Phase 1
Completed N=69
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
Neoplasms
Source: ClinicalTrials.gov NCT02783300 ↗
Enrolled (actual)
69
Serious AEs
42.8%
Results posted
Mar 2025
Primary outcomePrimary: Part 1: Number of Participants With Any Adverse Events (AEs) and Serious Adverse Events (SAEs) — 1; 1; 1; 1 Participants
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).
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Part 1: Number of Participants With Any Adverse Events (AEs) and Serious Adverse Events (SAEs) |
1; 1; 1; 1; 7; 3 | — |
| PRIMARY Part 1: Number of Participants Withdrawn Due to AEs |
0; 0; 0; 0; 2; 0 | — |
| PRIMARY Part 1: Number of Participants With Dose Limiting Toxicities (DLTs) |
0; 0; 0; 0; 0; 1 | — |
| PRIMARY Part 1: Number of Participants With Dose Modifications of GSK3326595 |
1; 1; 1; 1; 5; 3 | — |
| PRIMARY Part 1: Number of Participants With Worst Case Change From Baseline in Clinical Chemistry Parameters |
0; 0; 0; 0; 2; 0 | — |
| PRIMARY Part 1: Number of Participants With Worst Case Change From Baseline in Hematology Parameters |
0; 0; 0; 0; 0; 0 | — |
| PRIMARY Part 1: Number of Participants With Worst Case Change From Baseline in Coagulation Parameters |
0; 0; 0; 0; 0; 0 | — |
| PRIMARY Part 1: Number of Participants With Worst Case Change From Baseline in Urinalysis Parameters |
0; 1; 0; 1; 5; 2 | — |
| PRIMARY Part 1: Changes From Baseline in Urine Potential of Hydrogen (pH) |
5.00; 5.50; 7.00; 6.50; 6.00; 6.17 | — |
| PRIMARY Part 1: Changes From Baseline in Urine Specific Gravity |
1.02; 1.03; 1.01; 1.02; 1.02; 1.02 | — |
| PRIMARY Part 1: Number of Participants With Maximum Grade Worst Case Increase Post-baseline Relative to Baseline in Vital Signs |
0; 0; 0; 0; 1; 0 | — |
| PRIMARY Part 3: Number of Participants With Any Adverse Events (AEs) and Serious Adverse Events (SAEs) |
9; 5 | — |
| PRIMARY Part 3: Number of Participants Withdrawn Due to AEs |
1 | — |
| PRIMARY Part 3: Number of Participants With Dose Modifications of GSK3326595 and Pembrolizumab |
1; 0; 1; 0 | — |
| PRIMARY Part 3: Number of Participants With Worst Case Change From Baseline in Clinical Chemistry Parameters |
2; 3; 4; 3; 6; 0 | — |
| PRIMARY Part 3: Number of Participants With Worst Case Change From Baseline in Hematology Parameters |
0; 9; 0; 0; 8; 1 | — |
| PRIMARY Part 3: Number of Participants With Worst Case Change From Baseline in Coagulation Parameters |
1; 5; 3; 1; 6; 2 | — |
| PRIMARY Part 3: Number of Participants With Worst Case Change From Baseline in Urinalysis Parameters |
7; 3; 8; 2; 7; 3 | — |
| PRIMARY Part 3: Changes From Baseline in Urine Potential of Hydrogen (pH) |
5.60; 0.00; 0.38; 0.33; 0.33; 0.31 | — |
| PRIMARY Part 3: Changes From Baseline in Urine Specific Gravity |
1.02; 0.00; -0.01; 0.00; -0.01; 0.00 | — |
| PRIMARY Part 3: Number of Participants With Maximum Worst-case Increase Post-baseline Relative to Baseline in Vital Signs |
0; 6; 3; 0; 9; 0 | — |
| SECONDARY Part 2: Number of Participants With Any Adverse Events (AEs) and Serious Adverse Events (SAEs) |
22; 16; 27; 37; 28; 34 | — |
| SECONDARY Part 2: Number of Participants Withdrawn Due to AEs |
4; 4; 4; 3; 1; 3 | — |
| SECONDARY Part 2: Number of Participants With Dose Modifications of GSK3326595 |
13; 12; 11; 22; 20; 28 | — |
| SECONDARY Part 2: Number of Participants With Worst Case Change From Baseline in Clinical Chemistry Parameters |
1; 1; 0; 2; 1; 9 | — |
| SECONDARY Part 2: Number of Participants With Worst Case Change From Baseline in Hematology Parameters |
0; 0; 0; 2; 2; 1 | — |
| SECONDARY Part 2: Number of Participants With Worst Case Change From Baseline in Coagulation Parameters |
2; 0; 3; 0; 0; 1 | — |
| SECONDARY Part 2: Number of Participants With Worst Case Change From Baseline in Urinalysis Parameters |
19; 10; 20; 28; 18; 20 | — |
| SECONDARY Part 2: Changes From Baseline in Urine Potential of Hydrogen (pH) |
5.95; 6.19; 5.97; 6.35; 6.00; 6.15 | — |
| SECONDARY Part 2: Changes From Baseline in Urine Specific Gravity |
1.02; 1.02; 1.02; 1.02; 1.02; 1.02 | — |
| SECONDARY Part 2: Number of Participants With Maximum Grade Worst Case Increase Post-baseline Relative to Baseline in Vital Signs |
0; 3; 2; 3; 2; 6 | — |
| SECONDARY Part 1: Maximum Observed Plasma Concentration (Cmax) of GSK3326595 |
14.1; 70.7; 288; 508; 653; 853 | — |
| SECONDARY Part 3: Maximum Observed Plasma Concentration (Cmax) of GSK3326595 |
291 | — |
| SECONDARY Part 1: Area Under the Plasma Concentration-time Curve (AUC) Extrapolated From Time Zero to Infinity (AUC[0-inf]) of GSK3326595 |
349; 926; 1710; 3240; 3800; 6760 | — |
| SECONDARY Part 3: Area Under the Plasma Concentration-time Curve (AUC) Extrapolated From Time Zero to Infinity (AUC[0-inf]) of GSK3326595 |
1770 | — |
| SECONDARY Part 1: AUC From Time Zero to the Last Quantifiable Concentration After Dosing (AUC[0-t]) of GSK3326595 |
249; 858; 1610; 3090; 3690; 6560 | — |
| SECONDARY Part 3: AUC From Time Zero to the Last Quantifiable Concentration After Dosing (AUC[0-t]) of GSK3326595 |
1480 | — |
| SECONDARY Part 1: AUC Over the Dosing Interval Tau (AUC[0-tau]) of GSK3326595 |
331; 924; 1710; 3120; 3730; 6600 | — |
| SECONDARY Part 3: AUC Over the Dosing Interval Tau (AUC[0-tau]) of GSK3326595 |
1640 | — |
| SECONDARY Part 1: Terminal Phase Half-life (t1/2) of GSK3326595 |
5.58; 2.66; 2.32; 4.82; 3.71; 4.46 | — |
| SECONDARY Part 3: Terminal Phase Half-life (t1/2) of GSK3326595 |
5.44 | — |
| SECONDARY Part 1: Oral Clearance (CL/F) of GSK3326595 |
71.7; 54.0; 58.5; 61.8; 79.0; 59.2 | — |
| SECONDARY Part 3: Oral Clearance (CL/F) of GSK3326595 |
56.4 | — |
| SECONDARY Part 1: Accumulation Ratio (AR) of GSK3326595 |
0.840; 0.719; 1.20; 1.34; 1.11; 1.34 | — |
| SECONDARY Part 3: Accumulation Ratio (AR) of GSK3326595 |
— | — |
| SECONDARY Part 1: Time Invariance (TI) of GSK3326595 |
0.797; 0.717; 1.20; 1.29; 1.09; 1.31 | — |
| SECONDARY Part 3: Time Invariance (TI) of GSK3326595 |
— | — |
| SECONDARY Part 1: Overall Response Rate (ORR) Based on RECIST 1.1 |
0; 0; 0; 0; 25.0; 0 | — |
| SECONDARY Part 2: Overall Response Rate (ORR) (Non-glioblastoma Multiforme [GBM] Cohorts) |
0; 0; 2.7; 0; 2.9; 6.3 | — |
| SECONDARY Part 2: Six-month Progression Free Survival (PFS) Rate (GBM Cohort) |
4 | — |
| SECONDARY Part 2: Duration of Response (DOR) (ACC Tablet Cohort) |
NA | — |
| SECONDARY Part 3: ORR Based on Immune-based RECIST (iRECIST) Criteria |
— | — |
| SECONDARY Part 2: ORR (GBM Cohort) Based on Response Assessment Neuro-Oncology (RANO) Working Group Criteria |
— | — |
| SECONDARY Part 2: ORR (Non-Hodgkin's Lymphoma (NHL) Cohorts) Based on Lugano Criteria |
12.5; 10.0; 9.1 | — |
| SECONDARY Part 2: Overall Survival (OS) (ACC Tablet Cohort) |
NA | — |
| SECONDARY Part 2: Progression-free Survival |
1.5; 3.6; 2.1; 3.2; 7.2; 7.1 | — |
| SECONDARY RP2D Phase: Number of Participants With Any Adverse Events (AEs) and Serious Adverse Events (SAEs) |
199; 14; 31; 92; 3; 11 | — |
| SECONDARY RP2D Phase: Number of Participants Withdrawn Due to AEs |
25; 1; 3 | — |
| SECONDARY RP2D Phase: Number of Participants With Dose Modifications of GSK3326595 |
127; 9; 27; 123; 6; 11 | — |
| SECONDARY RP2D Phase: Number of Participants With Worst Case Change From Baseline in Clinical Chemistry Parameters |
15; 1; 11; 165; 11; 20 | — |
| SECONDARY RP2D Phase: Number of Participants With Worst Case Change From Baseline in Hematology Parameters |
5; 0; 0; 183; 13; 31 | — |
| SECONDARY RP2D Phase: Number of Participants With Worst Case Change From Baseline in Coagulation Parameters |
6; 2; 3; 72; 4; 15 | — |
| SECONDARY RP2D Phase: Number of Participants With Worst Case Change From Baseline in Urinalysis Parameters |
133; 10; 23; 64; 4; 8 | — |
| SECONDARY RP2D Phase: Changes From Baseline in Urine Potential of Hydrogen (pH) |
6.11; 5.64; 5.98; -0.13; -0.04; -0.11 | — |
| SECONDARY RP2D Phase: Changes From Baseline in Urine Specific Gravity |
1.02; 1.02; 1.02; 0.00; 0.00; 0.00 | — |
| SECONDARY RP2D Phase: Number of Participants With Worst-case Increase Post-baseline Relative to Baseline in Vital Signs |
19; 0; 5; 124; 11; 17 | — |
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.
Data sourced from ClinicalTrials.gov (NCT02783300). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.