Metastatic HER2-Negative Breast Carcinoma

Buying RGT-419B continues Roche’s push into HR-positive breast cancer. Genentech is paying $850 million upfront for Regor Pharmaceuticals’ portfolio of CDK inhibitors, taking ownership of a breast cancer candidate that has shown signs of single-agent efficacy in patients failed by existing options. The deal was announced on Roche's Pharma Day, where the Swiss Big Pharma—which owns Genentech—also disclosed (PDF) the acquisition of Wnt signaling-focused biotech AntlerA Therapeutics.Regor, a Chinese-American biotech, presented phase 1a results on its next-generation CDK inhibitor late last year. The biotech designed the drug candidate to have high potency against CDK4, additional activity versus CDK2 and selectivity against CDK6. Those features are intended to overcome resistance to CDK4/6 inhibition and reduce hematologic toxicity.The biotech is testing the molecule, which is called RGT-419B, in hormone receptor (HR)-positive, HER2-negative advanced or metastatic breast cancer patients who progressed on prior CDK4/6 inhibitors. All 12 of the women in the analysis had previously received Pfizer’s CDK4/6 inhibitor Ibrance. Two patients had also taken Novartis’ Kisqali or Eli Lilly’s Verzenio, other approved CDK inhibitors.Regor saw (PDF) two confirmed and one unconfirmed partial responses during dose escalation. The monotherapy’s 28.6% confirmed partial response rate in seven patients with measurable disease, plus absence of grade 3 or higher adverse events, led Regor to plan dose expansions of RGT-419B as a single agent and in combination with endocrine therapy. The biotech will manage two ongoing phase 1 trials of RGT-419B to completion. After that, Genentech will be responsible for clinical development, manufacturing and commercialization worldwide. As the CDK inhibitors advance, Genentech could pay development, regulatory and commercial milestones of undisclosed size.Buying RGT-419B continues Roche’s push into HR-positive breast cancer, which represents around 70% of all cases. The Swiss drugmaker is developing giredestrant, a selective endocrine receptor degrader, and inavolisib, a PI3K inhibitor, in HR-positive disease. Roche sees giredestrant as a potential replacement for endocrine therapies that combines tolerably with CDK inhibitors. The ability to combine inavolisib with CDK inhibitors is central to Roche’s attempt to differentiate the PI3K inhibitor.To date, Roche has paired its candidates with CDK inhibitors from Lilly, Novartis and Pfizer. Genentech’s acquisition of the Regor portfolio, which is expected to close in the fourth quarter, will give Roche its own CDK inhibitors.After selling the CDK inhibitor portfolio, Regor will focus on its remaining oncology, metabolic disease and autoimmune assets. The pipeline is led by an oral GLP-1 receptor agonist that is in clinical development in diabetes and obesity. Lilly partnered with the biotech to work on metabolic disorders in 2021.  Meanwhile, the acquisition of AntlerA, which Roche called a leader in Wnt signaling, gives the pharma ownership of a library of anti-FZD/LRP drug candidates. Roche sees AntlerA’s preclinical lead asset as a potential best-in-class treatment for neovascular age-related macular degeneration and diabetic macular edema.Roche wouldn't disclose the financial details of the deal, but a spokesperson told Fierce Biotech that the biotech's pipeline is “a strong fit with our interest in ophthalmology and ... the Wnt pathway could be very promising for the treatment of other diseases.”Today's oncology and eye-focused deals strengthen Roche’s pipeline in two of the five priority areas for its new pharma strategy, which the company reaffirmed at its Pharma Day in London this morning. Roche’s 10-year ambition is to deliver 20 transformative medicines addressing diseases with the highest societal burden, executives explained to attendees at the event.

First and only AKT inhibitor approved in the EU for breast cancer patients with specific biomarker alterations (PIK3CA, AKT1 or PTEN) Approval based on CAPItello-291 results which showed this combination reduced the risk of disease progression or death by 50% vs. Faslodex alone in a biomarker-altered population LONDON, UK I June 20, 2024 I AstraZeneca’s Truqap (capivasertib) in combination with Faslodex (fulvestrant) has been approved in the European Union (EU) for the treatment of adult patients with estrogen receptor (ER)-positive, HER2‑negative locally advanced or metastatic breast cancer with one or more PIK3CA, AKT1, or PTEN-alterations following recurrence or progression on or after an endocrine-based regimen. The approval by the European Commission follows the positive opinion of the Committee for Medicinal Products for Human Use and is based on results from the CAPItello-291 Phase III trial published in The New England Journal of Medicine . 1 In the trial, Truqap in combination with Faslodex reduced the risk of disease progression or death by 50% versus Faslodex in combination with placebo in patients with tumours harbouring PI3K, AKT or PTEN alterations (based on hazard ratio of 0.50, 95% confidence interval 0.38-0.65; p=<0.001; median progression-free survival (PFS) 7.3 versus 3.1 months). 1 In Europe, breast cancer remains the leading cause of cancer death, with more than 140,000 deaths in 2022 and more than 550,000 patients diagnosed in the same year. 2 Hormone receptor (HR)-positive breast cancer (expressing estrogen or progesterone receptors, or both), is the most common subtype of breast cancer with 70% of tumours considered HR-positive and HER2-negative. 3 More than 97% of HR-positive breast cancer tumours are ER-positive. 4,5 Collectively, mutations in PIK3CA, AKT1 and alterations in PTENoccur frequently, affecting approximately 50% of patients with advanced HR-positive breast cancer. 6-8 Mafalda Oliveira, MD, PhD, Vall d’Hebron University Hospital, and Senior Clinical Investigator of the Vall d’Hebron Institute of Oncology’s Breast Cancer Group in Barcelona, Spain, said: “Patients with advanced ER-positive breast cancer typically experience tumour progression or resistance with widely used endocrine-based treatment regimens, and there is an urgent need to provide them more time with their disease under control. Today’s approval is welcome news for approximately half of ER-positive breast cancer patients in Europe who have tumours with these biomarkers, and it is important for clinicians to test and identify eligible patients who may be able to benefit from this combination.” Dave Fredrickson, Executive Vice President, Oncology Business Unit, AstraZeneca, said: “ Truqap is now the first and only AKT inhibitor approved in the European Union for patients with ER-positive breast cancer who have tumours harbouring these specific biomarkers. Breast cancer continues to be the leading cause of cancer-related death in Europe, and today’s news represents a significant step forward in providing an important new treatment option for patients in need of new, innovative therapies.” In the CAPItello-291 trial, the safety profile of Truqap plus Faslodex was similar to that observed in previous trials evaluating this combination. 1 Regulatory applications are currently under review in China and several other countries. Similar indications for Truqap in combination with Faslodex are already approved in the US , Japan and several other countries based on the CAPItello-291 trial. Financial considerations Following this approval in the EU, Astex Therapeutics is eligible to receive a milestone payment from AstraZeneca on first commercial sale of the drug in the EU as well as royalties on future sales in line with the agreement between the two companies. Notes HR-positive breast cancer The growth of HR-positive breast cancer cells is often driven by estrogen receptors, and endocrine therapies that target ER-driven disease are widely used as 1st-line treatment in the advanced setting, and often paired with CDK4/6 inhibitors. 9-11 However, resistance to CDK4/6 inhibitors and current endocrine therapies develops in many patients with advanced disease. 10 Once this occurs, treatment options are limited– with chemotherapy being the current standard of care – and survival rates are low with approximately 35% of patients anticipated to live beyond five years after diagnosis. 3,10,12 The optimisation of endocrine therapy and overcoming resistance to enable patients to continue benefiting from these treatments, as well as identifying new therapies for those who are less likely to benefit, are active areas of focus for breast cancer research. CAPItello-291 CAPItello-291 is a Phase III, double-blind, randomised trial evaluating the efficacy of Truqap in combination with Faslodex versus placebo plus Faslodex for the treatment of locally advanced (inoperable) or metastatic HR-positive (ER-positive and ER-positive, progesterone receptor-positive), HER2-low or negative (immunohistochemistry (IHC) 0 or 1+, or IHC 2+/in-situ hybridisation (ISH)-negative) breast cancer. The global trial enrolled 708 adult patients with histologically confirmed HR-positive, HER2-low or negative breast cancer whose disease has recurred or progressed during or after aromatase inhibitor therapy, with or without a CDK4/6 inhibitor, and up to one line of chemotherapy for advanced disease. The trial has dual primary endpoints of PFS in the overall patient population and in a population of patients whose tumours have qualifying alterations in the PI3K/AKT pathway (PIK3CA, AKT1 or PTEN genes). In the trial, approximately 40% of tumours had these alterations and approximately 70% of patients received a prior CDK4/6 inhibitor. Truqap Truqap is a first-in-class, potent, adenosine triphosphate (ATP)-competitive inhibitor of all three AKT isoforms (AKT1/2/3). Truqap 400mg is administered twice daily according to an intermittent dosing schedule of four days on and three days off. This was chosen in early phase trials based on tolerability and the degree of target inhibition. Truqap is approved in the US, EU, Japan and several other countries for the treatment of adult patients with HR-positive (or ER-positive), HER2-negative locally advanced or metastatic breast cancer with one or more biomarker alterations (PIK3CA, AKT1 or PTEN) following recurrence or progression on or after an endocrine-based regimen based on the results from the CAPItello-291 trial. Truqap is also approved in Australia for the treatment of adult patients with HR-positive, HER2-negative locally advanced or metastatic breast cancer following recurrence or progression on or after an endocrine based regimen based on these trial results. Truqap is currently being evaluated in Phase III trials for the treatment of breast cancer (CAPItello-292) and prostate cancer (CAPItello-280 and CAPItello-281) in combination with established treatments. Truqap was discovered by AstraZeneca subsequent to a collaboration with Astex Therapeutics (and its collaboration with the Institute of Cancer Research and Cancer Research Technology Limited). Faslodex Faslodex is an endocrine therapy indicated for the treatment of ER-positive, locally advanced or metastatic breast cancer in postmenopausal women not previously treated with endocrine therapy, or with disease relapse on or after adjuvant anti-estrogen therapy, or disease progression on anti-estrogen therapy. In the US, EU and Japan , Faslodex is also approved in combination with CDK4/6 inhibitors for the treatment of women with HR-positive, HER2-negative advanced or metastatic breast cancer, whose cancer has progressed after endocrine medicine . Faslodex represents a hormonal treatment approach that helps to slow tumour growth by blocking and degrading the estrogen receptor – a key driver of disease progression. Faslodex is approved as monotherapy or in combination with medicines from various drug classes including CDK4/6, PI3K and AKT inhibitors for the treatment of patients with HR-positive advanced breast cancer and is being evaluated in combination with medicines from other drug classes. AstraZeneca in breast cancer Driven by a growing understanding of breast cancer biology, AstraZeneca is starting to challenge, and redefine, the current clinical paradigm for how breast cancer is classified and treated to deliver even more effective treatments to patients in need – with the bold ambition to one day eliminate breast cancer as a cause of death. AstraZeneca has a comprehensive portfolio of approved and promising compounds in development that leverage different mechanisms of action to address the biologically diverse breast cancer tumour environment. With Enhertu (trastuzumab deruxtecan), a HER2-directed antibody drug conjugate (ADC), AstraZeneca and Daiichi Sankyo are aiming to improve outcomes in previously treated HER2-positive and HER2-low metastatic breast cancer and are exploring its potential in earlier lines of treatment and in new breast cancer settings.. In HR-positive breast cancer, AstraZeneca continues to improve outcomes with foundational medicines Faslodex and Zoladex (goserelin) and aims to reshape the HR-positive space with first-in-class AKT inhibitor, Truqap , and next-generation SERD and potential new medicine camizestrant. AstraZeneca is also collaborating with Daiichi Sankyo to explore the potential of TROP2-directed ADC, datopotamab deruxtecan, in this setting. PARP inhibitor Lynparza (olaparib) is a targeted treatment option that has been studied in early and metastatic breast cancer patients with an inherited BRCA mutation. AstraZeneca with MSD (Merck & Co., Inc. in the US and Canada) continue to research Lynparza in these settings and to explore its potential in earlier disease. To bring much-needed treatment options to patients with triple-negative breast cancer, an aggressive form of breast cancer, AstraZeneca is evaluating the potential of datopotamab deruxtecan alone and in combination with immunotherapy Imfinzi (durvalumab), and Imfinzi in combination with other oncology medicines, including Lynparza and Enhertu . AstraZeneca in oncology AstraZeneca is leading a revolution in oncology with the ambition to provide cures for cancer in every form, following the science to understand cancer and all its complexities to discover, develop and deliver life-changing medicines to patients. The Company’s focus is on some of the most challenging cancers. It is through persistent innovation that AstraZeneca has built one of the most diverse portfolios and pipelines in the industry, with the potential to catalyse changes in the practice of medicine and transform the patient experience. AstraZeneca has the vision to redefine cancer care and, one day, eliminate cancer as a cause of death. AstraZeneca AstraZeneca (LSE/STO/Nasdaq: AZN) is a global, science-led biopharmaceutical company that focuses on the discovery, development, and commercialisation of prescription medicines in Oncology, Rare Diseases, and BioPharmaceuticals, including Cardiovascular, Renal & Metabolism, and Respiratory & Immunology. Based in Cambridge, UK, AstraZeneca’s innovative medicines are sold in more than 125 countries and used by millions of patients worldwide. Please visit astrazeneca.com and follow the Company on social media @AstraZeneca References SOURCE: AstraZeneca

Data from study using Guardant360® blood test show Black patients with PIK3CA mutations in advanced breast cancer were less likely than White patients to be enrolled in clinical trials and receive targeted therapy Study is part of collaboration between Guardant Health and Multicenter Precision Medicine Academic Consortium (PMAC) using liquid biopsy to achieve equitable use of precision medicine therapies in patients with metastatic breast cancer PALO ALTO, Calif.--(BUSINESS WIRE)-- Guardant Health, Inc. (Nasdaq: GH), a leading precision oncology company, announced its research collaborators from Washington University’s Siteman Cancer Center will lead an oral presentation today at the 2024 American Society for Clinical Oncology (ASCO) Annual Meeting highlighting the potential role of liquid biopsy in addressing racial inequities in enrollment in clinical trials and in the use of targeted therapies for advanced breast cancer. The Rapid Oral Abstract Session (#1017), titled “Racial differences in genomic profiles and targeted treatment use in ER+ HER2- metastatic breast cancer,” will be held between 11:30 am and 1:00 pm CT in Hall D1. The retrospective study, led by first author Emily Podany, MD, and senior author Andrew Davis, MD, both from Washington University, focused on patients with hormone receptor positive (HR+), HER2 negative (HER2-) metastatic breast cancer with PIK3CA mutations, which had an equal incidence in Black and White patients. The 1,327 patients in the study, who were treated at Washington University in St. Louis, Massachusetts General Hospital, and Northwestern University, had the Guardant360 liquid biopsy test as part of clinical care and these results were combined with annotated clinical data. Results indicated that Black patients were significantly less likely than White patients to receive PIK3CA targeted therapy or to be enrolled in a clinical trial for biomarkers that required targetable mutations identified via circulating tumor DNA (ctDNA). There were no differences in the use of therapies that did not require a targetable mutation identified via ctDNA. “These data show clinical inequities in the use of targeted therapies and enrollment in clinical trials, which must be the focus of future interventions,” said Podany. “We must now identify ways to ensure all patients equitably receive the recommended precision medicine treatments based on the results of ctDNA testing.” “These data highlight the importance of using ctDNA to identify targetable mutations,” noted Davis. “And they reinforce the urgent need to ensure equitable implementation of precision medicine therapies for patients of all races.” The study is part of an ongoing collaboration between Guardant Health and the multicenter Precision Medicine Academic Consortium (PMAC) aimed at advancing the use of liquid biopsy in patients with metastatic breast cancer. “This landmark study highlights the importance of equitable access to precision medicine,” said Craig Eagle, MD, chief medical officer of Guardant Health. “The results confirm the potential role liquid biopsy can have in helping researchers and clinicians equitably match patients with appropriate trials and clinically effective therapies.” Currently, PMAC is working with Guardant Health to validate genomic findings from this and prior projects using the GuardantINFORM clinical-genomic dataset of over 400,000 patients with advanced cancer. The collaboration will continue to pursue future research focused on increasing equitable utilization of targeted therapies. “The current study demonstrates the importance of studying real-world annotated molecular data related to the use of ctDNA testing and targeted therapies in advanced cancer,” said Massimo Cristofanilli, MD, co-founder of PMAC. “It provides valuable insights that can help us understand the complex relation among biological, ethnic and social diversity and offers potential tools to overcome inequity in care.” The full abstract for the study and a list of all abstracts being presented at the meeting can be found at the ASCO website. For more information and updates from the meeting, follow Guardant Health on LinkedIn and X (Twitter) or visit ASCO booth #28115. About Guardant Health Guardant Health is a leading precision oncology company focused on guarding wellness and giving every person more time free from cancer. Founded in 2012, Guardant is transforming patient care by providing critical insights into what drives disease through its advanced blood and tissue tests, real-world data and AI analytics. Guardant tests help improve outcomes across all stages of care, including screening to find cancer early, monitoring for recurrence in early-stage cancer, and helping doctors select the best treatment for patients with advanced cancer. For more information, visit guardanthealth.com and follow the company on LinkedIn, X (Twitter) and Facebook. Forward-Looking Statements This press release contains forward-looking statements within the meaning of federal securities laws, including statements regarding the potential utilities, values, benefits and advantages of Guardant Health’s liquid biopsy tests or assays, which involve risks and uncertainties that could cause the actual results to differ materially from the anticipated results and expectations expressed in these forward-looking statements. These statements are based on current expectations, forecasts and assumptions, and actual outcomes and results could differ materially from these statements due to a number of factors. These and additional risks and uncertainties that could affect Guardant Health’s financial and operating results and cause actual results to differ materially from those indicated by the forward-looking statements made in this press release include those discussed under the captions “Risk Factors” and “Management’s Discussion and Analysis of Financial Condition and Results of Operation” and elsewhere in its Annual Report on Form 10-K for the year ended December 31, 2023, and in its other reports filed with or furnished to the Securities and Exchange Commission thereafter. The forward-looking statements in this press release are based on information available to Guardant Health as of the date hereof, and Guardant Health disclaims any obligation to update any forward-looking statements provided to reflect any change in its expectations or any change in events, conditions, or circumstances on which any such statement is based, except as required by law. These forward-looking statements should not be relied upon as representing Guardant Health’s views as of any date subsequent to the date of this press release.