A Study to Investigate the Safety, Pharmacokinetics, and Preliminary Effectiveness of GSK4418959 Alone or in Combination With Other Anti-cancer Agents in Participants With Solid Tumors (SYLVER)

January 29, 2026 updated by: GlaxoSmithKline

A Phase 1/2 First-Time-in-Human, Open-label, Multicenter, Dose Escalation and Expansion Study of the Oral DNA Helicase Werner Inhibitor (WRNi) GSK4418959 Alone or in Combination With Other Anti-cancer Agents in Adult Participants With Mismatch Repair-deficient (dMMR) or Microsatellite Instability-High (MSI-H) Solid Tumors (SYLVER)

Solid tumours are abnormal lumps of tissue that can occur in different parts of the body. The tumours involved in this study have specific genetic characteristics that can make them more aggressive and challenging to treat. The study will test whether GSK4418959 alone or in combination with a PD-1 inhibitor agent can decrease tumor size, is safe, well-tolerated, and how amounts of the study drug decrease in the body over time.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Active, not recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
14

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Contact Backup

Study Locations

  • Australia
    • Victoria
      • Melbourne, Victoria, Australia, 3000
        • GSK Investigational Site
  • Belgium
      • Brussels, Belgium, 1200
        • GSK Investigational Site
      • Ghent, Belgium, 9000
        • GSK Investigational Site
      • Leuven, Belgium, 3000
        • GSK Investigational Site
  • Japan
      • Chiba, Japan, 277-8577
        • GSK Investigational Site
      • Shizuoka, Japan, 411-8777
        • GSK Investigational Site
      • Tokyo, Japan, 104-0045
        • GSK Investigational Site
      • Tokyo, Japan, 135-8550
        • GSK Investigational Site
  • Netherlands
      • Amsterdam, Netherlands, 1066 CX
        • GSK Investigational Site
  • South Korea
      • Daegu, South Korea, 41404
        • GSK Investigational Site
      • Gyeonggi-do, South Korea, 10408
        • GSK Investigational Site
      • Seoul, South Korea, 03080
        • GSK Investigational Site
  • Spain
      • Barcelona, Spain, 08035
        • GSK Investigational Site
      • Barcelona, Spain, 08023
        • GSK Investigational Site
      • Madrid, Spain, 28040
        • GSK Investigational Site
      • Málaga, Spain, 29010
        • GSK Investigational Site
  • United States
    • California
      • Los Angeles, California, United States, 90095
        • GSK Investigational Site
    • Colorado
      • Denver, Colorado, United States, 80218
        • GSK Investigational Site
    • Michigan
      • Detroit, Michigan, United States, 48201
        • GSK Investigational Site
    • New York
      • New York, New York, United States, 10016
        • GSK Investigational Site
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19107
        • GSK Investigational Site
      • Philadelphia, Pennsylvania, United States, 19104
        • GSK Investigational Site

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

Parts 1, 2, and 3 inclusion criteria:

  • Has a histologically diagnosed advanced (unresectable, metastatic or recurrent) solid tumor
  • Has a known dMMR/MSI-H status as determined by a certified local laboratory at the time of Pre-screening or has an unknown Mismatch repair (MMR)/ Microsatellite Instability (MSI) status at the time of Pre-screening and MMR/MSI status will be determined by central reference laboratory
  • Provides an archival or fresh (preferred) formalin fixed, paraffin embedded (FFPE) sample
  • Intends to receive GSK4418959 (alone or in combination with PD-1 inhibitor, as determined between Investigator and sponsor) as next line of treatment
  • Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0-2
  • Is expected to have a minimum of 3 months life expectancy
  • Has adequate organ function, as defined in the protocol

Parts 1 and 3 inclusion criteria:

• Has histologically diagnosed advanced (unresectable, metastatic or recurrent) solid tumor and has exhausted all standard of care treatment options

Part 2 inclusion criteria:

  • Has histologically diagnosed advanced (unresectable, metastatic or recurrent) Colorectal cancer (CRC) or Endometrial cancer (EC)
  • Has received at least 1 but no more than 3 lines of systemic anticancer therapy for their advanced (unresectable, metastatic or recurrent) disease including at least one line of Immune checkpoint inhibitors (ICI) therapy
  • Has measurable disease (i.e., at least 1 target lesion) during the Screening period per RECIST 1.1, as determined by the investigator

Exclusion Criteria:

Parts 1, 2, and 3 exclusion criteria:

  • Has not recovered (i.e., to Grade ≤1 or to baseline) from prior anticancer therapy-induced AEs
  • Has received prior treatment with a WRN inhibitor
  • Is unable to swallow and retain orally administered study treatment
  • Has symptomatic uncontrolled brain or leptomeningeal metastases
  • Has a known additional malignancy that progressed or required active treatment within the last 2 years because reoccurrence of another malignancy would confound interpretation by RECIST 1.1 criteria. Exceptions include basal cell carcinoma of the skin, squamous cell carcinoma of the skin that has undergone potentially curative therapy, or in situ cancer that is considered to be low risk for progression by the investigator
  • Has any impairment of gastrointestinal function or gastrointestinal disease that may significantly alter the absorption of study drugs
  • Has severe liver fibrosis
  • Has cirrhosis or current unstable liver or biliary disease
  • Has known hypersensitivity to any of the study interventions or any of their excipients
  • Has known WRN syndrome
  • Has an active autoimmune disease that has required systemic treatment in the past 2 years

Part 3 exclusion criteria:

  • Has experienced any of the following with prior immunotherapy: any immune mediated adverse events (imAE) of Grade ≥3, immune-related severe neurologic events of any grade, exfoliative dermatitis of any grade (Stevens-Johnson Syndrome, toxic epidermal necrolysis, or Drug rash with eosinophilia and systemic signs syndrome [DRESS] syndrome), or myocarditis of any grade. Non-clinically significant laboratory abnormalities are not exclusionary
  • Has any history of interstitial lung disease or pneumonitis

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Sequential Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Part 1: Dose escalation of GSK4418959 monotherapy
Participants will receive GSK4418959 as monotherapy.
Drug: GSK4418959
GSK4418959 will be administered.
Experimental: Part 2: Dose expansion of GSK4418959 monotherapy
Participants will receive GSK4418959 as monotherapy.
Drug: GSK4418959
GSK4418959 will be administered.
Experimental: Part 3: Dose escalation of GSK4418959 plus PD-1 inhibitor
Participants will receive GSK4418959 plus PD-1 inhibitor.
Drug: GSK4418959
GSK4418959 will be administered.
Biological: PD-1 inhibitor
PD-1 inhibitor will be administered.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Part 1: Number of participants with dose limiting toxicities (DLTs) during DLT observation period
Time Frame: Up to 21 days
Up to 21 days
Part 3: Number of participants with dose limiting toxicities (DLTs) during DLT observation period
Time Frame: Up to 21 days
Up to 21 days
Part 1: Number of participants with treatment emergent adverse events (TEAEs) during DLT observation period
Time Frame: Up to 21 days
Up to 21 days
Part 3: Number of participants with treatment emergent adverse events (TEAEs) during DLT observation period
Time Frame: Up to 21 days
Up to 21 days
Part 1: Number of participants with dosage interruptions, dose reductions, and drug discontinuations for TEAEs during DLT observation period
Time Frame: Up to 21 days
Up to 21 days
Part 3: Number of participants with dosage interruptions, dose reductions, and drug discontinuations for TEAEs during DLT observation period
Time Frame: Up to 21 days
Up to 21 days
Part 2: Objective Response Rate (ORR)
Time Frame: Up to approximately 26 months
ORR is defined as percentage of participants with confirmed complete response (CR) or partial response (PR) per Response Evaluation Criteria in Solid Tumors, version 1.1 (RECIST 1.1) by investigator assessment.
Up to approximately 26 months

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Part 1: Area under the concentration-time curve (AUC) for GSK4418959
Time Frame: From first day of dosing for the duration of treatment until end of interventional phase (EOI) (up to approximately 42 months)
From first day of dosing for the duration of treatment until end of interventional phase (EOI) (up to approximately 42 months)
Part 1: Maximum concentration (Cmax) for GSK4418959
Time Frame: From first day of dosing for the duration of treatment until end of interventional phase (EOI) (up to approximately 42 months)
From first day of dosing for the duration of treatment until end of interventional phase (EOI) (up to approximately 42 months)
Part 1: Time to maximum concentration (Tmax) for GSK4418959
Time Frame: From first day of dosing for the duration of treatment until end of interventional phase (EOI) (up to approximately 42 months)
From first day of dosing for the duration of treatment until end of interventional phase (EOI) (up to approximately 42 months)
Part 3: AUC for GSK4418959
Time Frame: From first day of dosing for the duration of treatment until end of interventional phase (EOI) (up to approximately 42 months)
From first day of dosing for the duration of treatment until end of interventional phase (EOI) (up to approximately 42 months)
Part 3: Cmax for GSK4418959
Time Frame: From first day of dosing for the duration of treatment until end of interventional phase (EOI) (up to approximately 42 months)
From first day of dosing for the duration of treatment until end of interventional phase (EOI) (up to approximately 42 months)
Part 3: Tmax for GSK4418959
Time Frame: From first day of dosing for the duration of treatment until end of interventional phase (EOI) (up to approximately 42 months)
From first day of dosing for the duration of treatment until end of interventional phase (EOI) (up to approximately 42 months)
Part 1: Number of participants with TEAEs
Time Frame: Up to approximately 42 months
Up to approximately 42 months
Part 2: Number of participants with TEAEs
Time Frame: Up to approximately 42 months
Up to approximately 42 months
Part 3: Number of participants with TEAEs
Time Frame: Up to approximately 42 months
Up to approximately 42 months
Part 1: Number of participants with dosage interruptions, dose reductions, and drug discontinuations for TEAEs
Time Frame: Up to approximately 42 months
Up to approximately 42 months
Part 2: Number of participants with dosage interruptions, dose reductions, and drug discontinuations for TEAEs
Time Frame: Up to approximately 42 months
Up to approximately 42 months
Part 3: Number of participants with dosage interruptions, dose reductions, and drug discontinuations for TEAEs
Time Frame: Up to approximately 42 months
Up to approximately 42 months
Part 1: Number of participants with clinical laboratory abnormalities
Time Frame: Up to approximately 42 months
Up to approximately 42 months
Part 2: Number of participants with clinical laboratory abnormalities
Time Frame: Up to approximately 42 months
Up to approximately 42 months
Part 3: Number of participants with clinical laboratory abnormalities
Time Frame: Up to approximately 42 months
Up to approximately 42 months
Part 2: Progression-free Survival (PFS)
Time Frame: Up to approximately 42 months
PFS is defined as time from first dose to progressive disease (as assessed per RECIST 1.1 by Investigator assessment) or death from any cause, whichever is earlier.
Up to approximately 42 months
Part 2: Duration of Response (DoR)
Time Frame: Up to approximately 42 months
DoR is defined as time from first documented PR or CR to progressive disease (as assessed per RECIST 1.1 by investigator assessment) or death from any cause, whichever is earlier for participants who have achieved a confirmed CR or PR.
Up to approximately 42 months
Part 2: Plasma concentration of GSK4418959
Time Frame: From first day of dosing for the duration of treatment until end of interventional phase (EOI) (up to approximately 42 months)
From first day of dosing for the duration of treatment until end of interventional phase (EOI) (up to approximately 42 months)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
GlaxoSmithKline

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
IDEAYA Biosciences

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
December 13, 2024

Primary Completion (Estimated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
June 22, 2026

Study Completion (Estimated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
June 22, 2026

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
November 26, 2024

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
November 26, 2024

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
November 29, 2024

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
February 2, 2026

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
January 29, 2026

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
January 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 221971
  • 2024-519721-37-00 (Ctis)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

Qualified researchers may request access to anonymized individual patient-level data (IPD) and related study documents of the eligible studies via the Data Sharing Portal. Details on GSK's data sharing criteria can be found at: https://www.gsk.com/en-gb/innovation/trials/data-transparency/

IPD Sharing Time Frame

Anonymized IPD will be made available within 6 months of publication of primary, key secondary and safety results for studies in product with approved indication(s) or terminated asset(s) across all indications.

IPD Sharing Access Criteria

Anonymized IPD is shared with researchers whose proposals are approved by an Independent Review Panel and after a Data Sharing Agreement is in place. Access is provided for an initial period of 12 months but an extension may be granted, when justified, for up to 6 months.

IPD Sharing Supporting Information Type

  • STUDY_PROTOCOL
  • SAP
  • ICF
  • CSR

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

Yes

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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