Clinical trial NCT06560645: A Study of PRT7732, an Oral SMARCA2 Degrader, in Patients With Advanced or Metastatic Solid Tumors With a SMARCA4 Mutation
Official title: A Phase 1 Open-Label, Multi-Center, Safety and Efficacy Study of PRT7732, an Oral SMARCA2 Degrader, in Patients With Advanced or Metastatic Solid Tumors With a SMARCA4
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Advanced Solid Tumor
Metastatic Solid Tumor
Non-small Cell Lung Carcinoma
SMARCA4 Mutation
Keywords: Advanced Solid Tumors
BRG1
BRM
Degrader
Metastatic Solid Tumors
Non-Small Cell Lung Cancers
NSCLC
PRT7732
SMARCA2
SMARCA4
Lead sponsor: Prelude Therapeutics
Sponsor class: INDUSTRY
First posted: 2024-08-19
Enrollment: 104
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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.

Eligibility criteria: Inclusion Criteria:

* 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)

Exclusion Criteria:

* 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).

Primary outcomes:
measure: Dose Limiting toxicity (DLT) of PRT7732
timeFrame: Baseline through Day 21
measure: Safety and tolerability of PRT7732 as measured by incidence of DLTs
timeFrame: Baseline through completion of study, an average of 2 years
measure: Safety and tolerability of PRT7732 as measured by incidence of laboratory deviations
timeFrame: Baseline through study completion, an average of 2 years
measure: Safety and tolerability as measured by rates of dose modification due to AEs according to NCI CTCAE
timeFrame: Baseline through study completion, an average of 2 years
measure: Maximum tolerated dose (MTD) of PRT7732
timeFrame: Baseline through study completion, an average of 2 years
measure: Recommended dose for expansion (RDE) of PRT7732
timeFrame: Baseline through study completion, an average of 2 years
Secondary outcomes:
measure: Efficacy of PRT7732
timeFrame: Baseline through study completion, an average of 2 years
measure: Pharmacokinetic profile of PRT7732 as a single agent: Maximum observed plasma concentration
timeFrame: Baseline through study completion, an average of 2 years
measure: Pharmacokinetic profile of PRT7732 as a single agent: Area under the curve
timeFrame: Baseline through study completion, an average of 2 years
measure: Pharmacokinetic profile of PRT7732 as a single agent: Time of maximum concentration (Tmax) and half-life (T1/2)
timeFrame: Baseline through study completion, an average of 2 years
measure: Pharmacodynamic effects of PRT7732 as a single agent
timeFrame: Baseline through study completion, an average of 2 years
Other outcomes:
Locations:
city: San Francisco
country: United States
facility: UCSF Helen Diller Family Comprehensive Cancer Center
state: California
city: Westwood
country: United States
facility: University of Kansas Cancer Center
state: Kansas
city: Detroit
country: United States
facility: Brigitte Harris Cancer Pavilion
state: Michigan
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center - Main Campus
state: New York
city: Cleveland
country: United States
facility: University Hospitals Cleveland Medical Center
state: Ohio
city: Philadelphia
country: United States
facility: Hospital of the University of Pennsylvania
state: Pennsylvania
city: Nashville
country: United States
facility: SCRI Oncology Partners
state: Tennessee
city: Houston
country: United States
facility: The University of Texas MD Anderson Cancer Center
state: Texas
city: Charlottesville
country: United States
facility: University of Virginia Comprehensive Cancer Center
state: Virginia
city: Albury
country: Australia
facility: Border Medical Oncology Research Unit
state: New South Wales
city: Bowral
country: Australia
facility: Southern Highlands Cancer Centre
state: New South Wales
city: Randwick
country: Australia
facility: Scientia Clinical Research Ltd
state: New South Wales
city: Clayton
country: Australia
facility: Monash Health
state: Victoria
city: Nedlands
country: Australia
facility: Linear Clinical Research Ltd
state: Western Australia
city: Cologne
country: Germany
facility: University Clinic Cologne, Clinic for Internal Medicine
state: North Rhine-Westfalia
city: Dresden
country: Germany
facility: Technische Universitat Dresden, Medizinlsche Fakultat Carl Gustav Carus Nationales Centrum fur Tumorerkrankungen Dresden, Early Clinical Trial Unit (NCT/UCC ECTU)
state: Saxony
city: Chuo Ku
country: Japan
facility: National Cancer Center Hospital
state: Tokyo
city: Koto-ku
country: Japan
facility: Cancer Institute Hospital of JFCR
state: Tokyo
city: Goyang-Si
country: Korea, Republic of
facility: National Cancer Center
state: Gyeonggi-do
city: Seoul
country: Korea, Republic of
facility: Severance Hospital, Yonsei University Health System
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center
city: Barcelona
country: Spain
facility: Hospital Universitario Vall d'Hebron
city: Madrid
country: Spain
facility: Start Madrid-FJD, Hospital Universitario Fundacion Jimenez Diaz-Servicio de Oncologia
city: Madrid
country: Spain
facility: Hospital Universitario HM Sanchinarro
Study officials:
References: