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Pertuzumab
About: Pertuzumab is a research topic. Over the lifetime, 1453 publications have been published within this topic receiving 73219 citations. The topic is also known as: 2C4 Antibody & MOAB 2C4.
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TL;DR: It is demonstrated that the novel antibody mixture Sym005 has a unique set of HER2 inhibitory mechanisms, which translates into superior anti-cancer activity in HER2-positive tumor xenografts and provides a clear rationale for evaluation of Sym005 in clinical trials on patients with HER2 positive tumors.
Abstract: Proceedings: AACR 102nd Annual Meeting 2011‐‐ Apr 2‐6, 2011; Orlando, FL
Human epidermal growth factor receptor 2 (HER2) is involved in development and maintenance of malignant phenotypes of several human cancers and therefore represent an attractive therapeutic target. Trastuzumab is currently the only anti-HER2 antibody approved for treatment of human cancers and although succesful more efficacious treatments are warranted. Mixtures of recombinant monoclonal antibodies are promising candidates as the next generation of antibody therapeutics due to their multipotent activities.
The aim of the present study was to identify mixtures of anti-HER2 antibodies with superior activity to existing monoclonal antibodies. Anti-HER2 antibodies were raised in mice by immunizations with HER-2 in different antigen presenting formats. A large antibody repertoire consisting of approximately 150 unique anti-HER-2 antibodies was cloned from the mice using the mSymplex™ technology. Based on a thorough sequence and binding analysis, 40 antibodies were selected for functional evaluation. The 40 antibodies were tested as individual antibodies and in mixtures of two and three for the ability to inhibit the growth of four human cancer cell lines using a standard viability assay. In total, more than 1300 mixtures were evaluated for ability to inhibit growth of the four cell lines. The 20 mixtures with the highest levels of growth inhibition were further characterized with regard to potency (IC50) and ability to engage in ADCC and CDC. The results demonstrated that HER2 mixtures were superior to trastuzumab, pertuzumab and the mixture of the two at inhibiting the growth of seven of the 10 cell lines investigated. Interestingly, the mixtures also inhibited the growth of the trastuzumab resistant breast cancer cell line HCC202, reflecting the differentiated mechanisms of anti-HER2 antibody mixtures. In vivo, anti-HER2 mixtures had superior activity compared to the monoclonal anti-HER2 antibody trastuzumab in two models of human gastric cancer. Based on these results, a candidate mixture was selected and referred to as Sym005.
In conclusion, these data demonstrate that the novel antibody mixture Sym005 has a unique set of HER2 inhibitory mechanisms, which translates into superior anti-cancer activity in HER2-positive tumor xenografts. Furthermore, the results provide a clear rationale for evaluation of Sym005 in clinical trials on patients with HER2 positive tumors.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 4562. doi:10.1158/1538-7445.AM2011-4562
4 citations
TL;DR: Interestingly, although the non-competitive anti-ErbB2 mAbs trastuzumAB and pertuzumab, either alone or in combination, were ineffective at inducing ErbBB2 internalization, TPL, a bispecific antibody engineered from trastzumab and pertizumAB, potently down-regulated the Erb B2 molecule, suggesting that it may be a promising agent for the treatment of gastric cancer.
4 citations
TL;DR: The authors sought to assess the clinical and pathological response rates at the time of surgery in patients who received neoadjuvant dual anti‐HER2 and taxane therapy in a multidisciplinary breast cancer unit.
Abstract: Aims Internationally, there has recently been growing interest in the use of neoadjuvant pertuzumab and trastuzumab in patients with non-metastatic HER-2 positive breast cancer following the NEOSPHERE trial in 2012. However, pertuzumab is currently not funded by the Pharmaceutical Benefits Scheme (PBS) in Australia for use in this setting. The authors sought to assess the clinical and pathological response rates at the time of surgery in patients who received neoadjuvant dual anti-HER2 and taxane therapy in a multidisciplinary breast cancer unit. Methods A retrospective case series of all patients treated with the neoadjuvant therapy, and who had definitive surgery was conducted. Demographic data, size, grade, tumor type, receptor status prior to neoadjuvant treatment, pathological complete response (pCR) rates, and adverse effects were analyzed. Results Nineteen patients were included in the study. Sixty-eight percent of all patients achieved pCR, of which 54% further demonstrated no residual ductal carcinoma in situ. Eight patients (42%) had N1 disease pretreatment, of these 88% demonstrated total pCR in the axilla and the breast. Most adverse effects to treatment were manageable grade 1-2 side effects. Conclusion This is the first reported Australian experience using neoadjuvant dual anti-HER2 and taxane therapy for HER-2 positive nonmetastatic breast cancer. The authors have demonstrated favorable pCR rates for invasive disease compared to the NEOSPHERE trial (68% vs 46%), with reasonable patient tolerability. Larger collaborative data sets are required to fully evaluate correlation of pCR with survival outcomes, and cost-effectiveness. National funding models need to be considered.
4 citations
TL;DR: This retrospective analysis of neoadjuvant treated HER2-positive breast cancer patients shows a gradual increase of neoadedjuvant treatment and a very fast implementation of pertuzumab when it became available in Sweden.
Abstract: Introduction: Over the last few years, neoadjuvant therapy has become a standard of care in HER2-positive early breast cancer. This standard has recently been confirmed by the St. Gallen Consensus for stage II and III HER2-positive disease. In neoadjuvant treatment adding anti HER2 treatment almost doubled the pathological complete response (pCR) rate. Later studies have shown a better outcome for patients achieving a pCR compared with those with a non-pCR. The aim of this study is to present a comprehensive description of preoperative treatment in HER2-positive, according to ASCO and Swedish guidelines, breast cancer with detail treatment routines, choice of drugs and regimens as well as adherence to national guidelines and treatment changes over time. Material: During the period October 2010 to December 2017 6572 patients with early breast cancer were diagnosed in the Skane region of South Sweden and included in the SCAN-B project (Sweden Cancerome Analysis Network - Breast project, ClinicalTrials.gov identifier NCT02306096). The SCAN-B project is a population based study that during the period included 76.7% of all primary breast cancer patients in the catchment area. The majority of all tumors have been analyzed by NGS-based RNA sequencing, RNAseq. Results: Of the 6572 patients 672 (10.2%) were HER2 positive and of these 101 (15%) were treated in a neoadjuvant setting with chemotherapy and HER2 directed antibodies. The proportion of HER2-positive patients receiving neoadjuvant treatment with trastuzumab increased from 9% in 2010 to 29% in 2017. Patient age was 27 to 89 years, median age 54 years. Pertuzumab was introduced in 2016 and in 2017 85% of patients received the combination of trastuzumab and pertuzumab. At diagnosis tumor stage T1, T2, T3 and T4d was 19%, 60%, 14% and 5% respectively and 50% were node negative at sentinel node biopsy pre treatment. Of tumors 52% were estrogen receptor positive (ie >10% stained nuclei). During the neoadjuvant treatment period 31 patients were hospitalized at median 2 times for toxicity and a total of medium 4.7 days. At surgery 62% had a mastectomy and 38% breast conserving surgery. Follow up time is median 3.9 years and overall survival 94%. Conclusions: This retrospective analysis of neoadjuvant treated HER2-positive breast cancer patients shows a gradual increase of neoadjuvant treatment and a very fast implementation of pertuzumab when it became available in Sweden. Overall survival is high but the follow up time is short and the material to small to analyze subgroups. Data on tumor RNAseq will be presented. Citation Format: Martin Malmberg, Christer Larsson, Johan Vallon-Christersson, Anna Ehinger, Cecilia Hegardt, Fredrika Killander, Lisa Ryden, Lao H. Saal, Niklas Loman, Ake Borg. Preoperative treatment of HER2-positive breast cancer in South Sweden. A retrospective, comprehensive survey of neo-adjuvant treated HER2-positve breast cancer in the SCAN-B project 2010-2017 [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P1-18-10.
4 citations
TL;DR: Pertuzumab or placebo combined with gemcitabine is well tolerated with no unexpected additive toxicity and adverse events evaluated after 40 pts did not meet the prespecified criteria to call for an independent safety monitoring board evaluation of unblinded data.
Abstract: 13001 Background: Pertuzumab (P), a humanized HER2 antibody, represents a new class of targeted agents called HER dimerization inhibitors (HDIs). P inhibits dimerization of HER2 with EGFR, HER3 and...
4 citations