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

NCT06710847 | Active Not Recruiting Phase 1 FDA Drug

• 2 other identifiers: 2219712024-519721-37-00
• Study Type: interventional
• Target: 14
• Locations: 7 countries
• Sites: 22

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.

Conditions

Neoplasms, Colorectal; Solid Tumor; Colon Cancer; Rectal Cancer; Endometrial Cancer

Keywords

GSK4418959; DNA Helicase Werner Inhibitor (WRNi); PD-1 inhibitor; Solid tumors; Colon cancer; Rectal cancer; Colorectal cancer; Endometrial cancer; Mismatch repair deficient; dMMR; microsatellite instability high; MSI-H

Outcome Measures

Primary Outcomes (7)

• Part 1: Number of participants with dose limiting toxicities (DLTs) during DLT observation period

  Up to 21 days

• Part 3: Number of participants with dose limiting toxicities (DLTs) during DLT observation period

  Up to 21 days

• Part 1: Number of participants with treatment emergent adverse events (TEAEs) during DLT observation period

  Up to 21 days

• Part 3: Number of participants with treatment emergent adverse events (TEAEs) during DLT observation period

  Up to 21 days

• Part 1: Number of participants with dosage interruptions, dose reductions, and drug discontinuations for TEAEs during DLT observation period

  Up to 21 days

• Part 3: Number of participants with dosage interruptions, dose reductions, and drug discontinuations for TEAEs during DLT observation period

  Up to 21 days

• Part 2: Objective Response Rate (ORR)

  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 Outcomes (18)

• Part 1: Area under the concentration-time curve (AUC) for GSK4418959

  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

  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

  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

  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

  From first day of dosing for the duration of treatment until end of interventional phase (EOI) (up to approximately 42 months)

Study Arms (3)

Part 1: Dose escalation of GSK4418959 monotherapy

EXPERIMENTAL

Participants will receive GSK4418959 as monotherapy.

Drug: GSK4418959

Part 2: Dose expansion of GSK4418959 monotherapy

EXPERIMENTAL

Participants will receive GSK4418959 as monotherapy.

Drug: GSK4418959

Part 3: Dose escalation of GSK4418959 plus PD-1 inhibitor

EXPERIMENTAL

Participants will receive GSK4418959 plus PD-1 inhibitor.

Drug: GSK4418959; Biological: PD-1 inhibitor

Interventions

GSK4418959 DRUG

GSK4418959 will be administered.

Part 1: Dose escalation of GSK4418959 monotherapy; Part 2: Dose expansion of GSK4418959 monotherapy; Part 3: Dose escalation of GSK4418959 plus PD-1 inhibitor

PD-1 inhibitor BIOLOGICAL

PD-1 inhibitor will be administered.

Part 3: Dose escalation of GSK4418959 plus PD-1 inhibitor

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

• 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
• Has any history of interstitial lung disease or pneumonitis

Sponsors & Collaborators

• GlaxoSmithKline: lead
• IDEAYA Biosciences: collaborator

Study Sites (22)

GSK Investigational Site

Los Angeles, California, 90095, United States

Location

GSK Investigational Site

Denver, Colorado, 80218, United States

Location

GSK Investigational Site

Detroit, Michigan, 48201, United States

Location

GSK Investigational Site

New York, New York, 10016, United States

Location

GSK Investigational Site

Philadelphia, Pennsylvania, 19104, United States

Location

GSK Investigational Site

Philadelphia, Pennsylvania, 19107, United States

Location

GSK Investigational Site

Melbourne, Victoria, 3000, Australia

Location

GSK Investigational Site

Brussels, 1200, Belgium

Location

GSK Investigational Site

Ghent, 9000, Belgium

Location

GSK Investigational Site

Leuven, 3000, Belgium

Location

GSK Investigational Site

Chiba, 277-8577, Japan

Location

GSK Investigational Site

Shizuoka, 411-8777, Japan

Location

GSK Investigational Site

Tokyo, 104-0045, Japan

Location

GSK Investigational Site

Tokyo, 135-8550, Japan

Location

GSK Investigational Site

Amsterdam, 1066 CX, Netherlands

Location

GSK Investigational Site

Daegu, 41404, South Korea

Location

GSK Investigational Site

Gyeonggi-do, 10408, South Korea

Location

GSK Investigational Site

Seoul, 03080, South Korea

Location

GSK Investigational Site

Barcelona, 08023, Spain

Location

GSK Investigational Site

Barcelona, 08035, Spain

Location

GSK Investigational Site

Madrid, 28040, Spain

Location

GSK Investigational Site

Málaga, 29010, Spain

Location

MeSH Terms

Conditions

Colorectal Neoplasms; Colonic Neoplasms; Rectal Neoplasms; Endometrial Neoplasms; Turcot syndrome

Interventions

Immune Checkpoint Inhibitors

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases; Uterine Neoplasms; Genital Neoplasms, Female; Urogenital Neoplasms; Uterine Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases

Intervention Hierarchy (Ancestors)

Molecular Mechanisms of Pharmacological Action; Pharmacologic Actions; Chemical Actions and Uses; Antineoplastic Agents, Immunological; Antineoplastic Agents; Therapeutic Uses

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 26, 2024
• First Posted: November 29, 2024
• Study Start: December 13, 2024
• Primary Completion (Estimated): June 22, 2026
• Study Completion (Estimated): June 22, 2026
• Last Updated: February 2, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• 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.
• 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.

Locations

US (6); ES (4); BE (3); KR (3); AU (1); JP (4); NL (1)