P4, N=25, Completed, Gilead Sciences | Enrolling by invitation --> Completed | N=200 --> 25

P2, N=348, Recruiting, West German Study Group | Not yet recruiting --> Recruiting

P2, N=23, Not yet recruiting, University of California, Irvine

P1, N=26, Recruiting, Sichuan Baili Pharmaceutical Co., Ltd. | Trial completion date: Oct 2024 --> Jun 2025 | Trial primary completion date: Oct 2024 --> Jun 2025

P1/2, N=56, Active, not recruiting, Institut für Klinische Krebsforschung IKF GmbH at Krankenhaus Nordwest | Recruiting --> Active, not recruiting

P2, N=130, Not yet recruiting, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology; Union Hospital, Tongji Medical College, Huazhong University of

P2, N=100, Active, not recruiting, Gustave Roussy, Cancer Campus, Grand Paris | Recruiting --> Active, not recruiting | Trial completion date: Nov 2025 --> Mar 2028 | Trial primary completion date: Nov 2022 --> Mar 2025

P2, N=20, Not yet recruiting, MedSIR

For the treatment of breast cancer, there are three ADCs approved for breast cancer treatment: Trastuzumab emtansine (T-DM1), Trastuzumab Deruxtecan (T-Dxd) targeting HER-2, and Sacituzumab Govitecan (SG) targeting Trop-2. This review summarizes the efficacy and adverse effects of ADC therapies that have completed or are currently undergoing phase I-III clinical trials. Additionally, it analyzes potential combination strategies to overcome ADC resistance, aiming to provide clinicians with a comprehensive clinical guide to the use of ADCs in breast cancer treatment.

P3, N=420, Not yet recruiting, Sichuan Kelun Pharmaceutical Research Institute Co., Ltd.

ADCs offer the opportunity for a more effective and personalized treatment approach for gynecologic cancer patients. Side effects must be closely monitored, and preventive measures must be followed to maximize benefit and minimize toxicity. A better understanding of the role of target proteins as biomarkers to predict response to ADCs will be critical for successful clinical implementation of ADCs and further research in this area is necessary.

P1/2, N=54, Recruiting, Icahn School of Medicine at Mount Sinai | Not yet recruiting --> Recruiting

From gemtuzumab ozogamicin to trastuzumab emtansine (T-DM1), and now to third-generation agents such as trastuzumab deruxtecan (DS-8201) and disitamab vedotin (RC48), improvements have been made in target selectivity, potency, linker stability, and reduced off-target effects. ADCs represent a promising frontier in precision cancer treatment, with continued research enhancing their potential in breast cancer and beyond. This review provides a comprehensive exploration of ADCs' evolution in breast cancer therapy, offering a molecular perspective to inform clinical practice and update colleagues on this dynamic field.

P2, N=20, Not yet recruiting, British Columbia Cancer Agency

We describe the rationale and design of TROPION-Lung07, a randomized, open-label Phase III study assessing Dato-DXd in combination with pembrolizumab with/without platinum-based chemotherapy versus pembrolizumab plus pemetrexed and platinum-based chemotherapy in patients with advanced/metastatic non-squamous NSCLC without actionable genomic alterations and <50% PD-L1 expression. Primary study objectives are progression-free survival and overall survival.Clinical Trial Registration: NCT05555732 (ClinicalTrials.gov).

P1/2, N=112, Recruiting, Bio-Thera Solutions | N=204 --> 112

P3, N=630, Recruiting, AstraZeneca | Not yet recruiting --> Recruiting

In the analysis using human- leukemia monocytic cell, the concentration of eribulin released from TROP2-eribuilin was significantly reduced by the use of an Fc receptor inhibitor (P < 0.05). These results revealed that Fcγ-receptor-mediated uptake by alveolar macrophages releases cytotoxic payload into lung tissue, helping to clarify the pathogenesis of ADC-induced ILD.

Approximately 15% of TNBC patients have a germline mutation in BRCA1 and/or BRCA2, and for these patients, innovative therapeutic options such as olaparib and talazoparib, which are PARP inhibitors, are available. Sacituzumab govitecan (SG) is a humanized monoclonal antibody-drug conjugate directed against the surface antigen of human trophoblastic cells (Trop-2) expressed in approximately 90% of TNBC, coupled with SN-38, the active metabolite of irinotecan, a topoisomerase I inhibitor. Here, we present the case of a woman who was initially diagnosed with localized luminal B breast cancer (ER-positive; HER2-negative) and was treated with curative therapy. However, she later experienced a recurrence with metastatic TNBC (ER-negative/HER2-negative) and received treatment with sacituzumab govitecan, which resulted in prolonged disease control.

In this report we describe the case of a patient with TNBC diagnosed at the metastatic level when the primary breast tumour presented overexpression of ER end PgR. An important tumoral heterogeneity has been described in breast cancer during its natural evolution and for that reason is important to perform metastatic lesions re-biopsy, when feasible, in order to re-evaluate the biological characteristics and define the optimal therapeutic strategy.

Knockdown of TROP2 also resulted in decreased expression of vimentin, along with reduced migratory capacity. These findings suggest that TROP2 plays a crucial role in cSCC cell proliferation and migration, and highlight the potential of sacituzumab govitecan as a promising therapeutic option for cSCC.

P1/2, N=204, Recruiting, Bio-Thera Solutions | N=50 --> 204

In the subcutaneous xenograft model using BxPC3 cells, the combined administration of αTROP2-MMAE and an autophagy inhibitor elevated the tumor inhibition rate of αTROP2-MMAE from 71.6 % to 99.0 %, resulting in the eradication of tumors in half of the mice. Collectively, our research demonstrated for the first time the cytoprotective role of autophagy in TROP2-targeted antibody-drug conjugate therapy for pancreatic cancer, providing new perspectives for mechanistic exploration and therapeutic strategies in the treatment of pancreatic cancer.

P3, N=540, Recruiting, Gilead Sciences | Trial completion date: May 2027 --> Jul 2028 | Trial primary completion date: May 2027 --> Jul 2028

P1/2, N=32, Not yet recruiting, Merck Sharp & Dohme LLC

Pretreatment [18F]FDG PET/CT-derived biomarkers, namely TMTV and Dmax, have significant prognostic value in patients with mTNBC and HER2-low mBC treated with SG and T-DXd. These biomarkers improve prognostic prediction and may optimize treatment strategies, warranting their clinical use, but larger studies are needed to validate these findings.

P2, N=30, Recruiting, M.D. Anderson Cancer Center | Trial primary completion date: Dec 2024 --> Dec 2025

In a real-world cohort of heavily pretreated patients with mTNBC, SG retains its clinical activity. In a subgroup with HER2-low disease, T-DXd continues to demonstrate promising clinical activity after SG, supporting the use of sequential antibody-drug conjugates in this population.

SG represents a promising treatment option for Asian patients with HR+HER2- mBC (ClinicalTrials.gov identifier no. NCT04639986 ).

However, the current ADC, sacituzumab govitecan, fails to overcome the crucial role of adenosine in the suppressive immune microenvironment characteristic of this "cold tumor"...Thus, it kills tumor cells with cytotoxic drugs, comprehensively regulates immunosuppression, and restores a durable immune response. This study proposes an antibody-polymeric drug complex with immunomodulatory and immunoagonist roles, offering new insights into TNBC treatment.

Sacituzumab Govitecan (SG) is an antibody-drug conjugate (ADC) comprised of an anti-Trop-2 IgG1 molecule conjugated to SN-38, the active metabolite of irinotecan, via a pH-sensitive hydrolysable linker. The most common AEs were neutropenia, diarrhea, nausea, fatigue, alopecia, and anemia. This review outlines AE management recommendations for SG based on clinical trial protocols and Canadian guidelines, incorporating treatment delay, dose reductions, and the use of prophylactic and supportive medications.

P1/2, N=220, Active, not recruiting, Suzhou Suncadia Biopharmaceuticals Co., Ltd. | Recruiting --> Active, not recruiting | N=120 --> 220

P3, N=350, Recruiting, Shanghai Fudan-Zhangjiang Bio-Pharmaceutical Co., Ltd. | Not yet recruiting --> Recruiting

P1/2, N=76, Not yet recruiting, MedSIR

P2, N=42, Recruiting, Grupo Espanol de Tumores Neuroendocrinos | Not yet recruiting --> Recruiting

P3, N=520, Recruiting, Gilead Sciences | Not yet recruiting --> Recruiting

This study not only elucidates the current landscape of ADCs in breast cancer but also sets the stage for the next generation of oncological therapeutics. This study not only elucidates the current landscape of ADCs in breast cancer but also sets the stage for the next generation of oncological therapeutics, with particular attention to their broader applications and associated risks.

P2, N=40, Recruiting, The University of Texas Health Science Center at San Antonio | Trial completion date: Feb 2025 --> Aug 2026 | Trial primary completion date: Aug 2024 --> Feb 2026

P1/2, N=119, Active, not recruiting, AstraZeneca | Trial completion date: May 2024 --> Dec 2024

SG RP2D was established as 10 mg/kg in Japanese patients. SG showed efficacy in Japanese patients with previously treated mTNBC, a manageable safety profile, and no new safety signals, consistent with the previous ASCENT study.

P1, N=890, Recruiting, Daiichi Sankyo Co., Ltd. | Trial completion date: Jan 2025 --> Jan 2026 | Trial primary completion date: Jan 2025 --> Jan 2026

P2, N=498, Recruiting, Klus Pharma Inc. | N=278 --> 498