients with a single type of KRAS mutation (G12C). About Quanta TherapeuticsQuanta Therapeutics is a private biopharmaceutical company focused on the most prevalent and elusive target in oncology—RAS. Our vision is to develop novel small molecule cancer medicines by selectively targeting protein-protein interactions that are key to oncogenic RAS activity. Driving Quanta's success is our unique high-throughput platform that applies Second Harmonic Generation (SHG) optical technology to identify allosteric modulators of protein complexes. The Quanta team has extensive drug development expertise and substantial research experience in the RAS space. By applying innovative medicinal chemistry and its unique protein conformation detection technology, Quanta aims to advance differentiated, next-generation RAS programs that address the resistance paradigms of targeted therapy in oncology. Quanta’s KRAS inhibitor pipeline includes three programs: QTX3034, a multi-KRAS inhibitor with G12D-preferring activity (G12D+ multi-KRAS), currently in a Phase 1 clinical trial as monotherapy and in combination with cetuximab; QTX3046, a G12D-selective KRAS inhibitor, currently in a Phase 1 clinical trial as monotherapy and in combination with cetuximab; QTX3544, a multi-KRAS inhibitor with G12V-preferring activity (G12V+ multi-KRAS) currently in a Phase 1 clinical trial as a monotherapy and in combination in patients with KRASG12V-driven solid tumors. Quanta is headquartered in South San Francisco, CA, and has a site in Radnor, PA. Find more information at https://www.quantatx.com/. Follow us on LinkedIn: Quanta Therapeutics. Quanta Therapeutics Heather Meeks 661-992-6907 heather.meeks@quantatx.com Media Contact Kelli Perkins kelli@redhousecomms.com

LOS ANGELES--(BUSINESS WIRE)--Researchers with City of Hope®, one of the largest and most advanced cancer research and treatment organizations in the U.S. with its National Medical Center named top 5 in the nation for cancer by U.S. News & World Report, will present more than 74 chaired, plenary, educational, minisymposium, poster and other sessions on innovative clinical trial results, breakthrough diagnostic techniques and advances in treatment options at the AACR Annual Meeting, which started April 25 and ends April 30 in Chicago. In addition to City of Hope’s innovative research being presented throughout the meeting, David W. Craig, Ph.D., professor and founding chair of the Department of Integrative Translational Sciences within Beckman Research Institute of City of Hope, is chairing the final plenary session of the conference, “Opportunities in Predictive Oncology,” on Wednesday from 8 to 10 a.m. CT. He will also present an educational session on using a biological analysis approach called multiomics to investigate the unique genetic makeup of different cell populations in solid tumors on Friday from 4:46 to 5:06 p.m. CT. On Saturday from 10:00 to 11:30 a.m. CT, Michael A. Caligiuri, M.D., former president of City of Hope National Medical Center and professor in the Department of Hematology & Hematopoietic Cell Transplantation, will chair a session on advances in the application of natural killer (NK) cells and present on “Innate immune lymphocytes, including NK cells.” He will also chair “Academic Entrepreneurship: Getting Your Discovery to Patients, Part 1—Liftoff” on Saturday from 8:00 to 9:30 a.m. CT, which will help define the steps required for translating research from the bench to the bedside. As part of a session on advances in diagnostics and therapeutics, Hope Rugo, M.D., who recently joined City of Hope as director of its Women’s Cancers Program, will talk about new findings in managing toxicities from antibody-drug conjugates on Monday from 1:25 to 1:45 p.m. CT. Dr. Rugo will also serve as a discussant at the Clinical Trials Plenary Session on Biologics and T-cell Engagers on Tuesday from 10:15 a.m. to 12:15 p.m. CT. Highlights of City of Hope research presented at the AACR conference include: Phase 3 clinical trial shows promising results for novel immunotherapy Cancer of the nasopharynx, or the upper part of the throat that plays a crucial role in breathing and swallowing, is relatively rare. However, in certain regions like China and North Africa, the disease is much more common. To combat recurrent or metastatic nasopharyngeal carcinoma, a new immunotherapy drug has been tested in combination with standard chemotherapy. Data from a phase 3 clinical trial of the medication called penpulimab resulted in the Food and Drug Administration (FDA) approving its use this past week in combination with cisplatin or carboplatin and gemcitabine for the first-line treatment of adult patients with recurrent or metastatic nasopharyngeal carcinoma. The FDA also approved penpulimab as a single agent for similar patients with disease progression on or after platinum-based chemotherapy and at least one other prior line of therapy. Medical oncologist Aditya Shreenivas, M.D., M.S. will present the supporting data from “Penpulimab versus placebo in combination with chemotherapy as first-line treatment for recurrent or metastatic nasopharyngeal carcinoma: A global, multicenter, randomized, double-blind, phase 3 trial (AK105-304)” during a clinical trials minisymposium session on Sunday from 3:50 to 4:00 p.m. CT. Penpulimab is an anti-PD-1 inhibitor, a type of treatment that helps the immune system recognize and attack cancer. Building on previous studies that have shown that the combination of PD-1 inhibitors with chemotherapy exhibits promising efficacy as a first-line treatment for Asian patients, phase 3 of the trial included 291 patients from both Asian and non-Asian countries. Patients received either a combination of penpulimab and standard chemotherapy or a placebo plus chemotherapy. The study’s findings showed that patients who had penpulimab added to their treatment plan had their cancer controlled for 9.63 months on average, compared to just 7.00 months for those who did not. This represents a 55% reduction in the risk of disease progression. The researchers also found that the combination of penpulimab with chemotherapy had a manageable safety profile with tolerable side effects. “What makes penpulimab unique is that it is an anti-PD-1 antibody with a modified structure designed to potentially improve efficacy while reducing immune-related side effects,” said Dr. Shreenivas, who led at the study at City of Hope, one of 46 trial sites worldwide. “This research supports use of penpulimab plus chemotherapy as a new first-line treatment option for patients with recurrent or metastatic nasopharyngeal carcinoma.” He also says that since penpulimab has already been approved in China for some other cancers, like relapsed or refractory classic Hodgkin's lymphoma and metastatic squamous non-small-cell lung cancer, this study might lead to expanded approvals for penpulimab in additional countries. According to Dr. Shreenivas, future findings from the clinical trial could include explorations of how to identify which patients benefit most from this treatment, as the researchers analyzed various subgroups including those with liver metastases, different protein expression levels, and different DNA levels of Epstein-Barr virus, which is considered a strong risk factor for nasopharyngeal carcinoma. The clinical trial was sponsored by Akeso, a Chinese biopharmaceutical company that developed penpulimab. Researchers use innovative technologies to learn more about treatment responses on ovarian, prostate and breast cancer patients Ovarian cancer Not all patients with aggressive, high-grade serous ovarian cancer — the most common type of the disease — respond the same way to immunotherapy. To elucidate differences that might help tailor immunotherapy strategies for individual patients, a group of researchers from City of Hope and USC led by Jing Qian, a doctoral student in the lab of John D. Carpten, Ph.D., City of Hope’s chief scientific officer, Irell & Manella Cancer Center Director's Distinguished Chair and Morgan & Helen Chu Director's Chair of the Beckman Research Institute, sought to characterize the cancer and immune cells within the tumor environments of patients with different responses to treatment. By using spatial transcriptomic technologies to map interactions between cancer and immune cells, the team was able to reveal differing immune cell behavior and composition in tumors with varied responses to immunotherapy. Spatial transcriptomic methods can provide valuable insights into gene expression within tissue and the technology is an area of rapid development in medical research. “In the future, this approach could help identify patients who are more likely to benefit from immunotherapy and uncover new targets to improve treatment for those who don’t respond,” said Qian. “Ultimately, it pushes the field closer to precision immuno-oncology in high-grade serous ovarian cancer.” Next, the team plans to use cell models and additional patient cohorts to explore whether targeting specific immune cell types can improve responses to immunotherapy in ovarian cancer. Qian will present “Spatial transcriptomics reveals differences in the tumor and immune microenvironment of high-grade serous ovarian cancers with differing responses to immune checkpoint inhibitors” as a late breaking poster session on Sunday from 2:00 to 5:00 p.m. CT. Prostate cancer Recent studies suggest that a complex interplay between ethnicity and disease biology could influence how metastatic hormone sensitive prostate cancer (mHSPC) behaves in different patients. To investigate differences in tumor tissue from patients of Hispanic background compared to those not of Hispanic background, a team of City of Hope researchers led by Tanya Barauskas Dorff, M.D., professor in the Department of Medical Oncology & Therapeutics Research, borrowed pre-treatment prostate biopsy specimens from an existing clinical trial. Using digital spatial profiling, a technology used to study gene and protein expression in tissues, the researchers were able to interrogate the tumor microenvironment from different patients with mHSPC with greater granularity and depth. They found a difference in expression of certain proteins like Foxp3, PARP and STING, all of which are targets of certain cancer medications, between Hispanic and non-Hispanic patients. “This type of exploration in tissue samples from patients of diverse backgrounds may help uncover factors that could account for differences in treatment response,” said Dr. Dorff. “As we complete the testing on additional tissue samples, we hope to compare results against treatment outcomes, to see a clearer signal emerge identifying candidate proteins for future validation.” She said the team hopes to increase the variety of samples being tested and compare their findings to clinical outcomes from the trial, which should become available early 2026. Peter Zang, M.D., a hematology & oncology fellow and first author on “Digital spatial profiling with GeoMx to identify differential protein expression in Non-Hispanic/Latino and Hispanic/Latino Patients with metastatic hormone sensitive prostate cancer,” will present the team’s poster abstract on Tuesday from 2:00 to 5:00 p.m. CT. Breast cancer A poster presentation by Sydney Grant, a postdoctoral fellow, and Aritro Nath, Ph.D., assistant professor in the Department of Medical Oncology & Therapeutics Research, on Tuesday from 9:00 a.m. to 12:00 p.m. CT, “Integrating multimodal data with survival-based variational autoencoders to predict recurrence-free survival in breast cancer,” will highlight a powerful new AI-based approach the team developed to predict recurrence-free survival in breast cancer patients. By enhancing existing generative AI models to process a broader range of real-world patient data, which extend far beyond traditional biomarkers currently used in the clinic, Grant and Nath established an approach that enables more accurate and personalized predictions about cancer patient outcomes. “This work could lead to new clinical tests used at the time of diagnosis to guide treatment decisions and bring us closer to truly personalized care,” said Dr. Nath. “For example, these tools would help doctors identify which patients need more aggressive therapy and which patients could avoid overtreatment and unnecessary side effects.” The team is now working to extend their models to predict which types of treatment or drug classes will work best for individual patients, with the goal of guiding therapy selection in the clinic using AI. New technology identifies unique genetic changes in early-onset colorectal cancer among Hispanic and Latino patients Colorectal cancer is the second leading cause of cancer-related deaths and cases among younger patients are rising, particularly among Hispanic and Latino populations. A new study from the lab of Enrique Velazquez Villarreal, M.D., Ph.D., M.P.H., M.S., assistant professor in the Department of Integrative Translational Sciences, has found that early-onset colorectal cancer in Hispanic and Latino patients has unique genetic changes that help explain how the cancer grows and spreads. “This is the first study to look closely at the genetics of colorectal cancer in Hispanic and Latino patients from the Los Angeles area, a group that’s often left out of cancer research,” said postdoctoral fellow Francisco (Paco) Carranza, who is first author on the study. “By understanding how colorectal cancer affects different populations, especially those who are often overlooked, we can help create better and more targeted treatments.” To find genetic changes, the research team used DNA and RNA sequencing plus a powerful new technology called 10x Genomics Visium that let them see which genes are turned on or off in specific parts of a tumor. This helped them better understand how cancer cells interact with the immune system and how the disease behaves in this patient population. “This kind of research brings us closer to making sure all patients—no matter their background—have access to the best possible care and the same chance at successful outcomes,” said Dr. Velazquez Villarreal, whose research is focused on addressing colorectal cancer health disparities in Hispanic and Latino communities. Next, Carranza and his collaborators plan to move this research even closer to patient care by using an advanced version of the 10x Genomics Visium platform that allows researchers to look at tumors one cell at a time to give even more detailed information that could lead to better tailored therapies and help design new clinical trials. Carranza will discuss the team’s work during a minisymposium session called “Multi-omics analysis of MYC gene and WNT signaling pathway alterations in early-onset colorectal cancer in Hispanic/Latino patients, enhanced with spatial transcriptomics approaches” on Monday from 2:35 to 2:50 p.m. CT. AI tool developed at City of Hope makes precision medicine more accessible and inclusive Dr. Velazquez Villarreal will also present a poster on his lab’s development of a new precision medicine AI tool that addresses key challenges in the integration of different data sets to promote better equity in cancer research. The new tool, called the Precision Medicine Artificial Intelligence Agent (PM-AI), is a conversational AI system that can understand plain-language questions and automatically run complex data analyses. It combines clinical information, genetic data, and social factors like income or access to care to make it easier for scientists to study cancer in a more complete and inclusive way. “By making it easier to analyze large and complex datasets, PM-AI can help researchers and doctors discover which treatments work best for different groups of people,” said Dr. Velazquez Villarreal. This means patients could one day receive more personalized care based on their genetics, health history, and social conditions—leading to better outcomes for everyone, especially underserved communities.” He said the research team plans to keep expanding PM-AI’s capabilities by applying it to more types of cancer and integrating even more kinds of data. The goal is to support clinical decisions, help design new studies and ultimately make precision medicine more accessible for all patients. The study, “PM-AI agent: A conversational artificial intelligence system for precision medicine and advancing health equity through integrative clinical, genomic and social determinants of health data analysis,” is the first accepted by AACR to use a cutting-edge technology known as an AI-driven conversational agent and will be presented during a poster session on Sunday from 2:00 to 5:00 p.m. CT. Combination treatment found to overcome therapy resistance in ER+ breast cancer In patients with estrogen receptor-positive (ER+) breast cancer — the most common type of the disease — 30-50% eventually develop resistance to primary endocrine therapy and progress to advance disease. While cell cycle inhibitor therapies help slow down metastatic ER+ breast cancer, patients often become resistant to these treatments, too. Now, a new study by City of Hope researchers has revealed that ER+ breast cancers resistant to cell cycle inhibitors undergo dynamical rewiring of both apoptosis (or cell death) pathways and proliferative pathways, which regulate cell division and growth, to survive. To overcome this resistance, the team looked for add-on therapies that target growth factor receptors. Their goal was to find a combination that provides a blockade of proliferative pathways with sustained upregulation of apoptosis pathways to maintain treatment effectiveness. Using leading-edge integration of short- and long-term biological experimentation cell models with mathematical and computational analysis, they discover a new proposed combination therapy of ribociclib (a cell cycle inhibitor) plus afatinib (a growth factor inhibitor) that can durably control breast cancer cell growth over time. “Although cell growth-targeted drugs have improved outcomes for hormone-dependent breast cancer patients, resistance remains a major clinical challenge limiting their long-term benefit,” said Andrea Bild, Ph.D., professor in the Department of Medical Oncology & Therapeutics Research and senior author of the study. “Our research presents a novel strategy to enhance the durability and effectiveness of current treatments.” Next, the research team aims to translate their findings for patient benefit in the clinic. To do so, Dr. Bild said they will expand their use of temporal computational and mathematical modeling to monitor molecular changes over time and identify dynamic biomarkers that can guide future treatment strategies. Kimya Karimi, a doctoral student in Dr. Bild’s lab, will present the team’s study “Overcoming intrinsic mechanisms of cell cycle inhibitor resistance in estrogen receptor-positive (ER+) breast cancer” during a minisymposium on Tuesday from 3:05 to 3:20 p.m. CT. About City of Hope City of Hope's mission is to make hope a reality for all touched by cancer and diabetes. Founded in 1913, City of Hope has grown into one of the largest and most advanced cancer research and treatment organizations in the United States, and one of the leading research centers for diabetes and other life-threatening illnesses. City of Hope research has been the basis for numerous breakthrough cancer medicines, as well as human synthetic insulin and monoclonal antibodies. With an independent, National Cancer Institute-designated comprehensive cancer center that is ranked Top 5 in the nation for cancer care by U.S. News & World Report at its core, City of Hope brings a uniquely integrated model that spans cancer care, research and development, academics and training, and a broad philanthropy program that powers its work. City of Hope’s growing national system includes its Los Angeles campus, a network of clinical care locations across Southern California, a new cancer center in Orange County, California, and cancer treatment centers and outpatient facilities in the Atlanta, Chicago and Phoenix areas. City of Hope’s affiliated group of organizations includes Translational Genomics Research Institute and AccessHope™. For more information about City of Hope, follow us on Facebook, X, YouTube, Instagram and LinkedIn.