Trodelvy (sacituzumab govitecan-hziy) / Everest Medicines, Gilead - LARVOL DELTA

Early Access Program in oncology: Retrospective study at a Portuguese hospital (ECOP 2024) - "During the study period were submitted 163 EAP requests for abiraterone, amivantamab, bevacizumab, durvalumab, encorafenib, enfortumab, everolimus, erdafitinib, lenvatinib, lurbinectedin, niraparib, nivolumab, olaparib, pembrolizumab, pertuzumab, ramucirumab, sacituzumab govitecan, selpercatinib, trifluridine/tipiracil, trametinib+dabrafenib, trastuzumab-deruxtecan and tucatinib. Conclusion Most cases correspond to metastatic disease, EAPs facilitate timely access to innovative therapies for patients with high unmet medical needs. The majority of situations were financed, which confirms the importance of EAPs in an era where oncology is constantly innovating."

Retrospective data • Gastrointestinal Disorder • Oncology

MORPHEUS mUC: Study Evaluating the Efficacy and Safety of Multiple Immunotherapy-Based Treatments and Combinations in Patients With Urothelial Carcinoma (MORPHEUS-UC) (clinicaltrials.gov) - P1/2 | N=645 | Active, not recruiting | Sponsor: Hoffmann-La Roche | Recruiting ➔ Active, not recruiting | Trial completion date: Nov 2027 ➔ May 2026

Enrollment closed • Trial completion date • Bladder Cancer • Genito-urinary Cancer • Oncology • Solid Tumor • Urothelial Cancer • PD-L1

Disparities in urothelial carcinoma (UC) drug approval: Contrasting North America and Europe (ESMO 2024) - "All countries approved antiPD-1/PDL1 therapy in second-line (2L) and maintenance avelumab (AVE) in first-line (1L-M). Only POR did not approve adjuvant (adj) nivolumab (NIVO)...In third-line (3L), erdafitinib (ERDA) and enfortumab vedotin (EV) were approved only in 3 and 4 countries, respectively...Abbreviations: ATEZO: atezolizumab, CGP: cisplatin-based plus PEM, EVP: efortumab-vedotin plus PEM, NFV: nadofaragene firadenovec, SG: Sacituzumab-govitecan, and Y: yes... The US led in drugs approvals for UC, followed by CAN and FRA. Significant disparities were observed across Europe, even for drugs with SCB. Additionally, most of indications lacked evidence on OS, QoL, or SCB."

Bladder Cancer • Oncology • Solid Tumor • Urothelial Cancer

PMDA regulatory update on approval and revision of the precautions for use of anticancer drugs; approval of sacituzumab govitecan for breast cancer, fruquintinib for colorectal cancer, amivantamab for lung cancer, repotrectinib for lung cancer, tasurgratinib for biliary tract cancer, enfortumab vedotin plus pembrolizumab for urothelial cancer, and dabrafenib plus trametinib for glioma in Japan. (PubMed, Int J Clin Oncol) - No abstract available

Japanese regulatory • Journal • Biliary Cancer • Biliary Tract Cancer • Brain Cancer • Breast Cancer • CNS Tumor • Colorectal Cancer • Gastrointestinal Cancer • Genito-urinary Cancer • Glioma • Lung Cancer • Oncology • Solid Tumor • Urothelial Cancer

Phase I/II study of ipilimumab plus nivolumab combined with sacituzumab govitecan in patients with metastatic cisplatin-ineligible urothelial carcinoma (ESMO 2024) - P1/2 | "SG and pembrolizumab is safe and active following PBC. The combination of IPI-NIVO with SG at 8mg/kg is active in cisplatin-ineligible mUC. However, the trial was terminated early due to higher than anticipated grade 5 toxicities. Correlative studies are underway to determine biomarkers for activity and severe myocarditis."

Clinical • IO biomarker • Metastases • P1/2 data • Oncology • Solid Tumor • Urothelial Cancer

Gilead Provides Update on U.S. Indication for Trodelvy in Metastatic Urothelial Cancer (Gilead Press Release) - "Gilead Sciences, Inc. today announced plans to voluntarily withdraw the U.S. accelerated approval for Trodelvy (sacituzumab govitecan-hziy; SG) for the treatment of adult patients with locally advanced or metastatic urothelial cancer who have previously received a platinum-containing chemotherapy and either programmed death receptor-1 (PD-1) or programmed death-ligand 1 (PD-L1) inhibitor. This decision was made in consultation with the U.S. Food and Drug Administration (FDA). This decision does not affect the other approved Trodelvy indications within or outside of the U.S....Continued approval for this indication was contingent on verification and description of clinical benefit in the confirmatory TROPiCS-04 study. As previously announced, the TROPiCS-04 study did not meet the primary endpoint of overall survival (OS) in the intention-to-treat (ITT) population. These data will be presented at an upcoming medical meeting."

FDA event • Urothelial Cancer

TROP2 Expression and Therapeutic Implications in Cutaneous Squamous Cell Carcinoma: Insights From Immunohistochemical and Functional Analysis. (PubMed, Exp Dermatol) - "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."

IO biomarker • Journal • Genetic Disorders • Non-melanoma Skin Cancer • Oncology • Skin Cancer • Squamous Cell Carcinoma • Squamous Cell Skin Cancer • BCL2 • CCND1 • TACSTD2 • VIM

Large-Scale ADC Efficacy Testing in an Organoid Drug Screening Platform Highlights the Need for Functional Assays to Predict Tumor Sensitivity (EORTC-NCI-AACR 2024) - "Here, an organoid-based ADC testing platform is presented, combining the strength of patient-derived organoids with our advanced 3D high content imaging (HCI) platform.METHODSThe efficacy of two FDA-approved ADCs, Kadcyla (traztuzumab emtansine[DM1]) and Trodelvy (sacituzumab govitecan[SN-38]), was determined in 50 NGS characterized (WES, RNA-seq) organoid models, spanning 7 indications including tumor and normal models. It offers insight into the lack of correlation between ADC target mRNA expression levels and efficacy, and highlights that functional screening is essential for preclinical ADC development. Ultimately, the platform comes with the unique possibility to expand characterization to patient stratification and biomarker discovery."

Clinical • Oncology

Prevalence of treatment-related adverse events (TRAEs) with antibody-drug conjugates in metastatic breast cancer patients: a systematic review and meta-analysis. (PubMed, Crit Rev Oncol Hematol) - "Gastrointestinal disorders were highly prevalent during Trastuzumab Deruxtecan, general disorders were extremely common during Trastuzumab Emtansine, and blood system disorders and gastrointestinal disorders were the most prevalent during Sacituzumab Govitecan. Despite each ADC having specific toxicities, gastrointestinal symptoms were highly prevalent in all treatments. This study lays the groundwork for developing personalized risk-stratified care pathways."

Adverse events • Journal • Metastases • Retrospective data • Review • Breast Cancer • Gastroenterology • Gastrointestinal Disorder • Oncology • Solid Tumor

Assessing interstitial lung disease (ILD) risk in metastatic breast cancer (MBC): A comprehensive meta and network analysis of antibody-drug conjugates (ADCs) compared to available treatment options beyond first-line (1L) (ESMO 2024) - "Furthermore, a greater ILD risk was observed in pts treated with ADCs such as Trastuzumab-emtansine (T-DM1), Trastuzumab-deruxtecan (T-DXd), Trastuzumab-duocarmazine (T-Duo), Sacituzumab govitecan (SG), and Datopotamab-deruxtecan (Dato-DXd) compared to endocrine therapy (ET), chemotherapy (CT) and target therapy [including TKIs like lapatinib/neratinib/tucatinib and PARP inhibitors (PARPi)] (5.55% incidence in ADCs group vs 0.39% in non-ADC group, 95% CI: 2.45-12.09; p-value <0.0001). Pts treated with ADCs demonstrated a higher risk of ILD compared to those receiving ET, TKIs, PARPi, and CT, including regimens containing everolimus. These data may inform treatment and monitoring decision making, especially for pts with respiratory risk factors."

Clinical • Metastases • Breast Cancer • Oncology • Solid Tumor • HER-2

ASCENT-03: Study of Sacituzumab Govitecan-hziy Versus Treatment of Physician's Choice in Patients With Previously Untreated Locally Advanced Inoperable or Metastatic Triple-Negative Breast Cancer (clinicaltrials.gov) - P3 | N=540 | Recruiting | Sponsor: Gilead Sciences | Trial completion date: May 2027 ➔ Jul 2028 | Trial primary completion date: May 2027 ➔ Jul 2028

Metastases • Trial completion date • Trial primary completion date • Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • PD-L1

A Phase II Trial of Sacituzumab Govitecan (IMMU-132) (NSC #820016 ) for Patients with HER2-Negative Breast Cancer and Brain Metastases (SWOG-Fall 2024) - "Participants may have received systemic therapy, noncytotoxic hormonal therapy, anti-cancer biologic agents, nitrosoureas or mitomycin C, metronomic/protracted low-dose chemotherapy, other cytotoxic chemotherapy, or enzyme-inducing antiepileptic agents per timing specified in the protocol...Participants must not be receiving or planning to receive enzyme-inducing anti-epileptic agents, warfarin, or any concomitant anti-cancer therapy while on protocol treatment. Participants must not require ongoing systemic treatment with corticosteroids (>4 mg daily dexamethasone or bioequivalent) or other immunosuppressive medications Participants must be offered the opportunity to participate in specimen banking for future studies...Among the 21 patients evaluated for adverse events, five patients experienced Grade 4 treatment-related adverse events, four with decreased neutrophil count (including one patient who experienced leukopenia and lymphopenia as well) and one with sepsis...."

Clinical • P2 data • Brain Cancer • Breast Cancer • CNS Disorders • Diabetes • Epilepsy • Hematological Disorders • Hepatitis C • HER2 Breast Cancer • HER2 Negative Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Breast Cancer • Human Immunodeficiency Virus • Infectious Disease • Leukopenia • Metabolic Disorders • Oncology • Septic Shock • Solid Tumor • HER-2

A Phase III Randomized Trial of Eribulin (NSC #707389) with Gemcitabine versus Standard of Care (Physician’s Choice) for Treatment of Metastatic Urothelial Carcinoma Refractory to, or Ineligible for, Anti PD1/PDL1 Therapy (SWOG-Fall 2024) - "Participants will be described by physician’s planned choice of chemotherapy regimen: docetaxel vs gemcitabine vs paclitaxel vs sacituzumab govitecan. The study was redesigned and reopened on February 15, 2024 with only two arms, physician’s choice chemotherapy and eribulin + gemcitabine. The eribulin alone arm was permanently closed to accrual at this time, and the eight participants enrolled to this arm will not be reported in the Report of Studies going forward."

Clinical • Metastases • P3 data • Hematological Disorders • Human Immunodeficiency Virus • Infectious Disease • Oncology • Septic Shock • Solid Tumor • Urothelial Cancer

Intraoperative evaluation of tumor margins using a TROP2 near-infrared imaging probe to enable human breast-conserving surgery. (PubMed, Sci Transl Med) - "We demonstrated that the intensity of PET signals in the tumors was nearly five times higher than in normal breast tissue with a zirconium-89 tracer conjugated to sacituzumab govitecan (SG) in a mouse spontaneous breast cancer model, enabling the identification of tumors...Moreover, the rapid incubation imaging method was applied to distinguish benign and malignant breast lesions in samples from 26 patients with breast cancer. Therefore, we have developed both nuclide and optical probes targeting TROP2 for rapid and precise identification of tumor margins during breast-conserving surgery in humans."

Journal • Surgery • Breast Cancer • Oncology • Solid Tumor

NCCN has published updates to the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) and the NCCN Drugs & Biologics Compendium (NCCN Compendium) for Hematopoietic Growth Factors,Version 1.2025. (NCCN)

NICE • Breast Cancer • Hodgkin Lymphoma • Ovarian Cancer

Sacituzumab Govitecan in the Treatment of Recurrent Triple-Negative Breast Cancer in a Patient with HRD-Positive and BRCA1/2 Wild-Type Germline: A Case Report (ESMO Asia 2024) - No abstract available

Case report • Clinical • Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • BRCA1 • BRCA2 • HRD

Neoadjuvant Sacituzumab Govitecan, followed by radical cystectomy, for Patients With Muscle-Invasive Bladder Cancer (MIBC): Updated Interim Results of SURE-01 trial (ESMO Asia 2024) - No abstract available

Clinical • Bladder Cancer • Genito-urinary Cancer • Oncology • Solid Tumor

Safety analysis of pooled data on sacituzumab govitecan (Sg) in different types of solid tumors (DGHO 2024) - P1/2, P2, P3 | "The pooled safety results were consistent with previous clinical trials, where neutropenia was the most common grade ≥3 TEAE. Neutropenia and diarrhea were generally manageable, and limited TEAEs led to discontinuation. The *28/*28 UGT1A1 genotype was associated with higher rates of grade ≥ 3 TEAEs, as previously observed."

Clinical • Anemia • Breast Cancer • Fatigue • Febrile Neutropenia • Genito-urinary Cancer • Hematological Disorders • HER2 Breast Cancer • HER2 Positive Breast Cancer • Infectious Disease • Leukopenia • Neutropenia • Oncology • Pneumonia • Respiratory Diseases • Solid Tumor • Triple Negative Breast Cancer • Urothelial Cancer • HER-2 • UGT1A1

SAGA - a single-arm, multicenter phase Ib/ll study with sacituzumab govitecan for the treatment of patients with metastatic gastroesophageal adenocarcinoma (Trial in Progress) (DGHO 2024) - P1/2 | "Patients can be treated in the second line setting or in later lines but are not eligible if they have previously received a topoisomerase inhibitor, e.g. irinotecan or nal-irinotecan. After a run-in phase of 20 patients, safety and efficacy will be evaluated and the trial will proceed to a recruitment goal of 56 patients when at least two tumor responses are documented in the run-in phase. A hypothesis of an ORR of 16% is tested against a null hypothesis of an ORR of 5%."

Clinical • IO biomarker • Metastases • Esophageal Adenocarcinoma • Esophageal Cancer • Gastric Adenocarcinoma • Gastric Cancer • Gastroesophageal Junction Adenocarcinoma • Gastrointestinal Cancer • Oncology • Solid Tumor • TACSTD2

Expression and therapeutic potential of TROP-2 in cisplatin-resistant non-seminomatous germ cell tumors (DGHO 2024) - "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."

Embryonal Tumor • Germ Cell Tumors • Oncology • Solid Tumor • TACSTD2

Evaluation of circulating TROP2 in patients of the Molecular Tumor Board at the UCCSH (DGHO 2024) - "Introduction: The antibody-drug-conjugate sacituzumab govitecan (SG) targets the transmembrane glycoprotein TROP2... This project aims to improve the prediction of therapy response to TROP2-targeted therapies. 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."

Clinical • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • TACSTD2

A meta-analysis of health-related quality of life outcomes of sacituzumab govitecan compared with physician's choice from the Phase III TROPiCS-02 and EVER-132-002 trials (DGHO 2024) - "Conclusions : This meta-analysis of two phase III RCTs demonstrated superior HRQoL outcomes for SG vs TPC, confirming the generalizability of each trial individually. These findings support the use of SG as a standard of care for pretreated, endocrine-resistant HR+/HER2- MBC irrespective of previously treated CDK4/6i exposure."

HEOR • P3 data • Retrospective data • Breast Cancer • Fatigue • HER2 Breast Cancer • HER2 Positive Breast Cancer • Oncology • Pain • Pulmonary Disease • Solid Tumor • HER-2

ORIENTA: Organoid-based Functional Precision Therapy for Advanced Breast Cancer (clinicaltrials.gov) - P2 | N=252 | Recruiting | Sponsor: Guangdong Provincial People's Hospital | Initiation date: Jan 2024 ➔ Sep 2024

Metastases • Trial initiation date • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Negative Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • ER • HER-2 • PGR

TOPOISOMERASE I INHIBITING ANTIBODY-DRUG-CONJUGATES SYNERGIZE WITH POLY(ADP-RIBOSE) POLYMERASE INHIBITORS IN TRIPLE NEGATIVE BREAST CANCER (IGCS 2024) - "Two ADCs are approved for TNBC: Sacituzumab govitecan-hziy (SG) and trastuzumab deruxtecan (T-DXd). The combination of each ADC (SG and T-DXd) with PARP inhibitors (olaparib, talazoparib, saruparib) were synergistic across the TNBC panel. Further functional analysis is currently ongoing investigating apoptosis induction and DNA-damaging effects of the combinations. Conclusion/Implications: The combination of TOP1 inhibiting ADCs with DNA-damaging therapies is synergistic, enhancing target therapies for TNBC patients; providing a rationale for further investigation."

IO biomarker • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • HER-2 • TOP1

WIN-B: Clinical Study to Evaluate Debio0123 + Sacituzumab Govitecan Combination in TNBC or HR+/HER2- Advanced Breast Cancer (clinicaltrials.gov) - P1/2 | N=76 | Not yet recruiting | Sponsor: MedSIR

Combination therapy • Metastases • New P1/2 trial • Breast Cancer • HER2 Breast Cancer • Hormone Receptor Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • HER-2