Combining PRT3789 with Pembrolizumab for Patients with Advanced Solid Tumors and SMARCA4 Mutation
A Phase 2, Safety and Efficacy Study of PRT3789 in Combination With Pembrolizumab in Patients With Advanced or Metastatic Solid Tumors With a SMARCA4 Mutation
This study is testing if a new drug called PRT3789, when combined with pembrolizumab, can help people with advanced solid tumors that have a SMARCA4 mutation feel better and respond to treatment.
Quick facts
| Phase | Phase 2 |
|---|---|
| Study type | Interventional |
| Enrollment | 60 (estimated) |
| Ages | 18 Years and up |
| Sex | All |
| Sponsor | Prelude Therapeutics Industry-sponsored |
| Drugs / interventions | pembrolizumab |
| Locations | 9 sites (West Palm Beach, Florida and 8 other locations) |
| Trial ID | NCT06682806 on ClinicalTrials.gov |
What this trial studies
This Phase 2 open-label, multi-center study evaluates the safety and efficacy of PRT3789, a targeted protein degrader, in combination with pembrolizumab, an immunotherapy agent, for patients with advanced or metastatic solid tumors harboring a SMARCA4 mutation. The study consists of two parts: a safety run-in to determine the appropriate dosage of PRT3789, followed by a main study assessing the overall response rate and duration of response in patients with specific tumor types. Approximately 46 to 60 patients will be enrolled across both parts of the study.
Who should consider this trial
Good fit: Ideal candidates include patients with advanced, recurrent, or metastatic solid tumors, specifically esophageal cancer or non-small cell lung cancer, with a confirmed SMARCA4 mutation.
Not a fit: Patients without a SMARCA4 mutation or those who have not progressed on standard of care therapy may not benefit from this study.
Why it matters
Potential benefit: If successful, this combination therapy could provide a new treatment option for patients with advanced solid tumors that have a SMARCA4 mutation.
How similar studies have performed: While this approach is novel in targeting SMARCA4 mutations specifically, similar studies combining targeted therapies with immunotherapy have shown promise in other contexts.
Eligibility criteria
Show full inclusion / exclusion criteria
Inclusion Criteria: * Patients who are willing and able to comply with all scheduled visits, treatment plan, laboratory tests, lifestyle considerations and other study procedures, including providing informed consent. * Patients must either progress on standard of care therapy or be ineligible for standard of care therapy in order to be eligible for enrollment on the study. * Part 1 Safety Run-in: Patients with advanced, recurrent, or metastatic histologically or cytologically confirmed solid tumor malignancy and any mutation of SMARCA4 detected by next generation sequencing in tumor tissue or blood, or absence of SMARCA4 protein (BRG1). Part 2 Main Study: Patients with advanced, recurrent, or metastatic histologically confirmed esophageal cancer or NSCLC and have a deleterious SMARCA4 mutation, or absence of SMARCA4 protein (BRG1) detected by immunohistochemistry in tumor tissue using a clinically validated laboratory test. * Part 1 Run-in: Measurable or non-measurable (but evaluable) disease per RECIST v1.1 as assessed by the local site investigator/radiologist. Part 2 Main Study: Measurable disease per RECIST v1.1 as assessed by the local site investigator/radiologist. Lesions situated in a previously irradiated area are considered measurable if progression has been shown in such lesions. * Willingness and ability to provide tumor tissue (i.e., archived or fresh tumor biopsy if archived tumor tissue is unavailable) * Adequately controlled blood pressure with or without antihypertensive medications. * Patients with HIV must have well-controlled HIV on antiretroviral therapy. * Adequate organ function Exclusion Criteria: * Patients who have adverse events due to previous anticancer therapies and/or complications from prior surgical intervention must have recovered to ≤ Grade 1 or baseline before starting study treatment. Patients with endocrine-related AEs who are adequately treated with hormone replacement or patients who have ≤ Grade 2 neuropathy are eligible. * Other acute or chronic medical or psychiatric conditions that would make the patient inappropriate for entry into this study. * Patients with solid tumors with a known concomitant SMARCA2 mutation or loss of protein expression. * Uncontrolled or symptomatic central nervous system (CNS) metastases or leptomeningeal disease and/or carcinomatous meningitis). * History of or current (noninfectious) pneumonitis/interstitial lung disease * Diagnosis of immunodeficiency disease/disorder. * Known additional malignancy that is progressing or has required active treatment within the past 3 years. * Patients who received prior treatment with an agent directed to a stimulatory or co-inhibitory T-cell receptor. * Currently taking a strong or moderate CYP3A4 inhibitor or inducer and St. John's Wort and are unable to discontinue use within 15 days of the first dose of study treatment. * Receipt of any targeted therapy directed against BRM/BRG1 (SMARCA2/SMARCA4). * Pregnant or breastfeeding or plan to become pregnant during the duration of the study.
Where this trial is running
West Palm Beach, Florida and 8 other locations
- Florida Cancer Specialists — West Palm Beach, Florida, United States (Recruiting)
- Karmanos Cancer Institute — Detroit, Michigan, United States (Recruiting)
- John Theurer Cancer Center at Hackensack University Medical Center — Hackensack, New Jersey, United States (Recruiting)
- SCRI Oncology Partners — Nashville, Tennessee, United States (Recruiting)
- Tennessee Oncology, PLLC - Greco-Hainsworth Centers for Research — Nashville, Tennessee, United States (Recruiting)
- The University of Texas MD Anderson Cancer Center — Houston, Texas, United States (Recruiting)
- IOB - Next Oncology - Hospital Quironsalud Barcelona — Barcelona, Spain (Not_yet_recruiting)
- START Barcelona - HM Nou Delfos — Barcelona, Spain (Recruiting)
- Hospital Universitario Fundacion Jimenez Diaz - Servicio de Oncologia — Madrid, Spain (Recruiting)
Study contacts
- Study coordinator: Study Contact (Please Do Not Disclose Personal Information)
- Email: clinicaltrials@preludetx.com
- Phone: See Email
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.