P2, N=30, Not yet recruiting, Samsung Medical Center

P3, N=436, Not yet recruiting, Sichuan Baili Pharmaceutical Co., Ltd.

P3, N=428, Not yet recruiting, Sichuan Baili Pharmaceutical Co., Ltd.

P3, N=558, Not yet recruiting, Sichuan Baili Pharmaceutical Co., Ltd.

In lung cancer, trastuzumab deruxtecan (T-DXd) is approved in human epidermal growth factor receptor 2 (HER2)-mutated, unresectable or metastatic non-small cell lung cancer, with ADCs targeting HER3 (patritumab deruxtecan), trophoblast cell-surface antigen 2 (datopotamab deruxtecan and sacituzumab govitecan [SG]) and mesenchymal-epithelial transition factor (telisotuzumab vedotin) in late-stage clinical development. In breast cancer, several agents are already approved and widely used, including trastuzumab emtansine, T-DXd and SG, and multiple late-stage trials are ongoing...The ETOP IBCSG Partners Foundation are driving strong collaborations in this field and promoting the generation/sharing of databases, repositories and registries to enable greater access data. This will allow the most important research questions to be identified and prioritised, which will ultimately accelerate progress and help to improve patient outcomes.

These finding demonstrated that DB-1310 exerted potent antitumor activities against HER3 + tumors in in vitro and in vivo models, and showed acceptable safety profiles in nonclinical species. Therefore, DB-1310 may be effective for the clinical treatment of HER3 + solid tumors.

In JIMT-1 breast cancer xenograft mice, a single injection of bispecific ADC (3 mg/kg, i.v.) significantly inhibited the tumor growth with an efficacy comparable to that caused by combined injection of HER2 and HER3-monospecific ADCs (3 mg/kg for each). Our study demonstrates that the bispecific ADC concept can be applied to development of more potent new cancer therapeutics than the monospecific ADCs.

P1, N=26, Recruiting, Sichuan Baili Pharmaceutical Co., Ltd. | Trial completion date: Feb 2024 --> Aug 2024 | Trial primary completion date: Feb 2024 --> Aug 2024

P1, N=96, Recruiting, Sichuan Baili Pharmaceutical Co., Ltd. | Trial completion date: Mar 2024 --> Aug 2024 | Trial primary completion date: Mar 2024 --> Aug 2024

P1, N=96, Recruiting, Sichuan Baili Pharmaceutical Co., Ltd. | Trial completion date: Mar 2024 --> Aug 2024 | Trial primary completion date: Mar 2024 --> Aug 2024

P2, N=277, Active, not recruiting, Daiichi Sankyo | N=420 --> 277

P3, N=382, Not yet recruiting, Sichuan Baili Pharmaceutical Co., Ltd.

This review focuses on three approved anti-HER2 ADCs (T-DM1, DS-8201a, and RC48) and reviews ongoing clinical trials and failed trials based on anti-HER2 ADCs. Finally, we address the notable challenges linked to ADC development and underscore potential future avenues for tackling these hurdles.

P3, N=488, Recruiting, Sichuan Baili Pharmaceutical Co., Ltd. | Not yet recruiting --> Recruiting

P2, N=120, Recruiting, Daiichi Sankyo | Not yet recruiting --> Recruiting

P3, N=488, Not yet recruiting, Sichuan Baili Pharmaceutical Co., Ltd.

P1, N=144, Not yet recruiting, Shanghai Institute Of Biological Products

P2, N=121, Recruiting, Sichuan Baili Pharmaceutical Co., Ltd. | Not yet recruiting --> Recruiting

In patients with EGFR-mutated NSCLC after EGFR TKI and PBC, HER3-DXd treatment was associated with a clinically meaningful OS. The tumor biomarker characterization comprised the first description of potential mechanisms of resistance to HER3-DXd therapy.

P1/2, N=120, Recruiting, Innovent Biologics (Suzhou) Co. Ltd. | Not yet recruiting --> Recruiting

This article reviews recent advances in the application of ADCs in the treatment of HER2-low breast cancer. Additionally, this review explores the underlying factors contributing to the impact of target selection on ADC efficacy to provide new insights for optimizing the clinical application of ADCs in individuals with low HER2 expression in advanced breast cancer.

P1/2, N=350, Not yet recruiting, Shandong Suncadia Medicine Co., Ltd.

P2, N=16, Not yet recruiting, The Netherlands Cancer Institute

Preliminary results indicate combining HER3-specific treatments with EGFR TKIs enhances antitumor effects, leading to an increased objective response rate (ORR) and prolonged overall survival (OS) in resistant cases. Embracing HER3-targeting therapies represents a transformative approach against EGFR TKI resistance and emphasizes the importance of further research to optimize patient stratification and understand resistance mechanisms.

Monoclonal antibodies such as lumretuzumab, seribantumab, and patritumab have shown potential in targeting HER3 to overcome resistance to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs). Additionally, antibody-drug conjugates (ADCs) like HER3-DXd (patritumab deruxtecan) are new drug candidates that have demonstrated selective delivery of cytotoxic chemicals to NSCLC cells by exploiting HER3's widespread expression, minimizing cytotoxicity. This review aims to evaluate the efficacy of current HER3 therapeutics in development and their therapeutic potential in NSCLC, incorporating evidence from clinical trials.

P2, N=60, Recruiting, MedSIR | Not yet recruiting --> Recruiting

P1, N=72, Not yet recruiting, Multitude Therapeutics (Australia) Pty Ltd

P2, N=200, Recruiting, MediLink Therapeutics (Suzhou) Co., Ltd. | Not yet recruiting --> Recruiting

P2, N=121, Not yet recruiting, Sichuan Baili Pharmaceutical Co., Ltd. | N=90 --> 121

P2, N=420, Active, not recruiting, Daiichi Sankyo, Inc.

P2, N=52, Recruiting, Sichuan Baili Pharmaceutical Co., Ltd. | Not yet recruiting --> Recruiting

P2, N=58, Recruiting, Sichuan Baili Pharmaceutical Co., Ltd. | Not yet recruiting --> Recruiting

From the first-generation ADC, trastuzumab emtansine (T-DM1), approved in 2013 for HER2+ breast cancer, to next generation ADCs such as sacituzumab govitecan and trastuzumab deruxtecan, to emerging ADCs on the horizon, we continue to see unparalleled efficacy compared to traditional chemotherapy...Highlighting emerging ADCs and ongoing clinical trials, we will anticipate the changes in the breast cancer treatment paradigm. Lastly, we will outline the available data and current approaches for adverse event management and sequencing strategies for ADCs in clinical practice, including proposed mechanisms of resistance.

Osimertinib, a third-generation tyrosine kinase inhibitor, is approved as first-line therapy for advanced NSCLC and in the adjuvant setting for Stage IB-IIIA resected NSCLC...Trastuzumab deruxtecan has received accelerated FDA approval in HER2-mutated NSCLC. ADCs offer a possible solution to finding a new treatment that could bypass the intracellular resistance mechanism. In this review article, we summarize the mechanism of ADCs and investigational ADCs for EGFR-mutated NSCLC, which include targets to MET amplification, HER3, Trop2, and EGFR, along with other ADC targets being investigated in NSCLC, and discuss future directions that may arise with ADCs in EGFR-mutated NSCLC.

P2, N=90, Not yet recruiting, Sichuan Baili Pharmaceutical Co., Ltd.

P2, N=98, Recruiting, Sichuan Baili Pharmaceutical Co., Ltd. | N=50 --> 98

P1/2, N=184, Completed, Daiichi Sankyo Co., Ltd. | Active, not recruiting --> Completed | Trial completion date: Dec 2024 --> Sep 2023

P2, N=120, Not yet recruiting, Daiichi Sankyo, Inc.

HERTHENA-Lung02 is the first phase III trial to evaluate the safety and efficacy of HER3-DXd versus PBC in patients with progression on a third-generation EGFR TKI. Clinical Trial Registration: NCT05338970 (clinicaltrials.gov); 2021-005879-40 (EudraCT Number).

P1/2, N=120, Not yet recruiting, Innovent Biologics (Suzhou) Co. Ltd.

P3, N=368, Recruiting, Sichuan Baili Pharmaceutical Co., Ltd. | Not yet recruiting --> Recruiting

P2, N=32, Recruiting, Sichuan Baili Pharmaceutical Co., Ltd. | Phase classification: P2a/2b --> P2