uterus adenocarcinoma

Study shows ctDNA positivity is the most prognostic factor, demonstrating the potential for Signatera to redefine adjuvant treatment pathways in endometrial cancer AUSTIN, Texas--(BUSINESS WIRE)--Natera, Inc. (NASDAQ: NTRA), a global leader in cell-free DNA testing, today announced a new study published in Gynecologic Oncology validating its personalized and tumor-informed molecular residual disease (MRD) test, Signatera, in endometrial cancer. The full study can be found here. Endometrial cancer (EC) is the most common gynecologic malignancy in the United States. Disease incidence has been rising, but mortality has been rising even faster, potentially due to a higher frequency of aggressive high-risk subtypes of the disease.1-4 More accurate risk stratification is needed to identify those patients who will benefit from therapeutic interventions with curative intent. Current guidelines rely on clinicopathological risk factors to define risk groups and aid in adjuvant treatment decision-making.5,6 However, the decision to administer adjuvant therapy for patients with high-risk and high-intermediate-risk EC remains unclear, creating the need for better diagnostic tools to help determine who is most likely to benefit from treatment.7-10 This real-world study analyzed 267 plasma samples drawn after surgery from 101 patients with EC. The patient cohort was composed of multiple histological subtypes, with patients stratified based on clinicopathological risk factors into high-risk (52%), high-intermediate (22%), low-risk (15%), and other (12%). Key findings include: Patients who tested Signatera MRD-positive at either a single time point or longitudinally experienced significantly higher rates of recurrence than those who remained Signatera-negative (58% and 52%, vs. 6% and 0%, respectively), regardless of mismatch repair (MMR) or p53 status. Signatera MRD status was the only significant risk factor for recurrence when adjusted for clinicopathological risk groups and molecular subgroups such as MMR and p53 status (HR=18.9, p=.001). “This study provides clinical validation of Signatera as a powerful post-surgical biomarker of recurrence risk for patients with endometrial cancer,” said Minetta Liu, MD, chief medical officer of oncology at Natera. “Use of Signatera in clinical workflows may help physicians and patients tailor their adjuvant treatment decisions based on direct evidence of molecular residual disease.” About Signatera Signatera is a personalized, tumor-informed, molecular residual disease test for patients previously diagnosed with cancer. Custom-built for each individual, Signatera uses circulating tumor DNA to detect and quantify cancer left in the body, identify recurrence earlier than standard of care tools, and help optimize treatment decisions. The test is available for clinical and research use and is covered by Medicare for patients with colorectal cancer, breast cancer (stage IIb and higher) and muscle invasive bladder cancer, as well as for immunotherapy monitoring of any solid tumor. Signatera has been clinically validated across multiple cancer types and indications, with published evidence in more than 60 peer-reviewed papers. About Natera Natera™ is a global leader in cell-free DNA testing, dedicated to oncology, women’s health, and organ health. We aim to make personalized genetic testing and diagnostics part of the standard of care to protect health, and inform earlier, more targeted interventions that help lead to longer, healthier lives. Natera’s tests are validated by more than 180 peer-reviewed publications that demonstrate high accuracy. Natera operates ISO 13485-certified and CAP-accredited laboratories certified under the Clinical Laboratory Improvement Amendments (CLIA) in Austin, Texas and San Carlos, California. For more information, visit . Forward-Looking Statements All statements other than statements of historical facts contained in this press release are forward-looking statements and are not a representation that Natera’s plans, estimates, or expectations will be achieved. These forward-looking statements represent Natera’s expectations as of the date of this press release, and Natera disclaims any obligation to update the forward-looking statements. These forward-looking statements are subject to known and unknown risks and uncertainties that may cause actual results to differ materially, including with respect to whether the results of clinical or other studies will support the use of our product offerings, the impact of results of such studies, our expectations of the reliability, accuracy and performance of our tests, or of the benefits of our tests and product offerings to patients, providers and payers. Additional risks and uncertainties are discussed in greater detail in "Risk Factors" in Natera’s recent filings on Forms 10-K and 10-Q and in other filings Natera makes with the SEC from time to time. These documents are available at and . References Temkin SM, Kohn EC, Penberthy L, Cronin KA, Rubinsak L, Dickie LA, et al. Hysterectomy-corrected rates of endometrial cancer among women younger than age 50 in the United States. Cancer Causes Control. 2018;29:427–33. Siegel RL, Miller KD, Fuchs HE, and Jemal A. "Cancer statistics, 2022. CA Cancer J Clin. 2022;72(1):7-33. National Cancer Institute. Surveillance, Epidemiology, and End Results Program. Cancer stat facts: uterine cancer. Accessed February 2, 2024. . Siegenthaler F, Lindemann K, Epstein E, et al. Time to first recurrence, pattern of recurrence, and survival after recurrence in endometrial cancer according to the molecular classification. Gynecol Oncol. 2022;165(2):230-238. Concin N, Matias-Guiu X, Vergote I, et al. ESGO/ESTRO/ESP guidelines for the management of patients with endometrial carcinoma. Int J Gynecol Cancer. 2021;31(1):12-39. Abu-Rustum N, Yashar C, Arend R, et al. Uterine Neoplasms, Version 1.2023, NCCN Clinical Practice Guidelines in Oncology. J Natl Compr Canc Netw. 2023;21(2):181-209. Keys HM, Roberts JA, Brunetto VL, et al. A phase III trial of surgery with or without adjunctive external pelvic radiation therapy in intermediate risk endometrial adenocarcinoma: a Gynecologic Oncology Group study. Gynecol Oncol. 2004;92(3):744-51. Nout RA, Smit VT, Putter H et al. Vaginal brachytherapy versus pelvic external beam radiotherapy for patients with endometrial cancer of high-intermediate risk (PORTEC-2): an open-label, non-inferiority, randomised trial. Lancet. 2010;375(9717):816-23. Group AS, Kitchener H, Swart AM, Qian Q, Amos C, and Parmar MK. Efficacy of systematic pelvic lymphadenectomy in endometrial cancer (MRC ASTEC trial): a randomised study. Lancet. 2009;373(9658):125-36. de Boer SM, Powell ME, Mileshkin L, et al. Adjuvant chemoradiotherapy versus radiotherapy alone for women with high-risk endometrial cancer (PORTEC-3): final results of an international, open-label, multicentre, randomised, phase 3 trial. Lancet Oncol. 2018;19(3):295-309.

Findings from the ongoing Phase 1 MYTHIC study demonstrated a favorable and distinctive tolerability pro monotherapy lunresertib Monotherapy antitumor activity observed, including confirmed partial response and several patients with long stable disease Identified both intermittent and continuous schedules to enable combination studies Encouraging early responses across gemcitabine, camonsertib and FOLFIRI clinical combinations Repare to host a virtual webcast event to discuss initial results from MYTHIC study and provide updates on the lunresertib program including early combination trial insights today at 4:30 p.m. ET CAMBRIDGE, Mass. & MONTREAL--(BUSINESS WIRE)-- Repare Therapeutics Inc. (“Repare” or the “Company”) (Nasdaq: RPTX), a leading clinical-stage precision oncology company, today reported initial proof of concept monotherapy data from its Phase 1 MYTHIC clinical trial evaluating lunresertib (RP-6306), a first-in-class, oral PKMYT1 inhibitor in molecularly selected advanced solid tumors. “These initial proof of concept results for lunresertib monotherapy show a favorable and distinct tolerability pro preliminary antitumor activity that support our development plans for this program,” said Maria Koehler, MD, PhD, Chief Medical Officer of Repare. “The data demonstrate that lunresertib effectively inhibits PKMYT1 and offers a synthetic lethal combination with CCNE1 amplification or inactivating mutations in FBXW7 and PPP2R1a. These genetic alterations have previously been considered undruggable and represent a significant unmet medical need. These findings, along with the continued advancement of the lunresertib program across multiple ongoing combination clinical trials, validate our proprietary STEP2 platform and precision medicine approach.” “While early, these promising proof-of-concept data continue to support our belief in the potential transformative role that lunresertib could play, either alone or in combination with other therapies, in patients with molecularly selected advanced solid tumors,” said Lloyd M. Segal, President and Chief Executive Officer of Repare. “We look forward to reporting initial combination data of lunresertib with camonsertib, as well as lunresertib with gemcitabine, in the fourth quarter of this year, while also advancing multiple other trials to further our understanding of our first-in-class PKMYT1 inhibitor program.” Key Initial Findings from the Phase 1 MYTHIC Clinical Trial: MYTHIC (NCT04855656) Module 1 is a first-in-human, global, open-label Phase 1 dose-escalation study to evaluate safety, pharmacokinetics, pharmacodynamics and preliminary anti-tumor activity of a novel and potent small molecule PKMYT1 inhibitor, lunresertib. MYTHIC Module 2 will investigate lunresertib in combination with camonsertib (RP-3500/RG6526), a potent and selective oral inhibitor of ATR developed by Repare and now partnered with Roche (excluding the lunresertib combination), in molecularly selected advanced solid tumors. As of the data cutoff date of April 28, 2023, 63 patients were enrolled in lunresertib monotherapy Module 1 of the MYTHIC study, which is ongoing and accruing patients. Tolerability pro lunresertib monotherapy appears favorable and differentiated from other clinical cell cycle inhibitors, which have been characterized with myelotoxicity and diarrhea. No grade 4 toxicity was observed with lunresertib, where grade 3 treatment emergent adverse events of interest included rash (7.9%), anemia (6.3%) and nausea or vomiting (1.6%) The only dose limiting toxicity was reversible rash, alleviated with dose modifications and simple supportive measures. Two recommended dose/schedules were identified – 240mg daily continuously and 80-100mg BID intermittent weekly – to offer maximum flexibility in combination studies. Pharmacodynamic analysis confirmed lunresertib treatment results in PKMYT1 target inhibition at active doses and increases DNA damage. Preliminary anti-tumor activity was observed, including moderate tumor shrinkages and a confirmed partial response per RECIST 1.1 criteria. Several patients demonstrated long stable disease and remain on treatment for greater than 11 months and ongoing. Early clinical combination insights demonstrated greater anti-tumor activity in patients treated with the combination of lunresertib and camonsertib than lunresertib alone, based on higher molecular response rates and RECIST 1.1 responses. Examples of confirmed partial responses are provided for the three tested sensitivity genotypes in endometrial adenocarcinoma, cholangiocarcinoma and colorectal cancer, with more details planned for the Q4 scientific presentation. Encouraging early responses observed across gemcitabine, camonsertib, and FOLFIRI clinical combinations in multiple tumor types and genotypes. Favorable and distinct tolerability pro preliminary antitumor activity demonstrated thus far support potential development plans that may include further trials of lunresertib in various combination and maintenance approaches. Repare is also currently evaluating lunresertib in combination with gemcitabine in the Phase 1 MAGNETIC study and in combination with FOLFIRI in the Phase 1 MINOTAUR study. Repare is working with Princess Margaret Cancer Center to initiate clinical testing, as part of an investigator-sponsored trial (IST), of a fourth lunresertib combination with carboplatin and paclitaxel for the treatment of recurrent TP53 mutated ovarian and uterine cancer, with first patient dosing expected this year. The Company is also collaborating with the Canadian Cancer Trials Group in an ongoing basket Phase 2 IST that is enrolling patients with selected, advanced cancers receiving lunresertib as combination (NCT05605509), and in a second active study that will evaluate lunresertib in combination with gemcitabine in patients with CDK4/6 inhibitor treated ER+/HER2- metastatic breast cancer (NCT05601440). These studies aim to expand the treatment opportunities for lunresertib to earlier stages of cancer treatment or additional tumor types. Company Virtual Webcast Event: The Company will host a virtual investor webcast with accompanying slides for analysts and investors today at 4:30 p.m. Eastern Time to further discuss the lunresertib program, including initial proof-of-concept monotherapy data from MYTHIC and an update on ongoing combination clinical trials. To access the call, please dial (877) 870-4263 (U.S. and Canada) or (412) 317-0790 (international) at least 10 minutes prior to the start time and ask to be joined to the Repare Therapeutics call. A live video webcast will be available in the Investor section of the Company’s website at . A webcast replay will also be archived for at least 30 days. About Repare Therapeutics’ SNIPRx® Platform Repare’s SNIPRx® platform is a genome-wide CRISPR-based screening approach that utilizes proprietary isogenic cell lines to identify novel and known synthetic lethal gene pairs and the corresponding patients who are most likely to benefit from the Company’s therapies based on the genetic pro their tumors. Repare’s platform enables the development of precision therapeutics in patients whose tumors contain one or more genomic alterations identified by SNIPRx® screening, in order to selectively target those tumors in patients most likely to achieve clinical benefit from resulting product candidates. About Repare Therapeutics, Inc. Repare Therapeutics is a leading clinical-stage precision oncology company enabled by its proprietary synthetic lethality approach to the discovery and development of novel therapeutics. The Company utilizes its genome-wide, CRISPR-enabled SNIPRx® platform to systematically discover and develop highly targeted cancer therapies focused on genomic instability, including DNA damage repair. The Company’s pipeline includes lunresertib (RP-6306), a PKMYT1 inhibitor currently in Phase 1 clinical development; camonsertib (RP-3500/RG6526), a potential leading ATR inhibitor currently in Phase 1/2 clinical development and partnered with Roche; a preclinical Polθ inhibitor program; as well as several additional, undisclosed preclinical programs, including RP-1664. For more information, please visit reparerx.com. SNIPRx® is a registered trademark of Repare Therapeutics Inc. Forward-Looking Statements This press release contains “forward-looking statements” within the meaning of the Private Securities Litigation Reform Act of 1995 and securities laws in Canada. All statements in this press release other than statements of historical facts are “forward-looking statements. These statements may be identified by words such as “aims,” “anticipates,” “believes,” “could,” “estimates,” “expects,” “forecasts,” “goal,” “intends,” “may,” “plans,” “possible,” “potential,” “seeks,” “will” and variations of these words or similar expressions that are intended to identify forward-looking statements, although not all forward-looking statements contain these words. Forward-looking statements in this press release include, but are not limited to, statements regarding: the safety, efficacy and clinical progress of the Company’s clinical programs, including lunresertib (RP-6306) and camonsertib; the clinical and preclinical development of the Company’s pipeline and its research and development programs, including the anticipated timing, anticipated patient enrollment, trial outcomes or associated costs of its clinical trials of lunresertib and camonsertib; and the status of clinical trials (including, without limitation, expectations regarding the data that is being presented, the expected timing of data releases and development, as well as completion of clinical trials) and development timelines for the Company’s product candidates. These forward-looking statements are based on the Company’s expectations and assumptions as of the date of this press release. Each of these forward-looking statements involves risks and uncertainties that could cause the Company’s clinical development programs, future results or performance to differ materially from those expressed or implied by the forward-looking statements. Many factors may cause differences between current expectations and actual results, including: the impacts of macroeconomic conditions, including the COVID-19 pandemic, the conflict in Ukraine, rising inflation, and uncertain credit and financial markets on the Company’s business, clinical trials and financial position; unexpected safety or efficacy data observed during preclinical studies or clinical trials; clinical trial site activation or enrollment rates that are lower than expected; changes in expected or existing competition; changes in the regulatory environment; the uncertainties and timing of the regulatory approval process; and unexpected litigation or other disputes. Other factors that may cause the Company’s actual results to differ from those expressed or implied in the forward-looking statements in this press release are identified in the section titled "Risk Factors" in the Company’s Annual Report on Form 10-K for the year ended December 31, 2022 filed with the Securities and Exchange Commission (“SEC”) and the Québec Autorité des Marchés Financiers ("AMF") on February 28, 2023, and its other documents subsequently filed with or furnished to the SEC and AMF. The Company expressly disclaims any obligation to update any forward-looking statements contained herein, whether as a result of any new information, future events, changed circumstances or otherwise, except as otherwise required by law. For more information, please visit reparerx.com and follow Repare on Twitter at @RepareRx and on LinkedIn at .

Data demonstrates compelling clinical activity, highlights adagrasib potential as monotherapy in solid tumors Clinical data also presented at the ASCO Plenary Series: April 2023 Session Data follows recent inclusion of KRAZATI® (adagrasib) in NCCN Guidelines for CNS Cancers SAN DIEGO, April 26, 2023 /PRNewswire/ -- Mirati Therapeutics, Inc.® (NASDAQ: MRTX), a commercial stage biotechnology company, announced today the Journal of Clinical Oncology published in a Rapid Communication data indicating adagrasib, a potent and selective KRASG12C inhibitor, is well tolerated and demonstrates meaningful clinical activity in patients with pancreatic ductal adenocarcinoma (PDAC), biliary tract cancer (BTC), and other solid tumors harboring a KRASG12C mutation. Rapid Communications are reserved for publications deemed to represent timely and late breaking research that may have an immediate impact on patient care. In addition, findings were presented last week at the April session of the American Society of Clinical Oncology (ASCO) Plenary Series Program. This publication follows the recent inclusion of KRAZATI® (adagrasib) in the National Comprehensive Center Network (NCCN) Guidelines for Central Nervous System (CNS) Cancers for patients living with previously treated KRASG12C-mutant non-small cell lung cancer (NSCLC) and CNS metastases. The Phase 2 data of the KRYSTAL-1 study demonstrates the potential of adagrasib as a monotherapy in patients with unresectable or metastatic KRASG12C-mutated solid tumors beyond NSCLC and colorectal cancer (CRC). The data presented was based on confirmed blinded, independent, central review (BICR) responses. This is the largest Phase 2 dataset evaluating KRAS G12C mutated solid tumors other than non-small cell lung cancer and colorectal cancer. The enrolled and treated population (n=63) included 21 PDAC, 12 BTC, 9 appendiceal adenocarcinoma, 4 gastroesophageal/esophageal adenocarcinoma, 3 small bowel adenocarcinoma, 5 ovarian adenocarcinoma, 4 unknown primary, 3 endometrial adenocarcinoma, 1 breast adenocarcinoma and 1 glioblastoma. The median prior lines of systemic therapy was two. Results showed an objective response rate (ORR) of 35% for the overall cohort. In patients with PDAC, ORR was 33%; for patients with BTC, ORR was 42%. Notably, findings demonstrate the safety pro adagrasib is aligned with previously reported data in patients with pretreated NSCLC and CRC. These findings demonstrate a meaningful improvement relative to the historically reported standard of care for PDAC and BTC. For patients with previously treated metastatic PDAC, current standard of care (gemcitabine + nab-paclitaxel or liposomal irinotecan + 5FU/leucovorin) has resulted in limited ORR (3-16%).1-2 In a biomarker-unselected BTC patient population, the ABC-06 phase 3 trial investigating FOLFOX in the second-line setting reported an ORR of 5%.3 "We are thrilled to see the results of this Phase 2 study, which demonstrate a marked improvement on the current standard of care for patients with unresectable or metastatic KRASG12C-mutated solid tumors, including PDAC, BTC, other gastrointestinal (GI) and non-GI tumors, where few treatment options exist. It is particularly encouraging to see meaningful clinical activity in pancreatic and biliary tract cancers tumors," said Shubham Pant, M.D., M.B.B.S., The University of Texas MD Anderson Cancer Center. "The data indicates that adagrasib has the potential to be an effective treatment for KRASG12C-mutated solid tumor types in addition to NSCLC and CRC." "We're pleased to share this data which demonstrates meaningful clinical activity in KRASG12C-mutated tumor types in addition to NSCLC and CRC, indicating a potential path to regulatory approval for adagrasib in additional indications," said Alan Sandler, M.D., chief medical officer, Mirati Therapeutics, Inc. "We look forward to continuing to advance adagrasib as a potential best-in-class treatment option for patients harboring a KRASG12C mutation." The primary endpoint for the Phase 2 cohort of the KRYSTAL-1 study was objective response rate. Secondary endpoints included duration of response, progression-free survival, overall survival and safety. Findings were presented last week at the April session ASCO Plenary Series Program as a data presentation (Abstract 425082) titled, "KRYSTAL-1: Activity and Safety Of Adagrasib (MRTX849) In Patients With Advanced Solid Tumors Harboring A KRASG12C Mutation." The full abstract for the presentation can be found here: Program Guide – ASCO Meeting Program Guide. The full Journal of Clinical Oncology article can be found here. About KRAZATI® (adagrasib) In the U.S., KRAZATI was approved by the FDA for Accelerated Approval (Subpart H), which allows for the approval of drugs that treat serious conditions, and that fill an unmet medical need based on surrogate endpoints. KRAZATI was reviewed under the FDA Real-Time Oncology Review (RTOR) pilot program, which aims to explore a more efficient review process that ensures safe and effective treatments are made available to patients as early as possible. Mirati submitted a Marketing Authorization Application (MAA) in the EU in May 2022. In 2021, adagrasib achieved Breakthrough Therapy Designation in the U.S. as a potential treatment for patients with NSCLC harboring the KRASG12C mutation who have received at least one prior systemic therapy. For Prescribing Information, visit Mirati.com/KRAZATI_USPI Adagrasib continues to be evaluated as monotherapy and in combination with other anti-cancer therapies in patients with advanced KRASG12C-mutated solid tumors, including NSCLC, colorectal cancer, and pancreatic cancer. For more information, visit Mirati.com/science. KRAZATI (adagrasib) U.S. Indication KRAZATI is indicated for the treatment of adult patients with KRASG12C-mutated locally advanced or metastatic non-small cell lung cancer (NSCLC), as determined by an FDA-approved test, who have received at least one prior systemic therapy. This indication is approved under accelerated approval based on objective response rate (ORR) and duration of response (DOR). Continued approval for this indication may be contingent upon verification and description of a clinical benefit in a confirmatory trial(s). About Mirati Therapeutics, Inc.® Mirati Therapeutics, Inc.® is a commercial stage biotechnology company whose mission is to discover, design and deliver breakthrough therapies to transform the lives of patients with cancer and their loved ones. The company is relentlessly focused on bringing forward therapies that address areas of high unmet need, including lung cancer, and advancing a pipeline of novel therapeutics targeting the genetic and immunological drivers of cancer. Unified for patients, Mirati's vision is to unlock the science behind the promise of a life beyond cancer. For more information about Mirati, visit us at Mirati.com or follow us on Twitter, LinkedIn and Facebook. Forward Looking Statements This press release includes forward-looking statements regarding Mirati's business, financial guidance and the therapeutic and commercial potential of KRAZATI® (adagrasib), sitravatinib (TAM receptor inhibitor), MRTX1719 (MTA-cooperative PRMT5 inhibitor), MRTX0902 (SOS1 inhibitor), and MRTX1133 (selective KRASG12D inhibitor), Mirati's technologies and Mirati's other products in development. Any statement describing Mirati's goals, expectations, intentions or beliefs, financial or other projections, is a forward-looking statement and should be considered an at-risk statement. Such statements are subject to certain risks and uncertainties, including those related to the impact COVID-19 could have on our business, and including those inherent in the process of discovering, developing and commercializing medicines that are safe and effective for use as human therapeutics, and in the endeavor of building a business around such medicines. Mirati's forward-looking statements also involve assumptions that, if they never materialize or prove correct, could cause its results to differ materially from those expressed or implied by such forward-looking statements. Although Mirati's forward-looking statements reflect the good faith judgment of its management, these statements are based only on facts and factors currently known by Mirati. As a result, you are cautioned not to rely on these forward-looking statements. These and other risks concerning Mirati's programs are described in additional detail in Mirati's annual report on Form 10-K, and most recent Form 10-Q, which are on the Securities and Exchange Commission and available at the SEC's Internet site ( ). These forward-looking statements are made as of the date of this press release, and Mirati assumes no obligation to update the forward-looking statements, or to update the reasons why actual results could differ from those projected in the forward-looking statements, except as required by law. Mirati Contacts Investor Relations: ir@mirati.com Media Relations: media@mirati.com References 1. Wang-Gillam A, Hubner RA, Siveke JT et al. NAPOLI-1 phase 3 study of liposomal irinotecan in metastatic pancreatic cancer: Final overall analysis and characteristics of long-term survivors. Eur J Cancer 2019. 108:78-87 2. Huffman BD, Basu Mallick A, Horick NK, et al. Effect of MUC5AC Antibody (NPC-1C) administered with second-line gemcitabine and nab-paclitaxel on the survival of patients with advanced pancreatic ductal adenocarcinoma. JAMA Network Open 2023;6(1)e2249720 3. Lamarca A, Palmer DH, Singh Wasan H, et al. Second-line FOLFOX chemotherapy versus active symptom control for advanced biliary tract cancer (ABC-06): a phase 3 open-label, randomised, controlled trial. Lancet Oncol 2021;22:690-701 Company Codes: NASDAQ-SMALL:MRTX