Skip to content

Updates from Industry

Tiger-Trials-Logo-No-Background-1024x1024-300x300

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.

August 2024 

  • Learning More About Antibody-Drug ConjugatesRecently, Daiichi Sankyo and AstraZeneca combined forces with patient advocates, patients, and advocacy organizations to co-create an informational video to support patient education and awareness about a category of treatments called Antibody-Drug Conjugates (ADCs). With these treatments, a specific type of chemotherapy is attached to an antibody that can help target specific cells or tissues where the chemotherapy can destroy the tumor cells. To learn more about how this type of treatment approach works, watch the video here. 

  • New Data From The HER2CLIMB TrialSeagen has recently released data from their pivotal HER2CLIMB trial, which examined tucatinib (TUKSYA) in combination with trastuzumab and capecitabine for treatment of adult patients with advanced unresectable or metastatic HER2-positive breast cancer, including patients with brain metastases, who have received one or more prior anti-HER2-based regimens in the metastatic setting. This study was randomized and double-blind, so participants were sorted into different treatment arms by chance and neither participants nor physicians knew which arm of the study the participants were in. Data from this study showed that 80-83% of enrolled participants were aged 65 years or younger, 7-10% of enrolled participants identified as Black, and 37-39% of enrolled participants were ER and PR negative. Data from the study showed a median progression-free survival of 7.6 months in participants receiving TUKSYA with brain metastases and 9.6 months in those without, compared to 5.4 months and 6.8 months in the control arm, respectively. Long-term follow-up analysis showed a median survival of 9.1 months longer in those that received TUKSYA and had brain metastases and a median survival of 4.7 months longer in those that received TUKSYA but did not have brain metastases. Overall, for participants with brain metastases, there was a 61% reduction of DNS progression or death. Similarly, the overall response rate was twice as high with the addition of TUKSYA and the median time to response was 6 weeks. For more information on the HER2CLIMB trial and TUKSYA, click here. 

  • Developing Vaccines Against Breast Cancer: A First Look Into Early Immunization TrialsVaccines have been a long-established tool in the medical field and have been used primarily as a preventive approach against a number of targets, most commonly infectious diseases. Vaccines and other immunizations can help the body produce antibodies that will fight against a specific target. More recently, this approach is being examined as a treatment for different specific subtypes of breast cancer since it can be used to target specific proteins or receptors that appear on cancer cells. Below, we share information on a few different examples. 

    • FLAMINGO-01FLAMINGO-01 is a Phase 3 clinical trial led by Greenwich LifeSciences that is currently ongoing at 37 U.S.-based clinical sites; it is the very first Phase 3 trial of a vaccine for HER2-positive patients. This trial is evaluating a novel HER2-positive breast cancer vaccine called GLSI-100 in HER2-positive breast cancer patients that are at high risk for recurrence and have completed both neoadjuvant and postoperative trastuzumab standard of care therapy. Eligible patients must also be HLA-A*02 positive, which is a specific serotype of HLA antigen that is likely to be found on cancer cells and helps the vaccine target these cancer cells specifically. The HLA or Human Leukocyte Antigen system is involved in immune responses of the body. In the initial two comparative arms of the FLAMINGO-01 study, the vaccine will be compared against a placebo immunization; a future planned arm of the study will consider patients with other HLA subtypes. Results from an earlier Phase 2b study indicated an estimated 5-year disease-free survival rate of 100% in the vaccinated patients, which shows promise for the larger Phase 3 study. As this study is currently enrolling, no results have yet been shared. For more information on this study, visit the study website here or the ClinicalTrials.gov webpage here. 

    • Alpha-Lactalbumin Vaccine  – Another vaccine in clinical trials targets alpha-lactalbumin, a protein that is expressed at high levels in more than 70% of triple negative breast cancer (TNBC) tumors but generally otherwise not expressed in normal aging breast tissue. This trial is a Phase 1 trial being led by the research team at Case Comprehensive Cancer Center in Cleveland, OH; early results show that the vaccine is safe in humans and that more than half of the patients in the trial produced the desired T-cell responses against the target protein. This trial has focused on enrolling patients with a history of early-stage TNBC who have completed treatment but are at risk of recurrence and are within three years of their diagnosis or initiation of treatment. Other planned groups for this study will be cancer-free patients who are at high genetic rick for breast cancer and have BRCA1, BRCA2, and/or PALB mutations as well as patient with early-stage TNBC who have received preoperative chemotherapy and surgery and are being treated with pembrolizumab postoperatively. For more information on this ongoing study, visit the National Cancer Institute webpage here or the ClinicalTrials.gov webpage here. 

    • STEMVACSTEMVAC is a DNA plasmid-based vaccine that targets proteins on breast cancer stem cells and boosts the immune system to recognize and destroy these cancer cells. STEMVAC is currently being studied in a Phase 2 trial in patients with curatively treated stage I-III triple negative breast cancer (TNBC). This vaccine trial is taking place at three locations across the U.S.: Johns Hopkins University – Sidney Kimmel Cancer Center, University of Washington Medical Center – Montlake, and University of Wisconsin – Carbone Cancer Center. This Phase 2 study plans to measure the immune response generated by the vaccine, to assess the safety profile of the vaccine, and to determine whether immunization with this vaccine improves relapse-free survival rates when compared to historical controls. Data available from an earlier Phase 1 trial demonstrated that STEMVAC produces high level, persistent immune responses, showing promise for the current ongoing study. For more information on this study, visit the National Cancer Institute webpage here or the ClinicalTrials.gov webpage here. 

       

      MUC1 Peptide Vaccine 

      The MUC1 peptide vaccine is a new vaccine that is being studied in post-menopausal women with biopsy-proven ER+ ductal carcinoma in situ (DCIS) at University of Pittsburgh Medical Center’s Magee Womens Hospital. All trial participants will receive neoadjuvant therapy with an aromatase inhibitor such as anastrozole, letrozole, or exemestane prior to surgery; those in the cohort examining the effect of the vaccine will also be immunized three times prior to surgery. This vaccine consists of the MUC1 peptide, which is commonly expressed in DCIS, and Hiltonol®, a synthetic RNA mimic that helps activate the immune system. MUC1 is found on the outside of tumor cells and is involved in tumor growth, invasion, and metastasis; since it is on the outside of the cells, it can be used to effectively help the body create antibodies that target those tumor cells. Vaccines with MUC1 have been shown to be safe and decrease the rate of recurrence of high-risk premalignant lesions in colon cancer; read about the study examining a similar MUC1 peptide vaccine in colon cancer here. Additional information on MUC1 and how it can be used to create tumor-targeting vaccines can be found in this article. For more information on this study, read a recent CBS News article here or visit the ClinicalTrials.gov webpage here. 

       

  •  

June 2024 

  • Breakthrough Therapy Designation for Genentech’s InavolisibRecently, 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-DXdThe 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 ENHERTUAstraZeneca 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.