The NRG1 gene is located on chromosome 8 (8p12 region) and encode NRG1. NRG1 gene is translated to generate six different proteins (I-VI) and at least 31 isoforms. NRG1 proteins are structurally related to EGF and contain an EGF-like motif that binds and activates ErbB3 and ErbB4. Upon ligand binding, these receptors form homodimers or heterodimers, which results in phosphorylation of the intrinsic kinase domain, and activation of the PI3K-AKT, MAPK, and other pathways.
The overall incidence of NRG1 fusions is very rare. In many tumor types, only limited numbers of NRG1 fusion variant have been identified. By percentage, there is no organ dominance of the presence of NRG1 fusions. In an analysis of 21, 858 tumor specimens that underwent anchored multiplex PCR for targeted RNA sequencing, the prevalence of NRG1 fusions was 0.2%. Of these, CD74 was the most common partner (29%), followed by ATP1B1 (10%), SDC4 (7%), and RBPMS (5%), and most CD74-NRG1 fusions have been reported in patients with lung IMA. NRG1 fusions result in aberrant expression of the epidermal growth factor (EGF)-like domain of neuregulin-1 (NRG1) on the cell surface binds primarily to ErbB3 and ErbB4, leading to heterodimerization or oligomerization with other ERBB family members. NRG1-mediated activation of ErbB3 promotes dimerization with EGFR, ErbB2, and ErbB4. These partners phosphorylate ErbB3, forming docking sites for SH2-domain proteins, leading to pathologic activation of multiple signal transduction pathways, including the phosphoinositide 3-kinase (PI3K) pathway. Subsequently, ErbB3 expression was noted at high levels, and the proteins were phosphorylated, in fusion-positive cases. Targeting ErbB3 signaling therefore represents a promising therapeutic approach for patients with NRG1 fusion-positive malignancies.

Start Date30 May 2024

Sponsor / Collaborator

Samsung Medical Center

NCT05982678 / RecruitingPhase 2

Basket Study for Oligo-metastatic Breast Cancer Part 1: Trastuzumab-deruxtecan for HER2-positive Oligo-metastatic Breast Cancer

The study will include patients with HER2-positive breast cancer and 1- 3 distant metastatic lesions, all amenable for curative intervention. Patients will be stratified by prior therapy and ER expression. In the initial baskets patients with be treated with trastuzumab-deruxtecan.
Patients are treated with T-DXd 5.4mg/kg on a three weekly (21 day) basis, with the goal of 16 cycles leading to a treatment period of year, including local treatment. The first 8 cycles of T-DXd are administered neo-adjuvant, and 8 cycles adjuvant, after completion of local treatment.
The proposed M22BOL trial is based on an important knowledge gap for regarding breast cancer patients with 'oligo-metastatic' disease who are usually not included in clinical trials for patients with metastatic disease since loco-regional treatments (radiation, surgery) with curative intent is not allowed in clinical trials for metastatic breast cancer. Moreover, neo-adjuvant trial protocols for early breast cancer exclude patients with distant metastases that can be treated with curative intent. This basket trial evaluates T-DXd for oligo-metastatic breast cancer with the goal to induce deep responses and subsequently long-lasting disease remissions and potentially cure.

Start Date02 May 2024

Sponsor / Collaborator

Netherlands Cancer Insitute

[+2]

NCT06222489 / Not yet recruitingPhase 2

Whole Body HER3 Quantification With Radiolabelled Patritumab Deruxtecan (HER3-DXd) PET/CT

Activity of patritumab deruxtecan (U3-1402; HER3-DXd) has been shown in a phase I/II study in patients with HER3 expressing breast cancer as well as in a phase I study in patients with EGFR TKI refractory EGFR mutation positive NSCLC with a preliminary ORR of 25%. HER3 expression can be seen in multiple tumor types and is therefore an attractive target for antibody drug conjugate (ADC) treatment. However, intra- and intertumor heterogeneity of HER3 expression might be substantial, as is seen for HER2, and might contribute to treatment failure or heterogeneous responses. In addition, HER3 expression is dynamic and has been shown to change over time.
In order to identify patients that may benefit most from treatment with patritumab deruxtecan, better knowledge of the in vivo behaviour of the drug is warranted. One way to visualize this behaviour is positron emission tomography (PET) imaging with radiolabelled antibodies (immune-PET). 89Zr-Patritumab deruxtecan PET/CT can assess HER3 expression non-invasively at a whole body level, including sites that may be difficult to biopsy. It also visualizes and quantifies biodistribution of patritumab deruxtecan, thereby obtaining valuable information for safety and toxicity analyses.

Start Date01 May 2024

Sponsor / Collaborator

Netherlands Cancer Insitute

[+1]

100 Clinical Results associated with Patritumab Deruxtecan

100 Translational Medicine associated with Patritumab Deruxtecan

100 Patents (Medical) associated with Patritumab Deruxtecan

Literatures (Medical) associated with Patritumab Deruxtecan

31 Dec 2024·mAbs

Antibodies to watch in 2024

Article

Author: Reichert, Janice M ; Crescioli, Silvia ; Kaplon, Hélène ; Wang, Lin ; Visweswaraiah, Jyothsna ; Chenoweth, Alicia

The 'Antibodies to Watch' article series provides an annual summary of commercially sponsored monoclonal antibody therapeutics currently in late-stage clinical development, regulatory review, and those recently granted a first approval in any country. In this installment, we discuss key details for 16 antibody therapeutics granted a first approval in 2023, as of November 17 (lecanemab (Leqembi), rozanolixizumab (RYSTIGGO), pozelimab (VEOPOZ), mirikizumab (Omvoh), talquetamab (Talvey), elranatamab (Elrexfio), epcoritamab (EPKINLY), glofitamab (COLUMVI), retifanlimab (Zynyz), concizumab (Alhemo), lebrikizumab (EBGLYSS), tafolecimab (SINTBILO), narlumosbart (Jinlitai), zuberitamab (Enrexib), adebrelimab (Arelili), and divozilimab (Ivlizi)). We briefly review 26 product candidates for which marketing applications are under consideration in at least one country or region, and 23 investigational antibody therapeutics that are forecast to enter regulatory review by the end of 2024 based on company disclosures. These nearly 50 product candidates include numerous innovative bispecific antibodies, such as odronextamab, ivonescimab, linvoseltamab, zenocutuzumab, and erfonrilimab, and antibody-drug conjugates, such as trastuzumab botidotin, patritumab deruxtecan, datopotamab deruxtecan, and MRG002, as well as a mixture of two immunocytokines (bifikafusp alfa and onfekafusp alfa). We also discuss clinical phase transition and overall approval success rates for antibody therapeutics, which are crucial to the biopharmaceutical industry because these rates inform decisions about resource allocation. Our analyses indicate that these molecules have approval success rates in the range of 14-32%, with higher rates associated with antibodies developed for non-cancer indications. Overall, our data suggest that antibody therapeutic development efforts by the biopharmaceutical industry are robust and increasingly successful.

15 Jan 2024·Current medicinal chemistry

The Therapeutic Significance of HER3 in Non-small Cell Lung Cancer (NSCLC): A Review Study

Article

Author: Ding, Ke ; Zhang, Jinwei ; Trinder, Amelia

Abstract::

HER3 (Human Epidermal Growth Factor Receptor 3) is frequently overexpressed in various cancers, including non-small cell lung cancer (NSCLC), with a prevalence of 83% in primary tumors. Its involvement in tumorigenesis and resistance to targeted therapies makes HER3 a promising target for cancer treatment. Despite being initially considered “undruggable” due to its lack of catalytic activity, significant progress has been made in the development of anti-HER3 therapeutics. Monoclonal antibodies such as lumretuzumab, seribantumab, and patritumab have shown potential in targeting HER3 to overcome resistance to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs). Additionally, antibody-drug conjugates (ADCs) like HER3-DXd (patritumab deruxtecan) are new drug candidates that have demonstrated selective delivery of cytotoxic chemicals to NSCLC cells by exploiting HER3's widespread expression, minimizing cytotoxicity. This review aims to evaluate the efficacy of current HER3 therapeutics in development and their therapeutic potential in NSCLC, incorporating evidence from clinical trials.

News (Medical) associated with Patritumab Deruxtecan

20 Jun 2024

·pipelinereview.com

Truqap plus Faslodex approved in the EU for patients with advanced ER-positive breast cancer

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

Phase 3Drug ApprovalClinical ResultImmunotherapy

18 Jun 2024

·pipelinereview.com

Update on the CAPItello-290 Phase III trial for Truqap plus chemotherapy in advanced or metastatic triple-negative breast cancer

LONDON, UK I June 18, 2024 I The CAPItello-290 Phase III trial for Truqap (capivasertib) in combination with paclitaxel in patients with locally advanced (inoperable) or metastatic triple-negative breast cancer (TNBC) did not meet the dual primary endpoints of improvement in overall survival (OS) versus paclitaxel in combination with placebo in either the overall trial population or in a subgroup of patients with tumours harbouring specific biomarker alterations (PIK3CA, AKT1 or PTEN). Breast cancer is the second most common cancer and one of the leading causes of cancer-related deaths worldwide. 1 While some breast cancers may test positive for estrogen receptors, progesterone receptors or overexpression of human epidermal growth factor receptor 2 (HER2), TNBC is defined as negative for all three. 2 In the 1st-line setting, approximately 59,000 patients with TNBC are treated with a medicine. 3 Collectively, mutations in PIK3CA, AKT1 and alterations in PTEN affect approximately 35% of patients with TNBC. 4 Peter Schmid, MD, Barts Cancer Institute, London, UK, and principal investigator for the trial said: “Despite modest advances, triple-negative breast cancer remains one of the most challenging forms of disease to treat due to the lack of known actionable biomarker targets, and chemotherapy-based regimens continue to be the mainstay of treatment. While the CAPItello-290 trial results have not shown what we hoped, they provide important information to further understand this aggressive form of breast cancer where patients are in urgent need of new treatments.” Susan Galbraith, Executive Vice President, Oncology R&D, AstraZeneca, said: “We are committed to advancing science for patients in some of the most challenging cancers, including this heterogeneous subtype of breast cancer. While we are disappointed in the CAPItello-290 outcome, these results will further our understanding of the role of the PI3K/AKT pathway in breast cancer as we continue our clinical research across the Truqap clinical development programme and across our pipeline.” The safety profile of Truqap in combination with paclitaxel in CAPItello-290 was broadly consistent with the known safety profile of each medicine with no new safety concerns identified. Data will be shared in due course. 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. Notes Triple-negative breast cancer 1st-line treatment for advanced or metastatic TNBC usually consists of chemotherapy alone or in combination with an immunotherapy – options generally associated with response rates between 30 to 50%. 2,5,6 Among patients with tumours that do respond to initial treatment, disease progression is common and rapid, often occurring within two years. 2,6-8 The average overall survival of patients living with advanced or metastatic TNBC is 12 to 18 months, with only about 14% of patients living five years following diagnosis. 9,10 CAPItello-290 CAPItello-290 is a Phase III, double-blind, randomised trial evaluating the efficacy and safety of Truqap in combination with paclitaxel versus placebo in combination with paclitaxel in the 1st-line treatment of patients with locally advanced (inoperable) or metastatic TNBC. The global trial enrolled 923 adult patients with histologically confirmed locally advanced or metastatic TNBC. The trial has dual primary endpoints of OS 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). 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, Japan and several other countries for the treatment of adult patients with HR-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). 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 operates in over 100 countries and its innovative medicines are used by millions of patients worldwide. Please visit astrazeneca.com and follow the Company on social media @ AstraZeneca . References SOURCE: AstraZeneca

Phase 3Clinical ResultDrug ApprovalImmunotherapyADC

05 Jun 2024

·www.echemi.com

Breakthrough in Metastatic Breast Cancer Treatment: Trastuzumab Deruxtecan Shows Impressive 13.2-Month mPFS

In a remarkable development, the phase 3 DESTINY-Breast06 trial has revealed that the antibody-drug conjugate trastuzumab deruxtecan (marketed as Enhertu) significantly improves progression-free survival (PFS) in patients with HR-positive, HER2-low metastatic breast cancer. The results were presented at the 2024 American Society of Clinical Oncology (ASCO) Annual Meeting. The study found that trastuzumab deruxtecan reduced the risk of disease progression or death by 38% compared to standard chemotherapy in the HR-positive, HER2-low metastatic breast cancer population. Importantly, the median PFS was 13.2 months in the trastuzumab deruxtecan arm, compared to just 8.1 months in the chemotherapy arm. These benefits extended to the overall study population, which included patients with HR-positive, HER2-low and HER2-negative disease. Trastuzumab deruxtecan demonstrated a 37% reduction in the risk of disease progression or death, with a median PFS of 13.2 months versus 8.1 months for chemotherapy. "The DESTINY-Breast06 results are truly remarkable, as trastuzumab deruxtecan is the first HER2-targeted agent to demonstrate clinically meaningful improvements in this patient population," said Dr. Jane Doe, a leading oncologist. "This represents a significant advancement in the treatment of metastatic breast cancer, especially for those with HR-positive, HER2-low disease who have limited options." The study also revealed impressive response rates with trastuzumab deruxtecan. In the HER2-low subgroup, the confirmed objective response rate (ORR) was 56.5%, including 9 complete responses (CR) and 194 partial responses (PR). In the overall population, the confirmed ORR was 57.3%, with 13 CRs and 237 PRs. Importantly, the safety profile of trastuzumab deruxtecan was consistent with previous breast cancer trials, with no new safety concerns identified. The most common grade ≥3 treatment-related adverse events included neutropenia (20.7%), leukopenia (6.9%), and anemia (5.8%). "These data further validate the potential of trastuzumab deruxtecan in addressing the significant unmet needs of patients with metastatic breast cancer, particularly those with HR-positive, HER2-low disease," said Dr. John Smith, Chief Medical Officer at Daiichi Sankyo. "We are excited to work with our partner AstraZeneca to bring this important new treatment option to patients as quickly as possible." The DESTINY-Breast06 trial represents a major breakthrough in the management of metastatic breast cancer, offering renewed hope for patients with limited treatment options. With its impressive efficacy and manageable safety profile, trastuzumab deruxtecan is poised to become a new standard of care in this patient population.

Clinical ResultASCOPhase 3

100 Deals associated with Patritumab Deruxtecan

R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
EGFR-mutated non-small Cell Lung Cancer	NDA/BLA	US	Daiichi Sankyo Co., Ltd.	22 Dec 2023
EGFR-mutated non-small Cell Lung Cancer	NDA/BLA	US	Merck & Co., Inc.	22 Dec 2023
Non-squamous non-small cell lung cancer	Phase 3	US	Daiichi Sankyo Co., Ltd.	08 Jul 2022
Non-squamous non-small cell lung cancer	Phase 3	CN	Daiichi Sankyo Co., Ltd.	08 Jul 2022
Non-squamous non-small cell lung cancer	Phase 3	JP	Daiichi Sankyo Co., Ltd.	08 Jul 2022
Non-squamous non-small cell lung cancer	Phase 3	AU	Daiichi Sankyo Co., Ltd.	08 Jul 2022
Non-squamous non-small cell lung cancer	Phase 3	AT	Daiichi Sankyo Co., Ltd.	08 Jul 2022
Non-squamous non-small cell lung cancer	Phase 3	BE	Daiichi Sankyo Co., Ltd.	08 Jul 2022
Non-squamous non-small cell lung cancer	Phase 3	CA	Daiichi Sankyo Co., Ltd.	08 Jul 2022
Non-squamous non-small cell lung cancer	Phase 3	FR	Daiichi Sankyo Co., Ltd.	08 Jul 2022

Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT04619004 (HERTHENA-Lung01, CTgov)	Phase 2	metastatic non-small cell lung cancer \| EGFR-mutated non-small Cell Lung Cancer	277	Patritumab Deruxtecan (Patritumab Deruxtecan 5.6 mg/kg)	aoddifwszc(dsuwlzclui) = isoketdnxq dpyodzubxg (lvbfmwjpze, vpurzxdaoq - gottredvec) View more	-	02 Apr 2024
NCT04619004 (HERTHENA-Lung01, CTgov)	Phase 2		277	Patritumab Deruxtecan (Patritumab Deruxtecan Up-Titration)	aoddifwszc(dsuwlzclui) = batsjbdxvs dpyodzubxg (lvbfmwjpze, oizatvmzpd - tlcbtgrajp) View more	-	02 Apr 2024
NCT04619004 (HERTHENA-Lung01, ESMO_ELCC2024) Manual	Phase 2	EGFR-mutated non-small Cell Lung Cancer EGFR Mutation	225	HER3-DXd 5.6 mg/kg IV Q3W	txejqcgjvw(xdakyloliv) = evhlbtcnrc xwrzfowrnq (ghntxzifrk ) View more	Positive	22 Mar 2024
NCT04619004 (HERTHENA-Lung01, ESMO2023) Manual	Phase 2	EGFR-mutated non-small Cell Lung Cancer EGFR mutation	95	HER3-DXd 5.6 mg/kg	pfcqzuwuaj(mxmqklgeyg) = ywmejvellj jsbacrbmay (kfxjfoblpw ) View more	Positive	22 Oct 2023
NCT04619004 (HERTHENA-Lung01, ESMO2023) Manual	Phase 2	EGFR-mutated non-small Cell Lung Cancer EGFR mutation	95	HER3-DXd 5.6 mg/kg (Prior local CNS-directed radiotherapy <6 mo from start)	pfcqzuwuaj(mxmqklgeyg) = liwciwvoha jsbacrbmay (kfxjfoblpw ) View more	Positive	22 Oct 2023
NCT04619004 (HERTHENA-Lung01, WCLC2023) Manual	Phase 1/2	EGFR-mutated non-small Cell Lung Cancer EGFR Mutation	-	U3-1402 (Prior EGFR TKI (any) and PBC)	ezluvavugx(qmskaihrtk) = qwrsfkbpzz ffddpgvmsm (jdfbwzxzsg ) View more	Positive	10 Sep 2023
NCT04619004 (HERTHENA-Lung01, WCLC2023) Manual	Phase 1/2	EGFR-mutated non-small Cell Lung Cancer EGFR Mutation	-	U3-1402 (Prior 3G EGFR TKI and PBC)	ezluvavugx(qmskaihrtk) = dxmnmouahe ffddpgvmsm (jdfbwzxzsg ) View more	Positive	10 Sep 2023
NCT04699630 (ASCO2023) Manual	Phase 2	Metastatic breast cancer	60	HER3-DXd	usoicjxclr(byoqjpjniz) = ajxgtpoihm znfuizfvqh (jqvacagcnj, 23.1 - 48.1) View more	Positive	31 May 2023
AACR2022	Not Applicable	Estrogen receptor positive breast cancer	-	HER3-DXd	srgjmwwihk(akgzwgotnc) = reprogrammed cell cycle progression from G2/M arrest to G1 arrest iutfmjcvhn (surqnntugd )	-	15 Jun 2022
NCT03260491 (ASCO2022) Manual	Phase 1	Non-Small Cell Lung Cancer	47	Patritumab Deruxtecan 5.6 mg/ kg	nuvsqyvgne(ukfrmvyiop) = zizpplwwpj numyyxbeyc (lsxujkneon, 16 - 43) View more	Positive	02 Jun 2022
JPRN-JapicCTI-163401 \| NCT02980341 (ASCO2022)	Phase 1/2	Metastatic breast cancer	182	Patritumab deruxtecan	ikfblodtgo(qufwspopvc) = jnipkbcorw elqwwfmtxw (qwaagfmhzr ) View more	-	02 Jun 2022
NCT04610528 (SOLTI TOT-HER3, ESMO_BC2022)	Early Phase 1	Early Stage Breast Carcinoma	78	HER3-DXd	kkcdvizadi(izgnjmckcs) = Overall, 74 (95%) patients reported any grade AEs ixdcepjkal (rzczufgsuu ) View more	-	03 May 2022
NCT04610528 (TOT-HER3, AACR2022) Manual	Early Phase 1	Breast Cancer ERBB3 Expression	30	deruxtecan	fmpfcpycyh(rfxzjpblru) = a statistically significant increase in CelTIL was observed between paired samples (p=0.028) uzcfwyzjsn (ojcsaavisr ) View more	Positive	15 Feb 2022

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