Neoplasms

All Conditions

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Blood and Lymph Conditions

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Rare Diseases

Carcinoma

Melanoma

Carcinoma, Non-Small-Cell Lung

Carcinoma, Squamous Cell

Squamous Cell Carcinoma of Head and Neck

Lung Neoplasms

Lymphoma

Carcinoma, Adenoid Cystic

Lymphoma, Non-Hodgkin

Neoplasms by Histologic Type

Lymphoproliferative Disorders

Lymphatic Diseases

Immunoproliferative Disorders

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Adenoid Cystic Carcinoma

Antineoplastic Agents

All Drugs and Chemicals

Pembrolizumab

Hormones

GSK-3326595

Antineoplastic Agents, Immunological

Immune Checkpoint Inhibitors

Enzyme Inhibitors

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).

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.

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

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

GSK3326595

GSK Clinical Trials

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).

This will be a three-part study where Part 1 is dose escalation, including assessment of Food Effect and Relative Bioavailability, Part 2 is disease specific expansion cohorts to better characterize the clinical activity and safety profile of GSK3326595 and Part 3 is dose determination of GSK3326595 in combination with pembrolizumab.

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

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

IPD for this study will be made available via the Clinical Study Data Request site.

All AEs, SAEs and dose modifications will be collected.

An event is considered to be a DLT if the event occurs within the first 21 days of treatment and meets the dose-limiting toxicity criteria, unless it can be clearly established that the event is unrelated to treatment.

Blood and urine samples will be collected for analysis of lab parameters. Vital signs, physical examinations and organ-specific parameters will be collected at specified time points.

ORR is defined as the percentage of participants achieving a confirmed complete response (CR) or partial response (PR) based on RECIST 1.1 criteria.

ORR is defined as the percentage of participants achieving CR or PR based on Lugano criteria.

PFS is defined as the percentage of participants free from radiographic progression per Response Assessment in Neuro-Oncology (RANO) criteria, or death due to any cause, for six months after starting GSK3326595.

Blood samples will be collected at given time points to determine the Cmax of GSK3326595.

Blood samples will be collected at given time points to determine the AUC (0-inf) of GSK3326595.

Blood samples will be collected at given time points to determine the AUC (0-t) of GSK3326595.

Blood samples will be collected at given time points to determine the AUC (0-tau) of GSK3326595.

Blood samples will be collected at given time points to determine the half-life of GSK3326595.

Blood samples will be collected at given time points to determine the CL/F of GSK3326595.

Blood samples will be collected at given time points to determine the AR of GSK3326595.

Blood samples will be collected at given time points to determine the TI of GSK3326595.

ORR is defined as the percentage of participants achieving confirmed CR or confirmed PR based on immune-based RECIST (iRECIST) criteria.

Progression-free survival (PFS) is defined as the time from first dose until radiographic progression per standard criteria or death due to any cause, whichever is earlier.

ORR is defined as the percentage of participants achieving a confirmed complete response (CR) or partial response (PR) based on RANO working group criteria.

DOR is defined as the time from first evidence of response (CR or PR per RECIST 1.1) to earlier date of disease progression or death due to any cause, as determined by Investigator Assessment.

OS is defined as the time from first dose until death from any cause.

Spots Global Cancer Trial Database for adenoid cystic carcinoma (acc)