PM54 / PharmaMar - LARVOL DELTA

Study of PM54 in Combination With Cytotoxic and Targeted Agents in Adult Participants With Advanced Malignancies (clinicaltrials.gov) - P1/2 | N=231 | Not yet recruiting | Sponsor: PharmaMar

New P1/2 trial • Oncology • Solid Tumor

Safety and Preliminary Activity of PM54 in Two Phase I Clinical Studies With Different Treatment Schedules (ESMO 2026) - No abstract available

Clinical • P1 data • Oncology

Antitumor activity of novel transcriptional inhibitors ecubectedin and PM54 in soft tissue sarcoma patient-derived xenografts. (PubMed, Cancer Res Commun) - "Mice were randomized to six groups and treated via tail vein injection with 1) vehicle, 2) doxorubicin, 3) trabectedin, 4) lurbinectedin, 5) ecubectedin, or 6) PM54...Both translocation-related models showed significant antitumor effect on histopathological evaluation in response to the novel drugs, compared to trabectedin. Ecubectedin and PM54 have modest antitumor activity in STS PDX models, with the strongest effects seen in the translocation-related sarcoma models, showing the potential of this class of drugs in treatment of STS."

Journal • Leiomyosarcoma • Liposarcoma • Oncology • Sarcoma • Soft Tissue Sarcoma • Solid Tumor • Synovial Sarcoma • Transplantation

The structures of ecteinascidin anticancer agents bound to DNA shed light on their mechanism of action. (PubMed, Nucleic Acids Res) - "The structures show that trabectedin, lurbinectedin, and PM54 bind through their shared A- and B-subunits, forming a covalent bond with the N2 atom of guanine and an extensive network of noncovalent interactions, leading to significant minor groove widening. These structural findings, supported by Förster resonance energy transfer and biochemical assays, reveal the molecular determinants underlying differential sequence selectivity and reactivity. Our results provide a mechanistic framework for the anticancer activity of ecteinascidins and a structural basis to guide the design of next-generation analogues with improved therapeutic potential."

Journal • Oncology

PharmaMar enrolls First Patient in Phase 1/2 Trial Evaluating PM54 Plus Pembrolizumab in Advanced Solid Tumors (Pharmamar Press Release) - "The study, for which the IND application was cleared by the FDA in December 2025, is designed to assess the safety, tolerability, and preliminary efficacy of this combination therapy in patients with previously treated advanced malignancies....The study includes patients with tumors characterized by significant unmet medical needs, including advanced-stage melanoma, endometrial cancer, extrapulmonary neuroendocrine tumors and mesothelioma."

Trial status • Endometrial Cancer • Melanoma • Mesothelioma • Neuroendocrine Tumor

Study of PM54 in Combination With Immunotherapy in Adult Participants With Advanced Malignancies (clinicaltrials.gov) - P1/2 | N=119 | Recruiting | Sponsor: PharmaMar

New P1/2 trial • Oncology

PM54 targets oncogenic transcriptional networks across multiple cancer types (AACR 2026) - "Background: PM54, a synthetic ecteinascidin analog derived from lurbinectedin, binds GC-rich promoter regions to block transcription, induce DNA double-strand breaks, and trigger S-phase arrest and apoptosis. PM54 rapidly suppresses proliferative/MYC-driven programs and elicits adaptive metabolic/immune responses. Baseline transcriptional state predicts response and may guide patient selection and combination strategies."

Breast Cancer • Gastric Cancer • Genito-urinary Cancer • Lung Cancer • Melanoma • Oncology • Ovarian Cancer • Prostate Cancer • Small Cell Lung Cancer • Solid Tumor • Triple Negative Breast Cancer • POU2F3

Ecubectedin and PM54 demonstrate antitumor activity in patient-derived xenograft models of soft tissue sarcoma (AACR 2024) - "Doxorubicin (DOX)-based chemotherapy is the standard for advanced or metastatic STS, despite low response rates and poor disease control. We explored the antitumor activity of two novel compounds, ecubectedin (ECU; PM14) and PM54 (PharmaMar), in two patient-derived xenograft (PDX) models of STS, leiomyosarcoma (LMS) and CIC-rearranged sarcoma (CRS). Mode of action of ECU and PM54 is similar to lurbinectedin (LUR), inhibiting oncogenic transcription by eviction of oncogenic transcription factors from gene promotors' recognition sequences, while inducing the generation of double strand breaks through DNA adduct formation. Female NMRI nu/nu mice (n=104) were transplanted bilaterally with STS PDX: UZLX-STS134 (CRS) and UZLX-STS22_2 (LMS). Xenografted mice were randomized to six treatment groups: 1) vehicle (VEH) (5% dextrose) 5 mL/kg once weekly (QW) intravenously (IV); 2) DOX 5 mg/kg QW IV; 3) trabectedin (TRA) 0.15 mg/kg QW IV; 4) LUR 0.18 mg/kg QW IV; 5) ECU 1.2 mg/kg..."

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

The next generation transcriptional inhibitor PM54 demonstrates strong antitumor activity in patient-derived xenograft models of soft tissue sarcoma (AACR 2025) - "Doxorubicin (DOX)-based chemotherapy is standard of care for advanced, metastatic STS, despite low response rates and poor disease control...Mice were randomized to 5 treatment groups and treated by tail vein injection once weekly: 1) vehicle (VEH) (5% dextrose) 5 mL/kg; 2) DOX 5 mg/kg; 3) trabectedin (TRA) 0.15 mg/kg; 4) lurbinectedin (LUR) 0.18 mg/kg; 5) PM54 1.2 mg/kg... PM54 has strong antitumor activity in PDX models of STS, with the most pronounced effects in STS134. Further steps include investigation of the role of DNA repair mechanisms in response to treatment with PM54 and the clinical development of this next generation transcriptional inhibitor in STS."

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

PharmaMar…has received from the U.S Food and Drug Administration (FDA) an investigational new drug (IND) approval, to start a Phase 1/2 multicenter clinical trial for the combination of PM54 with immunotherapy for the treatment of advanced stage solid tumors. (Pharmamar Press Release) - "This refers a Phase 1 study for the evaluation of the safety, followed by a Phase 2 to evaluate the safety and efficacy profile in patients affected by tumors with significant unmet medical needs such as advanced-stage melanoma, endometrial cancer, extrapulmonary neuroendocrine cancer and mesothelioma."

IND • New P1/2 trial • Endometrial Cancer • Melanoma • Mesothelioma • Neuroendocrine Tumor

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

Clinical Trial of PM54 in Advanced Solid Tumors Patients. (clinicaltrials.gov) - P1 | N=125 | Recruiting | Sponsor: PharmaMar | Trial completion date: Mar 2026 ➔ Apr 2027 | Trial primary completion date: Mar 2026 ➔ Dec 2026

Platinum resistant • Trial completion date • Trial primary completion date • Adrenal Cortex Carcinoma • Breast Cancer • Endometrial Cancer • Esophageal Adenocarcinoma • Esophageal Cancer • Gastric Cancer • Lung Cancer • Melanoma • Non Small Cell Lung Cancer • Ovarian Cancer • Prostate Adenocarcinoma • Prostate Cancer • Renal Cell Carcinoma • Small Cell Lung Cancer • Solid Tumor • BRAF • BRCA1 • BRCA2

PharmaMar presents eleven scientific publications at the Annual Meeting of the American Association for Cancer Research (AACR) (Pharmamar Press Release) - "On this occasion, the Company is presenting eleven new studies with results on the activity of its compounds: lurbinectedin (Zepzelca), ecubectedin, PM54, PM534, and trabectedin (Yondelis)....The main conclusions from the presented studies highlight the potential of two novel transcription inhibitors, PM54 and ecubectedin as innovative antitumor agents. Ecubectedin has demonstrated encouraging antitumor efficacy in both gastric and neuroendocrine-prostate cancer models. In collaboration with KU Leuven University (Belgium), data also confirm promising antitumor activity of both ecubectedin and PM54 in representative models of soft tissue sarcomas (STS)....Additionally, data on PM534 are being presented. PM534 is a novel tubulin-targeting agent, that may bypass the most common resistance mechanisms, limiting the effectiveness of standard microtubule-binding drugs."

Clinical data • Preclinical • Gastric Cancer • Neuroendocrine Carcinoma • Prostate Cancer • Soft Tissue Sarcoma • Solid Tumor

Ecteinascidin synthetic analogues: a new class of selective inhibitors of transcription, exerting immunogenic cell death in refractory malignant pleural mesothelioma. (PubMed, J Exp Clin Cancer Res) - "Collectively, these findings reveal a previously unknown mechanism of action of ecteinascidins that merits further investigation for potential clinical applications in the treatment of MPM, as new first line treatment in monotherapy or in association with immunotherapy."

Journal • Gene Therapies • Malignant Pleural Mesothelioma • Mesothelioma • Oncology • Solid Tumor • CD8

THE DNA MINOR GROOVE BINDING AGENTS ECUBECTEDIN AND PM54 DEMONSTRATE ANTITUMOR ACTIVITY IN PATIENT-DERIVED XENOGRAFT MODELS OF SOFT TISSUE SARCOMA (CTOS 2024) - "Objective: We explored the antitumor activity of two DNA minor groove binding derivatives of lurbinectedin (LUR), under development by PharmaMar (Spain): ecubectedin (ECU) and PM54, in four patient-derived xenograft (PDX) models of soft tissue sarcoma (STS)...Xenografted mice were randomized to six treatment groups: 1) vehicle (VEH) (5% dextrose) 5 mL/kg once weekly (QW) intravenously (IV); 2) doxorubicin (DOX) 5mg/kg QW IV; 3) trabectedin (TRA) 0.15 mg/kg QW IV; 4) LUR 0.18 mg/kg QW IV; 5) ECU 1.2mg/kg QW IV; 6) PM54 1.2 mg/kw QW IV... The novel compounds ECU and PM54 have antitumor activity in the PDX models tested here. We are now exploring the agents in additional PDX models of synovial sarcoma and DDLPS. We will also study the impact of the DNA repair capacity of the models on the antitumor effects observed with the drugs."

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

Pharma Mar launches a new drug in the midst of the slowdown in sales of Yondelis and Zepzelca [Google translation] (Economia Digital) - "The company chaired by José María Fernández de Sousa has announced this Thursday the recruitment of the first patient in a new Phase I clinical trial for the treatment of patients with different types of solid tumors with its new molecule of marine origin. This is PM54 , the new compound that is being tested in hospitals in Spain, Europe and the United States to find the recommended dose for its treatment."

Enrollment open • Oncology • Solid Tumor

Clinical Trial of PM54 in Advance Solid Tumors Patients. (clinicaltrials.gov) - P1 | N=125 | Recruiting | Sponsor: PharmaMar

New P1 trial • Adrenal Cortex Carcinoma • Breast Cancer • Endometrial Cancer • Esophageal Adenocarcinoma • Esophageal Cancer • Gastric Cancer • Gastrointestinal Cancer • HER2 Breast Cancer • Hormone Receptor Breast Cancer • Lung Cancer • Melanoma • Non Small Cell Lung Cancer • Oncology • Ovarian Cancer • Ovarian Serous Adenocarcinoma • Prostate Cancer • Renal Cell Carcinoma • Small Cell Lung Cancer • Solid Tumor • BRAF • BRCA1 • BRCA2