P2, N=36, Recruiting, Fudan University | Not yet recruiting --> Recruiting

T-DM1 demonstrated a manageable safety profile, and the adverse events were consistent with those reported in randomized trials. The data are not yet sufficient to allow for a formal analysis of RFS and OS, and long-term follow-up is required.

This narrative review explores key predictive factors influencing the efficacy of ADCs, focusing on HER2-targeted therapies, such as trastuzumab emtansine and trastuzumab deruxtecan, as well as sacituzumab govitecan for triple-negative breast cancer. Finally, future perspectives on the sequential use of ADCs and potential combination therapies are highlighted, along with emerging agents targeting alternative antigens like HER3 and LIV-1. Overall, identifying predictive biomarkers and overcoming resistance mechanisms are essential for optimizing the use of ADCs in metastatic breast cancer, thereby improving patient outcomes.

We searched the FAERS database for reports of cardiovascular adverse events in patients with HER2-positive breast cancer receiving trastuzumab, ado-trastuzumab emtansine (T-DM1), and trastuzumab deruxtecan (T-Dxd). Proportionate analysis showed age and weight were the two key factors contributing to the occurrence of T-DCs induced MACE. HER2-positive breast cancer patients receiving T-DCs require additional cardiac monitoring, particularly for stroke in younger patients.

P=N/A, N=100, Active, not recruiting, IRCCS Azienda Ospedaliero-Universitaria di Bologna

P2, N=25, Recruiting, Guangdong Provincial People's Hospital

P=N/A, N=178, Active, not recruiting, Hoffmann-La Roche | Recruiting --> Active, not recruiting | N=500 --> 178 | Trial completion date: Mar 2025 --> Sep 2025 | Trial primary completion date: Mar 2025 --> Sep 2025

P2, N=22, Terminated, Sanofi | Active, not recruiting --> Terminated; Sponsor decision, the decision is not related to any safety concern.

P2, N=100, Not yet recruiting, Beijing Biostar Pharmaceuticals Co., Ltd.

P2, N=20, Recruiting, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins | Not yet recruiting --> Recruiting

While a novel TF-ADC (MRG004A) demonstrated efficacy for PDAC and TNBC in a Phase I/II trial [Ref...Thus, TF-inhibition reshapes an "immune hot" tumor environment. TF-targeted therapy warrants clinical investigation as a single agent or in combination with immunotherapy for treating TF-positive PDAC and TNBC.

P1/2, N=125, Active, not recruiting, Eisai Co., Ltd. | Phase classification: P1b/2 --> P1/2 | Trial completion date: Jan 2024 --> Mar 2026 | Trial primary completion date: Jan 2024 --> Mar 2026

P1/2, N=316, Terminated, Pierre Fabre Medicament | Active, not recruiting --> Terminated; delay in participants recruitment in cohort A3 and IMP manufacturing issues

These include single-agent brentuximab vedotin, histone deacetylase inhibitors, duvelisib, ruxolitinib, EZH2 inhibitors, and azacitidine, among others. Follicular helper T-cell lymphomas, given frequent mutations in epigenetic regulator genes, may preferentially respond to agents such as histone deacetylase inhibitors, EZH2 inhibitors, and hypomethylating agents. As these therapies evolve in their use for both relapsed/refractory disease and then into frontline treatment, subtype-specific therapy will likely help personalize care for patients with PTCL.

We demonstrate in our exploratory study that biomarkers involved in the process of EMT could have a prognostic impact in a cohort of patients with BC uniformly treated and with long-term follow-up. Genes known to be involved in EMT were associated with improved eribulin efficacy, while suggesting a poorer outcome with CDK4/6i.

While 12-month PFS failed to reach statistical significance, subgroup analyses favor Pola-R-CHP. Further research with a wider population, longer follow-up, and screening of advantageous groups are warranted.

•Mirvetuximab soravtansine (MIRV) is used in the treatment of FRα positive, platinum-resistant epithelial ovarian cancer.•MIRV is associated with ocular events, leading to dose delays, dose reductions, and discontinuations of chemotherapy.•Mitigation strategies to prevent treatment disruption have historically relied on corticosteroid and lubricating drops.•Dehydrated amniotic membrane patch to treat MIRV related ocular events is a novel therapeutic option.

This analysis offers the most comprehensive overview of ado-trastuzumab emtansine induced hemorrhage to date, shedding new light on this severe complication. Understanding the underlying mechanisms of these positive PTs can provide useful insights for further research.

P2, N=116, Active, not recruiting, M.D. Anderson Cancer Center | Trial completion date: Dec 2024 --> Dec 2026 | Trial primary completion date: Dec 2024 --> Dec 2026

P2, N=35, Active, not recruiting, Sanofi | Trial completion date: Jun 2024 --> Dec 2024

P3, N=1046, Not yet recruiting, Merck Sharp & Dohme LLC

Our results highlight a need for standardized protocols for FRα testing to ensure accurate biomarker evaluation across varied clinical settings. The heterogeneity in FRα expression, influenced by tumor histology and anatomical origin, warrant further investigation to optimize therapeutic outcomes.

P1, N=20, Not yet recruiting, Atridia Pty Ltd. | Initiation date: Nov 2024 --> Mar 2025

P=N/A, N=26, Completed, Takeda | Recruiting --> Completed | N=50 --> 26

P1, N=20, Recruiting, Atridia Pty Ltd. | Not yet recruiting --> Recruiting

P2, N=230, Recruiting, TORL Biotherapeutics, LLC | Not yet recruiting --> Recruiting

P2, N=32, Not yet recruiting, University of Michigan Rogel Cancer Center | Trial completion date: Jul 2027 --> Nov 2027 | Initiation date: Oct 2024 --> Feb 2025 | Trial primary completion date: Jul 2027 --> Nov 2027

P2, N=139, Terminated, Jules Bordet Institute | N=1065 --> 139 | Trial completion date: Mar 2029 --> Nov 2024 | Suspended --> Terminated | Trial primary completion date: Jun 2027 --> Nov 2024; Serious concerns on the slow recruitment of the study that impacts the robustness of the scientific rationale and the study financial provision. It aims to assess carefully the situation and to evaluate the potential solutions to overcome the issues.

P2, N=57, Active, not recruiting, Dana-Farber Cancer Institute | Trial primary completion date: Aug 2025 --> Jul 2024

Recent data on combining brentuximab vedotin, doxorubicin, vinblastine, and dacarbazine demonstrated improved overall survival compared to ABVD but increased adverse events (AEs). Further evaluation of programmed death receptor 1 inhibitor and CD30 antibody-drug conjugate combination regimens in frontline advanced stage cHL is warranted. Trial registration: NCT03646123.

Future research should focus on a more detailed examination of responses in varied patient populations, long-term outcomes, and a thorough economic evaluation of T-DM1, along with an exploration into treatment resistance. This will provide a more nuanced understanding of T-DM1's role in the treatment landscape of HER2-positive breast cancer.

MIRV as ≥3L treatment in heavily pretreated recurrent FRα-positive PSOC demonstrated notable efficacy and tolerable safety, including among those with prior PD on or within 30 days of PARPi. (Funding, ImmunoGen, Inc; NCT05041257).

P1, N=20, Active, not recruiting, Dana-Farber Cancer Institute | Phase classification: P1b --> P1

P2, N=135, Recruiting, Eisai Inc. | Trial completion date: Oct 2026 --> Mar 2026 | Trial primary completion date: Oct 2026 --> Mar 2026

Both MBZ and paclitaxel treatments inhibited of cell proliferation and microtubule formation by reducing the PI3K/AKT pathway in CAL-27 and UM-SCC-1 cells, with the combination demonstrating synergistic effects. Our study suggests MBZ and paclitaxel as potential agents for the treatment of OTSCC.

Currently, there are three ADCs available for use in breast cancer: trastuzumab emtansine for HER2 positive breast cancer (early stage and metastatic), trastuzumab deruxtecan for HER2 positive and HER2 low breast cancer (metastatic) and sacituzumab govitecan for triple negative and hormone receptor positive (HR +), HER2 negative breast cancer(metastatic). The future of this class of compounds is very exciting. This field is rapidly evolving with new ADCs being investigated and clinical trials looking at the use of known ADCs in earlier stage disease.

P2, N=74, Not yet recruiting, University of Chicago | Initiation date: Jul 2024 --> Jan 2025

P1, N=18, Active, not recruiting, Seagen Inc. | Recruiting --> Active, not recruiting | N=110 --> 18

We summarize the mechanisms of the action of various therapeutic strategies based on FRα, including MABs (monoclonal antibodies), ADCs (antibody-drug conjugates), FDCs (folate-drug conjugates), SMDCs (small molecule-drug conjugates), vaccines, and CAR-T (chimeric antigen receptor T) cells, and present the most significant clinical trials of some FRα-based drugs. Furthermore, we discuss the pros and cons of different FR-based therapies, highlighting mirvetuximab soravtansine (MIRV) as the currently most promising EOC-targeting drug.

These findings are paradigm-shifting given that chemotherapy is traditionally considered immunosuppressive. Our study reveals the novel effect of low-dose eribulin chemotherapy in inhibiting bladder tumor growth by enhancing anti-tumor NK cell immunity, challenging previous assumptions and opening new therapeutic approaches to improve antitumor immunity.

P1, N=19, Completed, Groupe Oncologie Radiotherapie Tete et Cou | Suspended --> Completed | N=32 --> 19 | Trial completion date: Sep 2027 --> Oct 2024 | Trial primary completion date: Sep 2026 --> Oct 2024

P1, N=423, Recruiting, ImmunoGen, Inc. | N=227 --> 423