Phase 1
Completed N=54
Study of a Combination of GSK1795091 and Immunotherapies in Subjects With Advanced Solid Tumors
Neoplasms
Source: ClinicalTrials.gov NCT03447314 ↗
Enrolled (actual)
54
Serious AEs
33.3%
Results posted
Jul 2021
Primary outcomePrimary: Part 1: Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious TEAEs (STEAEs) — 9; 6; 9; 4 Participants
Summary
GSK1795091 is being developed for administration in combination with other immune system modulators for the treatment of cancers. The study will be conducted in two parts. In Part 1, dose escalation will be performed to identify combination dose levels comprising GSK1795091 with either 24 milligrams (mg) GSK3174998 (Part 1a), 80 mg GSK3359609 (Part 1b), or 200 mg pembrolizumab (Part 1c). One dose level of GSK3174998, GSK3359609, or pembrolizumab with up to 5 dose levels of GSK1795091 are planned for evaluation. In Part 2 (dose-expansion), subjects will receive a single dose level of GSK1795091 as identified based on data from Part 1, in combination with either GSK3174998, GSK3359609, or pembrolizumab.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Part 1: Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious TEAEs (STEAEs) |
9; 6; 9; 4; 1; 6 | — |
| PRIMARY Part 2: Number of Participants With TEAEs and STEAEs |
— | — |
| PRIMARY Part 1: Number of Participants With Dose-limiting Toxicity (DLT) |
0; 0; 1; 0; 0; 0 | — |
| PRIMARY Part 1: Number of Participants With TEAEs Leading to Discontinuation |
0; 0; 1; 0; 0; 0 | — |
| PRIMARY Part 2: Number of Participants With TEAEs Leading to Discontinuation |
— | — |
| PRIMARY Part 1: Number of Participants With TEAEs Leading to Dose Reductions or Dose Delays |
4; 2; 1; 1; 0; 2 | — |
| PRIMARY Part 2: Number of Participants With TEAEs Leading to Dose Reductions or Dose Delays |
— | — |
| PRIMARY Part 1: Number of Participants With Change From Baseline in Hematology Parameters With Respect to the Normal Range |
0; 0; 0; 0; 0; 0 | — |
| PRIMARY Part 2: Number of Participants With Change From Baseline in Hematology Parameters With Respect to the Normal Range |
— | — |
| PRIMARY Part 1: Number of Participants With Change From Baseline in Chemistry Parameters With Respect to the Normal Range |
2; 1; 1; 0; 0; 0 | — |
| PRIMARY Part 2: Number of Participants With Change From Baseline in Chemistry Parameters With Respect to the Normal Range |
— | — |
| PRIMARY Part 1: Number of Participants With Worst Case Urinalysis Results Relative to Normal Range Criteria |
0; 0; 0; 0; 0; 0 | — |
| PRIMARY Part 2: Number of Participants With Worst Case Urinalysis Results Relative to Normal Range Criteria |
— | — |
| PRIMARY Part 1: Number of Participants With Increase From Baseline in Vital Signs According to Markedly Abnormal Criteria |
7; 3; 6; 3; 1; 1 | — |
| PRIMARY Part 2: Number of Participants With Vital Signs Any Increases From Baseline According to Markedly Abnormal Criteria |
— | — |
| PRIMARY Part 1: Number of Participants With Any Decrease From Baseline in Vital Sign According to Markedly Abnormal Criteria |
0; 0; 0; 0; 0; 0 | — |
| PRIMARY Part 2: Number of Participants With Vital Signs Any Decreases From Baseline According to Markedly Abnormal Criteria |
— | — |
| PRIMARY Part 1: Number of Participants With Any Increase From Baseline in Corrected QT Interval Using Fredericia's Formula (QTcF) According to Markedly Abnormal Criteria |
2; 1; 2; 0; 0; 3 | — |
| PRIMARY Part 2: Number of Participants With Any QTcF Interval Increases From Baseline According to Markedly Abnormal Criteria |
— | — |
| SECONDARY Part 1: Objective Response Rate |
11.1; 0.0; 0.0; 0.0; 0.0; 0.0 | — |
| SECONDARY Part 2: Objective Response Rate |
— | — |
| SECONDARY Part 1: Disease Control Rate |
44.4; 33.3; 33.3; 25.0; 0.0; 16.7 | — |
| SECONDARY Part 2: Disease Control Rate |
— | — |
| SECONDARY Part 1: Time to Response |
5.6; 2.0 | — |
| SECONDARY Part 2: Time to Response |
— | — |
| SECONDARY Part 1: Duration of Response |
13.73; NA | — |
| SECONDARY Part 2: Duration of Response |
— | — |
| SECONDARY Part 1: Progression-free Survival |
2.79; 3.29; 2.60; 2.25; NA; 2.28 | — |
| SECONDARY Part 2: Progression-free Survival |
— | — |
| SECONDARY Part 1: Overall Survival |
9.03; 7.75; 16.69; 6.72; 11.14; 4.48 | — |
| SECONDARY Part 2: Overall Survival |
— | — |
| SECONDARY Part 1a: Plasma Concentration of GSK1795091 |
0.000; 0.000; 0.000; 0.000; 0.000; 3.960 | — |
| SECONDARY Part 1b: Plasma Concentration of GSK1795091 |
0.000; 0.000; 12.870; 32.300; 14.100; 29.770 | — |
| SECONDARY Part 1c: Plasma Concentration of GSK1795091 |
0.000; 0.000; 13.600; 27.965; 11.475; 28.775 | — |
| SECONDARY Part 1a: Maximum Plasma Concentration (Cmax) of GSK1795091 |
4.180; 4.920; 29.20; 59.95; 82.18; 4.720 | — |
| SECONDARY Part 1b: Cmax of GSK1795091 |
14.95; 32.30; 15.28; 29.55; 16.00; 27.80 | — |
| SECONDARY Part 1c: Cmax of GSK1795091 |
13.75; 30.56; 13.53; 25.35; 10.19; 28.02 | — |
| SECONDARY Part 1a: Area Under the Concentration-time Curve Over the Dosing Interval (AUC[0-tau]) GSK1795091 |
48.08; 227.6; 1804; 3615; 4166; 256.7 | — |
| SECONDARY Part 1b: AUC(0-tau) GSK1795091 |
819.1; 1840; 661.9; 1453; 845.2; 1757 | — |
| SECONDARY Part 1c: AUC(0-tau) GSK1795091 |
851.7; 1611; 566.9; 1189; 778.0; 1640 | — |
| SECONDARY Part 1a: Predose Concentration (Cpre) of GSK1795091 |
0.000; 0.000; 0.000; 4.590; 4.160; 0.000 | — |
| SECONDARY Part 1b: Cpre of GSK1795091 |
0.000; 2.215; 0.000; 0.000; 0.000; 1.015 | — |
| SECONDARY Part 1c: Cpre of GSK1795091 |
0.000; 2.060; 0.000; 0.000; 0.000; 0.000 | — |
| SECONDARY Part 1a: Number of Participants With Present Antidrug Antibody (ADA) Against GSK3174998 |
5; 0; 2; 1; 0 | — |
| SECONDARY Part 1b: Number of Participants With the Present ADA Against GSK3359609 |
0; 1 | — |
| SECONDARY Part 1c: Number of Participants With the Present ADA Against Pembrolizumab |
NA; NA | — |
| SECONDARY Part 2a: Number of Participants With the Present ADA Against GSK3174998 |
— | — |
| SECONDARY Part 2b: Number of Participants With the Present ADA Against GSK3359609 |
— | — |
| SECONDARY Part 2c: Number of Participants With the Present ADA Against Pembrolizumab |
— | — |
Eligibility Criteria
Inclusion Criteria
- Subject must be >=18 years of at the time of signing the informed consent.
- Histological documentation of advanced solid tumor.
- Archival tumor tissue obtained at any time from the initial diagnosis to study entry. Although a fresh biopsy obtained during screening is preferred, archival tumor specimen is acceptable if it is not feasible to obtain a fresh biopsy. Subjects enrolled in a PK/Pharmacodynamic Cohort must provide a fresh biopsy of a tumor lesion not previously irradiated during the screening period and must agree to provide at least one additional on-treatment biopsy.
- Disease that has progressed after standard therapies or for which standard therapy is otherwise unsuitable (example, intolerance).
- Measurable disease, that is, presenting with at least 1 measurable lesion per Response Evaluation Criteria in Solid Tumors (RECIST version 1.1).
- Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0-1.
- Life expectancy of at least 12 weeks.
- Adequate organ function.
- In France, a subject will be eligible for inclusion in this study only if either affiliated to or a beneficiary of a social security category.
- Male or female subjects will be included. A female subject is eligible to participate if she is not pregnant, not breastfeeding, and at least 1 of the following conditions applies: a) Not a woman of childbearing potential (WOCBP) OR b). A WOCBP who agrees to follow the contraceptive guidance during the treatment period and for at least 120 days after the last dose of study treatment.
- Capable of giving signed informed consent which includes compliance with the requirements and restrictions specified.
Additional Inclusion criteria for Subjects in Part 2a (GSK3174998 expansion) and Part 2b (GSK3359609 expansion):
- Histological or cytological documentation of squamous cell carcinoma of the head and neck (SCCHN) (oral cavity, oropharynx, hypopharynx, or larynx) that is recurrent, locally advanced, or metastatic and is not amenable to curative treatment options, surgery or definitive chemoradiation therapy.
- Received, ineligible for, or otherwise unsuitable for platinum-based therapy and anti-Programmed death receptor-1 (PD-1)/programmed death-ligand 1 (PD-L1) therapy
- Received no more than 3 prior lines of systemic therapy for metastatic disease.
Additional Inclusion Criteria for Subjects in Part 2c (pembrolizumab expansion):
- Histological or cytological documentation of SCCHN (oral cavity, oropharynx, hypopharynx, or larynx) that is recurrent, locally advanced, or metastatic and is not amenable to curative treatment options, surgery or definitive chemoradiation therapy.
- Received no more than 2 prior lines of systemic therapy for metastatic disease.
Exclusion Criteria
- Malignancy other than disease under study with the exception of those from which the subject has been disease-free for more than 2 years and not expected to affect the safety of the subject or the endpoints of the trial.
- Symptomatic central nervous system (CNS) metastases or asymptomatic CNS metastases that have required steroids within 2 weeks prior to first dose of study treatment.
- Active autoimmune disease that has required systemic disease modifying or immunosuppressive treatment within the last 2 years. Replacement therapy (example, thyroxine or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is permitted.
- Concurrent medical condition requiring the use of systemic immunosuppressive treatment within 28 days before the first dose of study treatment.
- Known human immunodeficiency virus infection.
- Current unstable liver or biliary disease per investigator assessment defined by the presence of ascites, encephalopathy, coagulopathy, hypoalbuminemia, esophageal or gastric varices, persistent jaundice, or cirrhosis.
- Presence of Hepatitis B surface antigen (HBsAg) at screening or within 3 months prior to first dose of study treatment.
- Positive Hepati
Data sourced from ClinicalTrials.gov (NCT03447314). 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.