A Study of Unesbulin in Participants With Advanced Leiomyosarcoma (LMS) (SUNRISELMS)

A Phase 2/3 Study to Evaluate the Efficacy and Safety of Unesbulin in Unresectable or Metastatic, Relapsed or Refractory Leiomyosarcoma

This study will compare the efficacy and safety of unesbulin plus dacarbazine versus placebo plus dacarbazine in participants with unresectable or metastatic, relapsed or refractory LMS who have received at least 1 prior line of systemic therapy.

Study Overview

• Status: Terminated
• Conditions: Leiomyosarcoma
• Intervention / Treatment: Drug: Unesbulin; Drug: Dacarbazine; Other: Placebo

• Study Type: Interventional
• Enrollment (Actual): 359
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• Australia
  • Camperdown, Australia, 2050
    • Chris O'Brien Lifehouse
  • East Melbourne, Australia, 3000
    • Peter Maccallum Cancer Institute
  • Randwick, Australia, 2031
    • Prince of Wales Hospital
• Brazil
  • Barretos, Brazil
    • Fundacao PIO XII - Hospital de Amor
  • Porto Alegre, Brazil
    • Santa Casa de Misericordia de Porto Alegre
  • Rio de Janeiro, Brazil, 20220-410
    • INCA I - Instituto Nacional de Cancer
  • Salvador, Brazil
    • Hospital Sao Rafael - Instituto D'Or da Bahia
  • São José do Rio Preto, Brazil
    • CIP - Centro Integrado de Pesquisas do Hospital de Base de Sao Jose do Rio Preto
  • São Paulo, Brazil
    • Instituto do Cancer do Estado de Sao Paulo (ICESP)
• Canada
  • Ontario
    • Ottawa, Ontario, Canada, K1H8L6
      • The Ottawa Hospital Cancer Centre
    • Toronto, Ontario, Canada
      • Princess Margaret Hospital
  • Quebec
    • Montreal, Quebec, Canada
      • Universite de Montreal - Hopital Maisonneuve-Rosemont (HMR)
• France
  • Bordeaux Cedex, France, 33076
    • Institut Bergonie
  • Lyon, France, 69008
    • Centre Leon Berard
  • Paris, France, 75005
    • Institut Curie
  • Villejuif cedex, France
    • Gustave Roussy
• Germany
  • Mannheim, Germany, 68167
    • Universitaetsmedizin Mannheim
  • Munchen, Germany, 81377
    • Klinikum der Ludwig-Maximilians-Universitaet Muenchen
• Hungary
  • Budapest, Hungary
    • Észak-Pesti Centrumkórház - Honvédkórház
• Italy
  • Milano, Italy, 20133
    • Fondazione IRCCS Istituto Nazionale dei Tumori
  • Torino, Italy, 10060
    • La Fondazione e l'Istituto di Candiolo
• Netherlands
  • Leiden, Netherlands
    • Leids Universitair Medisch Centrum
• Poland
  • Poznan, Poland
    • Niepubliczny Zaklad Opieki Zdrowotnej Zespól Poradni Specjalistycznych "TERMEDICA"
  • Warszawa, Poland, 02-781
    • Narodowy Instytut Onkologii im. Marii Sklodowskiej-Curie - Panstwowy Instytut Badawczy, Klinika Nowotworow Tkanek Miekkich, Kosci i Czerniakow
• Spain
  • Barcelona, Spain
    • Hospital Universitario Vall d'Hebron
  • Barcelona, Spain, 08908
    • Institut Català d'Oncologia (Hospital Duran y Reynals)
  • Madrid, Spain
    • Hospital Universitario 12 de Octubre
  • Madrid, Spain, 28040
    • Hospital Fundación Jiménez Diaz
• United Kingdom
  • Glasgow, United Kingdom, G12 0YN
    • Beatson, West of Scotland Cancer Centre
  • London, United Kingdom, SW3 6JJ
    • Royal Marsden Hospital
  • Manchester, United Kingdom
    • The Christie NHS Foundation Trust
• United States
  • California
    • Duarte, California, United States, 91010
      • City of Hope
    • Los Angeles, California, United States, 90024
      • University of California, Los Angeles (UCLA) - Jonsson Comprehensive Cancer Center
    • Santa Monica, California, United States, 90403
      • Sarcoma Oncology Research Center
    • Stanford, California, United States, 94305
      • Stanford Cancer Center
  • Colorado
    • Denver, Colorado, United States, 80045
      • University of Colorado Denver
  • Connecticut
    • New Haven, Connecticut, United States, 06511
      • Yale University
  • Florida
    • Jacksonville, Florida, United States, 32224
      • Mayo Clinic
    • Orlando, Florida, United States, 32806
      • University of Florida (UF) Health Cancer Center - Orlando Health
    • Tampa, Florida, United States, 33612
      • Moffitt
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Northwestern Memorial Hospital
    • Warrenville, Illinois, United States, 60555
      • Northwestern Medicine - Warrenville Cancer Center
  • Maryland
    • Baltimore, Maryland, United States, 21231
      • Johns Hopkins Oncology Group
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • University of Michigan
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Washington University
  • New York
    • New York, New York, United States, 10027
      • The Trustees of Columbia University
    • New York, New York, United States, 11101
      • David H. Koch Center for Cancer Care at Memorial Sloan Kettering Cancer Center
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Duke University Medical Center
  • Ohio
    • Columbus, Ohio, United States, 43210
      • The Ohio State University (OSU)
  • Oregon
    • Portland, Oregon, United States, 97239
      • Oregon Health & Science University
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • University of Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19144
      • Thomas Jefferson University
    • Pittsburgh, Pennsylvania, United States, 15232
      • University of Pittsburgh Medical Center
  • Texas
    • Houston, Texas, United States, 77030
      • MD Anderson Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Key Inclusion Criteria:

• Histological or cytological confirmation of LMS arising at any anatomic site except bone sarcoma, unresectable or metastatic, relapsed or refractory disease measurable per RECIST 1.1 criteria
• Disease progression on previous treatment before screening or intolerability to other oncology treatments
• Participants with liver metastases may be enrolled
• Participants with well-controlled asthma or chronic obstructive pulmonary disease may be enrolled.
• Toxicity from prior therapies recovered to Grade ≤1 or participant's baseline, except for alopecia. In addition, endocrinopathies associated with prior immunotherapy-based treatments that are well controlled on replacement medication are not exclusionary.
• At least 1 prior systemic cytotoxic or targeted therapy regimen for LMS, which may include but is not limited to single-agent doxorubicin or other anthracycline, doxorubicin plus ifosfamide, trabectedin, pazopanib, or gemcitabine with or without docetaxel.
• At least 4 weeks since prior surgery and recovered in the opinion of investigator

Key Exclusion Criteria:

• Received temozolomide or dacarbazine at any time
• Any other systemic anticancer therapy including investigational agents ≤3 weeks before initiation of study treatment. Additionally, participants may not have received radiation ≤3 weeks before initiation of study treatment.
• Known intolerance to dacarbazine or one or more of the excipients in unesbulin.
• Co-existing active infection or any co-existing medical condition likely to interfere with study procedures
• Gastrointestinal disease or other conditions that could affect absorption. Active peptic ulcer disease, active gastritis, or previous history of gastric perforation within the last 2 years
• Major surgery, open biopsy, or significant traumatic injury that has not recovered, in the opinion of the investigator, within 28 days of baseline
• Immunization with a live vaccine within 30 days before starting study drug due to the risk of serious and life-threatening infections.
• Prior malignancies, other than LMS, that required treatment or have shown evidence of recurrence (except for non-melanoma skin cancer or adequately treated cervical carcinoma in situ, prostate cancer in situ or any other low risk malignancy that is approved by the medical monitor) during the 5 years before initiation.
• Prior or ongoing clinically significant illness, medical or psychiatric condition, medical history, physical findings, electrocardiogram (ECG) findings, or laboratory abnormality that, in the investigator's opinion, could affect the safety of the participant, or alter the absorption, distribution, metabolism, or excretion of the study drugs, or could impair the assessment of study results.

Note: Other inclusion and exclusion criteria may apply.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Unesbulin and Dacarbazine; Participants will receive unesbulin 300 milligrams (mg) tablets administered orally twice weekly in each 3-week treatment cycle in combination with dacarbazine 1000 mg/meter squared (m^2) intravenously (IV) once every 21 days. Treatment will continue for each participant until evidence of unacceptable toxicity, disease progression, or treatment discontinuation for another reason.	Drug: Unesbulin; Unesbulin will be administered as per the dose and schedule specified in the arm description.; Other Names: PTC596; Drug: Dacarbazine; Dacarbazine will be administered as per the dose and schedule specified in the arm description.; Other Names: DTIC
Placebo Comparator: Placebo and Dacarbazine; Participants will receive placebo matching to unesbulin tablets administered orally twice weekly in each 3-week treatment cycle in combination with dacarbazine 1000 mg/m^2 IV once every 21 days. Treatment will continue for each participant until evidence of unacceptable toxicity, disease progression, or treatment discontinuation for another reason.	Drug: Dacarbazine; Dacarbazine will be administered as per the dose and schedule specified in the arm description.; Other Names: DTIC; Other: Placebo; Placebo will be administered as per the schedule specified in the arm description.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression Free Survival (PFS) Per Independent Central Review Using Response Evaluation Criteria in Solid Tumors (RECIST) V1.1	PFS was defined as the time from randomization to the documented disease progression or death due to any cause, whichever occurred first. Disease progression was defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 millimeters (mm). The appearance of one or more new lesions was also considered progression.	Up to approximately 2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Survival	Overall survival was defined as the time in months from the randomization date to the date of death from any cause or date last known alive for those who did not die.	Up to approximately 2 years
Objective Response Rate (ORR) Per Independent Central Review Using RECIST V1.1	ORR was defined as percentage of participants who achieved a confirmed best overall response (BOR) of complete response (CR) or partial response (PR). CR: Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. PR: At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.	Up to approximately 2 years
Disease Control Rate (DCR) Per Independent Central Review Using RECIST V1.1	DCR was defined as percentage of participants who achieved a confirmed BOR of CR, PR, or at least 3 months of stable disease (SD). CR: Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. PR: At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. SD: Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study.	Up to approximately 2 years
Duration of Response Per Independent Central Review Using RECIST V1.1	Duration of response was defined as the time from the date of first confirmed response of CR or PR to the date of the first documented disease progression or death due to any cause, whichever occurred first. CR: Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. PR: At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. Disease progression: At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. The appearance of one or more new lesions was also considered progression.	Up to approximately 2 years
Number of Participants With Treatment-emergent Adverse Events (TEAEs)	An adverse event (AE) was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. Serious adverse event (SAE) was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. AEs included both SAEs and non-serious AEs. A TEAE was defined as an AE that had an onset date on or after the first dose of study drug until 30 days after last dose or occurred prior to first dose of study drug and worsened in severity after first dose of study drug. A summary of other non-serious AEs and all SAEs, regardless of causality is located in the 'Reported AE section'.	From first dose of study drug up to approximately 2 years

Collaborators and Investigators

• Sponsor: PTC Therapeutics
• Investigators: Study Director: Mark Rance, MD, PTC Therapeutics

Study record dates

Study Major Dates

• Study Start (Actual): May 23, 2022
• Primary Completion (Actual): June 17, 2024
• Study Completion (Actual): July 17, 2024

Study Registration Dates

• First Submitted: February 25, 2022
• First Submitted That Met QC Criteria: February 25, 2022
• First Posted (Actual): March 8, 2022

Study Record Updates

• Last Update Posted (Actual): June 13, 2025
• Last Update Submitted That Met QC Criteria: June 3, 2025
• Last Verified: May 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Neoplasms by Histologic Type; Sarcoma; Neoplasms, Connective and Soft Tissue; Neoplasms, Muscle Tissue; Leiomyosarcoma; Antineoplastic Agents; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents, Alkylating; Alkylating Agents; Dacarbazine
• Other Study ID Numbers: PTC596-ONC-008-LMS; 2022-000073-12 (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