Datopotamab Deruxtecan in Advanced or Metastatic HR+/HER2– and Triple-Negative Breast Cancer: Results From the Phase I TROPION-PanTumor01 Study

Journal of Clinical Oncology, Год журнала: 2024, Номер 42(19), С. 2281 - 2294

Опубликована: Апрель 23, 2024

Datopotamab deruxtecan (Dato-DXd) is an antibody-drug conjugate consisting of a humanized antitrophoblast cell-surface antigen 2 (TROP2) monoclonal antibody linked to potent, exatecan-derived topoisomerase I inhibitor payload via plasma-stable, selectively cleavable linker.

Язык: Английский

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Telisotuzumab Vedotin Monotherapy in Patients With Previously Treated c-Met Protein–Overexpressing Advanced Nonsquamous EGFR-Wildtype Non–Small Cell Lung Cancer in the Phase II LUMINOSITY Trial

Journal of Clinical Oncology, Год журнала: 2024, Номер 42(25), С. 3000 - 3011

Опубликована: Июнь 6, 2024

Telisotuzumab vedotin (Teliso-V) is a c-Met-directed antibody-drug conjugate with monomethyl auristatin E cytotoxic payload. The phase II LUMINOSITY trial (ClinicalTrials.gov identifier: NCT03539536) aimed to identify the optimal c-Met protein-overexpressing non-small cell lung cancer (NSCLC) population for treatment Teliso-V (stage I) and expand selected group efficacy evaluation II). Stage enrolled patients nonsquamous epidermal growth factor receptor (

Язык: Английский

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BL-B01D1, a first-in-class EGFR–HER3 bispecific antibody–drug conjugate, in patients with locally advanced or metastatic solid tumours: a first-in-human, open-label, multicentre, phase 1 study

The Lancet Oncology, Год журнала: 2024, Номер 25(7), С. 901 - 911

Опубликована: Май 29, 2024

Язык: Английский

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Datopotamab Deruxtecan Versus Docetaxel for Previously Treated Advanced or Metastatic Non–Small Cell Lung Cancer: The Randomized, Open-Label Phase III TROPION-Lung01 Study

Journal of Clinical Oncology, Год журнала: 2024, Номер unknown

Опубликована: Сен. 9, 2024

PURPOSE The randomized, open-label, global phase III TROPION-Lung01 study compared the efficacy and safety of datopotamab deruxtecan (Dato-DXd) versus docetaxel in patients with pretreated advanced/metastatic non–small cell lung cancer (NSCLC). METHODS Patients received Dato-DXd 6 mg/kg or 75 mg/m 2 once every 3 weeks. Dual primary end points were progression-free survival (PFS) overall (OS). Objective response rate, duration response, secondary points. RESULTS In total, 299 305 randomly assigned to receive docetaxel, respectively. median PFS was 4.4 months (95% CI, 4.2 5.6) 3.7 2.9 4.2) (hazard ratio [HR], 0.75 [95% 0.62 0.91]; P = .004). OS 12.9 11.0 13.9) 11.8 10.1 12.8), respectively (HR, 0.94 0.78 1.14]; .530). prespecified nonsquamous histology subgroup, 5.5 3.6 0.63 0.51 0.79]) 14.6 12.3 0.84 0.68 1.05]). squamous 2.8 3.9 1.41 0.95 2.08]) 7.6 9.4 1.32 0.91 1.92]). Grade ≥3 treatment-related adverse events occurred 25.6% 42.1% patients, any-grade adjudicated drug-related interstitial disease/pneumonitis 8.8% 4.1% groups, CONCLUSION significantly improved NSCLC, driven by histology. showed a numerical benefit but did not reach statistical significance. No unexpected signals observed.

Язык: Английский

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Datopotamab Deruxtecan Versus Chemotherapy in Previously Treated Inoperable/Metastatic Hormone Receptor–Positive Human Epidermal Growth Factor Receptor 2–Negative Breast Cancer: Primary Results From TROPION-Breast01

Journal of Clinical Oncology, Год журнала: 2024, Номер unknown

Опубликована: Сен. 12, 2024

PURPOSE The global, phase 3, open-label, randomized TROPION-Breast01 study assessed the trophoblast cell surface antigen 2–directed antibody-drug conjugate datopotamab deruxtecan (Dato-DXd) versus investigator's choice of chemotherapy (ICC) in hormone receptor–positive/human epidermal growth factor receptor 2–negative (HR+/HER2–) breast cancer. METHODS Adult patients with inoperable/metastatic HR+/HER2‒ cancer, who had disease progression on endocrine therapy, for whom therapy was unsuitable, and received one to two previous lines setting, were randomly assigned 1:1 Dato-DXd (6 mg/kg once every 3 weeks) or ICC (eribulin/vinorelbine/capecitabine/gemcitabine). Dual primary end points progression-free survival (PFS) by blinded independent central review (BICR) overall (OS). RESULTS Patients (n = 365) 367). significantly reduced risk death (PFS BICR hazard ratio [HR], 0.63 [95% CI, 0.52 0.76]; P < .0001). Consistent PFS benefit observed across subgroups. Although OS data not mature, a trend favoring (HR, 0.84 0.62 1.14]). rate grade ≥3 treatment-related adverse events (TRAEs) lower than (20.8% v 44.7%). most common TRAEs (any grade; ≥3) nausea (51.1%; 1.4%) stomatitis (50%; 6.4%) neutropenia (grouped term, 42.5%; 30.8%) ICC. CONCLUSION receiving statistically significant clinically meaningful improvement favorable manageable safety profile, compared Results support as novel treatment option cancer have this setting.

Язык: Английский

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Datopotamab Deruxtecan in Advanced or Metastatic Non–Small Cell Lung Cancer With Actionable Genomic Alterations: Results From the Phase II TROPION-Lung05 Study

Journal of Clinical Oncology, Год журнала: 2025, Номер unknown

Опубликована: Янв. 6, 2025

PURPOSE Datopotamab deruxtecan (Dato-DXd) is a trophoblast cell-surface antigen-2–directed antibody-drug conjugate with highly potent topoisomerase I inhibitor payload. The TROPION-Lung05 phase II trial (ClinicalTrials.gov identifier: NCT04484142 ) evaluated the safety and clinical activity of Dato-DXd in patients advanced/metastatic non–small cell lung cancer (NSCLC) actionable genomic alterations progressing on or after targeted therapy platinum-based chemotherapy. PATIENTS AND METHODS Patients received 6 mg/kg once every 3 weeks. primary end point was objective response rate (ORR) by blinded independent central review. Secondary points included duration (DOR), safety, tolerability, survival. RESULTS Among 137 who at least 1 dose Dato-DXd, 71.5% three lines prior therapies for disease. Overall, 56.9% had EGFR mutations 24.8% ALK rearrangements. Median treatment 4.4 months (range, 0.7-20.6). confirmed ORR 35.8% (95% CI, 27.8 to 44.4) overall, 43.6% 32.4 55.3) 23.5% 10.7 41.2) those rearrangements, respectively. median DOR 7.0 4.2 9.8), overall disease control 78.8% 71.0 85.3). Grade ≥3 treatment-related adverse events (TRAEs) occurred 28.5% patients. most common TRAE stomatitis (preferred term; any grade: 56.2%; grade ≥3: 9.5%). Five (3.6%) experienced adjudicated interstitial disease/pneumonitis, (0.7%) 5 event. CONCLUSION Encouraging durable antitumor observed this heavily pretreated NSCLC population alterations. toxicities comparable previous observations, no new signals were observed.

Язык: Английский

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Clinical management, monitoring, and prophylaxis of adverse events of special interest associated with datopotamab deruxtecan

Cancer Treatment Reviews, Год журнала: 2024, Номер 125, С. 102720 - 102720

Опубликована: Март 11, 2024

Antibody drug conjugates (ADCs) are an emerging class of treatments designed to improve efficacy and decrease toxicity compared with other systemic therapies through the selective delivery cytotoxic agents tumor cells. Datopotamab deruxtecan (Dato-DXd) is a novel ADC comprising topoisomerase I inhibitor payload monoclonal antibody directed trophoblast cell-surface antigen 2 (TROP2), protein that broadly expressed in several types solid tumors. Dato-DXd being investigated across multiple indications. In ongoing, first-in-human TROPION-PanTumor01 phase study (ClinicalTrials.gov: NCT03401385), encouraging durable antitumor activity manageable safety profile was demonstrated patients advanced/metastatic hormone receptor-positive/human epidermal growth factor receptor 2-negative breast cancer (HR+/HER2– BC), triple-negative (TNBC), non-small cell lung (NSCLC). Improved understanding adverse events (AEs) associated their optimal management essential ensure safe successful administration. Interstitial disease/pneumonitis, infusion-related reactions, oral mucositis/stomatitis, ocular surface have been identified as AEs special interest (AESIs) for which appropriate prevention, monitoring, essential. This article summarizes incidence AESIs among HR+/HER2 − BC, TNBC, NSCLC reported TROPION-PanTumor01. We report our recommendations AESI prophylaxis, early detection, management, using experience gained from treating occur clinical trials.

Язык: Английский

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Trop2-targeted therapies in solid tumors: advances and future directions

Theranostics, Год журнала: 2024, Номер 14(9), С. 3674 - 3692

Опубликована: Янв. 1, 2024

Trophoblast cell surface antigen 2 (Trop2) is overexpressed in a range of solid tumors and participants multiple oncogenic signaling pathways, making it an attractive therapeutic target. In the past decade, rapid development various Trop2-targeted therapies, notably marked by advent antibody-drug conjugate (ADC), revolutionized outcome for patients facing Trop2-positive with limited treatment opinions, such as triple-negative breast cancer (TNBC). This review provides comprehensive summary advances including ADCs, antibodies, multispecific agents, immunotherapy, vaccines, small molecular inhibitors, along in-depth discussions on their designs, mechanisms action (MOAs), limitations. Additionally, we emphasize clinical research progress these emerging focusing application efficacy against tumors. Furthermore, propose directions future research, enhancing our understanding Trop2's structure biology, exploring best combination strategies, tailoring precision based Trop2 testing methodologies.

Язык: Английский

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Emerging Targeted Therapies in Non-Small-Cell Lung Cancer (NSCLC)

Cancers, Год журнала: 2025, Номер 17(3), С. 353 - 353

Опубликована: Янв. 22, 2025

Targeted therapies have changed the treatment landscape of non-small-cell lung cancer and led to improved patient survival across all stages cancer. Newer advances in common novel oncogenic drivers continue occur at vigorous speed, making it challenging stay up date with rapidly evolving field. In this article, we review emerging perspectives actionable targets We focus on development newer KRAS-directed therapies, particularly non-G12C mutations, pan-RAS inhibitors, RAS-GTP inhibitors. also describe current standard care for EGFR- ALK-altered NSCLC dive into treatments expected be clinic soon. A similar approach is taken toward MET, HER2, RET, ROS1, FGFR alterations as Finally, conclude body evidence targeting TROP-2 a target, potentially importance post-targeted therapy scenarios.

Язык: Английский

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Management of nausea and vomiting induced by antibody–drug conjugates

Breast Cancer, Год журнала: 2025, Номер unknown

Опубликована: Янв. 29, 2025

Язык: Английский

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