PLX-61639 for advanced SMARCA4-deficient solid tumors
A Phase 1, First-in-Human Study of the SMARCA2 Degrader, PLX-61639, in Patients With SMARCA4-Mutated Locally Advanced or Metastatic Solid Tumors
This trial will test a daily oral drug called PLX-61639 in people with advanced or metastatic solid tumors that have a SMARCA4 loss and who have no other approved treatment options.
Quick facts
| Phase | Phase 1 |
|---|---|
| Study type | Interventional |
| Enrollment | 155 (estimated) |
| Ages | 18 Years and up |
| Sex | All |
| Sponsor | Plexium, Inc. Industry-sponsored |
| Locations | 10 sites (Scottsdale, Arizona and 9 other locations) |
| Trial ID | NCT07284186 on ClinicalTrials.gov |
What this trial studies
This is a multicenter, single-arm, first-in-human Phase 1 trial of PLX-61639 given orally once daily to participants with relapsed or refractory, SMARCA4-deficient locally advanced or metastatic solid tumors. The study has three parts: dose escalation to find a safe dose, dose optimization, and cohort expansion to study activity in selected groups. Each participant undergoes up to 28 days of screening, then consecutive 28-day treatment cycles and post-treatment follow-up until progression, intolerance, death, or withdrawal. Key objectives include characterizing safety, pharmacokinetics, and preliminary antitumor activity by RECIST 1.1.
Who should consider this trial
Good fit: Adults with measurable, locally advanced or metastatic solid tumors harboring a SMARCA4 loss-of-function mutation who have progressed on, are intolerant of, or are not candidates for approved therapies, with ECOG 0–1 and adequate organ function are ideal candidates.
Not a fit: Patients with germline SMARCA4 mutations, known SMARCA2 mutation or loss of SMARCA2 expression, symptomatic CNS disease, significant heart disease, prolonged QT, or those who still have effective approved treatment options are unlikely to benefit from this study.
Why it matters
Potential benefit: If successful, PLX-61639 could provide a new targeted oral option that shrinks tumors or slows disease in patients with SMARCA4-deficient cancers who lack effective approved therapies.
How similar studies have performed: This is a first-in-human, SMARCA2-directed approach for SMARCA4-deficient tumors and similar strategies are largely preclinical or early clinical with limited proof of broad clinical benefit so far.
Eligibility criteria
Show full inclusion / exclusion criteria
Key Inclusion Criteria: * Participants with locally advanced or metastatic, relapsed/refractory, solid tumors harboring a SMARCA4 loss-of-function mutation that have progressed on, are intolerant of, or not otherwise candidates for available approved therapies * Adequate liver bone marrow, coagulation, renal, and cardiopulmonary function * Measurable disease per RECIST 1.1 * ECOG PS of 0 or 1 Key Exclusion Criteria: * Germline SMARCA4 mutations * Known SMARCA2 mutation or loss of expression * Symptomatic CNS disease * Prior treatment with another SMARCA2-directed therapy * History of other malignancies * Clinically significant heart disease * Uncontrolled hypertension * Prolongation of QT interval
Where this trial is running
Scottsdale, Arizona and 9 other locations
- Research Site — Scottsdale, Arizona, United States (Recruiting)
- Research Site — Duarte, California, United States (Not_yet_recruiting)
- Research Site — Orange, California, United States (Not_yet_recruiting)
- Research Site — Boston, Massachusetts, United States (Not_yet_recruiting)
- Research Site — St Louis, Missouri, United States (Recruiting)
- Research Site — New York, New York, United States (Recruiting)
- Research Site — Durham, North Carolina, United States (Recruiting)
- Research Site — Cleveland, Ohio, United States (Recruiting)
- Research Site — San Antonio, Texas, United States (Recruiting)
- Research Site — Fairfax, Virginia, United States (Recruiting)
Study contacts
- Study coordinator: Clinical Operations
- Email: ClinicalTrials@Plexium.com
- Phone: 619-631-3091
How to participate
- Review the eligibility criteria above with your treating physician.
- Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
- Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.