Kadcyla (ado-trastuzumab emtansine)

Neither group recorded any adverse event-related deaths. Pyrotinib plus capecitabine significantly improves median PFS compared to T-DM1 in patients with HER2-positive advanced breast cancer, demonstrating a favorable efficacy profile alongside manageable safety concerns.

P2/3, N=45, Recruiting, University of Virginia | Trial completion date: Oct 2026 --> Dec 2029 | Trial primary completion date: Dec 2024 --> Dec 2028

P2, N=2175, Active, not recruiting, ECOG-ACRIN Cancer Research Group | Recruiting --> Active, not recruiting

P=N/A, N=100, Recruiting, Seoul National University Hospital

P=N/A, N=50, Recruiting, Mayo Clinic | Trial completion date: Jun 2025 --> Jun 2026 | Trial primary completion date: Jun 2025 --> Jun 2026

While ADCs like trastuzumab emtansine (T-DM1), trastuzumab deruxtecan (T-DXd), and sacituzumab govitecan have shown significant efficacy, resistance mechanisms such as antigen loss, impaired internalization, and efflux of cytotoxic payloads challenge their effectiveness. The potential of combination therapies, such as ADCs with immune checkpoint inhibitors (ICIs), further highlights the evolving landscape of breast cancer treatment. As ADC technology advances, personalized approaches integrating biomarkers and optimized sequencing protocols offer promising avenues to enhance treatment outcomes and combat resistance in breast cancer.

P2, N=130, Recruiting, Population Health Research Institute | Trial completion date: Jun 2025 --> Jun 2026 | Trial primary completion date: Jan 2025 --> Dec 2025

P2, N=38, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Mar 2025 --> Mar 2026

Approximately one-quarter of the patients died or discontinued 1L therapy without receiving further treatment. Overall survival from the start of 1L was just over 3 years. This highlights a need for more effective therapies in earlier LoTs that prolong the time to progression and provide longer clinical benefits.

P2, N=72, Recruiting, Dana-Farber Cancer Institute | Not yet recruiting --> Recruiting

Our CRISPR screening approach with T-DM1 in HER2-positive breast cancer cell lines identified genes not previously implicated in T-DM1 sensitivity or resistance, including TSC1 and TSC2. These genes may inform new strategies to enhance T-DM1 therapy in the clinic.

P1, N=23, Completed, Dizal Pharmaceuticals | Active, not recruiting --> Completed

All patients received neoadjuvant trastuzumab and 86.1% of patients received neoadjuvant pertuzumab in addition to trastuzumab. This study describes the sociodemographic and clinicopathological characteristics of patients with early-stage HER2-positive breast cancer with residual disease after neoadjuvant therapy and provides real-life data on treatment with adjuvant TDM1. The findings support the manageable safety profile of the adjuvant TDM1 regimen with a low discontinuation rate.

 This real-world analysis revealed that the efficacy, safety, and tolerability of T-DXd in the Portuguese population are consistent with the outcomes observed in the DESTINY-Breast02 clinical trial.

P2, N=90, Completed, Jules Bordet Institute | Active, not recruiting --> Completed

The KATHERINE trial assessed HER2 status of residual disease from 845 patients with HER2-positive status on pretherapy biopsies, of which 70 were negative on retesting. With 8 years of median follow-up, 7-year IDFS was 60.3 % with trastuzumab compared to 95.2 % with T-DM1, consistent with clinically meaningful benefit from T-DM1 in these 70 patients.

Survival until the tumor volume in the canine OSA-engrafted mice reached mean final tumor volume in the T-DM1 group was significantly longer in the T-DM1 group, but not in the trastuzumab group, compared to the vehicle control group. These findings indicated that T-DM1 exerts antitumor effects on canine OSA cells in vitro and in vivo, possibly by inducing apoptosis due to DM1.

P3, N=228, Recruiting, Shanghai JMT-Bio Inc. | Not yet recruiting --> Recruiting

In this case report, we describe the case of a highly pretreated patient with HER-2 positive metastatic breast cancer.

P2, N=48, Recruiting, Carey Anders, M.D. | Trial completion date: Oct 2027 --> Jul 2026 | Trial primary completion date: Oct 2026 --> Apr 2026

P2, N=140, Recruiting, Memorial Sloan Kettering Cancer Center | Trial completion date: Feb 2025 --> Feb 2026 | Trial primary completion date: Feb 2025 --> Feb 2026

This study demonstrated that ERBB2-mutant NSCLC is uncommon among Latin American patients. Despite the vast majority of patients being treated with chemo-immunotherapy (ICB) in the first line, the median rwOS was similar to that reported for non-oncogene-addicted NSCLC.

P2, N=140, Active, not recruiting, Dana-Farber Cancer Institute | Trial completion date: Dec 2024 --> Dec 2025

Based on the available evidence, in breast cancer, ADCs were proved to with significant improvements in prolonging survival time and demonstrates a tolerable safety profile. Meanwhile, ADCs were proved to have enormous potential for the treatment of solid tumors. However, well-designed, multi-center RCTs need to further identify its potential in various solid tumors.

This review explores the application of antibody-drug conjugates (ADCs), such as trastuzumab emtansine (T-DM1), trastuzumab deruxtecan (T-DXd) and sacituzumab govitecan (SG), in treating breast cancer among elderly populations. Emerging ADCs, including datopotamab deruxtecan and ARX-788, show promise but lack extensive geriatric-specific data. While the ADCs offer encouraging results in terms of efficacy and safety, with appropriate dose adjustments, further research is needed to optimize their use in elderly patients with breast cancer.

P2, N=380, Completed, West German Study Group | Active, not recruiting --> Completed

P3, N=228, Not yet recruiting, Shanghai JMT-Bio Inc.

In the Kaplan-Meier survival analysis, both liver dysfunction and platelet reduction were correlated with significantly longer EFS (p=0.033 and p=0.038, respectively). This retrospective study demonstrated that AEs were associated with tumour efficacy in patients with HER2+ BC treated with TDM1.

P3, N=347, Active, not recruiting, Hoffmann-La Roche | Trial primary completion date: Mar 2025 --> Nov 2024

P2, N=55, Recruiting, Dana-Farber Cancer Institute | Trial completion date: Feb 2026 --> Feb 2027 | Trial primary completion date: Feb 2025 --> Feb 2026

P3, N=1450, Not yet recruiting, Sichuan Baili Pharmaceutical Co., Ltd.

P=N/A, N=10, Active, not recruiting, City of Hope Medical Center | Trial completion date: Dec 2024 --> Oct 2025

After multiple brain metastases appeared, whole-brain radiation therapy and T-DM1 led to tumor shrinkage. However, the tumors rapidly regrew, and T-DXd was started, resulting in a positive response. Ten months later, the disease progressed, and she died from carcinomatous meningitis 17.7 months after initial treatment.

Chemotherapy was initiated with a regimen of paclitaxel, trastuzumab, and pertuzumab...However, after 9 months of treatment, disease progression occurred, leading to sequential changes in the treatment regimen to T-DM1 and T-DXd...Postoperatively, the patient received radiation therapy to the chest wall, followed by continued treatment with trastuzumab and pertuzumab. As of 2 years after surgery, no recurrence has been observed.

P=N/A, N=2907, Active, not recruiting, Hoffmann-La Roche | Trial completion date: Nov 2025 --> Jun 2026 | Trial primary completion date: Nov 2025 --> Jun 2026

P2, N=64, Active, not recruiting, The University of Sydney | Recruiting --> Active, not recruiting

Although ADCs such as trastuzumab emtansine and trastuzumab deruxtecan have significantly improved survival for patients with breast cancer expressing HER2, there is still controversy over options after ADCs. The radiotherapy and ablation should also be used as an effective strategy for oligoprogressions. Herein, we conducted a review of ADCs, and then discussed several strategies to maximize the potential benefit to patients with HER2 expression breast cancer.

P1/2, N=582, Recruiting, Boehringer Ingelheim | N=240 --> 582

P2, N=74, Not yet recruiting, University of Chicago | Initiation date: Jan 2025 --> Jan 2026

P2, N=512, Active, not recruiting, Dana-Farber Cancer Institute | Trial completion date: Dec 2024 --> Dec 2025

In this review, we provide an overview of the autophagic machinery induced in response to HER2-targeted monoclonal antibodies, with a focus on trastuzumab and trastuzumab-emtansine, in an effort to determine whether autophagy targeting or modulation could be translated clinically to increase their effectiveness and/or overcome the development of resistance...This series of papers was developed in an effort to establish whether autophagy targeting or modulation is likely to be an effective adjuvant strategy to increase the efficacy of cancer chemotherapeutic agents. This review explores the relationship between the autophagic machinery and HER2-targeted therapies.

The standard of care for HER2-positive and hormone receptor-positive breast cancer patients who receive neoadjuvant chemotherapy (NACT) combined with trastuzumab, with or without pertuzumab, is to continue with adjuvant T-DM1 in cases of an incomplete response according to KATHERINE trial results. However, the optimal management for patients with residual disease with loss of HER2 expression is not widely studied. Loss of HER2 expression after NACT with anti HER2 is a rarer event with questionable value both as a predictive prognostic marker.