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

PTC Therapeutics

Status and phase: Active, not recruiting; Phase 3; Phase 2

Conditions: Leiomyosarcoma

Treatments: Other: Placebo; Drug: Dacarbazine; Drug: Unesbulin

Study type: Interventional

Funder types: Industry

Identifiers

NCT05269355

2022-000073-12 (EudraCT Number)

PTC596-ONC-008-LMS

Details and patient eligibility

About

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.

Enrollment: 360 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Triple Blind

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360 participants in 2 patient groups, including a placebo group

Unesbulin and Dacarbazine

Experimental group

Description:

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.

Treatment:

Drug: Unesbulin

Drug: Dacarbazine

Placebo and Dacarbazine

Placebo Comparator group

Description:

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.

Treatment:

Drug: Dacarbazine

Other: Placebo