Yondelis (trabectedin) / Otsuka, PharmaMar, Valeo Pharma, J&J, Specialised Therap, Taiho - LARVOL DELTA

Palliative Stereotactic Body Radiotherapy for Metastatic Clear Cell Sarcoma: A Case Report. (PubMed, Cureus) - "He had undergone seven surgical resections and chemotherapy (trabectedin and pazopanib) for the primary tumor and metastatic lesions. While receiving trabectedin therapy, he was referred to our facility for palliative radiotherapy. This was due to the rapid enlargement of a metastatic lesion in the right thigh. His symptom was pain in the right lower extremity. CT imaging performed seven weeks after SBRT showed further shrinkage of both lesions. The pain did not recur until the patient died of renal failure two months after SBRT. No adverse events occurred during the clinical course. SBRT may be a viable palliative treatment option for CCS."

Journal • Oncology • Pain • Palliative care • Renal Disease • Sarcoma • Solid Tumor

Final results of a randomized phase II trial of second-line treatment for advanced soft tissue sarcoma comparing trabectedin, eribulin, and pazopanib: 2ND-STEP study, JCOG1802. (ASCO 2026) - "Funded by Japan Agency for Medical Research and Development (AMED) Clinical Trial Registration Number: jRCTs031190152 Background: The optimal second-line treatment for advanced soft tissue sarcomas (STS) after doxorubicin therapy remains unclear. This trial aimed to identify the most promising agent among trabectedin, eribulin, and pazopanib for subsequent phase III comparison against gemcitabine plus docetaxel (GD), which has traditionally been considered a standard treatment... Consistent with the primary analysis, pazopanib generally showed favorable PFS, OS, and DCR among the three agents. Based on these results, pazopanib was identified as the most appropriate candidate to be compared with GD in a phase III trial, which is currently being planned."

Clinical • Metastases • P2 data • Leiomyosarcoma • Liposarcoma • Sarcoma • Soft Tissue Sarcoma • Solid Tumor

Association of Prior Local Therapy with Outcomes Within Systemic Therapy Regimen Cohorts in Advanced Soft Tissue Sarcoma: A Retrospective Cohort Study. (PubMed, Cancers (Basel)) - " This retrospective cohort included 75 patients with recurrent or metastatic STS who contributed 155 treatment episodes: doxorubicin (n = 44), trabectedin (n = 31), pazopanib (n = 42), and eribulin (n = 38). No between-regimen differences were formally tested. These findings support individualized multidisciplinary assessment and external validation."

Journal • Retrospective data • Leiomyosarcoma • Oncology • Sarcoma • Soft Tissue Sarcoma • Solid Tumor

SARC037: Results of phase I study of trabectedin given as a 1-hour (h) infusion in combination with low dose irinotecan in relapsed/refractory Ewing sarcoma (ES). (ASCO 2023) - P1/2 | "T+I can be safely administered to heavily pretreated pts with ES, demonstrating activity at the RD with 3 PRs (n=5 evaluable). The 18F-FLT PET may be useful to understand patterns of disease progression in ES. Correlative studies will be critical to understanding the mechanism of drug activity."

Combination therapy • P1 data • Anemia • Ewing Sarcoma • Febrile Neutropenia • Hematological Disorders • Neutropenia • Oncology • Sarcoma • Solid Tumor • Thrombocytopenia • FLI1

Doxorubicin-Trabectedin in Leiomyosarcoma. (PubMed, N Engl J Med) - No abstract available

Journal • Leiomyosarcoma • Oncology • Sarcoma • Solid Tumor

Toxicity and efficacy characterization of doxorubicin and trabectedin association versus doxorubicin alone in patients over 70 years with leiomyosarcoma: Analysis from LMS02 and LMS04 studies. (ASCO 2026) - "For pts over 70 yo, the efficacy of the combination Doxo+Trab followed by trabectedin maintenance in advanced LMS in the first line setting, as measured by PFS and OS, did not differ from that in younger patients. Toxicity analysis suggests that age alone is not a limiting factor for this combination. Therefore, age-related frailty should not prevent patients from receiving a potentially life-prolonging treatment."

Clinical • Febrile Neutropenia • Hematological Disorders • Leiomyosarcoma • Neutropenia • Sarcoma • Solid Tumor

SARC041: A phase 3 randomized double-blind study of abemaciclib versus placebo in patients with advanced dedifferentiated liposarcoma. (ASCO 2026) - P3 | "Approved drugs offer modest benefit such as trabectedin (median progression-free survival [mPFS] 2.2 months [m]) or eribulin (mPFS 2.0m)...In single-arm phase 2 studies, treatment with selective CDK4 inhibitors resulted in mPFS 4.2m with palbociclib and mPFS 7.7m with abemaciclib... Abemaciclib demonstrated a statistically significant improvement in PFS vs placebo in pts with dedifferentiated liposarcoma, with an encouraging OS trend. These results support abemaciclib as a new treatment option for dedifferentiated liposarcoma."

Clinical • Late-breaking abstract • Metastases • P3 data • Liposarcoma • Sarcoma • Solid Tumor

PHASE II MULTI-CENTER TRIAL OF TRABECTEDIN IN COMBINATION WITH OLAPARIB IN ADVANCED UNRESECTABLE OR METASTATIC SARCOMA (CTOS 2022) - No abstract available

Clinical • Combination therapy • P2 data • Oncology • Sarcoma • Solid Tumor

Safety and pharmacokinetics (PK) of lurbinectedin (lurbi) in pediatric patients (pts) with relapsed/refractory (R/R) solid tumors and preliminary antitumor activity in pediatric and young adult pts with R/R Ewing sarcoma (EwS): Results from a phase 1 study. (ASCO 2026) - P1/2 | "Lurbi is a trabectedin analogue that alkylates DNA and blocks transcription of EWS-FLI1, a primary driver of EwS. Based on these data, lurbi had a manageable safety profile, predictable PK properties, and encouraging preliminary clinical activity in pts with R/R EwS. Phase 2 expansion in pts ≤30 y with R/R EwS is ongoing. TRAEs in all pts and by dose."

Clinical • P1 data • PK/PD data • Acute Kidney Injury • Ewing Sarcoma • Nephrology • Oncology • Osteosarcoma • Pediatrics • Renal Disease • Respiratory Diseases • Sarcoma • Solid Tumor • EWSR1 • FLI1

Trabectedin with concomitant radiotherapy in resectable retroperitoneal L-sarcoma: A multicenter, prospective, phase I/II trial—A collaborative study by the Spanish (GEIS), Italian (ISG), and French (FSG) groups. (ASCO 2026) - P1/2 | "Preoperative concurrent T and RT was feasible and safe for resectable retroperitoneal L-sarcomas, yielding density responses in over 25% of pts and promising survival outcomes. A phase III trial is warranted to compare this regimen against RT alone. Clinical trial information: NCT02275286."

Clinical • P1/2 data • Febrile Neutropenia • Hematological Disorders • Leiomyosarcoma • Leukopenia • Neutropenia • Retroperitoneal Sarcoma • Sarcoma • Solid Tumor • Thrombocytopenia

Results of a phase I/II combination regimen with ipilimumab (I), nivolumab (N) and trabectedin (T) as first line therapy for advanced leiomyosarcoma (ESMO 2022) - P1/2 | "Conclusions Taken together, these data suggest that first-line combinatorial therapy with Ipilimumab, Nivolumab and Trabectedin may be (1) More effective than standard first line therapy, and (2) Safer than standard first line therapy for advanced LMS. Randomized Phase 2 studies are planned to confirm these findings."

Clinical • P1/2 data • Leiomyosarcoma • Oncology • Sarcoma • Soft Tissue Sarcoma • Solid Tumor

Neoadjuvant Chemotherapy in High-Risk Soft Tissue Sarcomas: Final Results of a Randomized Trial From Italian (ISG), Spanish (GEIS), French (FSG), and Polish (PSG) Sarcoma Groups. (PubMed, J Clin Oncol) - P3 | "In a population of patients with localized high-risk STS, HT was not associated with a better DFS or OS, suggesting that A+I should remain the regimen to choose whenever neoadjuvant chemotherapy is used in patients with high-risk STS."

Clinical • Journal • Leiomyosarcoma • Oncology • Sarcoma • Solid Tumor • Uterine Leiomyoma

MANTRA: A randomized, multicenter, phase 3 study of the MDM2 inhibitor milademetan versus trabectedin in patients with de-differentiated liposarcomas (AACR 2022) - P3 | "Exploratory endpoints: molecular markers in peripheral blood and/or tumor tissue; milademetan pharmacokinetics. To demonstrate a 3-month increase in PFS (from 3 to 6 months) corresponding to a hazard ratio of 0.5, approximately 160 patients will be required to observe 105 events with 93.9% power and 2-sided significance level of 5%."

Clinical • P3 data • Liposarcoma • Oncology • Sarcoma • Solid Tumor • MDM2

Single-Agent Trabectedin Versus Physician's Choice Chemotherapy in Patients With Recurrent Ovarian Cancer With BRCA-Mutated and/or BRCAness Phenotype: A Randomized Phase III Trial. (PubMed, J Clin Oncol) - "Trabectedin did not improve median OS and showed a worse safety profile in comparison with physician's choice control chemotherapy."

Journal • P3 data • Fallopian Tube Cancer • Oncology • Ovarian Cancer • Peritoneal Cancer • Solid Tumor • BRCA • BRCA1 • BRCA2

Efficacy and safety of nivolumab and trabectedin in pretreated patients with advanced soft tissue sarcomas (STS): Results of a phase II trial of the German Interdisciplinary Sarcoma Group (GISG-15, NitraSarc). (ASCO 2023) - P2 | "Our study confirms the activity of trabectedin plus nivolumab, particularly in patients with lipo- or leiomyosarcomas. There is a significant difference between ECC and LCC in terms of PFSR6, PFS and OS. The results in patients with non-L-sarcomas do not justify further investigation of this combination."

Clinical • Metastases • P2 data • Leiomyosarcoma • Liposarcoma • Oncology • Sarcoma • Soft Tissue Sarcoma • Solid Tumor

Management of Soft Tissue and Visceral Leiomyosarcomas. (PubMed, JAMA Oncol) - "In advanced disease, multiple systemic therapies demonstrate activity, including anthracycline-based and gemcitabine-based combinations, trabectedin, and tyrosine kinase inhibitors, although optimal sequencing after first-line therapy remains undefined. Key uncertainties persist, particularly regarding perioperative therapy, optimal sequencing and combination of systemic treatments, and integration of molecular data. Continued international collaboration and leiomyosarcoma-specific clinical trials are needed to refine treatment strategies and improve patient outcomes."

Journal • Leiomyosarcoma • Oncology • Sarcoma • Solid Tumor

SARC037: Phase II results of trabectedin given as a 1-hour (h) infusion in combination with low dose irinotecan in patients (pts) with relapsed/refractory Ewing sarcoma (ES). (ASCO 2024) - P1/2 | "T+I exhibited anti-tumor activity in heavily pretreated pts with ES and met its prespecified ORR with 5 PRs in 16 evaluable patients, all of which are ongoing at data cutoff. There were no unexpected safety signals. The combination of T given as a 1h infusion and low-dose I demonstrated meaningful clinical benefit and is worthy of further study in ES pts."

Clinical • Combination therapy • P2 data • Ewing Sarcoma • Oncology • Sarcoma • Solid Tumor • FLI1

TRABECTEDIN WITH CONCOMITANT RADIATION THERAPY FOR PATIENTS WITH RESECTABLE RETROPERITONEAL LIPOSARCOMA OR LEIOMYOSARCOMA: A PHASE I/II TRIAL OF SPANISH (GEIS), ITALIAN (ISG) AND FRENCH (FSG) GROUPS (CTOS 2022) - P1/2 | "Trabectedin concurrent with radiotherapy administered preoperatively is feasible and well tolerated in resectable retroperitoneal L-sarcomas. Trabectedin at 1.5 mg/m2 is the recommended dose for phase II part. Clinical trial information: NCT02275286."

Clinical • P1/2 data • Anemia • Febrile Neutropenia • Hematological Disorders • Leiomyosarcoma • Leukopenia • Liposarcoma • Neutropenia • Oncology • Sarcoma • Soft Tissue Sarcoma • Solid Tumor

Randomized phase III trial on trabectedin (ET-743) single agent versus clinician’s choice chemotherapy in recurrent ovarian, primary peritoneal, or fallopian tube cancers of BRCA-mutated or BRCAness phenotype patients (MITO23). (ASCO 2022) - P2 | " In this open-label, phase III, randomized trial, we assigned recurrent OC patients harboring BRCA 1/2 mutations or with BRCAness phenotype (defined as patients who had received and responded to at least 2 previous platinum-based treatments) to receive trabectedin 1.3 mg/mq q 21d or physician’s choice chemotherapy (among carboplatin, gemcitabine, weekly paclitaxel, pegylated liposomal doxorubicine or topotecan). Trabectedin as single agent does not improve survival outcomes when compared to standard chemotherapy in BRCA mut and BRCAness phenotype OC patients."

Clinical • Late-breaking abstract • P3 data • Fallopian Tube Cancer • Oncology • Ovarian Cancer • BRCA • BRCA1 • BRCA2

Integrated Transcriptomics of Human and Canine Osteosarcoma Reveals Species Stemness and Trabectedin Sensitivity. (PubMed, Cancer Sci) - "Collectively, our study provides a comprehensive comparative molecular framework for human and canine OS. These findings emphasize the necessity of accounting for species-specific stemness and immune landscapes, ultimately accelerating the precision development of next-generation OS therapeutics."

Journal • Oncology • Osteosarcoma • Sarcoma • Solid Tumor

Efficacy and safety findings from MANTRA: A global, randomized, multicenter, phase III study of the MDM2 inhibitor milademetan vs trabectedin in patients with dedifferentiated liposarcomas (ESMO Asia 2023) - P3 | "TEAEs were consistent with previous reports and manageable by dose interruptions/modifications. Further evaluation of milademetan is warranted in populations that may benefit from MDM2 inhibition."

Clinical • P3 data • Liposarcoma • Oncology • Sarcoma • Solid Tumor • MDM2

Doxorubicin-Trabectedin with Trabectedin Maintenance in Leiomyosarcoma. (PubMed, N Engl J Med) - P3 | "Combination therapy with doxorubicin and trabectedin induction, followed by trabectedin maintenance, was associated with improved overall survival and progression-free survival, as compared with doxorubicin alone, among patients with metastatic or surgically unresectable uterine or soft-tissue leiomyosarcoma. (Funded by PharmaMar and others; LMS04 ClinicalTrials.gov number, NCT02997358.)."

Clinical • Journal • Leiomyosarcoma • Oncology • Sarcoma • Solid Tumor

A randomized phase III trial comparing trabectedin to best supportive care in patients with pre-treated soft tissue sarcoma: T-SAR, a French Sarcoma Group trial. (PubMed, Ann Oncol) - "Trabectedin demonstrates superior disease control to BSC without impairing QoL in patients with recurrent STS of multiple histologies, with greater impact in patients with L-STS."

Clinical • Journal • P3 data • Hematological Disorders • Leiomyosarcoma • Leukopenia • Neutropenia • Oncology • Sarcoma • Soft Tissue Sarcoma • Solid Tumor

Doxorubicin alone versus doxorubicin with trabectedin followed by trabectedin alone as first-line therapy for metastatic or unresectable leiomyosarcoma (LMS-04): a randomised, multicentre, open-label phase 3 trial. (PubMed, Lancet Oncol) - P3 | "Doxorubicin plus trabectedin in first-line therapy was found to significantly increase progression-free survival in patients with metastatic or unresectable leiomyosarcomas compared with doxorubicin alone, despite a higher but manageable toxicity, and could be considered an option for the first-line treatment of metastatic leiomyosarcomas."

Journal • P3 data • Cardiovascular • Congestive Heart Failure • Febrile Neutropenia • Heart Failure • Hematological Disorders • Leiomyosarcoma • Neutropenia • Oncology • Sarcoma • Solid Tumor • Thrombocytopenia • Uterine Leiomyosarcoma

Trabectedin-olaparib combination or trabectedin in advanced soft tissue sarcomas after failure of anthracycline-based treatment (TOMAS2): a randomized phase 2 study from the Italian Sarcoma Group. (PubMed, Ann Oncol) - "Although trabectedin-olaparib combination reached the prespecified threshold for statistical significance for PFS (p<0.10), the benefit was marginal in the all-comers STS population. Nonetheless, patients affected by PARP1-expressing STS and uterine leiomyosarcoma derived substantial benefit from the combination, supporting further histology- and biomarker-driven investigation in these settings."

Journal • P2 data • Hematological Disorders • Leiomyosarcoma • Liposarcoma • Oncology • Sarcoma • Soft Tissue Sarcoma • Solid Tumor • Uterine Leiomyosarcoma • PARP1