Advanced Solid TumorPhase 1NCT05639751
PRT3789 Monotherapy and in Combo w/Docetaxel in Participants w/Advanced or Metastatic Solid Tumors w/SMARCA4 Mutation
A Phase 1 study testing PRT3789 and Docetaxel in people with Advanced Solid Tumor and Metastatic Solid Tumor, run by Prelude Therapeutics Incorporated at 32 sites in 5 countries.
Trial summary
This is a Phase 1 dose-escalation study of PRT3789, a SMARCA2 degrader, in participants with advanced or metastatic solid tumors with loss of SMARCA4 due to truncating mutation and/or deletion. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Advanced Solid Tumor, Metastatic Solid Tumor, Non-small Cell Lung Cancers
- What is being tested?
- PRT3789 and Docetaxel
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 135 participants
- Where
- 32 sitesin 5 countries
- Study dates
- 2 May 2023to 1 Oct 2025
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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 (dose escalation and combination cohorts) and loss of function mutation of SMARCA4 (backfill cohorts) by local testing that have either progress on or ineligible for standard of care therapy
- Must have measurable or non-measureable (but evaluable) disease per RECIST v1.1 for dose escalation and combination cohorts
- Must have measureable diseases per RECIST v1.1 for backfill cohort
- 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)
Who cannot join
- 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 noninvasive 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
- Concurrent treatment with strong or moderate CYP3A4 inhibitor or inducer
Trial locations and contacts
32 sites in 5 countries.
32 sites in 5 countries
United States20 sites
Winship Cancer Institute
Atlanta, Georgia, 30322
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Baltimore, Maryland, 21287
Massachusetts General Hospital
Boston, Massachusetts, 02114
Dana Farber Cancer Institute
Boston, Massachusetts, 02215
AdventHealth Medical Group Oncology Research at Celebration
Celebration, Florida, 34747
Northwestern Memorial Hospital
Chicago, Illinois, 60611
University Hospitals Cleveland Medical Center
Cleveland, Ohio, 44106
Cleveland Clinic
Cleveland, Ohio, 44195
NEXT Virginia
Fairfax, Virginia, 22031
The University of Texas MD Anderson Cancer Center
Houston, Texas, 77030
Mayo Clinic, Jacksonville
Jacksonville, Florida, 32224
Smilow Cancer Hospital Phase 1 Unit
New Haven, Connecticut, 06511
Laura & Isaac Perlmutter Cancer Center at NYU Langone Health
New York, New York, 10016
New York Presbyterian Hospital - Columbia University Medical Center
New York, New York, 10032
Memorial Sloan Kettering Cancer Center
New York, New York, 10065
Providence Cancer Institute Franz Clinic
Portland, Oregon, 97213
Mayo Clinic, Rochester
Rochester, Minnesota, 55905
University of California, Davis Comprehensive Cancer Center
Sacramento, California, 95817
UCLA Hematology/Oncology - Santa Monica
Santa Monica, California, 90404
Washington University School of Medicine - Siteman Cancer Center
St Louis, Missouri, 63110
France5 sites
lnstitut Bergonie Centre Regionale de Lutte Contre le cancer, Service Oncologie-Medicale
Bordeaux, 33000
Centre Leon Berard
Lyon, 69373
lnstitut Paoli Calmettes
Marseille, 13009
Oncopole Claudius Regaud IUCT ONCOPOLE
Toulouse, 31059
Institut Gustave Roussy
Villejuif, 94805
Spain4 sites
START Barcelona - HM Nou Delfos
Barcelona, Barcelona, 08023
Hospital Universitario Vall d'Hebron
Barcelona, 08035
START MADRID - FJD Hospital Universitario Fundacion Jimenez Diaz
Madrid, Madrid, 28040
Hospital Universitario HM Sanchinarro
Madrid, Madrid, 28050
Singapore2 sites
National University Hospital
Singapore, Singapore, 119074
National Cancer Centre Singapore
Singapore, Singapore, 168583
About this study
Official title: A Phase 1 Open-Label, Multi-Center, Safety and Efficacy Study of PRT3789 as Monotherapy and in Combination With Docetaxel in Participants With Advanced or Metastatic Solid Tumors With a SMARCA4 Mutation
This is a Phase 1 dose-escalation study of PRT3789, a SMARCA2 degrader, in participants with advanced or metastatic solid tumors with loss of SMARCA4 due to truncating mutation and/or deletion. The purpose of this study is to evaluate the safety, tolerability, pharmacokinetic (PK), and pharmacodynamic (PD) of PRT3789 monotherapy and in combination with docetaxel, describe any dose limiting toxicities (DLTs), define the dosing schedule, and to determine the maximum tolerated dose (MTD) and recommended phase 2 dose (RP2D) to be used in subsequent development of PRT3789.
Read the detailed description
This is an open-label, multi-center, dose-escalation, first in human, Phase 1 study of PRT3789 as monotherapy and in combination with docetaxel, a SMARCA2 degrader, evaluating participants with advanced or metastatic solid tumors with loss of SMARCA4 due to truncating mutation and/or deletion. The study will evaluate escalating doses of PRT3789 until the MTD or RP2D is determined. Taking into account pharmacokinetic and pharmacodynamic data from the preceding dose levels, the dose may be escalated until a dose limiting toxicity is identified. Approximately 186 participants will be enrolled in monotherapy, dose escalation, backfill, and combination cohorts.
- Conditions
- Advanced Solid Tumor, Metastatic Solid Tumor, Non-small Cell Lung Cancers, SMARCA4 Gene Mutation
- Being tested
- PRT3789, Docetaxel
- Keywords
- Advanced Solid Tumors, BRG1, BRM, Metastatic Solid Tumors, Non-Small Cell Lung Cancers, NSCLC, PRT3789, SMARCA2 Degrader, SMARCA4, Docetaxel
- Medical subject headings
- Neoplasm Metastasis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PRT3789Drug
PRT3789 will be administered by intravenous infusion
DocetaxelDrug
Docetaxel will be administered by intravenous infusion
| Study group | Role | What they receive |
|---|---|---|
| PRT3789 Monotherapy | Experimental | PRT3789 will be administered by intravenous infusion Receives: Drug: PRT3789 |
| PRT3789/Docetaxel Combination | Experimental | PRT3789 and Docetaxel will be administered by intravenous infusions Receives: Drug: PRT3789; Drug: Docetaxel |
What is being measured
The primary outcome is the main question the study is designed to answer.
Dose limiting toxicity (DLT) of PRT3789 monotherapy and in combination with docetaxel
Dose limiting toxicities will be evaluated over the 21-day observation period
Measured: Baseline through Day 21
Safety and tolerability of PRT3789 monotherapy and in combination with docetaxel: AEs, CTCAE Assessments
Safety and tolerability will be evaluated by incidence of DLTs, laboratory measurements, dose interruption, modification, and discontinuation due to adverse events (AEs) according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE)
Measured: Baseline through approximately 3 years
Maximum tolerated dose (MTD)/ Recommended phase 2 dose (RP2D) of PRT3789 monotherapy and in combination with docetaxel
The MTD/RP2D will be established for further investigation in participants with advanced solid tumors
Measured: Baseline through approximately 3 years
Secondary outcomes (7)
Efficacy of PRT3789 monotherapy and in combination with docetaxel: Objective response rate (ORR)
Best overall response of either complete response (CR) or partial response (PR), as assessed by the investigator per RECIST v1.1
Measured: Baseline through approximately 3 years
Efficacy of PRT3789 monotherapy and in combination with docetaxel: Progression-free survival (PFS)
Duration from Day 1 to the earliest date of first disease progression, as assessed by the investigator per RECIST v1.1, discontinuation because of disease progression, or death due to any cause
Measured: Baseline through approximately 3 years
Efficacy of PRT3789 monotherapy and in combination with docetaxel: Clinical benefit rate (CBR)
Best overall response of CR, PR, or durable stable disease (24 weeks or longer duration), as assessed by the investigator per RECIST v1.1
Measured: Baseline through approximately 3 years
Efficacy of PRT3789 monotherapy and in combination with docetaxel: Duration of response (DOR)
Duration from time of first observed response (CR or PR) to the earliest date of disease progression, as assessed by the investigator per RECIST v1.1, or death due to any cause
Measured: Baseline through approximately 3 years
Pharmacokinetic profile of PRT3789 monotherapy and in combination with docetaxel: Maximum observed plasma concentration
Pharmacokinetics will be calculated including the maximum observed plasma concentration
Measured: Baseline through approximately 3 years
Pharmacokinetic profile of PRT3789 monotherapy and in combination with docetaxel: Area under the curve
Pharmacokinetics will be calculated including the area under the plasma concentration versus time curve (AUC)
Measured: Baseline through approximately 3 years
Pharmacodynamic effect of PRT3789 monotherapy and in combination with docetaxel: Target engagement
Pharmacodynamic effect of PRT3789 monotherapy and in combination with docetaxel demonstrating target engagement by assessment of SMARCA2 protein in peripheral blood mononuclear cells (PBMCs) and tumor tissue
Measured: Baseline through approximately 3 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Dec 2022
- Study start2 May 2023
- Primary completion1 Oct 2025
- Study completion1 Oct 2025
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Advanced Solid TumorStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 135 participants (actual)
Sponsor and investigators
- Lead sponsor
- Prelude Therapeutics Incorporated
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05639751
- Sponsor's protocol ID
- PRT3789-01
- Status last verified
- Oct 2025
- First submitted
- 11 Nov 2022
- Last updated
- 16 Oct 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 16 Oct 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1 Open-Label, Multi-Center, Safety and Efficacy Study of PRT3789 as Monotherapy and in Combination With Docetaxel in Participants With Advanced or Metastatic Solid Tumors With a SMARCA4 Mutation
- ClinicalTrials.gov ID
- NCT05639751
- Acronym / sponsor ID
- PRT3789-01
- Conditions
- Advanced Solid Tumor, Metastatic Solid Tumor, Non-small Cell Lung Cancers, SMARCA4 Gene Mutation
- Keywords
- Advanced Solid Tumors, BRG1, BRM, Metastatic Solid Tumors, Non-Small Cell Lung Cancers, NSCLC, PRT3789, SMARCA2 Degrader
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 135 participants (actual)
- Lead sponsor
- Prelude Therapeutics IncorporatedIndustry (pharma, biotech, devices)
- Study start
- 2 May 2023 (actual)
- Primary completion
- 1 Oct 2025 (actual)
- Study completion
- 1 Oct 2025 (actual)
- First posted
- 6 Dec 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is a Phase 1 dose-escalation study of PRT3789, a SMARCA2 degrader, in participants with advanced or metastatic solid tumors with loss of SMARCA4 due to truncating mutation and/or deletion. The purpose of this study is to evaluate the safety, tolerability, pharmacokinetic (PK), and pharmacodynamic (PD) of PRT3789 monotherapy and in combination with docetaxel, describe any dose limiting toxicities (DLTs), define the dosing schedule, and to determine the maximum tolerated dose (MTD) and recommended phase 2 dose (RP2D) to be used in subsequent development of PRT3789.
Detailed description
This is an open-label, multi-center, dose-escalation, first in human, Phase 1 study of PRT3789 as monotherapy and in combination with docetaxel, a SMARCA2 degrader, evaluating participants with advanced or metastatic solid tumors with loss of SMARCA4 due to truncating mutation and/or deletion. The study will evaluate escalating doses of PRT3789 until the MTD or RP2D is determined. Taking into account pharmacokinetic and pharmacodynamic data from the preceding dose levels, the dose may be escalated until a dose limiting toxicity is identified. Approximately 186 participants will be enrolled in monotherapy, dose escalation, backfill, and combination cohorts.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| PRT3789 Monotherapy | Experimental | Drug: PRT3789PRT3789 will be administered by intravenous infusion |
| PRT3789/Docetaxel Combination | Experimental | Drug: PRT3789, Drug: DocetaxelPRT3789 and Docetaxel will be administered by intravenous infusions |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- 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 (dose escalation and combination cohorts) and loss of function mutation of SMARCA4 (backfill cohorts) by local testing that have either progress on or ineligible for standard of care therapy
- Must have measurable or non-measureable (but evaluable) disease per RECIST v1.1 for dose escalation and combination cohorts
- Must have measureable diseases per RECIST v1.1 for backfill cohort
- Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1
Key exclusion criteria (4 listed)
- 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 noninvasive 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
- Concurrent treatment with strong or moderate CYP3A4 inhibitor or inducer
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| PRT3789PRT3789 will be administered by intravenous infusion | Drug | PRT3789 Monotherapy, PRT3789/Docetaxel Combination |
| DocetaxelDocetaxel will be administered by intravenous infusion | Drug | PRT3789/Docetaxel Combination |
Primary outcome
Dose limiting toxicity (DLT) of PRT3789 monotherapy and in combination with docetaxel
Time frame: Baseline through Day 21
Dose limiting toxicities will be evaluated over the 21-day observation period
Safety and tolerability of PRT3789 monotherapy and in combination with docetaxel: AEs, CTCAE Assessments
Time frame: Baseline through approximately 3 years
Safety and tolerability will be evaluated by incidence of DLTs, laboratory measurements, 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)/ Recommended phase 2 dose (RP2D) of PRT3789 monotherapy and in combination with docetaxel
Time frame: Baseline through approximately 3 years
The MTD/RP2D will be established for further investigation in participants with advanced solid tumors
7 secondary outcomes
Efficacy of PRT3789 monotherapy and in combination with docetaxel: Objective response rate (ORR)
Time frame: Baseline through approximately 3 years
Efficacy of PRT3789 monotherapy and in combination with docetaxel: Progression-free survival (PFS)
Time frame: Baseline through approximately 3 years
Efficacy of PRT3789 monotherapy and in combination with docetaxel: Clinical benefit rate (CBR)
Time frame: Baseline through approximately 3 years
Efficacy of PRT3789 monotherapy and in combination with docetaxel: Duration of response (DOR)
Time frame: Baseline through approximately 3 years
Pharmacokinetic profile of PRT3789 monotherapy and in combination with docetaxel: Maximum observed plasma concentration
Time frame: Baseline through approximately 3 years
Pharmacokinetic profile of PRT3789 monotherapy and in combination with docetaxel: Area under the curve
Time frame: Baseline through approximately 3 years
Pharmacodynamic effect of PRT3789 monotherapy and in combination with docetaxel: Target engagement
Time frame: Baseline through approximately 3 years
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 Oct 2025.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
32 sites in 5 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing PRT3789 and Docetaxel in people with Advanced Solid Tumor and Metastatic Solid Tumor, run by Prelude Therapeutics Incorporated at 32 sites in 5 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 16 Oct 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 32 sites in United States, France, Spain, Singapore, Netherlands. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Dose limiting toxicity (DLT) of PRT3789 monotherapy and in combination with docetaxel (time frame: Baseline through Day 21). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 16 Oct 2025.