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

Study Overview
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Brief Summary
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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.

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

Conditions
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Leiomyosarcoma

Intervention / Treatment
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* Drug: Unesbulin
* Drug: Dacarbazine
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Unesbulin and Dacarbazine<br>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<br>* Unesbulin will be administered as per the dose and schedule specified in the arm description.<br>* Other names: PTC596;Drug: Dacarbazine<br>* Dacarbazine will be administered as per the dose and schedule specified in the arm description.<br>* Other names: DTIC;|
| Placebo Comparator: Placebo and Dacarbazine<br>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<br>* Dacarbazine will be administered as per the dose and schedule specified in the arm description.<br>* Other names: DTIC;Other: Placebo<br>* Placebo will be administered as per the schedule specified in the arm description.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free Survival per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 Assessed by an Independent Central Imaging Laboratory |  | From the date of randomization to the date of the first documented tumor progression or death due to any cause, whichever occurs first (up to approximately 2 years) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Survival |  | From the date of randomization to the date of death due to any cause (up to approximately 2 years) | 
| Objective Response Rate (ORR) | ORR is defined as the number of participants who achieve a confirmed best overall response (BOR) of complete response (CR) or partial response (PR) using RECIST 1.1 as per independent radiologist assessment. | From the date of randomization until the date of objectively documented progression or the date of initiation of subsequent therapy or palliative local therapy, whichever occurs first (up to approximately 2 years) | 
| Disease Control Rate (DCR) | DCR is defined as the number of participants with BOR of CR, PR, or at least 3 months of stable disease using RECIST 1.1 as per independent radiologist assessment. | From the date of randomization until the date of the first documented tumor progression or the date of initiation of subsequent therapy or palliative local therapy, whichever occurs first (up to approximately 2 years) | 
| Duration of Response per RECIST 1.1 Assessed by an Independent Central Imaging Laboratory |  | Time from the date of first confirmed response to the date of the first documented tumor progression or death due to any cause, whichever occurs first (up to approximately 2 years) | 
| Number of Participants with Treatment-emergent Adverse Events |  | From the date of randomization up to approximately 2 years |