A Study of PRT7732, an Oral SMARCA2 Degrader, in Patients With Advanced or Metastatic Solid Tumors With a SMARCA4 Mutation
- Conditions
- Metastatic Solid TumorAdvanced Solid TumorNon-small Cell Lung CarcinomaSMARCA4 Mutation
- Interventions
- Registration Number
- NCT06560645
- Lead Sponsor
- Prelude Therapeutics
- Brief Summary
This is a Phase 1 study to determine the safety, tolerability, pharmacokinetics, pharmacodynamics, and preliminary efficacy of PRT7732 in patients with select advanced or metastatic solid tumors with a SMARCA4 mutation.
- Detailed Description
This is an open-label, multi-center, first-in-human, Phase 1 study to determine the safety, tolerability, pharmacokinetics, pharmacodynamics, and preliminary efficacy of PRT7732 an oral SMARCA degrader in patients with select advanced or metastatic solid tumors with a SMARCA4 mutation. Approximately 104 participants will be enrolled.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 104
- Willing and able to comply with all scheduled visits, treatment plan, laboratory tests, lifestyle considerations (including contraception requirements), and other study procedures
- Histologically confirmed advanced, recurrent, or metastatic solid tumor malignancy with any mutation of SMARCA4 by local testing that has either progressed on or is ineligible for standard of care therapy
- Must have measurable or non-measurable (but evaluable) disease per RECIST v1.1
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
- Willing to provide either archival or fresh tumor tissue sample
- Adequate organ function (hematology, renal, and hepatic)
- Participants with solid tumors with known concomitant SMARCA2 mutation or loss of protein expression
- Clinically significant or uncontrolled cardiac disease, uncontrolled electrolyte disorders, uncontrolled or symptomatic central nervous system (CNS) metastases or leptomeningeal disease
- History of another malignancy within 3 years except for adequately treated basal cell or squamous cell skin cancer, superficial bladder cancer, prostate intraepithelial neoplasm, carcinoma in situ of the cervix, or other non-invasive or indolent malignancies, or malignancies previously treated with curative intent and not on active therapy or expected to require treatment or recurrence during the study
- Receipt of any targeted therapy directed against BRM/BRG1 (SMARCA2/SMARCA4).
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description PRT7732 PRT7732 PRT7732 is administered as an oral capsule once daily. Dose escalation/de-escalation decisions will be guided by the BLRM method until the RDE is determined.
- Primary Outcome Measures
Name Time Method Safety and tolerability of PRT7732 as measured by incidence of laboratory deviations Baseline through study completion, an average of 2 years Safety and tolerability will be evaluated by laboratory measurements
Recommended dose for expansion (RDE) of PRT7732 Baseline through study completion, an average of 2 years The RDE will be determined by the sponsor based on the Safety Review Committee's recommendation considering the totality of the available clinical safety, clinical efficacy, pharmacokinetics (PK), and pharmacodynamic data
Dose Limiting toxicity (DLT) of PRT7732 Baseline through Day 21 Incidence of dose limiting toxicities for patients in the dose escalation phase
Safety and tolerability of PRT7732 as measured by incidence of DLTs Baseline through completion of study, an average of 2 years Safety and tolerability will be evaluated by incidence of DLTs
Safety and tolerability as measured by rates of dose modification due to AEs according to NCI CTCAE Baseline through study completion, an average of 2 years Safety and tolerability will be evaluated by dose interruption, modification, and discontinuation due to adverse events (AEs) according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE)
Maximum tolerated dose (MTD) of PRT7732 Baseline through study completion, an average of 2 years Maximum tolerated dose will be determined by the sponsor based on the Safety Review Committee's recommendation considering the totality of the available clinical safety, clinical efficacy, pharmacokinetics (PK), and pharmacodynamic data
- Secondary Outcome Measures
Name Time Method Efficacy of PRT7732 Baseline through study completion, an average of 2 years Best overall response of either complete response (CR) or partial response (PR), as assessed by the investigator per RECIST v1.1
Pharmacokinetic profile of PRT7732 as a single agent: Time of maximum concentration (Tmax) and half-life (T1/2) Baseline through study completion, an average of 2 years Pharmacokinetic parameters will be calculated using standard non-compartmental techniques
Pharmacodynamic effects of PRT7732 as a single agent Baseline through study completion, an average of 2 years The pharmacodynamic effect of PRT7732 demonstrating target engagement by assessment of SMARCA2 protein in peripheral blood mononuclear cells and tumor tissue as assessed by reduction in protein levels of SMARCA2 in peripheral blood mononuclear cells and/or tumor tissue
Pharmacokinetic profile of PRT7732 as a single agent: Area under the curve Baseline through study completion, an average of 2 years Pharmacokinetics will be calculated including the area under the plasma concentration versus time curve (AUC)
Pharmacokinetic profile of PRT7732 as a single agent: Maximum observed plasma concentration Baseline through study completion, an average of 2 years Pharmacokinetics will be calculated including the maximum observed plasma concentration
Trial Locations
- Locations (22)
UCSF Helen Diller Family Comprehensive Cancer Center
🇺🇸San Francisco, California, United States
Brigitte Harris Cancer Pavilion
🇺🇸Detroit, Michigan, United States
Memorial Sloan Kettering Cancer Center - Main Campus
🇺🇸New York, New York, United States
University Hospitals Cleveland Medical Center
🇺🇸Cleveland, Ohio, United States
Hospital of the University of Pennsylvania
🇺🇸Philadelphia, Pennsylvania, United States
SCRI Oncology Partners
🇺🇸Nashville, Tennessee, United States
The University of Texas MD Anderson Cancer Center
🇺🇸Houston, Texas, United States
University of Virginia Comprehensive Cancer Center
🇺🇸Charlottesville, Virginia, United States
Southern Highlands Cancer Centre
🇦🇺Bowral, New South Wales, Australia
Scientia Clinical Research Ltd
🇦🇺Randwick, New South Wales, Australia
Monash Health
🇦🇺Clayton, Victoria, Australia
Linear Clinical Research Ltd
🇦🇺Nedlands, Western Australia, Australia
University Clinic Cologne, Clinic for Internal Medicine
🇩🇪Cologne, North Rhine-Westfalia, Germany
Technische Universitat Dresden, Medizinlsche Fakultat Carl Gustav Carus Nationales Centrum fur Tumorerkrankungen Dresden, Early Clinical Trial Unit (NCT/UCC ECTU)
🇩🇪Dresden, Saxony, Germany
National Cancer Center Hospital
🇯🇵Chuo Ku, Tokyo, Japan
Cancer Institute Hospital of JFCR
🇯🇵Koto-ku, Tokyo, Japan
National Cancer Center
🇰🇷Goyang-Si, Gyeonggi-do, Korea, Republic of
Severance Hospital, Yonsei University Health System
🇰🇷Seoul, Korea, Republic of
Samsung Medical Center
🇰🇷Seoul, Korea, Republic of
Hospital Universitario Vall d'Hebron
🇪🇸Barcelona, Spain
Start Madrid-FJD, Hospital Universitario Fundacion Jimenez Diaz-Servicio de Oncologia
🇪🇸Madrid, Spain
Hospital Universitario HM Sanchinarro
🇪🇸Madrid, Spain