Study of Lurbinectedin in Combination With Doxorubicin Versus Doxorubicin Alone as First-line Treatment in Participants With Metastatic Leiomyosarcoma (SaLuDo) (SaLuDo)

Randomized, Controlled, Open-label, Phase III Study of Lurbinectedin in Combination With Doxorubicin Versus Doxorubicin Alone as First-line Treatment in Patients With Metastatic Leiomyosarcoma

The primary objective of this phase III study is to evaluate whether the combination of lurbinectedin plus doxorubicin given as first line treatment for metastatic leiomyosarcoma (LMS) prolongs the progression-free survival (PFS) by Independent Review Committee (IRC) when compared to doxorubicin administered as a single agent.

Study Overview

• Status: Active, not recruiting
• Conditions: Leiomyosarcoma
• Intervention / Treatment: Drug: Lurbinectedin; Drug: Doxorubicin

• Study Type: Interventional
• Enrollment (Actual): 455
• Phase: Phase 3

Contacts and Locations

Study Locations

• Austria
  • Graz, Austria, 8036
    • Universitaetsklinikum Graz - Universitätsklinik für Innere Medizin
  • Innsbruck, Austria, 6020
    • Medizinische Universität Innsbruck
  • Linz, Austria, 4010
    • Ordensklinikum Linz GmbH Barmherzige schwestern
  • Vienna, Austria, 1090
    • Medizinische Universität Wien
• Belgium
  • Anderlecht, Belgium, 1070
    • Institut Jules Bordet
  • Brussels, Belgium, 1200
    • Cliniques Universitaires Saint-Luc
  • Leuven, Belgium, 3000
    • Universitair Ziekenhuis Leuven - Campus Gasthuisberg
  • Brussels Capital
    • Jette, Brussels Capital, Belgium, 1090
      • Universitair Ziekenhuis Bruseel
• France
  • Bordeaux, France, 33076
    • Institut Bergonie
  • Lille, France, 59000
    • Centre de Lutte contre le Cancer - Centre Oscar Lambret
  • Limoges, France, 87042
    • Centre Hospitalier Universitaire Dupuytren 1
  • Marseille, France, 13005
    • Hôspital de la Timone
  • Paris, France, 75005
    • Institut Curie
  • Poitiers, France, 86000
    • Centre Hospitalier Universitaire de Poitiers
  • Rennes, France, 35042
    • Centre Eugène Marquis
  • Saint-Herblain, France, 44805
    • Institut de Cancérologie de l'Ouest - Saint-Herblain - Site René Gauducheau
  • Villejuif, France, 94805
    • Gustave Roussy
  • Auvergne-Rhône-Alpes
    • Lyon, Auvergne-Rhône-Alpes, France, 69008
      • Centre Leon Berard
  • Doubs
    • Besançon, Doubs, France, 25030
      • Centre Hospitalier Regional et Universitaire de Besancon - Hopital Jean-Minjoz
  • Pays de la Loire Region
    • Angers, Pays de la Loire Region, France, 49055
      • Institut de Cancérologie de l'Ouest - Angers
  • Provence-Alpes-Côte d'Azur Region
    • Nice, Provence-Alpes-Côte d'Azur Region, France, 06189
      • Centre Antoine Lacassagne
• Germany
  • Bad Saarow, Germany, 15526
    • Helios Klinikum Bad Saarow
  • Dresden, Germany, 01307
    • Universitätsklinikum Carl Gustav Carus Dresden
  • Hanover, Germany, 30625
    • Medizinische Hochschule Hannover
  • Heidelberg, Germany, 69120
    • Universitätsklinikum Heidelberg
  • Manheim, Germany, 68167
    • Universitätsmedizin Mannheim
  • Münster, Germany, 48149
    • Universitätsklinikum Münster
  • Tübingen, Germany, 72016
    • Universitätsklinikum Tübingen
  • Bavaria
    • München, Bavaria, Germany, 81675
      • LMU Klinikum - Campus Großhadern
• Italy
  • Aviano, Italy, 33081
    • Centro di riferimento Oncologico
  • Bologna, Italy, 40136
    • Istituto Ortopedico Rizzoli
  • Bologna, Italy
    • Azienda Ospedaliero-Universitaria di Bologna - Policlinico Sant Orsola-Malpighi
  • Candiolo, Italy, 10060
    • Istituto di Candiolo - Fondazione del Piemonte per l'Oncologia
  • Orbassano, Italy, 10043
    • Azienda Ospedaliero - Universitaria San Luigi Gonzaga
  • Padova, Italy, 35128
    • Istituto Oncologico Veneto - IRCCS
  • Palermo, Italy, 90127
    • Azienda Ospedaliera Universitaria Policlinico Paolo Giaccone
  • Roma, Italy, 00144
    • Istituto Nazionale Tumori Regina Elena
  • Roma, Italy, 00128
    • Università Campus Bio-Medico di Roma
  • Torino, Italy, 10126
    • Azienda Ospedaliero-Universitaria Città della Salute e della Scienza di Torino
  • Milan
    • Rozzano, Milan, Italy, 20089
      • Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) - Istituto Clinico Humanitas
  • Naples
    • Naples, Naples, Italy, 80131
      • Istituto Nazionale Tumori IRCCS Fondazione G. Pascale
• Netherlands
  • North Holland
    • Amsterdam, North Holland, Netherlands, 1066 CX
      • Het Nederlands Kanker Instituut
  • South Holland
    • Leiden, South Holland, Netherlands, 2333 ZA
      • Leids Universitair Medisch Centrum (LUMC)
• Poland
  • Masovian Voivodeship
    • Warsaw, Masovian Voivodeship, Poland, 02-781
      • Narodowy Instytut Onkologii im. Marii Skłodowskiej-Curie - Państwowy Instytut Badawczy
  • Pomeranian Voivodeship
    • Gdynia, Pomeranian Voivodeship, Poland, 81-519
      • Szpitale Pomorskie Spółka Z Ograniczoną Odpowiedzialnością
• Portugal
  • Coimbra, Portugal, 3000-075
    • Unidade Local de Saude de Coimbra
  • Porto, Portugal, 4200-072
    • Instituto Portugues de Oncologia do Porto Francisco Gentil
  • Porto, Portugal, 4050-342
    • Unidade Local de Saúde de Santo António, E.P.E - Hospital Geral de Santo António
  • Lisbon District
    • Lisbon, Lisbon District, Portugal, 1099-023
      • Instituto Português de Oncologia de Lisboa Francisco Gentil
• Spain
  • A Coruña, Spain, 15006
    • Complejo Hospitalario Universitario A Coruna
  • A Coruña, Spain, 15006
    • Complejo Hospitalario Universitario de Santiago (CHUS)
  • Barcelona, Spain, 08025
    • Hospital de la Santa Creu i Sant Pau
  • Barcelona, Spain, 08035
    • Hospital Universitari Vall d'Hebron
  • Barcelona, Spain, 08908
    • Institut Català d'Oncologia - Hospital Duran i Reynals (ICO L'Hospitalet)
  • Madrid, Spain, 28040
    • Hospital Clinico San Carlos
  • Madrid, Spain, 28040
    • Hospital Universitario Fundacion Jimenez Diaz
  • Madrid, Spain, 28046
    • Hospital Universitario La Paz
  • Madrid, Spain, 28007
    • Hospital General Universitario Gregorio Marañón
  • Madrid, Spain, 28050
    • START Madrid - CIOCC - HM Sanchinarro
  • San Cristóbal de La Laguna, Spain, 38320
    • Hospital Universitario de Canarias
  • Seville, Spain, 41013
    • Hospital Universitario Virgen del Rocio
  • Valencia, Spain, 46026
    • Hospital Universitari i Politècnic La Fe
  • Valencia, Spain, 46010
    • Hospital Clinico Universitario de Valencia
  • Zaragoza, Spain, 50009
    • Hospital Universitario Miguel Servet
• Switzerland
  • Basel, Switzerland, 4031
    • Universitätsspital Basel
  • Lausanne, Switzerland, 1011
    • Centre Hospitalier Universitaire Vaudois Lausanne
• United Kingdom
  • Birmingham, United Kingdom, B15 2GW
    • University Hospital Birmingham NHS Foundation Trust
  • Cambridge, United Kingdom, CB2 0QQ
    • Cambridge University Hospitals NHS Foundation Trust
  • Liverpool, United Kingdom, L7 8YA
    • The Clatterbridge Cancer Centre NHS Foundation Trust
  • London, United Kingdom, SW3 6JJ
    • The Royal Marsden NHS Foundation Trust
  • London, United Kingdom, NW1 2BU
    • University College London Hospitals Nhs Foundation Trust
  • Manchester, United Kingdom, M20 4BX
    • The Christie NHS Foundation Trust
  • Oxford, United Kingdom, OX3 7LE
    • Oxford University Hospitals NHS Foundation Trust
• United States
  • Arizona
    • Phoenix, Arizona, United States, 85054
      • Mayo Clinic Hospital - Phoenix
  • California
    • Beverly Hills, California, United States, 90212
      • Precision NextGen Oncology & Research Center
    • Los Angeles, California, United States, 90033
      • Norris Comprehensive Cancer Center
    • Los Angeles, California, United States, 90025
      • Cedars-Sinai Medical Center
    • Los Angeles, California, United States, 90057
      • Sarcoma Oncology Center
    • Palo Alto, California, United States, 94304
      • Stanford University (Leland Stanford Junior University)
  • Colorado
    • Aurora, Colorado, United States, 80045
      • University of Colorado Hospital - Anschutz Medical Campus
  • Florida
    • Jacksonville, Florida, United States, 32224
      • Mayo Clinic - Jacksonville
    • Tampa, Florida, United States, 33612
      • Moffitt Cancer Center
  • Georgia
    • Augusta, Georgia, United States, 30912
      • Augusta University Georgia Cancer Center
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Dana-Farber Cancer Institute
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • University of Michigan
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic - Rochester
  • Missouri
    • St Louis, Missouri, United States, 63110
      • Washington University School of Medicine in St. Louis
  • New York
    • New York, New York, United States, 10065
      • Memorial Sloan Kettering Cancer Center - New York
  • Ohio
    • Cleveland, Ohio, United States, 44195
      • Cleveland Clinic Main Campus
  • Oregon
    • Portland, Oregon, United States, 97239
      • Oregon Health and Science University
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • University of Pennsylvania Abramson Cancer Center
    • Pittsburgh, Pennsylvania, United States, 15232
      • University of Pittsburgh Medical Center (UPMC) Hillman Cancer Center
  • Tennessee
    • Nashville, Tennessee, United States, 37232
      • Vanderbilt - Ingram Cancer Center
  • Texas
    • Dallas, Texas, United States, 75390-8562
      • UT Southwestern Harold C. Simmons Comprehensive Cancer Center
    • Houston, Texas, United States, 77030
      • University of Texas MD Anderson Cancer Center
  • Washington
    • Seattle, Washington, United States, 98109
      • Fred Hutchinson Cancer Center - Seattle Cancer Care Alliance (SCCA) Location

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Voluntary signed and dated written informed consent of the participants obtained before any study-specific procedure.
2. Age ≥ 18 years.
3. Histologically confirmed diagnosis of metastatic LMS, in participants not candidates for curative resection.
4. Radiologically measurable disease according to the Response Evaluation Criteria in Solid Tumors (RECIST) v.1.1.
5. No previous systemic therapy for metastatic disease (i.e., first-line setting) and no previous anthracyclines. Note: prior chemotherapy (without anthracycline) in the context of adjuvant or neoadjuvant therapy is allowed. Prior line/s of hormone therapy in the adjuvant/metastatic setting are also allowed.
6. Eastern Cooperative Oncology Group (ECOG) performance status (PS) ≤ 1.

7. Adequate hematological, renal, metabolic and hepatic function:

   1. Hemoglobin ≥ 9.0 g/dL (participants may have received prior red blood cell [Red Blood Cell] transfusion); absolute neutrophil count (ANC) ≥ 2.0 x 10^9/L, and platelet count

      ≥ 100 x 10^9/L.

   2. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 3.0 x upper limit of normal (ULN).
   3. Total bilirubin ≤ 1.5 x ULN or direct bilirubin ≤ ULN if total bilirubin is > ULN.
   4. Albumin ≥ 3.0 g/dL.
   5. Calculated creatinine clearance (CrCL) ≥ 30 mL/min (using Cockcroft and Gault's formula).
   6. Left ventricular ejection fraction (LVEF) > 50% assessed by multiple-gated acquisition scan (MUGA) or echocardiography (ECHO) or cardiac magnetic resonance imaging (MRI).

8. Wash-out periods:

   1. At least three weeks since last prior systemic treatment.
   2. At least three weeks since last prior major surgery and one week since last prior minor surgery (port placement is excluded from this wash-out period).
   3. At least two weeks since last prior radiotherapy.
9. Evidence of non-childbearing status for women of childbearing potential (WOCBP). WOCBP must agree to use a highly effective contraceptive measure up to seven months after treatment discontinuation. Fertile male participants with WOCBP partners should use condoms during treatment and for four months following the last investigational medicinal product (IMP) dose.

Exclusion Criteria:

1. Prior treatment with anthracyclines, lurbinectedin or trabectedin.
2. Known low grade leiomyosarcoma (i.e., grade I).
3. Known hypersensitivity to any of the components of the IV formulation of lurbinectedin or doxorubicin.

4. Concomitant diseases/conditions:

   1. History of cardiac disease: myocardial infarction or angina within the year prior to enrollment; severe vascular disease; or symptomatic arrhythmia despite ongoing treatment.
   2. Participants with any immunodeficiency, including those known to be infected by human immunodeficiency virus (HIV).
   3. Known chronic active hepatitis or cirrhosis. For Hepatitis B, this includes positive tests for both Hepatitis B surface antigen and quantitative Hepatitis B polymerase chain reaction (PCR). For Hepatitis C, this includes positive tests for both Hepatitis C antibody and quantitative Hepatitis C PCR.
   4. Active uncontrolled infection.
   5. Any other major illness that (including severe cardiovascular disease) or risk factors that, in the Investigator's judgment, will substantially increase the risk associated with the patient's participation in this study.
5. Use of strong inducers of CYP3A4 activity within two weeks prior to the first infusion of lurbinectedin.
6. Prior irradiation of a RECIST v.1.1 target lesion if only one target lesion is available, unless progression of the lesion has been confirmed.
7. Known myopathy (history of resolved steroid-induced myopathy is allowed).
8. History of malignancies other than LMS within three years prior to enrollment, except for malignancies with a negligible risk of metastasis or death (e.g., 5-year OS rate >90%), such as adequately treated carcinoma in situ of the cervix, non-melanoma skin carcinoma, localized prostate cancer, non-muscle-invasive urothelial carcinomas, ductal carcinoma in situ, or stage I uterine cancer. Prior malignancies should have received curative treatment and should remain in remission. The Investigator should ensure, based on histology or clinical information, that the current metastatic sites are leiomyosarcoma and not recurrence of the original malignancy.
9. Limitation of the participant's ability to comply with the treatment or to follow-up the protocol.
10. Women who are pregnant or breast feeding and fertile participants (men and women) who are not using a highly effective method of contraception.
11. Participants in whom rapid tumor shrinkage is needed (e.g., when a tumor is close to a critical structure).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Doxorubicin (Dose A) + Lurbinectedin (Dose B); Participants will receive doxorubicin and lurbinectedin intravenously (IV) every three weeks (q3wk) on Day 1 of each treatment cycle (treatment cycle = three weeks).	Drug: Lurbinectedin; IV Infusion; Drug: Doxorubicin; Short IV push or bolus (according to label)
Experimental: Doxorubicin (Dose C) + Lurbinectedin (Dose D); Participants will receive doxorubicin IV q3wk on Day 1 of each treatment cycle (treatment cycle = three weeks).	Drug: Lurbinectedin; IV Infusion; Drug: Doxorubicin; Short IV push or bolus (according to label)
Active Comparator: Doxorubicin; Participants will receive doxorubicin IV q3wk on Day 1 of each treatment cycle (treatment cycle = three weeks).	Drug: Doxorubicin; Short IV push or bolus (according to label)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
PFS by IRC	Up to approximately 41 months

Secondary Outcome Measures

Outcome Measure	Time Frame
Clearance of Lurbinectedin and Doxorubicin in the Plasma	Cycle 1 Day 1, and Day 5 (One cycle = 3 weeks)
Volume of Distribution of Lurbinectedin and Doxorubicin in the Plasma	Cycle 1 Day 1, and Day 5 (One cycle = 3 weeks)
Overall Survival (OS)	Up to approximately 66 months
PFS by Investigator's Assessment (IA)	Up to approximately 41 months
Overall Response Rate (ORR) by IRC and IA	Up to approximately 66 months
Duration of Response (DoR) by IRC and IA	Up to approximately 66 months
Clinical Benefit Rate (CBR) by IRC and IA	Up to approximately 66 months
PFS on Next-line Therapy (PFS2) by IA	Up to approximately 41 months
Number of Participants Experiencing Adverse Events (AE)	Up to approximately 66 months
Number of Participants Experiencing Serious Adverse Events (SAE)	Up to approximately 66 months
Change in Quality of Life by European Organization for Research and Treatment of Cancer (EORTC) 30-item Quality of Life Questionnaire (QLQ-C30)	Up to approximately 41 months
Number of Participants With Presence or Absence of Mutation per Molecular Biomarker Associated With Response and/or Resistance to Treatment	Up to approximately 41 months
Expression Levels of Molecular Biomarkers Associated with Response and/or Resistance to Treatment	Up to approximately 41 months

Collaborators and Investigators

• Sponsor: PharmaMar

Publications and helpful links

General Publications

• Cote GM, Chawla SP, Demetri G, Kasper B, Jones RL, Broto JM, Wooley J, Weiss MC, Tafuto S, Badalamenti G, Carrasco I, Peinado P, Blay JY, Boggio G, Fernandez C, Nieto A, Kahatt C, Alfaro V, Le Cesne A. SaLudo: a randomized phase IIb/III study of lurbinectedin plus doxorubicin as first-line treatment in leiomyosarcoma. Future Oncol. 2025 Apr;21(8):943-951. doi: 10.1080/14796694.2025.2463798. Epub 2025 Feb 11.

Study record dates

Study Major Dates

• Study Start (Actual): September 21, 2023
• Primary Completion (Estimated): August 30, 2029
• Study Completion (Estimated): August 30, 2029

Study Registration Dates

• First Submitted: September 28, 2023
• First Submitted That Met QC Criteria: October 16, 2023
• First Posted (Actual): October 18, 2023

Study Record Updates

• Last Update Posted (Actual): May 15, 2026
• Last Update Submitted That Met QC Criteria: May 14, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: Oncology; Leiomyosarcoma
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Sarcoma; Neoplasms, Connective and Soft Tissue; Neoplasms, Muscle Tissue; Neoplasms; Leiomyosarcoma; Organic Chemicals; Hydrocarbons; Hydrocarbons, Cyclic; Carbohydrates; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Polycyclic Compounds; Glycosides; Anthracyclines; Naphthacenes; Aminoglycosides; Daunorubicin; Doxorubicin; PM 01183
• Other Study ID Numbers: PM1183-C-010-22; 2022-502975-45 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No