- |||||||||| datopotamab deruxtecan (DS-1062a) / Daiichi Sankyo, AstraZeneca
P3 data, Journal, PD(L)-1 Biomarker, IO biomarker, Metastases: TROPION-Lung07: Phase III study of Dato-DXd (Pubmed Central) - Nov 16, 2024 P3 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).
- |||||||||| Trodelvy (sacituzumab govitecan-hziy) / Gilead
Clinical, Review, Journal: Sacituzumab Govitecan in Triple Negative Breast Cancer: A Systematic Review of Clinical Trials. (Pubmed Central) - Nov 15, 2024 The efficacy results showed a significantly greater clinical benefit with sacituzumab govitecan compared to standard chemotherapy in patients with triple-negative breast cancer. This drug will become a treatment of substantial impact in future treatment guidelines for this type of cancer.
- |||||||||| Journal: Modulating autophagy to boost the antitumor efficacy of TROP2-directed antibody-drug conjugate in pancreatic cancer. (Pubmed Central) - Nov 13, 2024
In the subcutaneous xenograft model using BxPC3 cells, the combined administration of ?TROP2-MMAE and an autophagy inhibitor elevated the tumor inhibition rate of ?TROP2-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.
- |||||||||| Trodelvy (sacituzumab govitecan-hziy) / Gilead
Journal, IO biomarker: Genomic, immunologic, and prognostic associations of TROP2 (TACSTD2) expression in solid tumors. (Pubmed Central) - Nov 13, 2024 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. TACSTD2 expression is associated with key driver alterations and a more active immune microenvironment, suggesting possible combinatorial strategies with TROP2-targeting ADCs plus immunotherapy in various solid tumors.
- |||||||||| datopotamab deruxtecan (DS-1062a) / Daiichi Sankyo, AstraZeneca
Biomarker, Enrollment closed, Trial completion date, Trial primary completion date, Metastases: ICARUS-LUNG01: Datopotamab Deruxtecan (Dato-DXd, DS-1062a) in Advanced and/or Unresectable Non-Small Cell Lung Cancer (clinicaltrials.gov) - Nov 7, 2024 P2, N=100, Active, not recruiting, Clinical studies on efficacy of novel treatment modalities such as PD-L1 inhibition or ADCs are urgently needed in this highly aggressive bladder cancer population. Recruiting --> Active, not recruiting | Trial completion date: Nov 2025 --> Mar 2028 | Trial primary completion date: Nov 2022 --> Mar 2025
- |||||||||| Review, Journal: The clinical landscape of antibody-drug conjugates in endometrial cancer. (Pubmed Central) - Nov 4, 2024
We focused particularly on the most promising antibody-drug conjugate targets in endometrial cancer under clinical investigation, such as human epidermal growth factor receptor 2 (HER2), folate receptor alpha (FR?), trophoblast cell-surface antigen-2 (TROP2), and B7-H4. We also briefly comment on the challenges, including the emergence of resistance mechanisms, and future development directions (especially agents targeting multiple antigens, combinatorial strategies, and sequential use of agents targeting the same antigen but using different payloads) in antibody-drug conjugate therapy for endometrial cancer.
- |||||||||| Review, Journal: Advances in Vulvar Cancer Biology and Management. (Pubmed Central) - Oct 31, 2024
Molecular-based preclinical models and rationally designed clinical trials, incorporating high-quality translational studies, are urgently required. These trials will require international collaboration to ensure feasibility and improvement of outcomes for women diagnosed with this disease.
- |||||||||| Journal: Antibody-drug conjugates as targeted therapy for treating gynecologic cancers: update 2025. (Pubmed Central) - Oct 31, 2024
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.
- |||||||||| Review, Journal: Antibody-Drug Conjugates in Breast Cancer: Toward a Molecular Perspective Into Clinical Practice. (Pubmed Central) - Oct 30, 2024
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.
- |||||||||| Trodelvy (sacituzumab govitecan-hziy) / Gilead
Journal, BRCA Biomarker, PARP Biomarker, PD(L)-1 Biomarker, IO biomarker: The evolution of a luminal breast cancer to a triple-negative and its impact on disease control with sacituzumab govitecan. (Pubmed Central) - Oct 24, 2024 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.
- |||||||||| Trodelvy (sacituzumab govitecan-hziy) / Gilead
Evaluation of circulating TROP2 in patients of the Molecular Tumor Board at the UCCSH (Guangzhou) - Oct 13, 2024 - Abstract #DGHO2024DGHO_1542; Additional factors such as tumor heterogeneity, shedding of TROP2, longitudinal regulation of TROP2 expression, as well as optimal sampling conditions for protein stabilization are considered and will be further explored using analysis of tissue and longitudinal plasma samples of patients receiving treatment with SG. By this means, we aim to investigate the significance of LB-based proteome analysis as a complementary tool for precision medicine.
- |||||||||| cisplatin / Generic mfg.
Expression and therapeutic potential of TROP-2 in cisplatin-resistant non-seminomatous germ cell tumors (Boston) - Oct 13, 2024 - Abstract #DGHO2024DGHO_698; Our objective was to evaluate the expression of TROP-2 in cisplatin-resistant non-seminomatous GCT metastases [MET(-R)] and to assess the cytotoxic efficacy of the anti-TROP-2 ADC Sacituzumab govitecan (SG) in non-seminomatous GCT cell lines. In summary, we identified TROP-2 as a putative target for patients with cisplatin refractory CC and TER, highlighting the potential benefit of TROP-2-directed ADCs such as SG for GCT patients with TROP-2 positivity.
- |||||||||| Journal: Selection of trophoblast cell surface antigen 2-targeted aptamer for the development of cytotoxic aptamer-drug conjugate. (Pubmed Central) - Oct 11, 2024
Significant cytotoxicity against HT29 cell by the conjugate of trophoblast cell surface antigen 2 aptamer and Emtansine was observed while resulting negligible therapeutic effect on human normal intestinal epithelial cell line HIEC in vitro, indicating that the conjugate shows potential as a promising therapeutic agent. Furthermore, the isolated aptamer demonstrated the ability for the targeted delivery, resulting excellent therapeutic effectiveness of aptamer-drug conjugate for xenograft tumor model of mice with human colorectal cancer.
- |||||||||| Trodelvy (sacituzumab govitecan-hziy) / Gilead
A TROP2/Claudin program mediates immune exclusion to impede checkpoint blockade in breast cancer (George R. Brown Convention Center - Level 3 - Grand Ballroom B) - Oct 4, 2024 - Abstract #SITC2024SITC_1485; Employing a humanized TROP2 syngeneic TNBC model, we show that TROP2 targeting via Sacituzumab govitecan (SG) induces an anti-PD1 response associated with broad immune cell activation, and TROP2 is highly associated with lack of response to anti-PD1 therapy in human breast cancer. Conclusions TROP2 mediates immune exclusion and may be targeted to enhance immunotherapy response.
- |||||||||| volrustomig (MEDI5752) / AstraZeneca
Enhanced in vitro T cell activation and cytotoxicity induced by a TROP2 ADC conjugated to the novel topoisomerase payload AZ14170133 in lung adenocarcinoma cells (Exhibit Halls AB - George R. Brown Convention Center) - Oct 4, 2024 - Abstract #SITC2024SITC_787; Co-cultures of primary MART-1-specific CD8 T cells and tumor cells with a tool TROP2 ADC (hRS7) conjugated with a novel topoisomerase 1 inhibitor payload AZ14170133, volrustomig (PD1/CTLA4 monovalent bispecific antibody), or in combination...Our study highlights an innovative approach to understanding the complex interplay between ADCs, immune cells, and tumor cells, with potential implications for the development of more effective ADC/IO combination treatment strategies. Ethics Approval Human materials used in the study were acquired from approved commercial vendors from donors who gave informed consent in accordance with AstraZeneca guidelines as determined by AstraZeneca human biological samples governance.
- |||||||||| Herceptin (trastuzumab) / Roche
The anti-tumor activity of a novel anti-Her2/anti-Trop2 bispecific VHH antibody-drug conjugate (ADC) (Exhibit Halls AB - George R. Brown Convention Center) - Oct 4, 2024 - Abstract #SITC2024SITC_782; The potency of its cytotoxic effect was comparable to Trastuzumab-MMAE (T-MMAE) in high Her2-expressing cancer cells and to hRS7-MMAE in high Trop2-expressing cancer cells.The in vivo efficacy of BB-201 was evaluated in an A431 model...Conclusions The novel anti-Her2/anti-Trop2 bispecific ADC BB-201 has superior anti-tumor activity in preclinical studies. BB-201 has a promising therapeutic potential as a first-in-class ADC drug candidate.
- |||||||||| ImmunoPET imaging of 89Zr-labeled antiTrop2 monoclonal antibody in lung cancer models (e-Poster Area) - Sep 27, 2024 - Abstract #EANM2024EANM_2462;
This study successfully developed a Trop2-targeted immunoPET probe, facilitating precise visualization of Trop2 and aiding in the diagnosis of lung cancer. The findings suggest strong potential for clinical translation and offer a promising diagnostic approach for Trop2-overexpressing tumors, including lung cancer.
- |||||||||| Trodelvy (sacituzumab govitecan-hziy) / Gilead
Review, Journal, Adverse events, Metastases: Canadian Expert Recommendations on Safety Overview and Toxicity Management Strategies for Sacituzumab Govitecan Based on Use in Metastatic Triple-Negative Breast Cancer. (Pubmed Central) - Sep 27, 2024 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.
- |||||||||| Trodelvy (sacituzumab govitecan-hziy) / Gilead
Enrollment open, Metastases: SETHY: Sacituzumab govitEcan in THYroid Cancers (clinicaltrials.gov) - Sep 25, 2024 P2, N=42, Recruiting, In summary, through mass spectrometry-based quantitative temporal proteomics, we identify proteomic adaptations to KRASi in PDAC and propose combination treatments with promising therapeutic potential. Not yet recruiting --> Recruiting
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