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Advanced Solid TumorPhase 2NCT06682806

A Study of PRT3789 in Combination With Pembrolizumab in Patients With Advanced or Metastatic Solid Tumors With a SMARCA4 Mutation

A Phase 2 study testing PRT3789 and pembrolizumab in people with Advanced Solid Tumor and Esophageal Cancer, run by Prelude Therapeutics Incorporated at 9 sites in 2 countries.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial summary

This is a Phase 2 an open-label, multi-center study to determine the safety, tolerability, efficacy, pharmacokinetics, pharmacodynamics, and anti-tumor activity of PRT3789 in combination with pembrolizumab in patients with advanced, recurrent or metastatic solid tumors with a SMARCA4 mutation. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
PRT3789 and pembrolizumab
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
6 participants
Where
9 sitesin 2 countries
Study dates
3 Jun 2025to 23 Jan 2026
Phase
Phase 2
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

  • 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

Who cannot join

  • 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.
Show all 11Show fewer
  • 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.

Trial locations and contacts

9 sites in 2 countries.

9 sites in 2 countries

United States6 sites

  • Karmanos Cancer Institute

    Detroit, Michigan, 48201

  • John Theurer Cancer Center at Hackensack University Medical Center

    Hackensack, New Jersey, 07601

  • The University of Texas MD Anderson Cancer Center

    Houston, Texas, 77030

  • SCRI Oncology Partners

    Nashville, Tennessee, 37203

  • Tennessee Oncology, PLLC - Greco-Hainsworth Centers for Research

    Nashville, Tennessee, 37203

  • Florida Cancer Specialists

    West Palm Beach, Florida, 33401

Other trials in United States

Spain3 sites

  • IOB - Next Oncology - Hospital Quironsalud Barcelona

    Barcelona, 08023

  • START Barcelona - HM Nou Delfos

    Barcelona, 08023

  • Hospital Universitario Fundacion Jimenez Diaz - Servicio de Oncologia

    Madrid, 28040

Other trials in Spain

About this study

Official title: 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 is a Phase 2 an open-label, multi-center study to determine the safety, tolerability, efficacy, pharmacokinetics, pharmacodynamics, and anti-tumor activity of PRT3789 in combination with pembrolizumab in patients with advanced, recurrent or metastatic solid tumors with a SMARCA4 mutation.

Read the detailed description

This is an open-label, multi-center Phase 2 study of PRT 3789, a first-in-class SMARCA2 targeted protein degrader, in combination with pembrolizumab, a potent humanized immunoglobulin G4 (IgG4) monoclonal antibody (mAb) with high specificity of binding to the programmed cell death 1 (PD-1) receptor, evaluating patients with Advanced or Metastatic Solid Tumors with a SMARCA4 Mutation. This study consists of 2 parts. Part 1 is a safety run-in and will establish the dose of PRT3789 to be used in combination with pembrolizumab in the main study (Part 2). For Part 2 (Main study) primary endpoints are ORR (defined as the proportion of patients with a confirmed best overall response of either complete response or partial response) and duration of response per investigator assessment per RECIST v1.1.

Approximately 46 to 60 patients will be enrolled in Part 1 and Part 2 based on the dose of PRT3789 selected/cleared during the safety run-in.

Being tested
PRT3789, pembrolizumab
Keywords
Advanced Solid Tumors, BRG1, BRM, Esophageal Cancer, Metastatic Solid Tumors, Non-Small Cell Lung Cancers, NSCLC, PRT3789, Pembrolizumab, Keytruda®, SMARCA2 Degrader, SMARCA4
Medical subject headings
Esophageal Neoplasms, Neoplasm Metastasis

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • PRT3789Drug

    PRT3789 is administered as an intravenous infusion once weekly for 3 weeks

  • pembrolizumabDrug

    Also called KEYTRUDA®

    Pembrolizumab is administered at 200 mg as an intravenous infusion over 30 min every 3 weeks

Study groups in NCT06682806
Study groupRoleWhat they receive
PRT3789/Pembrolizumab combinationExperimentalPRT3789 is administered as an intravenous infusion once weekly for 3 weeks; Pembrolizumab is administered at 200 mg as an intravenous infusion over 30 min every 3 weeks
Receives: Drug: PRT3789; Drug: pembrolizumab

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Safety and tolerability of PRT3789 in combination with pembrolizumab as measured by incidence of DLTs (Part 1)

    Safety and tolerability will be evaluated by incidence of dose-limiting toxicities (DLTs)

    Measured: Baseline through completion of study, an average of 2 years

  2. Safety and tolerability of PRT3789 in combination with pembrolizumab as measured by incidence and severity of AEs according to NCI CTCAE (Part 1)

    Safety and tolerability will be evaluated by incidence and severity of adverse events (AEs) according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE)

    Measured: Baseline through study completion, an average of 2 years

  3. Efficacy of PRT3789 in combination with pembrolizumab in patients with advanced or metastatic esophageal or NSCLC and deleterious SMARCA4 mutation: Objective Response Rate (Part 2)

    Objective response rate defined as the proportion of patients with a confirmed best overall response of either complete response or partial response, as determined per investigator assessment by RECIST v1.1

    Measured: Baseline through study completion, an average of 2 years

  4. Efficacy of PRT3789 in combination with pembrolizumab in patients with advanced or metastatic esophageal or NSCLC and deleterious SMARCA4 mutation: Duration of Response (Part 2)

    Duration of response defined as the time from the date of the first documented response (complete response or partial response) to the earliest date of disease progression, as determined per investigator assessment by RECIST v1.1, or death due to any cause

    Measured: Baseline through study completion, an average of 2 years

Secondary outcomes (11)

  1. Efficacy of PRT3789 in combination with pembrolizumab: Objective Response Rate (Part 1)

    Objective response rate defined as the proportion of patients with a confirmed best overall response of either complete response or partial response, as determined per investigator assessment by RECIST v1.1

    Measured: Baseline through study completion, an average of 2 years

  2. Efficacy of PRT3789 in combination with pembrolizumab: Duration of Response (Part 1)

    Duration of response defined as the time from the date of the first documented response (complete response or partial response) to the earliest date of disease progression, as determined per investigator assessment by RECIST v1.1, or death due to any cause

    Measured: Baseline through study completion, an average of 2 years

  3. Efficacy of PRT3789 in combination with pembrolizumab (part 1 and part 2): Clinical Benefit Response

    Clinical benefit response defined as the proportion of patients with a best overall response of complete response, partial response, or durable stable disease (24 weeks or longer), as determined per investigator assessment by RECIST v1.1

    Measured: Baseline through study completion, an average of 2 years

  4. Efficacy of PRT3789 in combination with pembrolizumab (part 1 and part 2): Progression-Free Survival

    PFS defined as the time from the date of first dose of investigational product to the date of first documented progressive disease, as determined per investigator assessment by RECIST v1.1, or death due to any cause

    Measured: Baseline through study completion, an average of 2 years

  5. Efficacy of PRT3789 in combination with pembrolizumab (part 1 and part 2): Overall Survival

    Overall survival defined as the time from the date of first dose of investigational product to death due to any cause

    Measured: Baseline through study completion, an average of 2 years

  6. Safety and tolerability of PRT3789 in combination with pembrolizumab as measured by AEs according to NCI CTCAE

    Safety and tolerability will be evaluated by incidence and severity of adverse events (AEs) according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v5.0

    Measured: Baseline through study completion, an average of 2 years

  7. Safety and tolerability of PRT3789 in combination with pembrolizumab: as measured by key clinical laboratory parameters

    Laboratory shift tables reflecting mean and CTCAE grade changes from baseline values for key laboratory analytes of alanine aminotransferase (ALT), aspartate aminotransferase (AST), bilirubin, creatinine, hemoglobin, platelet count, neutrophil count, lymphocyte count, and leukocyte count

    Measured: Baseline through study completion, an average of 2 years

  8. Safety and tolerability as measured by incidence of dose modification due to AEs

    Safety and tolerability will be evaluated by dose interruption, modification, and discontinuation due to adverse events (AEs)

    Measured: Baseline through study completion, an average of 2 years

  9. PK profile of PRT3789 in combination with pembrolizumab: Maximum observed plasma concentration: Maximum observed plasma concentration

    Pharmacokinetics will be calculated including the maximum observed plasma concentration

    Measured: Baseline through study completion, an average of 2 years

  10. PK profile of PRT3789 in combination with pembrolizumab: Area under the curve

    Pharmacokinetics will be calculated including the area under the plasma concentration versus time curve (AUC)

    Measured: Baseline through study completion, an average of 2 years

  11. PK profile of PRT3789 in combination with pembrolizumab: Time of maximum concentration (Tmax) and half-life (T1/2)

    Pharmacokinetic parameters will be calculated using standard non-compartmental techniques

    Measured: Baseline through study completion, an average of 2 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted12 Nov 2024
  2. Study start3 Jun 2025
  3. Primary completion23 Jan 2026
  4. Study completion23 Jan 2026

Why it stopped: Sponsor decision

Resources

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 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Sequential
Masking
None (open label)
Enrolment
6 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT06682806
Sponsor's protocol ID
PRT3789-02
Other IDs
KEYNOTE-G02, MK-3475-G02, 2024-516889-11-00
Status last verified
Jan 2026
First submitted
29 Oct 2024
Last updated
2 Feb 2026
Results posted
No
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing PRT3789 and pembrolizumab in people with Advanced Solid Tumor and Esophageal Cancer, run by Prelude Therapeutics Incorporated at 9 sites in 2 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 8 inclusion and 11 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: stopped early, as of the sponsor's last update on 2 Feb 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 9 sites in United States, Spain. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

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 was stopped early (reason given: Sponsor decision). Results are not available in the source record.

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?

Safety and tolerability of PRT3789 in combination with pembrolizumab as measured by incidence of DLTs (Part 1) (time frame: Baseline through completion of study, an average of 2 years). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT06682806.

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 2 Feb 2026.

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