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Updates from Industry

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The clinical trial field is always changing, bringing new treatments and new clinical trial opportunities to the table.
From our industry partners, we have selected some key updates in the world of breast cancer treatments and want to she these updates with you.

June 2024 

  • Breakthrough Therapy Designation for Genentech’s Inavolisib – Recently, the FDA granted breakthrough therapy designation to Genentech’s inavolisib for advanced hormone receptor-positive, HER2-begative breast cancer with PIK3CA mutation. This designation means that the development and review process for the drug can be quicker and allows the Sponsor access to more frequent and intensive FDA guidance in the submission process. Breakthrough therapy designations are generally limited to treatments that address unmet need for serious or life-threatening conditions. Receiving this designation means that inavolisib may be able to reach approval faster. This decision by the FDA was based on results from Genentech’s Phase III INAVO120 trial, which showed that inavolisib in combination with palbociclib and fulvestrant reduced risk of disease worsening or death by 57% compared to palbociclib and fulvestrant alone. This trial evaluated 325 patients to study the efficacy and safety of inavolisib in combination with palbociclib and fulvestrant versus placebo plus palbociclib and fulvestrant in people with PIK3CA-mutated, hormone receptor (HR)-positive, HER2-negative, locally advanced or metastatic breast cancer whose disease progressed during treatment or within 12 months of completing adjuvant endocrine therapy and who have not received prior systemic therapy for metastatic disease. Approximately 40% of people with HR-positive breast cancer have a PIK3CA mutation and often face poorer prognosis and experience resistance to endocrine treatments, thus there is a serious need for treatments specific to this mutation. Like with many other mutations, early testing for PIK3CA mutations can help identify appropriate treatments early on. For more information on this treatment and it’s designation, click here. 

  • Biologics License Application Granted for Daiichi Sankyo and AstraZeneca’s Dato-DXd – The FDA has also recently accepted Daiichi Sankyo and AstraZeneca’s Biologics License Application (BLA) for datopotamab deruxtecan (Dato-DXd). Granting a BLA request allows an entity to manufacture a biologic product (like a new drug treatment) and deliver it across the U.S. This is an important preliminary step in the FDA’s approval process for new treatments. The FDA has noted that they expect to provide a regulatory decision (i.e., whether or not this new treatment will be officially ‘approved’) early in 2025. These decisions were based on positive data from the Phase III TROPION-Breast01 trial in which Dato-DXd showed improvement in progression-free survival rates for patients that received this treatment compared to those that received other treatments. This study focused on patients with unresectable or metastatic HR-positive, HER2-negative breast cancer previously treated with endocrine-based therapy and at least one systemic therapy. Susan Galbraith, Executive Vice President, Oncology R&D, AstraZeneca, notes “despite marked progress in the treatment of HR-positive, HER2-negative breast cancer, most patients with advanced disease develop endocrine resistance and face the prospect of one or several lines of chemotherapy. If approved, datopotamab deruxtecan has the potential to provide these patients an efficacious and better tolerated alternative to conventional chemotherapy.” For more information on this treatment and it’s BLA request, click here. 

  • Early Results for AstraZeneca and Daiichi Sankyo’s DESTINY-Breast06 Trial with ENHERTU – AstraZeneca and Daiichi Sankyo have also recently shared results from their DESTINY-Breast06 trial in patients with HR-positive, HER2-low metastatic breast cancer. In this Phase III trial, ENHERTU® (fam-trastuzumab deruxtecan-nxki) shows improvement in progression-free survival rates in comparison to standard-of-care chemotherapy treatments such as capecitabine, paclitaxel, and Nab-paclitaxel in patients with patients with HR-positive, HER2-low (IHC 1+ or 2+/ISH-) metastatic breast cancer following one or more lines of endocrine therapy. Up to 65% of HR-positive, HER2-negative breast cancers are HER2-low and an additional 25% may be HER2-ultralow. Currently endocrine therapies are widely used but result in limited efficacy over the long term. ENHERTU is a HER2-directed antibody and topoisomerase inhibitor, which means it prevents specific enzymes involved in cell growth (topoisomerases) from signaling to keep the cells growing. This treatment is currently already FDA approved for individuals with unresectable or metastatic HER2-positive (IHC 3+ or ISH positive) breast cancer who have received a prior anti-HER2-based regimen, unresectable or metastatic HER2-low (IHC 1+ or IHC 2+/ISH-) breast cancer who have received a prior chemotherapy in the metastatic setting or developed disease recurrence during or within 6 months of completing adjuvant chemotherapy, and unresectable or metastatic non-small cell lung cancer (NSCLC) whose tumors have activating HER2 (ERBB2) mutations and who have received a prior systemic therapy. For more information on this trial and ENHERTU, click here. 

April 2024 

  • On April 5, 2024, the FDA granted accelerated approval to fam-trastuzumab deruxtecan-nxki (Enhertu®, Daiichi Sankyo, Inc.) for adults with unresectable or metastatic HER2+ solid tumors who have received prior systemic treatment and have no satisfactory alternative treatment options. Enhertu is an antibody-drug conjugate treatment that targets HER2 specifically. For this new tumor-agnostic indication, efficacy was evaluated in 192 adults with previously treated unresectable or metastatic HER2+ solid tumors who were enrolled in one of three key trials in the DESTINY trial series. Although Enhertu is most often thought of as a treatment for HER2+ breast cancer, this indication allows it to be used for other HER2+ cancers such as lung cancer, colorectal cancer, and others. The major efficacy outcome measure in all three trials was confirmed objective response rate (ORR), and an additional efficacy outcome was duration of response (DOR). Read more about this new expanded indication here and here!
  • Tissue taken from breast cancer tumors is often tested for biomarkers like ER, PR, and HER2. This information can help doctors guide specific treatments or other interventions. A new option that is becoming more prevalent is using circulating tumor DNA (ctDNA) to look for biomarkers. This type of DNA is released into the bloodstream when cancer cells die and break down. Because it contains the same biomarker components, it can be used to more easily identify their presence. Studying ctNDA requires a blood test whereas standard biopsies require a tissue sample. This approach can be used for many different things, including determining if a drug will work before prescribing it, predicting recurrence, identifying high-risk status, and looking for treatment resistance markers. Learn more about ctDNA on webpages here and here or in this journal article.
  • Agendia® has recently shared initial information from the I-SPY2 clinical trial showing the predictive ability of their Signature ImPrintTN test in assessing immunotherapy response for patients with Triple Negative Breast Cancer (TNBC). A recent presentation given at the 14th European Breast Cancer Conference in Milan, Italy, shows that the test was able to accurately predict both response and non-response in early-stage TNBC patients. Moving forward, this test may be able to be used to inform whether or not to use immunotherapy as a treatment approach for TNBC patients when physicians are assessing likely treatment strategies. The I-SPY2 trial was designed to assess patient tumor biomarkers and identify different treatment classes most likely to be effective based on the tumor biomarker profile. For more information on the I-SPY2 trial, visit the study website here. For more information on the results of the Signature ImPrintTN test in the I-SPY2 trial, read a recent press release shared here. 

February 2024:

  • Chimeric antigen receptor (CAR) T cell therapies are a big topic lately, especially in oncology fields where precision approaches in treatment are necessary. With CAR-T cell treatments, T cells are taken from the patient and modified to be able to recognize and attack specific patterns found only in the cells being targeted, like cancer cells. These modified T cells are then given back to the patient where they can attack only the targeted cancer cells. Currently, CAR-T cell therapy has shown success with this approach and one treatment developed by Novartis and the University of Pennsylvania has been FDA-approved to treat blood cancers like acute lymphoblastic leukemia (ALL); this approach is currently in development for the treatment of solid tumors like breast cancer. This type of treatment is currently being studied at research institutions like City of Hope in Duarte, California, where an ongoing study examines how these genetically engineered T cells can be designed to target and destroy HER2+ cancer cells. Additional ongoing studies examine potential targets for CAR-T cells in the treatment of triple negative breast cancer (TNBC), a breast cancer subtype that is notoriously difficult to target due to the lack of typical receptor targets such as HER2, ER, and PR. After positive results in early studies, a research team at Penn is planning a clinical trial that will study use of CAR-T cells in clearing residual tumor cells that may remain after surgical resection. 
  • Genomic diagnostic tests that can help physicians decide on the most effective therapies for specific breast cancer subtypes are becoming more specialized as new testing approaches are developed and paired together. The Breast Cancer Index® is a test that provides an individual assessment for those with hormone receptor-positive subtypes that can determine whether or not extended anti-estrogen therapy will be beneficial. Similarly, the HER2DX® test looks at biomarkers for several different genes and biological processes in individuals with early stage HER2+ breast cancer and can provide insight on the probability of response for several therapies. This type of diagnostic test can also be used to identify early cases of breast cancer as an addition to existing screening procedures, as highlighted in the coming INTERCEPT clinical trial which examines cancer biomarkers using a less-invasive liquid biopsy procedure rather than a typical tumor biopsy.

December 2023:

  • In November, the FDA approved the combination of capivasertib (Truqap, AstraZeneca Pharmaceuticals) and fulvestrant for patients with metastatic or locally advanced HR+, HER2- breast cancer that is positive for PIK3CA/AKT1/PTEN biomarker alterations. At the same time, the FDA also approved a new test designed to identify these specific biomarker alterations in order to assess whether patients should consider this new treatment combination. In the clinical trial that compared this combination versus fulvestrant without capivasertib, progression-free survival rates doubled in the group of patients that received both treatments together. Read more about this new approval here.
  • The American Cancer Society’s Blue-button Project team, supported by Amgen, has recently published several articles discussing ways to better match patients to clinical trials. One article demonstrates use of an automated screening tool that reviews electronic health records and compares with eligibility criteria for regionally-located clinical trials, finding trials for 91% more patients than traditional approaches. Another article recommends changes in policy, staffing, and procedures that could better support the opportunity to match eligible patients with trials. Lastly, the third article reviews existing methods for trial matching and identifies both challenges and solutions within through direct interviews with healthcare providers involved in clinical research. Read more about the ACS and the Blue-button Project here.
  • The White House Office of Science and Technology Policy is leading a new project to improve the way clinical trials are designed and managed. The Clinical Trials Readiness Initiative will support more inclusive clinical trials and will make them simpler and more accessible to all. Roundtables and listening sessions were held to capture unmet needs that this initiative is designed to address. The top-listed action for this initiative is to enable more diverse participation in clinical trials; to achieve this, more diverse workforces will be needed at hospitals and clinics and increased community outreach and education opportunities will come into play. Many other groups are partnering together on this project to ensure it’s plans can be met. In the long run, this initiative aims to increase distribution of trial sites to areas with minimal existing opportunities, to increase diverse participation in clinical research, to simplify study design for care providers and trial participants, and to better engage with communities in order to establish the trust necessary to support clinical research. Read more about The White House’s plans to support clinical research here. 

October 2023:

  • AstraZeneca announced the US Food and Drug Administration (FDA) has granted Priority Review for their investigational combination therapy for the treatment of adult patients with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative locally advanced or metastatic breast cancer following recurrence or progression on or after an endocrine-based regimen. The new drug application is based on data from the CAPItello-291 Phase III trial presented at the 2022 San Antonio Breast Cancer Symposium and recently published online in The New England Journal of Medicine. For more information regarding this announcement, please see AstraZeneca’s press release.   
  • Daiichi-Sankyo announced that the U.S. Food and Drug Administration (FDA) has approved ENHERTU®(fam-trastuzumab deruxtecan-nxki) for the treatment of adult patients with unresectable or metastatic HER2-low (IHC 1+ or IHC 2+/ISH-) breast cancer who have received a prior chemotherapy in the metastatic setting or developed disease recurrence during or within six months of completing adjuvant chemotherapy. This approval makes ENHERTU the first approved HER2-directed therapy for patients with low levels of HER2 expression. The approval by the FDA is based on the results of the historic DESTINY-Breast04 clinical trial presented at ASCO. Targeting this lower range of expression in the HER2 spectrum offers another approach to delay disease progression and extend survival in patients with metastatic breast cancer. For more information, please review Daiichi-Sankyo’s press release here.  
  • Novartis recently shared data from their NATALEE trial, examining Kisqali® (ribociclib) in HR-positive, HER2-negative early breast cancer. Kisqali is the first and only CDK4/6 inhibitor to demonstrate a consistent, clinically meaningful benefit across a broad population of patients with HR+/HER2- early breast cancer, regardless of disease stage, menopausal or nodal status. Results were also consistent across all secondary endpoints, including distant disease-free survival and recurrence-free survival, with a trend for improved overall survival. The safety profile of Kisqali was favorable at 400 mg with low rates of symptomatic adverse events and limited treatment modifications when administered up to three years. Collectively, NATALEE results have the potential to more-than-double the number of patients who could benefit from treatment with a CDK4/6 inhibitor in the adjuvant setting. Novartis plans to submit these Phase III data to regulatory authorities in the US and Europe before end of year. For more information from Novartis, please click here.