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NCT06710847 | RECRUITING | Neoplasms, Colorectal

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
Sponsor:

GlaxoSmithKline

Brief Summary:

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.

Condition or disease

Neoplasms, Colorectal

Solid Tumor

Colon Cancer

Rectal Cancer

Endometrial Cancer

Intervention/treatment

GSK4418959

PD-1 inhibitor

Phase

PHASE1

PHASE2

Study Type : INTERVENTIONAL
Estimated Enrollment : 73 participants
Masking : NONE
Primary Purpose : TREATMENT
Official Title : 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)
Actual Study Start Date : 2024-12-13
Estimated Primary Completion Date : 2027-02-16
Estimated Study Completion Date : 2028-06-16

Information not available for Arms and Intervention/treatment

Ages Eligible for Study: 18 Years
Sexes Eligible for Study: ALL
Accepts Healthy Volunteers:
Criteria
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 0-1
    • * 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
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

Location Details

NCT06710847

Please Choose a site

How to Participate

Want to participate in this study, select a site at your convenience, send yourself email to get contact details and prescreening steps.

Locations

RECRUITING

United States, Colorado

GSK Investigational Site

Denver, Colorado, United States, 80218

RECRUITING

United States, road cancer

GSK Investigational Site

Detroit, road cancer, United States, 48201

RECRUITING

United States, New York

GSK Investigational Site

New York, New York, United States, 10016

RECRUITING

United States, Pennsylvania

GSK Investigational Site

Philadelphia, Pennsylvania, United States, 19104

RECRUITING

United States, Pennsylvania

GSK Investigational Site

Philadelphia, Pennsylvania, United States, 19107

RECRUITING

Australia, Victoria

GSK Investigational Site

Melbourne, Victoria, Australia, 3000

RECRUITING

Japan,

GSK Investigational Site

Chiba, Japan, 277-8577

RECRUITING

Japan,

GSK Investigational Site

Shizuoka, Japan, 411-8777

RECRUITING

Japan,

GSK Investigational Site

Tokyo, Japan, 104-0045

RECRUITING

Japan,

GSK Investigational Site

Tokyo, Japan, 135-8550

RECRUITING

South Korea,

GSK Investigational Site

Daegu, South Korea, 41404

RECRUITING

South Korea,

GSK Investigational Site

Gyeonggi-do, South Korea, 10408

RECRUITING

South Korea,

GSK Investigational Site

Seoul, South Korea, 03080