DA 3111 (trastuzumab biosimilar) / Meiji Seika, Dong-A - LARVOL DELTA

Cystic-Like HER2-Positive Breast Cancer with Low Tumor-Infiltrating Lymphocytes and High Programmed Death-Ligand 1 Expression in a Young Woman: A Case Report. (PubMed, Case Rep Oncol) - "Adjuvant therapy with the TCbHP regimen (docetaxel, carboplatin, pertuzumab, and trastuzumab) was initiated, with a total of six cycles planned, followed by maintenance therapy with trastuzumab and pertuzumab (HP) for 1 year. To date, the patient has tolerated the treatment well without evidence of distant recurrence or metastasis. This case underscores the discordance between radiological and pathological findings in breast cancer, highlighting the clinical significance of low TILs and high PD-L1 expression in HER2-positive tumors, and emphasizes the importance of individualized surgical and adjuvant treatment strategies."

IO biomarker • Journal • Tumor-infiltrating lymphocyte • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor • HER-2 • PD-L1

A multiscale hybrid modelling methodology for cell cultures enabled by enzyme-constrained dynamic metabolic flux analysis under uncertainty. (PubMed, Metab Eng) - "As a relevant biopharmaceutical case study, we consider the production of Trastuzumab by Chinese Hamster Ovary (CHO) cells in batch. Model uncertainty is maintained at a low level, demonstrating the trustworthiness of the predictions. Overall, our comprehensive modelling framework has the potential to facilitate the development of digital twins in the biopharmaceutical industry."

Journal • Preclinical

Uptake of biosimilars in China: a retrospective analysis of the case of trastuzumab from 2018 to 2023. (PubMed, Glob Health Res Policy) - "The uptake of trastuzumab biosimilars in China was lower compared with major European countries. The introduction of trastuzumab biosimilars presented a substitutional effect. Perceptions of physicians and patients, the medicines procurement model, competition from other biologics, and health insurance payment methods may influence biosimilar uptake. Enhancing a comprehensive understanding of biosimilars among physicians and patients, including biologics with biosimilars in the national pooled procurement, and implementing provider payment reforms could foster biosimilar penetration."

Journal • Retrospective data

Targeting neutrophil elastase is a promising direction for future cancer treatment. (PubMed, Discov Oncol) - "In addition, the combination of sivelestat and trastuzumab can enhance the efficacy of human epidermal growth factor receptor 2(HER 2) positive breast cancer patients. Additionally, we discuss the challenges associated with the clinical application of sivelestat. By shedding light on the promising potential of NE, this review contributes to the advancement of cancer treatment strategies."

Journal • Review • Breast Cancer • Esophageal Cancer • Gastrointestinal Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor • ELANE • HER-2

Efficacy and safety of biosimilar trastuzumab (CT-P6) in routine clinical practice in the Republic of Korea: a real-world post-marketing surveillance study. (PubMed, Expert Opin Biol Ther) - "Among trastuzumab-naïve patients, 34/106 (32.1%) with EBC achieved pathological complete response; 30/74 (40.5%) MBC and 24/49 (49.0%) MGC patients achieved complete or partial response. In a real-world setting, CT-P6 demonstrated safety and efficacy findings consistent with previous CT-P6 studies."

Journal • P4 data • Real-world • Real-world evidence • Breast Cancer • Gastric Cancer • Gastrointestinal Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor • HER-2

BCAR4 facilitates trastuzumab resistance and EMT in breast cancer via sponging miR-665 and interacting with YAP1. (PubMed, FASEB J) - "Reciprocally, YAP1 could occupy the BCAR4 promoter to enhance its transcription, suggesting that there exists a positive feedback regulation between YAP1 and BCAR4. Targeting the BCAR4/miR-665/YAP1 axis may provide a novel insight of therapeutic approaches for TR in BC."

Journal • Breast Cancer • Oncology • Solid Tumor • BCAR4 • TGFB1 • YAP1

Cuproptosis-related genes predict prognosis and trastuzumab therapeutic response in HER2-positive breast cancer. (PubMed, Sci Rep) - "There was a negative correlation between TIDE and DLAT expression (r = - 0.292, p < 0.001), which means high DLAT expression is an indicator of sensitivity to immunotherapy. In conclusion, our study constructed a four CRGs signature prognostic prediction model and identified DLAT as an independent prognostic factor and associated with resistant to HER2-targeted therapy for HER2-positive breast cancer patients."

IO biomarker • Journal • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Breast Cancer • Oncology • Solid Tumor • DLAT • ER • HER-2

Real-world data of triplet combination of pyrotinib, trastuzumab, and chemotherapy in HER2-positive metastatic breast cancer: a multicenter, retrospective study. (PubMed, Ther Adv Med Oncol) - P | "The most prevalent chemotherapies paired with PyroH were capecitabine (36.3%)...Longer previous trastuzumab (⩾6.37 months) or lapatinib (⩾10.05 months) therapies could indicate improved PFS, while prior pyrotinib exposure negatively influenced PFS...PyroHC shows promising efficacy and a satisfactory safety profile for treating HER2+ MBC, both as a first-line option and for heavily treated patients, including those with brain metastasis. Our findings suggest the duration and history of anti-HER2 therapy as potential predictors for PyroHC efficacy in advanced settings."

Journal • Metastases • Real-world • Real-world evidence • Retrospective data • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor • HER-2

Identification of a novel potent CDK inhibitor degrading cyclinK with a superb activity to reverse trastuzumab-resistance in HER2-positive breast cancer in vivo. (PubMed, Eur J Med Chem) - "Compound 32e potently inhibited CDK12/cyclinK with IC = 3 nM, and suppressed the growth of the both trastuzumab-sensitive and trastuzumab-resistant HER2-positive breast cancer cell lines (GI's = 9-21 nM), which is superior to a potent, clinical pan-CDK inhibitor dinaciclib. Compound 32e could be developed as a drug for intractable trastuzumab-resistant HER2-positive breast cancers. Our current study would provide a useful insight in designing potent cyclinK degraders."

Journal • Preclinical • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor • CDK12 • HER-2

Phase II study to investigate the efficacy of trastuzumab biosimilar (Herzuma®) plus treatment of physician's choice (TPC) in patients with heavily pretreated HER-2+ metastatic breast cancer (KCSG BR 18-14/KM10B). (PubMed, Breast) - "We investigated the efficacy and safety of a trastuzumab biosimilar, Herzuma®, in combination with treatment of physician's choice (TPC) in patients with HER2+ metastatic breast cancer (MBC) who had failed at least two HER2 directed chemotherapies."

Journal • P2 data • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor • HER-2

Pyrotinib plus capecitabine for trastuzumab-resistant, HER2-positive advanced breast cancer (PICTURE): a single-arm, multicenter phase 2 trial. (PubMed, BMC Med) - P2 | "Pyrotinib plus capecitabine can be considered to be a treatment option in HER2-positive advanced breast cancer patients who have shown primary resistance to trastuzumab. Even in the era of modern anti-HER2 treatments, this clinical setting warrants more investigations to meet unmet needs."

Journal • Metastases • P2 data • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor • HER-2

Genomic analysis of plasma circulating tumor DNA in patients with heavily pretreated HER2 + metastatic breast cancer. (PubMed, Sci Rep) - "In conclusion, TP53 and PIK3CA mutations, as well as a higher ctDNA fraction, were associated with worse PFS with trastuzumab and cytotoxic chemotherapy. The enrichment of HRD-related gene mutations and newly detected variants in ctDNA may be related to resistance to treatment."

Circulating tumor DNA • Journal • Metastases • Breast Cancer • HER2 Breast Cancer • Oncology • Solid Tumor • BRCA2 • BRIP1 • ERBB3 • FANCA • HER-2 • HRD • PIK3CA • RAD50 • RB1 • TP53

Treatment outcomes of advanced/metastatic extramammary Paget's disease in Korean patients: KCSG-RC20-06. (PubMed, Cancer Med) - "Due to its rarity, advanced or metastatic EMPD still has no established standard treatment. Results of our study indicate that the combination of trastuzumab with taxane has longer survival than trastuzumab monotherapy or conventional platinum- or taxane-based chemotherapy."

Clinical • Journal • Metastases • Oncology • Rare Diseases

Neoadjuvant pyrotinib, trastuzumab, and docetaxel for HER2-positive breast cancer (PHEDRA): a double-blind, randomized phase 3 trial. (PubMed, BMC Med) - P3 | "The primary endpoint of the study was met. Neoadjuvant pyrotinib, trastuzumab, and docetaxel significantly improved the tpCR rate compared with placebo, trastuzumab, and docetaxel, with manageable toxicity, providing a new option for HER2-positive early or locally advanced breast cancer."

Journal • P3 data • Breast Cancer • Hematological Disorders • HER2 Breast Cancer • HER2 Positive Breast Cancer • Neutropenia • Oncology • Solid Tumor • HER-2

Data collection framework for electronic medical record-based real-world data to evaluate the effectiveness and safety of cancer drugs: a nationwide real-world study of the Korean Cancer Study Group. (PubMed, Ther Adv Med Oncol) - "We considered all patients who received ramucirumab plus paclitaxel (RAM/PTX) for gastric cancer and trastuzumab emtansine (T-DM1) for breast cancer at relevant institutions in South Korea. Mean missing values of the RAM/PTX and T-DM1 cohorts at the time of simulation of fictional cases and final data analysis decreased from 20.7% to 0.46% and from 18.5% to 0.76%, respectively. This real-world study provides a framework that ensures relevance and reliability of EMR-based RWD for evaluating the effectiveness and safety of cancer drugs."

Journal • Real-world evidence • Breast Cancer • Gastric Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor

Identification of Genes Predicting Poor Response of Trastuzumab in Human Epidermal Growth Factor Receptor 2 Positive Breast Cancer. (PubMed, J Immunol Res) - "Further survival analysis of hub genes showed that DLD overexpression was significantly associated with an unfavorable prognosis in HER2+ breast cancer patients. Ten novel trastuzumab resistance-related genes were discovered, of which DLD could be used for trastuzumab response prediction and prognostic prediction in HER2+ breast cancer."

Journal • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor • ASCL1 • HER-2 • NQO1

The Impact of Tumor Mutation Burden on the Effect of Frontline Trastuzumab Plus Chemotherapy in Human Epidermal Growth Factor Receptor 2-Positive Advanced Gastric Cancers. (PubMed, Front Oncol) - "The median progression-free survival (PFS) was not reached in the TMB-high group but was 8.0 months (95% CI, 7.6-8.5) in the TMB-low group (P=0.019). The status of TMB could be a novel biomarker in predicting the efficacy of trastuzumab plus chemotherapy in HER2-positive AGCs."

Journal • Gastric Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor • HER-2 • TMB

Large-scale genomic sequencing reveals adaptive opportunity of targeting mutated-PI3Kα in early and advanced HER2-positive breast cancer. (PubMed, Clin Transl Med) - "PIK3CA mutations acted as a protective factor in treatment-naïve patients; however, advanced/locally advanced patients harbouring mutated-PI3Kα exhibited a higher progressive disease rate (100% vs. 15%, p = .000053) and a lower objective response rate (81.7% vs. 95.4%, p = .0008) in response to trastuzumab-based therapy...PIK3CA functional mutations suppressed the growth of HER2+ cells, but conferred anti-HER2 resistance, which can be reversed by the PI3Kα-specific inhibitor BYL719. We proposed adaptive treatment strategies that the mutated PIK3CA and amplified ERBB2 should be concomitantly inhibited when exposing to continuous anti-HER2 therapy, while the combination of anti-HER2 and anti-PI3Kα treatment was not essential for anti-HER2 treatment-naïve patients. These findings improve the understanding of genomics-guided treatment in the different progressions of HER2+ breast cancer."

Journal • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor • HER-2 • PIK3CA

How government health insurance coverage of novel anti-cancer medicines benefited patients in China - a retrospective analysis of hospital clinical data. (PubMed, BMC Health Serv Res) - "The government health insurance coverage of novel anti-breast-cancer medicines benefited the patients generally. The utilization of novel medicines such as trastuzumab continuously increased. The insurance coverage benefited well the patients in the high-risk age groups. However, rural patients, patients enrolled in the "resident program", and patients from low-income residential areas and non-local patients benefited less from this policy. Improving the benefits package of the low-income patients and the "resident program" beneficiary would be of considerable significance for a more inclusive and equal health insurance coverage of novel anti-cancer medicines."

Clinical data • Journal • Reimbursement • Retrospective data • Breast Cancer • Oncology • Solid Tumor

Axillary response according to neoadjuvant single or dual human epidermal growth factor receptor 2 (HER2) blockade in clinically node-positive, HER2-positive breast cancer. (PubMed, Int J Cancer) - "In this study, 546 patients with clinically node-positive, HER2-positive breast cancer who received NST followed by axillary surgery were retrospectively selected and divided into 3 groups: chemotherapy alone, chemotherapy + trastuzumab, and chemotherapy + trastuzumab with pertuzumab. In conclusion, adding trastuzumab to chemotherapy increased the axillary pCR rate in patients with clinically node-positive, HER2-positive breast cancer; furthermore, dual HER2-blockade with trastuzumab and pertuzumab did not elevate the axillary response compared with trastuzumab alone. Breast pCR could be a strong predictor for axillary pCR in clinically node-positive patients treated with HER2-targeting therapy."

Clinical • Journal • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor • HER-2

Tamoxifen overcomes the trastuzumab-resistance of SK-BR-3 tumorspheres by targeting crosstalk between cytoplasmic estrogen receptor α and the EGFR/HER2 signaling pathway. (PubMed, Biochem Pharmacol) - "Taken together, our findings indicate that crosstalk between cytoplasmic ERα and the HER2/EGFR signaling pathway be considered a novel therapeutic target for quiescent cell populations within HER2-positive breast cancer and that simultaneous inhibition of ER and the EGFR/HER2 pathway may prevent trastuzumab resistance. We hope that these results provide a basis for the use of combinations of tamoxifen and trastuzumab in HER2-positive breast cancer patients."

Journal • Breast Cancer • Estrogen Receptor Positive Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Breast Cancer • Oncology • Solid Tumor • ER • HER-2

The Prognostic Impact of HER2 Genetic and Protein Expression in Pancreatic Carcinoma-HER2 Protein and Gene in Pancreatic Cancer. (PubMed, Diagnostics (Basel)) - "Using immunohistochemistry and dual-color silver-enhanced in situ hybridization based on the Trastuzumab for a gastric cancer scoring scheme, we evaluated HER2 protein expression, gene amplification, and genetic heterogeneity in three groups (HER2-neg, HER2-low, HER2-pos) of 55 patients. These findings support the hypothesis that low-level HER2 expression and heterogeneity have significant clinical implications in PDAC. HER2 heterogeneity might indicate the best strategies of combination therapies to prevent the development of subdominant clones with resistance potential."

Journal • Gastric Cancer • Gastrointestinal Cancer • Hepatology • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • Solid Tumor • HER-2

Meiji Seika Pharma: FY 2014 Results (Meiji Seika) - Anticipated completion of P1 trial for cancer in FY 2015

Anticipated trial completion date • Biosimilar

Meiji Seika Pharma: Annual Report 2013 (Meiji Seika) - Anticipated initiation of P1 trial for cancer in Q4 FY 2013 - H2 FY 2014

Anticipated new P1 trial • Anticipated trial completion date • Biosimilar • Oncology

Bioequivalence Study Evaluating the Pharmacokinetics of DMB-3111 and Trastuzumab in Healthy Japanese Male Adults (clinicaltrials.gov) - P1; N=70; Completed; Sponsor: Meiji Seika Pharma Co., Ltd.; Active, not recruiting -> Completed

Trial completion • Biosimilar