An Open-label, Dose Escalation Study to Investigate the Safety, Pharmacokinetics, Pharmacodynamics and Clinical Activity of GSK3326595 in Participants With Solid Tumors and Non-Hodgkin's Lymphoma

NCT ID: NCT02783300

Last Updated: 2025-03-10

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 297 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-08-30
• Study Completion Date: 2023-08-30

Brief Summary

This first time in human (FTIH) open-label, dose escalation study will assess the safety, pharmacokinetics (PK), pharmacodynamics (PD), and preliminary clinical activity of GSK3326595 in participants with advanced or recurrent solid tumors, as well as clinical activity in participants with a subset of solid tumors and non-Hodgkin's lymphoma (NHL).

Conditions

Neoplasms

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Part 1: Dose Escalation, Food effect and Relative Bioavailability of Capsule formulation to Tablet

Participants will receive escalating doses of GSK3326595 until the maximum tolerated dose level is reached. The recommended phase 2 dose (RP2D) will be determined. Participants will be dosed in a fed (high-fat, high-calorie meal) and fasted state to determine the effect of food on bioavailability of GSK3326595, and will be dosed with tablet and capsule to compare two formulations of GSK3326595 (capsule versus tablet).

Group Type: EXPERIMENTAL

GSK3326595

Intervention Type: DRUG

GSK3326595 will be administered with and without food, in tablet and capsule formulation.

Part 2: Disease-Specific Expansion cohort

Participants with triple-negative breast cancer (TNBC), metastatic transitional cell carcinoma of the urinary system (mTCC), Grade IV anaplastic astrocytoma (glioblastoma multiforme \[GBM\]), non-Hodgkin's lymphoma (NHL), adenoid cystic carcinoma (ACC), hormone receptor-positive adenocarcinoma of the breast (ER+BC), human papillomavirus (HPV)-positive solid tumors of any histology, and p53-wild type non-small cell lung cancer (NSCLC) will be administered GSK3326595 at the recommended phase 2 dose (RP2D) as determined in Part 1.

Group Type: EXPERIMENTAL

GSK3326595

Intervention Type: DRUG

GSK3326595 will be administered with and without food, in tablet and capsule formulation.

Part 3: GSK3326595 in combination with pembrolizumab

Participants with selected solid tumors will be administered GSK3326595 in combination with pembrolizumab as part of this dose determination study.

Group Type: EXPERIMENTAL

GSK3326595

Intervention Type: DRUG

GSK3326595 will be administered with and without food, in tablet and capsule formulation.

Pembrolizumab

Intervention Type: DRUG

Pembrolizumab will be administered.

Interventions

GSK3326595

GSK3326595 will be administered with and without food, in tablet and capsule formulation.

Intervention Type: DRUG

Pembrolizumab

Pembrolizumab will be administered.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Males and females greater than or equal to (>=)18 years of age (at the time consent is obtained)
• Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1 or 2
• Diagnosis of non-resectable or metastatic solid malignancy (as defined in the protocol) or NHL
• Presence of evaluable disease
• Adequate organ function (as defined in the protocol)
• Reproductive criteria (as defined in the protocol).

Exclusion Criteria

• Malignancy attributed to prior solid organ transplant
• Leptomeningeal disease, spinal cord compression, or brain metastases that require immediate central nervous system (CNS)-specific treatment in the opinion of the Investigator (for example [e.g.], for symptomatic disease)
• History of a second malignancy, excluding non-melanoma skin cell cancer within the last three years
• Evidence of severe or uncontrolled systemic diseases, or serious and/or pre-existing medical or other condition that could interfere with participant's safety, obtaining informed consent or compliance to the study procedures, in the opinion of the Investigator
• Any clinically significant gastrointestinal (GI) abnormalities that may alter absorption such as malabsorption syndrome or major resection of the stomach and/or bowels.
• Select cardiac abnormalities (as defined in the protocol)
• History of sensitivity to any of the study medications, or components thereof or a history of drug or other allergy that, in the opinion of the investigator or Medical Monitor, contraindicates their participation.
• History of optic nerve neuropathy or neuritis.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

GlaxoSmithKline

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

GSK Clinical Trials

Role: STUDY_DIRECTOR

GlaxoSmithKline

Locations

GSK Investigational Site

Denver, Colorado, United States

GSK Investigational Site

Miami, Florida, United States

GSK Investigational Site

New York, New York, United States

GSK Investigational Site

Nashville, Tennessee, United States

GSK Investigational Site

Dallas, Texas, United States

GSK Investigational Site

San Antonio, Texas, United States

GSK Investigational Site

Edmonton, Alberta, Canada

GSK Investigational Site

Ottawa, Ontario, Canada

GSK Investigational Site

Toronto, Ontario, Canada

GSK Investigational Site

Bordeaux, , France

GSK Investigational Site

Lyon, , France

GSK Investigational Site

Villejuif, , France

GSK Investigational Site

Amsterdam, , Netherlands

GSK Investigational Site

Leiden, , Netherlands

GSK Investigational Site

Rotterdam, , Netherlands

Countries

United States; Canada; France; Netherlands

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

2016-000278-39

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

204653

Identifier Type: -

Identifier Source: org_study_id