P3, N=550, Not yet recruiting, Shanghai Henlius Biotech

Adding HLX22 to HLX02 and XELOX prolonged PFS and enhanced antitumor response in the first-line treatment of HER2-positive gastric cancer, with manageable safety.

These results suggested that the application of non-competing antibodies HLX22 and HLX02 targeting HER2 subdomain IV together may be of substantial benefit to gastric cancer patients who currently respond suboptimal to trastuzumab therapy.

P2, N=150, Active, not recruiting, Shanghai Henlius Biotech | Recruiting --> Active, not recruiting | Trial completion date: Sep 2024 --> Dec 2025 | Trial primary completion date: Apr 2023 --> Dec 2024

Adding HLX22 to HLX02 + XELOX improved survival and antitumor response in patients with HER2-positive G/GEJ cancer in the first-line setting, with a manageable safety profile. Clinical trial information: NCT04908813. >*Hazard ratio (HR) was estimated between group A and C, as well as between group B and C. NE, not evaluable; NR, not reached.

HLX22 was well tolerated in patients with advanced solid tumors overexpressing HER2 after failure of standard therapies. The study results support further investigation of HLX22 in combination with trastuzumab and chemotherapy.

Progress has been made by optimizing the fragment crystallizable (Fc) domain of trastuzumab, an IgG1 monoclonal, chimeric anti-HER2 antibody, to develop margetuximab. This review summarizes studies on the efficacy of margetuximab, discusses its utility as an anti-HER2 monoclonal antibody drug for the treatment of HER2 + BC, and presents the latest advances in the treatment of BC. This review provides insights into the clinical implication of margetuximab in HER2 + MBC treatment.

F-FLT positron emission tomography (PET) detects response to PI3K-targeting therapy earlier than F-FDG PET in BC cells. However, therapy response can be underestimated after trastuzumab and everolimus owing to negative feedback loop and crosstalk between pathways.

The study did not meet its primary pCR endpoint possibly due to a high TCH pCR rate, and small numbers. TCHL produced a statistically significant improvement in RFS compared to TCH. TCHL produced a higher rate of gastro-intestinal toxicity, but the use of loperamide significantly reduced the frequency of diarrhoea.

While HER2 overexpression was a poor prognostic factor in breast cancer before trastuzumab (Herceptin) was available, TNBC is often reported as the worst BC subgroup since targeted therapy is currently not possible...While the duration of DFS and OS had no significant difference between TNBC and Luminal A-B subgroups, HER2 enriched subgroup had significantly shorter survival when compared to any other subgroup. HER2-enriched subgroup had a 10-fold greater risk of death compared to the Luminal A subgroup.

Activation of HER2 in normal lung fibroblasts led to a more invasive genetic program and worsened fibroblast invasion and lung fibrosis, while antagonizing HER2 signaling blunted fibroblast invasion and ameliorated lung fibrosis. These findings suggest that HER2 signaling may be a key driver of fibroblast invasion and serve as an attractive target for therapeutic intervention in IPF.

P1, N=11, Completed, Shanghai Henlius Biotech | Active, not recruiting --> Completed

P2, N=150, Recruiting, Shanghai Henlius Biotech | Not yet recruiting --> Recruiting

P1, N=232, Not yet recruiting, Xuanzhu Biopharmaceutical Co., Ltd.

In this cohort, no primary OEC showed HER2 overexpression, but two cases had scored 2+, one of which harboring HER2 amplification, indicating that OECs with equivocal HER2 expression by immunohistochemistry warrant testing for amplification by FISH as other tumor types. Our findings contribute to the growing evidence that HER2 is amplified in a small percentage of OECs and thus may serve as an attractive therapeutic target in patients with recurrent or metastatic disease, for which currently options for targeted therapy are limited.

Our strategy involves evaluation of two targeted small molecule agents, everolimus and dasatinib, with complementary inhibitory circuitries in the PI3K/Akt/mTOR pathway, along with a standard cytotoxic agent, paclitaxel. Our proposed triple combination therapy demonstrated synergism in JIMT-1 cells, thus corroborating our hypothesis. This effort may form the basis for further investigation of the triple combination therapy in vivo at a mechanistic level in HER2-therapy resistant BC cells.

P1, N=32, Not yet recruiting, Wuhan YZY Biopharma Co., Ltd. | Trial completion date: Mar 2021 --> Dec 2023 | Trial primary completion date: Dec 2020 --> Nov 2023

ER/PR expression may become a predictor of survival benefit in HER2+ early breast cancer and a higher ER/PR level might be associated with better DFS.

Immune checkpoint inhibitors are effective as monotherapy and in combination with platinum doublet chemotherapy. Therefore, ICI based treatments may be seen as the current standard of care and benchmark for targeted therapies in HER2mu NSCLC.

In the second-line setting, trastuzumab emtansine (T-DM1) improves OS compared with capecitabine/lapatinib in patients previously treated with trastuzumab-based chemotherapy. Differences in outcome likely reflect differences in patient population and previous lines of therapy in routine practice. Further work is needed to understand the effectiveness of T-DM1 after pertuzumab exposure.

These data indicate that rare germline coding variants in ERBB2 are associated with an increased risk for development of MPN. The ERBB2 gene is a novel susceptibility locus which likely contributes to cancer risk in combination with additional risk alleles.

HR-QoL was preserved for patients with HER2+ metastatic breast cancer who were treated with tucatinib added to trastuzumab and capecitabine and maintained longer with tucatinib therapy than without it among those with brain metastases.

Conclusions Our meta-analysis demonstrated that T-DM1 is associated with a relatively lower risk of all-grade PN and PSN than the taxane-based regimens for HER2-positive cancers. It could be an area of consideration in selecting therapy for HER2-positive breast cancer patients at high risk of developing or having pre-existing PN and PSN.

Moreover, ER and PR expressions were positively correlated with the absence of axillary lymph node enlargement (P < 0.05) and negatively correlated with the maximum tumor diameter (P < 0.05). The mammographic features of IBC are correlated with the expression of immunity indices ER, PR, and HER2 and reflect several pathological features.

Significantly reduced IBTR after BCS was observed in the patients who received 1 year of adjuvant/neoadjuvant trastuzumab treatment for HER2-positive breast cancer.

This secondary analysis of data from the STO-3 clinical trial indicated that, among the selected subgroup of patients, tumor size followed by tumor grade were the markers most significantly associated with long-term survival. Furthermore, a significant long-term tamoxifen treatment benefit was observed among patients with larger tumors, lower tumor grades, and PR-positive tumors.

pCR is sensitive biomarker and surrogate to survival outcomes in HER2+ breast cancer. Patients likely to achieve pCR may be predicted from traditional clinicopathological characteristics and molecular parameters.

HER2-positive COA may be more aggressive and may require further intensive treatments. This literature review may be helpful in determining treatment strategies for COA.

P1/2, N=152, Recruiting, Shanghai Miracogen Inc. | Initiation date: Aug 2020 --> May 2021

P1, N=74, Recruiting, Shanghai Miracogen Inc.

In this study, treatment with standard neoadjuvant combination DTP was equal to T-DM1. ClinicalTrials.gov Identifier: NCT02568839; EudraCT number: 2014-000808-10.

No abstract available

T-DM1, as second-line therapy in the treatment of HER2-positive breast cancer, is not a cost-effective option in China. Given the significant clinical efficacy, an appropriate price reduction of T-DM1 is required to benefit more HER2-positive breast cancer patients.

Atezolizumab with antibody-dependent cellular cytotoxicity or ADC agents appears safe and may activate the adaptive immune system of patients with HER2 eBC tumors more than those with mBC tumors.

In vivo studies demonstrated that the developed targeting system significantly reduced tumor growth and the appearance of lung metastasis compared to untreated controls. In summary, the efficacy of the NPs+Gem+Ab system to target cancer cells was established and validated both in vitro and in vivo, being a compelling alternative strategy to current chemotherapeutic approaches.

We randomly assigned participants (1:4), via an interactive response system using central block randomisation with block sizes of five, stratified by hormone receptor status, to either docetaxel (75 mg/m intravenous), carboplatin (area under the concentration-time curve 6 mg/mL  per  min intravenous), trastuzumab (subcutaneous 600 mg fixed dose), and pertuzumab (intravenous 840 mg loading dose, 420 mg maintenance doses; group A); or trastuzumab and pertuzumab (group B). Hormone receptor-positive patients allocated to group B were additionally given letrozole if postmenopausal (2·5 mg/day orally) or tamoxifen if premenopausal (20 mg/day orally)...Depending on the forthcoming results for the 3-year invasive disease-free survival endpoint, this strategy might be a valid approach to select patients not requiring chemotherapy. F Hoffmann-La Roche.

Immuno-MRM-MS can be used to quantify HER2 in FFPE and frozen BC biopsies, even at low HER2 expression levels.

CCI-based indices are the most appropriate indices to use in the general breast-cancer population. There is insufficient validation of any comorbidity index in HER2+ breast cancer to provide a recommendation, indicating a future need to validate these instruments in this population.

Most patients strongly preferred PH FDC SC over P + H IV. PH FDC SC was generally well tolerated, with no new safety signals (even when switching), and offers a quicker alternative to IV infusion.

We identified patients with HER2-positive EBC (n=254) who had received neoadjuvant chemotherapy with RTZ or CT-P6, plus pertuzumab, carboplatin and docetaxel (TCHP) and untreated stage IV MBC (n=103) who had received palliative first-line treatment with RTZ or CT-P6, plus pertuzumab and docetaxel (THP) between May 2014 and December 2019. The ORR, DCR, and cardiac safety profiles did not also show significant difference efficacy outcomes between two groups. These real-world data suggest that biosimilar trastuzumab CT-P6 has similar effectiveness and cardiac safety to RTZ in HER2-positive EBC and MBC patients, when administered as part of dual HER2-targeted therapy with pertuzumab plus chemotherapy in the neoadjuvant or palliative setting.

P4, N=20, Not yet recruiting, Wuhan University

Our findings indicate more similarities among groups 2, 4, and 5 than between groups 1 and 3, supporting the HER2 categorization in the latest guideline. Additional studies may be warranted to assess the outcomes of these patients with different management approaches.