Last update 03 Oct 2024

Trastuzumab

Last update 03 Oct 2024

Overview

R&D Status

Clinical Result

Translational Medicine

Overview

Basic Info

Drug Type

Monoclonal antibody

Synonyms

Anti-HER2/neu-MAb, Trastuzumab (Genetical Recombination), Trastuzumab (genetical recombination) (JAN)

+ [16]

Target

HER2

Mechanism

HER2 antagonists(Receptor protein-tyrosine kinase erbB-2 antagonists), ADCC(Antibody-dependent cell-mediated cytotoxicity (ADCC) effects)

Therapeutic Areas

NeoplasmsDigestive System DisordersMouth and Tooth Diseases+ [7]

Active Indication

HER2 Positive Colorectal CancerHER2 positive salivary gland cancerHER2-positive gastric cancer+ [35]

Inactive Indication

AdenocarcinomaAdvanced Gastric AdenocarcinomaAdvanced Urothelial Carcinoma+ [17]

Originator Organization

Genentech, Inc.

Active Organization

Genentech, Inc.

Array BioPharma, Inc.Roche Pharma (Schweiz) AG

+ [13]

Inactive Organization

Sanofi

Sanofi SA

Bristol Myers Squibb Co.

+ [4]

Drug Highest PhaseApproved

First Approval Date

US (25 Sep 1998),

Metastatic breast cancer

RegulationPriority Review (US), Accelerated Approval (US), Orphan Drug (US), Orphan Drug (JP)

Gene Sequence

Sequence Code 18481L

Source: *****

Sequence Code 44772H

Source: *****

972

Clinical Trials associated with Trastuzumab

NCT06532006 / Not yet recruitingPhase 3

A Randomized, Double-blinded, Multicenter, Phase Ⅲ Clinical Study of HLX22 (Recombinant Humanized Anti-HER2 Monoclonal Antibody Injection) in Combination With Trastuzumab and Chemotherapy (XELOX) Versus Trastuzumab and Chemotherapy (XELOX) With or Without Pembrolizumab for the First Line Treatment of Locally Advanced or Metastatic Gastroesophageal Junction and Gastric Cancer

This is a double-blind, randomized, multiregion, comparative phase Ⅲ clinical study designed to evaluate the efficacy and safety of HLX22 in combination with trastuzumab and chemotherapy as first-line treatment in patients with HER2-positive locally advanced/metastatic adenocarcinoma of the gastric and/or gastroesophageal junction (G/GEJ).Eligible subjects will be randomized to the two groups based on a 1:1 ratio. Enrolled subjects shall be treated with the study drug until the loss of clinical benefit, death, intolerable toxicity, withdrawal of informed consent, or other reasons specified by the protocol (whichever occurs first).

Start Date01 Nov 2024

Sponsor / Collaborator

Shanghai Henlius Biotech, Inc.

NCT06439693 / Not yet recruitingPhase 2IIT

A Single-Arm, Phase II Study of Sequential Therapy With Curative Intent in de Novo HER2+ Metastatic Breast Cancer: The SAPPHO Study:

The purpose of this study is to test the safety and effectiveness of a sequence of drugs (a Taxane plus Trastuzumab plus Pertuzumab followed by Trastuzumab Deruxtecan, followed by Tucatinib plus Ado-Trastuzumab Emtansine (T-DM1), followed by Trastuzumab plus Pertuzumab plus Tucatinib) in HER2+ Breast Cancer. The study will help investigators understand whether first intensifying therapy for a specific period and then stopping treatment is safe and effective for participants.
The names of the study drugs involved in this study are:
Paclitaxel (a type of anti-microtubule agent)
Docetaxel (a type of anti-microtubule agent)
Nab-Paclitaxel (a type of anti-microtubule agent)
Trastuzumab (a type of IgG1 kappa monoclonal antibody)
Pertuzumab (a type of monoclonal antibody)
Trastuzumab Deruxtecan (a type of HER2-directed antibody drug conjugate)
Tucatinib (Tyrosine Kinase HER2 Inhibitor)
Ado-trastuzumab emtansine or T-DM1 (a type of HER2-targeted antibody-drug conjugate)

Start Date01 Nov 2024

Sponsor / Collaborator

Dana-Farber Cancer Institute, Inc.

[+1]

NCT06245356 / Not yet recruitingPhase 2

TRIFLUOX-DP: Safety of Trifluridine/Tipiracil as Replacement of Fluoropyrimidines (5-fluorouracil and Capecitabine) Based Chemotherapy as First Line Metastatic Colorectal or Gastroesophageal Cancer Regimens in Patients With Dihydropyrimidine Dehydrogenase Deficiency: a Phase II Trial

The goal of this clinical trial is to test the safety of the trifluridine/tipiracil as replacement of fluoropyrimidines based chemotherapy as first line metastatic colorectal or gastroesophageal cancer regimens in patients with dihydropyrimidine dehydrogenase (DPD) deficiency.
The main questions it aims to answer are:
* Is this alternative chemotherapy option a better option in term of safety for this type of patients?
* Does the combination of treatments improves the overall safety?
* Does the combination of treatments improves the progression-free survival, overall survival, objective response rate and disease control rate?
* Does the combination of treatment have an effect on quality of life?
Participants will:
* Receive the trifluridine/tipiracil with oxaliplatin every 14 days, associated with:
* Panitumumab or bevacizumab for colorectal adenocarcinomas
* Nivolumab or trastuzumab for gastroesophageal adenocarcinomas.
* Have a CT-Scan every 2 months until disease progression
* Complete Health-related quality of life questionnaire every 2 months for a maximum of 6 months
* Participate to the optional translational research: Blood samples fo DPYD genotyping and pharmacokinetic analysis

Start Date20 Oct 2024

Sponsor / Collaborator

UNICANCER

[+1]

100 Clinical Results associated with Trastuzumab

100 Translational Medicine associated with Trastuzumab

100 Patents (Medical) associated with Trastuzumab

13,124

Literatures (Medical) associated with Trastuzumab

31 Dec 2024·mAbs

Nonclinical immunogenicity risk assessment for knobs-into-holes bispecific IgG ₁ antibodies

Article

Author: Tran, Peter ; Peng, Kun ; Brumm, Jochen ; Wu, Patrick ; Carter, Paul J ; Li, Yinyin ; Phung, Qui ; Tsai, Wen-Ting K ; Cohen, Sivan ; Tam, Sien ; Ye, Zhengmao ; Spiess, Christoph ; Wong, Manda ; Qin, Dan ; Yin, Zhaojun ; Zhou, Zhenru

Bispecific antibodies, including bispecific IgG, are emerging as an important new class of antibody therapeutics. As a result, we, as well as others, have developed engineering strategies designed to facilitate the efficient production of bispecific IgG for clinical development. For example, we have extensively used knobs-into-holes (KIH) mutations to facilitate the heterodimerization of antibody heavy chains and more recently Fab mutations to promote cognate heavy/light chain pairing for efficient in vivo assembly of bispecific IgG in single host cells. A panel of related monospecific and bispecific IgG₁ antibodies was constructed and assessed for immunogenicity risk by comparison with benchmark antibodies with known low (Avastin and Herceptin) or high (bococizumab and ATR-107) clinical incidence of anti-drug antibodies. Assay methods used include dendritic cell internalization, T cell proliferation, and T cell epitope identification by in silico prediction and MHC-associated peptide proteomics. Data from each method were considered independently and then together for an overall integrated immunogenicity risk assessment. In toto, these data suggest that the KIH mutations and in vitro assembly of half antibodies do not represent a major risk for immunogenicity of bispecific IgG₁, nor do the Fab mutations used for efficient in vivo assembly of bispecifics in single host cells. Comparable or slightly higher immunogenicity risk assessment data were obtained for research-grade preparations of trastuzumab and bevacizumab versus Herceptin and Avastin, respectively. These data provide experimental support for the common practice of using research-grade preparations of IgG₁ as surrogates for immunogenicity risk assessment of their corresponding pharmaceutical counterparts.

31 Dec 2024·mAbs

Antibody-epitope conjugates deliver immunogenic T-cell epitopes more efficiently when close to cell surfaces

Article

Author: Heemskerk, M H M ; Guelen, L ; Schuurman, J ; van der Wulp, W ; Ressing, M E ; Hoeben, R C ; Luu, W ; van Kasteren, S I ; Bleijlevens, B

Antibody-mediated delivery of immunogenic viral CD8⁺ T-cell epitopes to redirect virus-specific T cells toward cancer cells is a promising new therapeutic avenue to increase the immunogenicity of tumors. Multiple strategies for viral epitope delivery have been shown to be effective. So far, most of these have relied on a free C-terminus of the immunogenic epitope for extracellular delivery. Here, we demonstrate that antibody-epitope conjugates (AECs) with genetically fused epitopes to the N-terminus of the antibody can also sensitize tumors for attack by virus-specific CD8⁺ T cells. AECs carrying epitopes genetically fused at the N-terminus of the light chains of cetuximab and trastuzumab demonstrate an even more efficient delivery of the T-cell epitopes compared to AECs with the epitope fused to the C-terminus of the heavy chain. We demonstrate that this increased efficiency is not caused by the shift in location of the cleavage site from the N- to the C-terminus, but by its increased proximity to the cell surface. We hypothesize that this facilitates more efficient epitope delivery. These findings not only provide additional insights into the mechanism of action of AECs but also broaden the possibilities for genetically fused AECs as an avenue for the redirection of multiple virus-specific T cells toward tumors.

31 Dec 2024·Molecular & cellular oncology

Hypofunction of macrophage chemotaxis contributes to defective efficacy of herceptin in HER2-positive breast cancer patients

Article

Author: Song, Yu ; Zhang, Fu-Cheng ; An, Wen-Jing ; Deng, Zhi-Jian ; Zhao, Rui-Sheng ; Jiang, Ran ; Li, Heng ; Geng, Qiao-Chen

Breast cancer was considered as a kind of prone breast tumors with the complicated pathological mechanisms and diverse clinical classifications. In the clinical treatments of HER2-positive tumor patients, HER2 monoclonal antibodies, such as Herceptin, have shown well-defined therapeutic effects. Nevertheless, due to the heterogeneity of breast cancers, drug resistance inevitably appeared during the application of Herceptin. In order to fully understand the immune tolerance status of the tumor microenvironment in the population of sensitive and insensitive patients, this study carried out a series of studies through Luminex cytokines assay, clinicopathological analysis, immunofluorescence, and PCR. The results confirmed that in clinical samples sensitive to Herceptin, there were a large number of macrophages, and the protein expression levels and in situ expression of macrophage-related chemokines and inflammatory mediators are significantly higher than drug-resistant tumor samples. Further studies found that T cell function has a low correlation with tumor growth, and there are obvious obstacles in the process of peripheral blood immune cells entering the tumor microenvironment. In summary, this study provided clues for understanding the clinical drug resistance of HER2 monoclonal antibody and the clinical rational use of drugs and combination drugs.

785

News (Medical) associated with Trastuzumab

01 Oct 2024

·pipelinereview.com

ENHERTU® (fam-trastuzumab deruxtecan-nxki) granted Priority Review in the US for patients with HER2-low or HER2-ultralow metastatic breast cancer who have received at least one line of endocrine therapy

Based on DESTINY-Breast06 Phase III trial which demonstrated a statistically significant and clinically meaningful progression-free survival benefit for ENHERTU If approved, AstraZeneca and Daiichi Sankyo’s ENHERTU will be the first HER2 directed therapy and ADC for patients prior to receiving chemotherapy for metastatic breast cancer ENHERTU also granted Breakthrough Therapy Designation in the US for this patient population WILMINGTON, DE, USA I October 01, 2024 I AstraZeneca and Daiichi Sankyo’s supplemental Biologics License Application (sBLA) for ENHERTU ® (fam-trastuzumab deruxtecan-nxki) has been accepted and granted Priority Review in the US for the treatment of adult patients with unresectable or metastatic HER2-low (IHC 1+ or IHC 2+/ISH-) or HER2 ultralow (IHC 0 with membrane staining) breast cancer who have received at least one endocrine therapy in the metastatic setting based on positive results from the DESTINY-Breast06 Phase III trial which compared ENHERTU to chemotherapy. The Food and Drug Administration (FDA) grants Priority Review to applications for medicines that, if approved, would offer significant improvements over available options by demonstrating safety or efficacy improvements, preventing serious conditions or enhancing patient compliance. The Prescription Drug User Fee Act date, the FDA action date for their regulatory decision, is anticipated during the first quarter of 2025. ENHERTUwas also recently granted Breakthrough Therapy Designation (BTD) by the FDA in this setting. BTD accelerates the development and regulatory review of potential new medicines intended to treat a serious condition and address a significant unmet medical need. HR-positive, HER2-negative is the most common breast cancer subtype, accounting for approximately 70% of all breast cancers. 1 Despite being classified as HER2-negative, many of these tumors still carry some level of HER2 expression. 2 It is estimated that up to 85-90% of tumors historically classified as HR-positive, HER2-negative may be HER2-low or HER2-ultralow. 3,4 Susan Galbraith, Executive Vice President, Oncology R&D, AstraZeneca, said: “While endocrine therapies are widely used in the initial treatment of HR-positive metastatic breast cancer, most patients see limited benefit with additional lines of treatment, and subsequent chemotherapy is often associated with poor response rates and outcomes. The results from DESTINY-Breast06 show thatENHERTUhas the potential to evolve the current HR-positive treatment landscape and become the first targeted treatment for patients with HER2-low or HER2-ultralow expression following endocrine therapy.” Ken Takeshita, Global Head, R&D, Daiichi Sankyo, said: “This Priority Review highlights the potential to expand the existing indication of ENHERTU in HER2-low metastatic breast cancer to include use in an earlier disease setting as well as in a broader patient population that includes HER2-ultralow. We look forward to working closely with the FDA with the goal of bringing ENHERTU to more patients as quickly as possible.” The sBLA is based on data from the DESTINY-Breast06 Phase III trial presented at the 2024 American Society of Clinical Oncology (ASCO) Annual Meeting and recently published in The New England Journal of Medicine . In the trial, ENHERTU reduced the risk of disease progression or death by 37% by blinded independent central review (BICR) versus chemotherapy (hazard ratio [HR] 0.63; 95% confidence interval [CI]: 0.53-0.75; p< 0.0001) in the overall trial population. Median PFS was 13.2 months with ENHERTUcompared to 8.1 months with chemotherapy. Results were consistent between patients with HER2-low expression and HER2-ultralow expression. In the primary endpoint analysis of patients with HER2-low expression, ENHERTU showed a median PFS of 13.2 months compared to 8.1 months for chemotherapy (HR 0.62; 95% CI 0.51-0.74; p<0.0001). In a prespecified exploratory analysis of patients with HER2-ultralow expression, ENHERTU showed a median PFS of 13.2 months versus 8.3 months, respectively (HR 0.78; 95% CI 0.50-1.21). The safety profile of ENHERTU in DESTINY-Breast06 was consistent with previous clinical trials of ENHERTUin breast cancer with no new safety concerns identified. ENHERTU is a specifically engineered HER2-directed DXd antibody drug conjugate (ADC) discovered by Daiichi Sankyo and being jointly developed and commercialized by AstraZeneca and Daiichi Sankyo. ENHERTUis already approved in more than 65 countries, including the US, for patients with HER2-low metastatic breast cancer who have received a prior systemic therapy in the metastatic setting or developed disease recurrence during or within six months of completing adjuvant chemotherapy based on the results from the DESTINY-Breast04 trial. Indications ENHERTU is a HER2-directed antibody and topoisomerase inhibitor conjugate indicated for the treatment of adult patients with: Please see accompanying full Prescribing Information , including Boxed WARNINGS, and Medication Guide. Notes Breast cancer and HER2 expression Breast cancer is the second most common cancer and one of the leading causes of cancer-related deaths worldwide. 5 More than two million breast cancer cases were diagnosed in 2022 with more than 665,000 deaths globally. 5 While survival rates are high for those diagnosed with early breast cancer, only approximately 30% of patients who are diagnosed with or who progress to metastatic disease are expected to live five years after their diagnosis. 1 HER2 is a tyrosine kinase receptor growth-promoting protein expressed on the surface of many types of tumors, including breast cancer. 6 Patients with high levels of HER2 expression (IHC 3+ or 2+/ISH+) are classified as HER2-positive and treated with HER2-directed therapies, representing approximately 15-20% of all breast cancers. 7 Historically, tumors that were not classified as HER2-positive were classified as HER2-negative. 2 HR-positive, HER2-negative is the most common breast cancer subtype, accounting for approximately 70% of all breast cancers. 1 Despite being classified as HER2-negative, many of these tumors still carry some level of HER2 expression. 2 It is estimated that 60-65% of HR-positive, HER2-negative breast cancers are HER2-low and an additional 25% may be HER2-ultralow. 3,4 Endocrine therapies are widely used in the early lines of treatment for HR-positive metastatic breast cancer; however, after two lines of treatment, further efficacy from endocrine therapy is often limited. 8 The current standard of care following endocrine therapy is chemotherapy, which is associated with poor response rates and outcomes. 8-11 Prior to the approval of ENHERTU in HER2-low metastatic breast cancer post chemotherapy based on the DESTINY-Breast04 trial, there were no targeted therapies approved specifically for patients with HER2-low expression. There are no targeted therapies specifically approved for patients with HER2-low expression prior to chemotherapy or for patients with HER2-ultralow expression. 12 DESTINY-Breast06 DESTINY-Breast06 is a global, randomized, open-label, Phase III trial evaluating the efficacy and safety ofENHERTU (5.4 mg/kg) versus investigator’s choice of chemotherapy (capecitabine, paclitaxel or nab-paclitaxel) in patients with HR-positive, HER2-low (IHC 1+ or 2+/ISH-) or HER2-ultralow (defined as IHC 0 with membrane staining) advanced or metastatic breast cancer. Patients in the trial had no prior chemotherapy for advanced or metastatic disease and received at least two lines of prior endocrine therapy in the metastatic setting. Patients were also eligible if they had received one prior line of endocrine therapy combined with a CDK4/6 inhibitor in the metastatic setting and experienced disease progression within six months of starting 1st-line treatment or received endocrine therapy as an adjuvant treatment and experienced disease recurrence within 24 months. HER2 status in the trial was confirmed by central laboratory and was performed on an archival tumor sample obtained at the time of initial metastatic diagnosis or later. If archival tissue was not available, a fresh tissue sample was required. The primary endpoint is PFS in the HR-positive, HER2-low patient population as measured by BICR. Key secondary endpoints include PFS by BICR in the overall trial population (HER2-low and HER2-ultralow), OS in the HER2-low patient population and OS in the overall trial population. Other secondary endpoints include ORR, DOR, time to first subsequent treatment or death, time to second subsequent treatment or death and safety. DESTINY-Breast06 enrolled 866 patients (n=713 for HER2-low and n=153 for HER2-ultralow) randomized at multiple sites in Asia, Europe, Australia, North America and South America. For more information about the trial, visit ClinicalTrials.gov . ENHERTU (fam-trastuzumab deruxtecan-nxki) ENHERTU (fam-trastuzumab deruxtecan-nxki) is a HER2-directed ADC. Designed using Daiichi Sankyo’s proprietary DXd ADC Technology, ENHERTUis the lead ADC in the oncology portfolio of Daiichi Sankyo and the most advanced program in AstraZeneca’s ADC scientific platform. ENHERTU consists of a HER2 monoclonal antibody attached to a number of topoisomerase I inhibitor payloads (an exatecan derivative, DXd) via tetrapeptide-based cleavable linkers. ENHERTU (5.4mg/kg) is approved in more than 65 countries worldwide for the treatment of adult patients with unresectable or metastatic HER2-positive (immunohistochemistry [IHC] 3+ or in-situ hybridization [ISH]+) breast cancer who have received a prior anti-HER2-based regimen, either in the metastatic setting or in the neoadjuvant or adjuvant setting, and have developed disease recurrence during or within six months of completing therapy based on the results from the DESTINY-Breast03 trial. ENHERTU (5.4mg/kg) is approved in more than 65 countries worldwide 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 systemic therapy in the metastatic setting or developed disease recurrence during or within six months of completing adjuvant chemotherapy based on the results from the DESTINY-Breast04 trial. ENHERTU (5.4mg/kg) is approved in more than 45 countries worldwide for the treatment of adult patients with unresectable or metastatic NSCLC whose tumors have activating HER2 (ERBB2) mutations, as detected by a locally or regionally approved test, and who have received a prior systemic therapy based on the results from the DESTINY-Lung02 and/or DESTINY-Lung05 trials. Continued approval in the US for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial. ENHERTU (6.4mg/kg) is approved in more than 45 countries worldwide for the treatment of adult patients with locally advanced or metastatic HER2-positive (IHC 3+ or 2+/ISH+) gastric or gastroesophageal junction (GEJ) adenocarcinoma who have received a prior trastuzumab-based regimen based on the results from the DESTINY-Gastric01 , DESTINY-Gastric02 and/or DESTINY-Gastric06 trials. Full approval in China for this indication will depend on whether a randomized controlled confirmatory clinical trial can demonstrate clinical benefit in this population. ENHERTU (5.4mg/kg) is approved in the US for the treatment of adult patients with unresectable or metastatic HER2-positive (IHC 3+) solid tumors who have received prior systemic treatment and have no satisfactory alternative treatment options based on efficacy results from the DESTINY-PanTumor02 , DESTINY-Lung01 and DESTINY-CRC02 trials. Continued approval for this indication in the US may be contingent upon verification and description of clinical benefit in a confirmatory trial. ENHERTU development program A comprehensive global clinical development program is underway evaluating the efficacy and safety of ENHERTU monotherapy across multiple HER2-targetable cancers. Trials in combination with other anti-cancer treatments, such as immunotherapy, also are underway. Daiichi Sankyo collaboration AstraZeneca and Daiichi Sankyo entered into a global collaboration to jointly develop and commercialize ENHERTU in March 2019 and datopotamab deruxtecan in July 2020 , except in Japan where Daiichi Sankyo maintains exclusive rights for each ADC. Daiichi Sankyo is responsible for the manufacturing and supply of ENHERTU and datopotamab deruxtecan. 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 tumor environment. With ENHERTU (fam-trastuzumab deruxtecan-nxki), 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 goserelin and aims to reshape the HR-positive space with first-in-class AKT inhibitor, capivasertib, 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 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 olaparib 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 durvalumab, capivasertib in combination with chemotherapy, and durvalumab in combination with other oncology medicines, including olaparib 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 catalyze 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 is a global, science-led biopharmaceutical company that focuses on the discovery, development and commercialization of prescription medicines in Oncology, Rare Diseases and BioPharmaceuticals, including Cardiovascular, Renal & Metabolism, and Respiratory & Immunology. Based in Cambridge, UK, AstraZeneca operates in over 125 countries, and its innovative medicines are used by millions of patients worldwide. For more information, please visit www.astrazeneca-us.com and follow us on social media @AstraZeneca . References SOURCE: AstraZeneca

Phase 3Clinical ResultDrug ApprovalASCOBreakthrough Therapy

01 Oct 2024

·pipelinereview.com

Primary Endpoint Met in Phase 3 Comparative Clinical Study of Perjeta® (pertuzumab) Biosimilar Candidate HLX11

SHANGHAI, China & JERSEY CITY, NJ, USA I September 30, 2024 I Shanghai Henlius Biotech, Inc. (2696.HK) and Organon (NYSE: OGN) announced that the phase 3 comparative clinical trial for the investigational Perjeta ® (pertuzumab) biosimilar HLX11 met the primary endpoint. In 2022, Henlius entered into a license and supply agreement with Organon for the exclusive commercialization rights to two biosimilar candidates, including HLX11. The agreement licenses the global commercialization rights for the product, except for China, to Organon. The multicenter, randomized, double-blind, parallel-controlled phase 3 clinical study ( NCT05346224 ) aimed to compare the efficacy and safety of HLX11 with reference Perjeta ® (pertuzumab) as a neoadjuvant therapy in patients with HER2-positive, HR-negative early, or locally advanced breast cancer as part of a complete treatment regimen. Eligible patients were randomized 1:1 to receive either HLX11 or reference Perjeta ® (pertuzumab) in combination with trastuzumab and docetaxel every three weeks for four cycles. The primary endpoint of this study was the total pathological complete response (tpCR) rate assessed by Independent Review Committee (IRC). The secondary endpoints currently being analyzed included tpCR rate assessed by investigators, breast pathologic complete response (bpCR) rate, objective response rate (ORR), event-free survival (EFS), disease-free survival (DFS), safety, pharmacokinetics, and immunogenicity. The primary endpoint of this study was met. Pertuzumab has been approved in various countries and regions in combination with trastuzumab and chemotherapy for the neoadjuvant, first-line, and adjuvant treatment for certain advanced HER2-positive breast cancer. About Henlius Henlius (2696.HK) is a global biopharmaceutical company with the vision to offer high-quality, affordable, and innovative biologic medicines for patients worldwide with a focus on oncology, autoimmune diseases, and ophthalmic diseases. To date, 6 products have been launched in China, 3 have been approved for marketing in overseas markets, 24 indications are approved worldwide, and 3 marketing applications have been accepted for review in China and the EU, respectively. Since its inception in 2010, Henlius has built an integrated biopharmaceutical platform with core capabilities of high-efficiency and innovation embedded throughout the whole product life cycle including R&D, manufacturing and commercialization. It has established global innovation centre and Shanghai-based commercial manufacturing facilities certificated by China, the EU and U.S. GMP. Henlius has proactively built a diversified and high-quality product pipeline covering over 50 molecules and has continued to explore immuno-oncology combination therapies with proprietary HANSIZHUANG (anti-PD-1 mAb) as backbone. Apart from the launched products HANLIKANG (rituximab), the first China-developed biosimilar, HANQUYOU (trastuzumab, trade name: HERCESSI™ in the U.S., Zercepac ® in Europe), a China-developed mAb biosimilar approved in China, Europe and U.S., HANDAYUAN (adalimumab), HANBEITAI (bevacizumab) and HANNAIJIA (neratinib), the innovative product HANSIZHUANG has been approved by the NMPA for the treatment of MSI-H solid tumours, squamous non-small cell lung cancer (sqNSCLC) and extensive-stage small cell lung cancer (ES-SCLC), and esophageal squamous cell carcinoma (ESCC), making it the world’s first anti-PD-1 mAb for the first-line treatment of SCLC. What’s more, Henlius has conducted over 30 clinical studies for 16 products, expanding its presence in major markets as well as emerging markets. About Organon Organon is a global healthcare company formed to focus on improving the health of women throughout their lives. Organon offers more than 60 medicines and products in women’s health in addition to a growing biosimilars business and a large franchise of established medicines across a range of therapeutic areas. Organon’s existing products produce strong cash flows that support investments in innovation and future growth opportunities in women’s health and biosimilars. In addition, Organon is pursuing opportunities to collaborate with biopharmaceutical innovators looking to commercialize their products by leveraging its scale and presence in fast growing international markets. Organon has a global footprint with significant scale and geographic reach, world-class commercial capabilities, and approximately 10,000 employees with headquarters located in Jersey City, New Jersey. For more information, visit http://www.organon.com and connect with us on LinkedIn , Instagram , X (formerly known as Twitter) and Facebook . SOURCE: Organon

Phase 3License out/inImmunotherapyClinical ResultDrug Approval

01 Oct 2024

·www.pharmaceutical-technology.com

Genentech buys Regor’s CDK inhibitors in $850m deal

Roche announced the agreement at its annual pharma day in London, UK. Image shows Roche’s head office in California, USA. Credit: Michael Vi via Shutterstock. Genentech is strengthening its oncology pipeline by acquiring Regor Pharmaceuticals’ portfolio of breast cancer cyclin-dependent kinase (CDK) inhibitors in an $850m deal. The deal, anticipated to close in Q4 2024, was unveiled by Genentech’s parent company Roche at its pharma day in London. The pharmaceutical giant also shared that it is focusing on three major therapeutic areas – one being oncology. Regor will continue to oversee its two ongoing Phase I trials of the CDK4/2 inhibitor RGT-419B until their completion. At that point, Genentech will take over the global clinical development, manufacturing, and commercialisation of the candidate. The deal also includes preclinical candidate RGT-587, which is a “Phase I ready” CDK4 inhibitor, intended to treat brain metastases. One of Regor’s Phase Ia trials (NCT05304962) is investigating RGT-419B in 12 patients with HR+/HER2-negative advanced breast cancer who had previously undergone CDK4 treatment. Data showed that RGT-419B, administered as a monotherapy, achieved a 28.6% partial response rate and a 44% clinical benefit rate with no dose-limiting toxicities observed. The other Phase I trial (NCT06299124) is enrolling 40 subjects in China and is set to conclude at the end of this year. In the announcement accompanying the deal, Regor’s CEO Xiayang Qiu said: “Genentech is well-positioned to bring these novel therapeutics to their full potential to benefit patients with breast cancer around the world.” See Also: Fresenius Kabi wins FDA approval for Stelara biosimilar Otulfi BMS and Prime ink potential $3.5bn deal to develop T cell therapies During Roche’s 30 September presentation, CEO Teresa Graham said CDK inhibitors are “a perfect fit” with the company’s breast cancer franchise. Graham also touted some of the breast cancer assets that Roche already has on the market, including Phesgo (hyaluronidase, pertuzumab and trastuzumab), Kadcyla (trastuzumab emtansine), and Perjeta (pertuzumab). These three assets pulled in global sales of $1.25bn, $2.2bn, and $4.2bn respectively in 2023, as per Roche’s financials. Graham also highlighted inavolisib, a first-line PIK3CA-mutated hormone receptor for positive breast cancer. The candidate has a 27 November PDUFA date. Several companies have struck deals to acquire CDK inhibitors, targeted therapies that block proteins that regulate cell division to slow or stop the growth of cancer cells. In July 2024, Exscientia acquired a CDK7 inhibitor being trialled in patients with advanced or metastatic solid tumours. This is after buying out its development partner Apeiron Therapeutics’ shares of the programme. However, Roche’s global head of oncology and haematology product development Charles Fuchs highlighted that there is an unmet need for agents targeting CDK4/6i resistance, with most patients progressing after CDK4/6i treatment. According to Regor, RGT-419B is the most advanced CDK4/2 inhibitor in the clinic. It’s not the first time Regor has struck a deal with a big pharma company. In December 2021, the biotech entered into a $1.5bn agreement with Eli Lilly to discover, develop and market new treatments for metabolic disorders. Under the terms of the deal, Lilly secured a licence to select the intellectual property of Regor with an option for a licence extension.

Phase 1License out/inDrug ApprovalClinical Result

100 Deals associated with Trastuzumab

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KEGG	Wiki	ATC	Drug Bank
D03257	Trastuzumab	L01XC03	DB00072

R&D Status

Approved

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Indication	Country/Location	Organization	Date
HER2 Positive Colorectal Cancer	JP	Chugai Pharmaceutical Co., Ltd.	28 Mar 2022
HER2 positive salivary gland cancer	JP	Chugai Pharmaceutical Co., Ltd.	25 Nov 2021
HER2-positive gastric cancer	JP	Chugai Pharmaceutical Co., Ltd.	10 Mar 2011
Stomach Cancer	US	Genentech, Inc.	20 Oct 2010
Breast Cancer	JP	Chugai Pharmaceutical Co., Ltd.	04 Apr 2001
Early Stage Breast Carcinoma	EU	Roche Registration GmbH	28 Aug 2000
Early Stage Breast Carcinoma	IS	Roche Registration GmbH	28 Aug 2000
Early Stage Breast Carcinoma	LI	Roche Registration GmbH	28 Aug 2000
Early Stage Breast Carcinoma	NO	Roche Registration GmbH	28 Aug 2000
HER2 Positive Breast Cancer	EU	Roche Registration GmbH	28 Aug 2000
HER2 Positive Breast Cancer	IS	Roche Registration GmbH	28 Aug 2000
HER2 Positive Breast Cancer	LI	Roche Registration GmbH	28 Aug 2000
HER2 Positive Breast Cancer	NO	Roche Registration GmbH	28 Aug 2000
HER2 positive Gastroesophageal Junction Adenocarcinoma	EU	Roche Registration GmbH	28 Aug 2000
HER2 positive Gastroesophageal Junction Adenocarcinoma	IS	Roche Registration GmbH	28 Aug 2000
HER2 positive Gastroesophageal Junction Adenocarcinoma	LI	Roche Registration GmbH	28 Aug 2000
HER2 positive Gastroesophageal Junction Adenocarcinoma	NO	Roche Registration GmbH	28 Aug 2000
Metastatic Gastric Carcinoma	EU	Roche Registration GmbH	28 Aug 2000
Metastatic Gastric Carcinoma	IS	Roche Registration GmbH	28 Aug 2000
Metastatic Gastric Carcinoma	LI	Roche Registration GmbH	28 Aug 2000

Developing

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Indication	Highest Phase	Country/Location	Organization	Date
Bladder Cancer	Phase 3	GB	Hoffmann-La Roche Ltd.	07 Mar 2023
Colorectal Cancer	Phase 3	GB	Hoffmann-La Roche Ltd.	07 Mar 2023
Gallbladder Neoplasms	Phase 3	GB	Hoffmann-La Roche Ltd.	07 Mar 2023
Hematologic Neoplasms	Phase 3	GB	Hoffmann-La Roche Ltd.	07 Mar 2023
Lung Cancer	Phase 3	GB	Hoffmann-La Roche Ltd.	07 Mar 2023
Ovarian Cancer	Phase 3	GB	Hoffmann-La Roche Ltd.	07 Mar 2023
Pancreatic Cancer	Phase 3	GB	Hoffmann-La Roche Ltd.	07 Mar 2023
Prostatic Cancer	Phase 3	GB	Hoffmann-La Roche Ltd.	07 Mar 2023
Salivary Gland Neoplasms	Phase 3	GB	Hoffmann-La Roche Ltd.	07 Mar 2023
Skin Neoplasms	Phase 3	GB	Hoffmann-La Roche Ltd.	07 Mar 2023

Clinical Result

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT05275010 (CTgov)	Phase 1	-	151	Handheld Syringe+Fixed-Dose Combination of Pertuzumab and Trastuzumab SC (Arm 1: PH FDC SC Using a Handheld Syringe)	csxnnzxamr(kbyfgvokuy) = khejkvmroq dytoafsggl (yfiepsuwxv, ijnkeablpz - ftgbgicbuk) View more	-	23 Sep 2024
				On-Body Delivery System (Arm 2: PH FDC SC Using the OBDS)	csxnnzxamr(kbyfgvokuy) = mxaobsxmzo dytoafsggl (yfiepsuwxv, wwhrevllmr - xaigirbump) View more
NCT02510781 (not provided, ESMO2024)	Phase 2	HER2 Positive Breast Cancer Neoadjuvant	128	ATH-TH (doxorubicin/docetaxel/trastuzumab)	ruvdczjzrf(onzcqttllm) = vymprnymct qzdyrplrvx (aoxkpxndvb, 41.3% - 66.6%) View more	Negative	16 Sep 2024
				TCH (docetaxel/carboplatin/trastuzumab)	ruvdczjzrf(onzcqttllm) = zvhhxyvlzi qzdyrplrvx (aoxkpxndvb, 36.7% - 61.7%) View more
ESMO2024	Not Applicable	Breast Cancer	77	Trastuzumab	nwqrugbvaq(chldmsgqvm) = dniakqpzmt eiqzfsshbl (cnsxyhcwaa )	Positive	14 Sep 2024
NCT02091141 (MyPathway, CTgov)	Phase 2	Advanced Malignant Solid Neoplasm \| Bladder Cancer \| Biliary Tract Neoplasms ... View more	673	Trastuzumab+Pertuzumab (Trastuzumab Plus Pertuzumab)	ktptbafpcn(kliqueoioi) = hmerknosij qolpqhrcqz (fhywlwlahi, ucsaastxxz - nsvvkxenje) View more	-	23 Jul 2024
				atezolizumab (Atezolizumab)	ktptbafpcn(kliqueoioi) = pouybyfrly qolpqhrcqz (fhywlwlahi, uxiyplpbai - wrbquombup) View more
NCT04569747 (ADEPT trial, Pubmed)	Phase 2	HER2 Positive Breast Cancer Adjuvant human epidermal growth factor receptor 2-positive	22	Subcutaneous Trastuzumab/Pertuzumab	bbpouzpnfv(eqkfwxuacq) = nupjslzmqd hgqeqwpjbz (sdwnoqflag )	Positive	19 Jul 2024
				Intravenous Trastuzumab/Pertuzumab	bbpouzpnfv(eqkfwxuacq) = iilgisggxy hgqeqwpjbz (sdwnoqflag )
NCT03425656 (CTgov)	Phase 3	HER2 Positive Breast Cancer	108	Trastuzumab+cyclophosphamide+Doxorubicin+docetaxel (Trastuzumab (AryoTrust))	jpsjnlhfiu(wzifjiehyg) = qqxnxconsy ydknamzmjb (vkwpegvapq, ijugfibxxh - obzlexnjgr) View more	-	28 Jun 2024
				Trastuzumab+cyclophosphamide+Doxorubicin+docetaxel (Trastuzumab (Herceptin))	jpsjnlhfiu(wzifjiehyg) = tcdxpufead ydknamzmjb (vkwpegvapq, dvsevywxzl - gepnyseiqg) View more
ESMO_GI2024 Manual	Not Applicable	Gallbladder adenocarcinoma HER2/Neu Positive	14	Trastuzumab + Gemcitabine + Cisplatin	xsiecaonqu(xgflttqgtc) = jhusxfgnve tpvxmfujdi (nkloicfhbb, 7.03 - 9.86) View more	Positive	27 Jun 2024
ESMO_GI2024 Manual	Not Applicable	HER2 positive Biliary Tract Neoplasms Second line HER2 Positive	21	Trastuzumab plus lapatinib	kpoknruhdc(aessrgujlj) = vvdnbzxepc homzllaqnn (xtxjngiwpv, 28.6 - 57.1) View more	Positive	27 Jun 2024
NCT06136897 (CTgov)	Phase 2	Malignant Solid Neoplasm	35	Radiologic Examination+Trastuzumab+pertuzumab	uskufxukhv(dvajlljxlk) = dxpoqkimjq nviugeznfc (onpihlagmc, iiniyzlnbg - jlnkfdbxtn) View more	-	25 Jun 2024
ESMO_GI2024	Not Applicable	HER2-positive gastric cancer	-	Trastuzumab (HER2DX ERBB2 mRNA low)	edhplgfhmc(atfgdvcmrl) = glyjvmmpof pakemaautb (nqmdrjzsvs ) View more	-	20 Jun 2024
				Trastuzumab (HER2DX ERBB2 mRNA high)	edhplgfhmc(atfgdvcmrl) = jwkyeitfsq pakemaautb (nqmdrjzsvs ) View more

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