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

Inhibition of telomerase and ALT pathways in MDS/AML cell lines (ASH 2025) - "Cell death was increased by adding 4 nM Trabectedin (ALT inhibition) for an additional 3 days, leading to the viability rate results at 144 hours that were 1% for MDS-L, 0% for MDS92, and 9% for OCI-AML3... Inhibition of both telomere maintenance pathways in MDS/AML cell lines demonstrated a decrease in cell viability and increased cell death while primary fibroblasts showed no significant effect on survival. In future, study of primary cells from patients is necessary to confirm these results and to pave the way for cancer treatment in hematological and solid tumor neoplasias with molecules and/or small molecules targeting telomerase and ALT pathways."

Preclinical • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Solid Tumor

Efficacy of trabectedin in translocation-related sarcomas based on cancer genomic profiling testing (ESMO Asia 2025) - "Our findings align with prior reports on trabectedin efficacy. Consistent with previous reports, our findings suggest that trabectedin is effective in FUS::DDIT3–positive myxoid liposarcomam and indicate that its therapeutic benefit may be limited to specific fusion genes within the broader category of TRS. Early CGP testing may enable personalized therapy and improve outcomes in TRS patients with specific fusion genes."

Clinical • Liposarcoma • Oncology • Sarcoma • Soft Tissue Sarcoma • Solid Tumor • DDIT3 • EWSR1 • FUS • NR4A3

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

EXCEPTIONAL RESPONSE TO COMBINATION IMMUNOTHERAPY WITH YH001 AND ENVAFOLIMAB IN METASTATIC SARCOMA. (CTOS 2025) - "Data from a group of patients at a single institution enrolled in a prematurely discontinued clinical trial are presented, focusing on one patient who showed an exceptional response. This discontinued phase 1/2 open-label study was designed to investigate the combination of YH001 (recombinant humanized anti-CTLA-4 IgG1 monoclonal antibody) and envafolimab (KN035, an anti-PD-L1 agent approved in China) in advanced sarcomas. A sustained disease response was identified in a patient with metastatic fibrosarcoma refractory to chemotherapy and TKI, after PD-L1/CTLA-4 treatment, underscoring potential for combined immunotherapeutics in sarcoma and the need for predictive biomarker identification beyond TMB and PD-L1."

IO biomarker • Metastases • Tumor mutational burden • Fibrosarcoma • Leiomyosarcoma • Liposarcoma • Oncology • Sarcoma • Solid Tumor • Synovial Sarcoma • TMB

DCMiC: a double-cylinder micro-chamber platform for high-throughput drug screening and modeling of microenvironmental resistance in Ewing sarcoma. (PubMed, Lab Chip) - "As a result, we identified Torin 2, talazoparib, and trabectedin as top 3 candidates with potent anti-Ewing sarcoma activity. Mechanistically, exogenous TGF-β1 was sufficient to induce resistance in tumor-only spheroids, whereas pharmacological inhibition of TGF-β1 signaling restored drug sensitivity in heterotypic spheroids. These findings establish the DCMiC platform as a low-cost, physiologically relevant system for modeling tumor-stroma interactions and enabling scalable drug discovery in clinically relevant contexts for Ewing sarcoma and other solid tumors."

Journal • Ewing Sarcoma • Oncology • Sarcoma • Solid Tumor • TGFB1

Immune checkpoint inhibitors in sarcomas: A meta-analysis of progression-free and overall survival from prospective studies of monotherapy and combination regimens (ESMO-IO 2025) - "Data on median PFS, OS, and 95% CIs were extracted from seven pivotal trials: A091401 (original/expansion), SARC028, the ASPS atezolizumab study, the avelumab + trabectedin phase I/II trial, and the EAGLES phase II trial of avelumab + gemcitabine...In SARC028, pembrolizumab achieved PFS 6.9 in UPS and 5.8 in DDLPS, OS ∼11.3...Combinations improved outcomes: nivolumab–ipilimumab reached 4.1/14.3 months, avelumab–trabectedin 8.1/27.0, and avelumab–gemcitabine 5.6/27.5...Combination strategies, dual ICI or ICI with chemotherapy, yield superior PFS and OS compared with historical single-agent benchmarks, with median OS approaching ∼27 months in selected regimens. Prospective randomized trials and biomarker-driven strategies are needed to confirm the survival advantage and to guide patient selection.Legal entity responsible for the study Istituto Nazionale Tumori-IRCCS-Fondazione G. Pascale."

Checkpoint inhibition • IO biomarker • Monotherapy • Retrospective data • Alveolar Soft Tissue Sarcoma • Oncology • Osteosarcoma • Sarcoma • Solid Tumor

INVESTIGATING THE SAFETY AND EFFICACY OF LURBINECTEDIN WITH IPILIMUMAB AND NIVOLUMAB FOR ADVANCED SOFT TISSUE SARCOMA: LINNOVATE PHASE 1/2 STUDY (NCT05876715) (CTOS 2025) - P1/2 | "Therefore, immune checkpoint inhibitors (ICIs) such as ipilimumab and nivolumab, which enhance sustained T-cell activation by suppressing regulatory T cells, are most effective when administered as first-line therapy in combination with lurbinectedin—a synthetic analog of the marine alkaloid trabectedin—that not only induces apoptosis in cancer cells and exposes tumor neoantigens for immune recognition but also depletes tumor-associated macrophages, thereby restoring immune surveillance and potentially enhancing the efficacy of ICIs. The observed 28% BORR and 100% CBR support the continuation of the phase 2 portion of the study, with manageable toxicity."

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

MTA-Cooperative PRMT5 Inhibitors Demonstrate Efficacy in MTAP-Deleted MPNST Models and Enhance Chemotherapy Response (SNO 2025) - "Furthermore, the combination of a PRMT5 inhibitor with doxorubicin or trabectedin had additive antiproliferative effects. In vivo, TNG908 and TNG462 demonstrated dose-dependent antitumor activity in MTAP-null MPNST PDX models WU-356 and WU-386, inducing tumor regressions at well-tolerated doses.CONCLUSIONTNG908 and TNG462 selectively inhibited MTAP-deleted MPNST cell growth in vitro and induced tumor regressions in vivo through PRMT5 inhibition and apoptosis induction. These findings support the therapeutic potential of MTA-cooperative PRMT5 inhibitors as a targeted treatment strategy for patients with MTAP-deleted MPNST."

Clinical • Brain Cancer • Neurofibrosarcoma • Sarcoma • Soft Tissue Sarcoma • Solid Tumor • CASP3 • CDKN2A • MTAP

Accelerator-based boron neutron capture therapy, a randomized controlled trial for refractory recurrent high-grade meningiomas (SNO 2025) - "Both PFS judged by committee and investigators showed statistical significance between treatment and control arms. Recently, the results of RCT of "Trabectedin" for recurrent HGMs, organized by EORTC, (EORTC-1320-BTG) was reported. Unfortunately, there was no effect of Trabectedin not only in PFS but in OS."

Clinical • Brain Cancer • Meningioma • Solid Tumor

PROTraSarc: Prospective Study to Evaluate Patient Reported Outcomes (PRO) During Rechallenge With Trabectedin in Sarcoma Patients (clinicaltrials.gov) - P=N/A | N=7 | Terminated | Sponsor: Institut für Klinische Krebsforschung IKF GmbH at Krankenhaus Nordwest | Completed ➔ Terminated; The study was terminated prematurely due to slow recruitment after inclusion of 7 patients (of initially planned 100 patients).

Trial termination • Oncology • Sarcoma • Soft Tissue Sarcoma • Solid Tumor

Use of doxorubicin and trabectedin in low-grade endometrial stromal sarcoma: A case report. (PubMed, Gynecol Oncol Rep) - "This is the first reported case of LG-ESS achieving prolonged stable disease with doxorubicin-trabectedin therapy and trabectedin maintenance. Given the manageable toxicity profile and encouraging tumor control, further studies should explore its potential role in LG-ESS management."

Journal • Leiomyosarcoma • Oncology • Sarcoma • Solid Tumor • Uterine Cancer

Excellent Response and Persistent Local Control of Metastatic Extraskeletal Myxoid Chondrosarcoma Repeatedly Treated with Surgical Excision or Stereotactic Radiotherapy Alone: A Case Report. (PubMed, Case Rep Oncol) - "Prospective studies evaluating the role of trabectedin, antiangiogenic agents, and immunotherapy are ongoing to assess the best systemic treatment...All metastatic sites of EMC were treated with either surgical excision or stereotactic ablative radiotherapy alone in three different occasions, showing complete or major response. This individualized approach enabled prolonged systemic therapy-free intervals with minimal toxicity, so could be considered in selected patients."

Journal • Oncology • Sarcoma • Soft Tissue Sarcoma • Solid Tumor

Chemotherapy Strategies and Their Efficacy for Mesenchymal Chondrosarcoma. (PubMed, Curr Oncol) - "Trabectedin demonstrates low disease control rate in translocation-related sarcomas, including few MCS cases. Anti-angiogenic tyrosine kinase inhibitors, such as apatinib and pazopanib, demonstrate activity in chondrosarcoma, but MCS-specific data are lacking. IDH1 inhibition benefits conventional subtypes rather than MCS. Early immunotherapy experience is limited, but pathway-directed strategies targeting BCL2 and PI3K-mTOR warrant evaluation."

Journal • Review • Oncology • Sarcoma • Solid Tumor • BCL2 • HEY1 • IDH1 • NCOA2

VALIDATION OF SYNGENEIC MURINE DEDIFFERENTIATED LIPOSARCOMA MODELS FOR PRECLINICAL EVALUATION OF THERAPEUTIC SENSITIVITY (CTOS 2025) - "Murine and human DDLPS cell lines show consistent doxorubicin sensitivity and transcriptional changes in cell cycle genes. N1011 cells were also uniquely sensitive to selinexor and dacarbazine, with moderate sensitivity to trabectedin observed in murine cell lines. The in vivo validation using a syngeneic murine model highlights its relevance for further mechanistic studies and the development of rational drug combination strategies in DDLPS."

Preclinical • Liposarcoma • Oncology • Sarcoma • Soft Tissue Sarcoma • Solid Tumor • ACPP • CDK4 • CDKN1A

EFFECTIVENESS OF ERIBULIN FOR MYXOID PLEOMORPHIC LIPOSARCOMA: INSIGHTS FROM A PATIENT-DERIVED MODEL AND CLINICAL TRANSLATION IN A PATIENT WITH ADVANCED DISEASE (CTOS 2025) - "Single-agent doxorubicin (max TVI 87%) and ifosfamide (max TVI 94%), as well as their combination (max TVI 97%) showed meaningful activity but tumor regrowth occurred in all mice. Trabectedin (max TVI 67%) and selinexor (max TVI 55%) exhibited limited effectiveness... Eribulin emerged as the most effective treatment option in a patient-derived preclinical model of MPL. These preclinical results were successfully translated to a patient with advanced disease, who experienced a significant period of disease stability after multiple prior therapeutic lines."

Clinical • Metastases • Liposarcoma • Oncology • Sarcoma • Soft Tissue Sarcoma • Solid Tumor

Olaparib and temozolomide combination in relapsed metastatic Ewing sarcoma brings a new ray of hope. (PubMed, Indian J Cancer) - "In Ewing sarcoma, EWS-FLI-1 translocation has been identified as a biomarker for Poly-ADP ribose Polymerase inhibitor (PARPi) sensitivity and olaparib has been shown to enhance the antitumor activity of chemotherapy agents like temozolomide, irinotecan, and trabectedin. We tried the combination of olaparib and temozolomide in an adult patient of Ewing sarcoma who had metastatic disease, and after 4 months of treatment, he showed excellent response to treatment."

Journal • Ewing Sarcoma • Oncology • Osteosarcoma • Sarcoma • Solid Tumor

EXPANSION OF A PHASE 1 STUDY OF SON-1010 (IL12-FHAB) ADDING TRABECTEDIN IN SOFT TISSUE SARCOMA: TRIAL IN PROGRESS (CTOS 2025) - P1 | "N/A"

P1 data • Oncology • Sarcoma • Soft Tissue Sarcoma • Solid Tumor • CD8 • IFNG • IL12A

SINGLE-ARM, OPEN-LABEL PHASE II TRIAL OF XL092 (ZANZALINTINIB) IN PATIENTS WITH ADVANCED LEIOMYOSARCOMA: TRIAL IN PROGRESS (CTOS 2025) - "Approved subsequent line agents such as trabectedin and pazopanib have demonstrated short-term improvements in progression-free survival (PFS). This trial will evaluate the clinical activity and tolerability of XL092 in heavily pretreated LMS. A 6-month PFS of ≥50% would strongly support further investigation of XL092 in this population. Protocol is being amended to include a second cohort of translocation-associated sarcomas"

Clinical • Metastases • P2 data • Leiomyosarcoma • Oncology • Sarcoma • Solid Tumor • AXL

UNRESECTABLE AND METASTATIC DEDIFFERENTIATED LIPOSARCOMA (DDLPS): INSIGHTS FROM A MULTICENTER REAL-WORLD COHORT (RWC) (CTOS 2025) - "First line (1L) Tx were Doxorubicin (D) (46.5%), anthracycline-ifosfamide (AI) (21%), trabectedin (Tr) (10.3%) brigimadlin (Bg) (7.1%) and eribulin (Er) (6.5%)...Among regimens, AI and Bg had the highest OS at 3 years (55%, 64%, respectively), though no Tx sequence demonstrated statistical significance.Second line (2L) CT was given in 56% of pts: Tr (41.4%; RR: 22%), DTIC-Gemcitabine DG (19.5%; RR: 5.9%), Er (16%; RR: 14%), and D (9.2%; RR: 14%), with mPFS of 3.9m... Tx patterns in UM DDLPS remain heterogeneous with modest outcomes. AI and Bg showed OS trends, though not statistically significant due to sample size. These data underscore the need for novel Tx strategies and randomized trials to improve care."

Clinical • Metastases • Real-world • Real-world evidence • Liposarcoma • Oncology • Sarcoma • Soft Tissue Sarcoma • Solid Tumor

EFFECTIVENESS OF LURBINECTEDIN PLUS IRINOTECAN IN PRECLINICAL MODEL OF DESMOPLASTIC SMALL ROUND CELL TUMOR (CTOS 2025) - "We demonstrated the effectiveness of the combination trabectedin plus irinotecan in a PDX model of DSRCT. Lurbinectedin and irinotecan exhibit potent antiproliferative activity in DSRCT models. These results lead to the design of a phase II study of lurbinectedin and irinotecan in adult and young adult patients with advanced DSRCT (EU 2024-519261-21-00). Further molecular studies on the effect of drugs on EWS::WT1 modulation both in vitro and in vivo are ongoing."

Preclinical • Oncology • Soft Tissue Sarcoma • WT1

POOLED ANALYSIS OF TRABECTEDIN EFFICACY IN MYXOID/ROUND CELL LIPOSARCOMA FROM THREE PROSPECTIVE CLINICAL TRIALS (CTOS 2025) - P=N/A, P2, P3 | "This represents one of the largest populations to date of pts with advanced MRCLS treated with trabectedin in prospective clinical trials. It is limited by typical factors affecting pooled analyses including heterogeneity across studies. Nevertheless, the results provide a trabectedin efficacy baseline against which to compare other therapies for MRCLS.Best Overall Responses in 49 Pts with Advanced MRCLS Receiving Trabectedin."

Retrospective data • Liposarcoma • Oncology • Sarcoma • Solid Tumor

TRIAL IN PROGRESS: A PHASE 2 STUDY OF METRONOMIC TRABECTEDIN, GEMCITIBAINE, AND DACARBAZINE IN PREVIOUSLY TREATED ADVANCED SOFT TISSUE SARCOMA (NCT04535271) (CTOS 2025) - P2 | "Objective: We hypothesize that metronomic dosing of trabectedin, gemcitabine, and dacarbazine will produce synergistic effects while limiting additive toxicities in advanced soft tissue sarcoma patients, potentially presenting a safer and more durable approach compared to standard chemotherapy regimens, which often cause unacceptable toxicity and chemoresistance. This is a phase 2 open-label single-site study (NCT04535271) evaluating the safety and efficacy of metronomic trabectedin, gemcitabine, and dacarbazine, which we hypothesize will increase progression free survival in patients with advanced soft tissue sarcoma (STS). N/A"

Metastases • P2 data • Oncology • Sarcoma • Soft Tissue Sarcoma • Solid Tumor

UNEXPECTED RESPONSE TO ERIBULIN IN A REFRACTORY LEIOMYOSARCOMA PATIENT WITH HEREDITARY P53 MUTATION (CTOS 2025) - "Over the next year, she tried single-agent doxorubicin, combo of doxorubicin/dacarbazine, pazopanib, and trabectedin. Wozniak et al showed that p53 mutations were associated with significantly better response to eribulin in the sarcoma cohort studied in EORTC trial. In patients with tumors that harbor p53 mutations somatically or even the hereditary p53 mutations, should eribulin be a more standard drug tried alone or in combination with more targeted therapy?"

Clinical • IO biomarker • P53mut • Tumor mutational burden • Leiomyosarcoma • Oncology • Sarcoma • Solid Tumor • BCL6 • PD-L1 • RB1 • TMB • TP53

COMPARATIVE ANALYSIS OF FIRST-LINE DOXORUBICIN-BASED COMBINATION REGIMENS IN METASTATIC LEIOMYOSARCOMA: IMPACT ON SURVIVAL AND DISEASE CONTROL (CTOS 2025) - "Doxorubicin + dacarbazine showed the longest first-line PFS and highest disease control rate, though overall survival was similar across regimens.Second-line PFS was longer when doxorubicin + trabectedin was used first. Excluding uterine leiomyosarcomas, doxorubicin + trabectedin showed a non-significant PFS advantage over doxorubicin + dacarbazineDescriptive analysis"

Clinical • Metastases • Leiomyosarcoma • Oncology • Sarcoma • Solid Tumor • Uterine Leiomyosarcoma

THE NOVEL TRANSCRIPTIONAL INHIBITORS ECUBECTEDIN AND PM54 DEMONSTRATE ANTITUMOR ACTIVITY IN PATIENT-DERIVED XENOGRAFT MODELS OF SOFT TISSUE SARCOMA (CTOS 2025) - "The novel compounds ECU and PM54 consistently showed the strongest antitumor activity in the PDX models tested, achieving prolonged TV-stabilization in STS336 even after treatment cessation. In ongoing experiments we are now exploring the impact of the DNA repair capacity of the models on the antitumor effects observed with the drugs.Tumor volume change on day 16 and comparison of mitotic and apoptotic activity of respective treatment groups compared to vehicle on day 16. ↓ decrease in activity, as compared to baseline."

Preclinical • Leiomyosarcoma • Liposarcoma • Oncology • Sarcoma • Soft Tissue Sarcoma • Solid Tumor • Synovial Sarcoma