Last updated: 09/09/2024 04:40:13
Study of a combination of GSK1795091 and immunotherapies in subjects with advanced solid tumors
EudraCT ID
EU CT Number
Not applicable
Trial status
Study complete
Study complete
Trial overview
Official title: A Phase I, Open-Label Study of GSK1795091 Administered in Combination with Immunotherapies in Participants with Advanced Solid Tumors
Trial description: 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.
Primary purpose:
Treatment
Trial design:
Sequential Assignment
Masking:
None (Open Label)
Allocation:
Non-randomized
Primary outcomes:
Number of subjects with adverse events (AEs) and serious adverse events (SAEs)
Timeframe: Up to 2 years
Number of subjects with dose-limiting toxicities (DLTs)
Timeframe: Up to 2 years
Number of subjects withdrawn due to AEs
Timeframe: Up to 2 years
Number of subjects with dose reductions or delays
Timeframe: Up to 2 years
Number of subjects with abnormal hematology parameters
Timeframe: Up to 2 years
Number of subjects with abnormal clinical chemistry parameters
Timeframe: Up to 2 years
Number of subjects with abnormal urine parameters
Timeframe: Up to 2 years
Number of subjects with abnormal temperature
Timeframe: Up to 2 years
Number of subjects with abnormal blood pressure
Timeframe: Up to 2 years
Number of subjects with abnormal pulse rate
Timeframe: Up to 2 years
Number of subjects with abnormal electrocardiogram (ECG) measurement
Timeframe: Up to 2 years
Secondary outcomes:
Objective response rate
Timeframe: Up to 2 years
Disease control rate
Timeframe: Up to 2 years
Time to response
Timeframe: Up to 2 years
Duration of response
Timeframe: Up to 2 years
Number of subjects with progression-free survival (PFS)
Timeframe: Up to 2 years
Number of subjects with overall survival
Timeframe: Up to 2 years
Plasma concentration of GSK1795091-Part 1
Timeframe: Day15 (pre-dose,10minutes,4hours post-dose),Day16 (24hours post-dose),Day22 (pre-dose),Day57 (pre-dose,10minutes,4hours post-dose),Day58 (24hours post-dose), Day64 (pre-dose,10minutes post-dose),10minutes post-dose on Day78 and every 12weeks for 2years
Plasma concentration of GSK1795091-Part 2
Timeframe: Day1 (pre-dose, 10minutes, 2, 4, 6hours post-dose), Day8 (pre-dose), Day22 (10minutes post-dose), Day43 (pre-dose, 10minutes, 4 hours post-dose), Day50 (pre-dose, 10minutes post-dose), 10minutes post-dose on Day64, Day85 and then every 12weeks for 2years
Maximum plasma concentration (Cmax) of GSK1795091-Part 1
Timeframe: Day15 (pre-dose,10minutes,4hours post-dose),Day16 (24hours post-dose),Day22 (pre-dose),Day57 (pre-dose,10minutes,4hours post-dose),Day58 (24hours post dose), Day64 (pre-dose,10minutes post-dose),10minutes post-dose on Day78 and every 12weeks for 2years
Cmax of GSK1795091-Part 2
Timeframe: Day1 (pre-dose, 10minutes, 2, 4, 6hours post-dose), Day8 (pre-dose), Day22 (10minutes post-dose), Day43 (pre-dose, 10minutes, 4 hours post-dose), Day50 (pre-dose, 10minutes post-dose), 10minutes post-dose on Day64, Day85 and then every 12weeks for 2years
Area under the concentration-time curve over the dosing interval (AUC [0-tau]) GSK1795091-Part 1
Timeframe: Day15 (pre-dose,10minutes,4hours post-dose),Day16 (24hours post-dose),Day22 (pre-dose),Day57 (pre-dose,10minutes,4hours post-dose),Day58 (24hours post-dose), Day64 (pre-dose,10minutes post-dose),10minutes post-dose on Day78 and every 12weeks for 2years
AUC (0-tau) of GSK1795091-Part 2
Timeframe: Day1 (pre-dose, 10minutes, 2, 4, 6hours post-dose), Day8 (pre-dose), Day22 (10minutes post-dose), Day43 (pre-dose, 10minutes, 4 hours post-dose), Day50 (pre-dose, 10minutes post-dose), 10minutes post-dose on Day64, Day85 and then every 12weeks for 2years
Trough plasma concentrations (Ctrough) of GSK1795091-Part 1
Timeframe: Day15 (pre-dose,10minutes,4hours post-dose),Day16 (24hours post-dose),Day22 (pre-dose),Day57 (pre-dose,10minutes,4hours post-dose),Day58 (24hours post-dose), Day64 (pre-dose,10minutes post-dose),10minutes post-dose on Day78 and every 12weeks for 2years
Ctrough of GSK1795091-Part 2
Timeframe: Day1 (pre-dose, 10minutes, 2, 4, 6hours post-dose), Day8 (pre-dose), Day22 (10minutes post-dose), Day43 (pre-dose, 10minutes, 4 hours post-dose), Day50 (pre-dose, 10minutes post-dose), 10minutes post-dose on Day64, Day85 and then every 12weeks for 2years
Number of subjects who develop detectable antidrug antibody (ADA) against GSK3174998
Timeframe: Up to 2 years
Number of subjects who develop ADA against GSK3359609
Timeframe: Up to 2 years
Number of subjects who develop ADA against pembrolizumab
Timeframe: Up to 2 years
Interventions:
Enrollment:
54
Primary completion date:
2020-01-07
Observational study model:
Not applicable
Time perspective:
Not applicable
Clinical publications:
Not applicable
Medical condition
Neoplasms
Product
GSK1795091, GSK3174998
Collaborators
IQVIA
Study date(s)
March 2018 to March 2022
Type
Interventional
Phase
1
Participation criteria
Sex
Female & Male
Age
18+ years
Accepts healthy volunteers
No
- Subject must be >=18 years of at the time of signing the informed consent.
- Histological documentation of advanced solid tumor.
- 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.
Inclusion and exclusion 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 Hepatitis C test result at screening or within 3 months prior to first dose of study treatment.
- QT interval corrected for heart rate according to Fridericia’s formula (QTcF) >450 milliseconds (msec) or QTcF >480 msec for subjects with bundle branch block
- Recent history (within the past 6 months) of acute diverticulitis, inflammatory bowel disease, intra-abdominal abscess, or gastrointestinal obstruction.
- Recent history of allergen desensitization therapy within 4 weeks of starting study treatment.
- History of severe hypersensitivity to monoclonal antibodies (mAbs).
- History or evidence of cardiovascular (CV) risk including any of the following: a) Recent (within the past 6 months) history of serious uncontrolled cardiac arrhythmia or clinically significant ECG abnormalities including second degree (Type II) or third degree atrioventricular block. b) Cardiomyopathy, myocardial infarction, acute coronary syndromes (including unstable angina pectoris), coronary angioplasty, stenting, or bypass grafting within the past 6 months before enrollment. c) Congestive heart failure (Class II, III, or IV) as defined by the New York Heart Association (NYHA) functional classification system. d) Recent (within the past 6 months) history of symptomatic pericarditis.
- History of idiopathic pulmonary fibrosis, pneumonitis, interstitial lung disease, or organizing pneumonia, or evidence of active, non-infectious pneumonitis.
- Recent history (within 6 months) of uncontrolled symptomatic ascites or pleural effusions.
- Any serious and/or unstable pre-existing medical, psychiatric disorder, or other condition that could interfere with the subject’s safety, obtaining informed consent, or compliance to the study procedures.
- Is or has an immediate family member (example, spouse, parent/legal guardian, sibling or child) who is investigational site or sponsor staff directly involved with this trial, unless prospective Institutional Review Board (IRB) approval (by chair or designee) is given allowing exception to this criterion for a specific subject.
- Prior treatment with the following agents: a) OX40, inducible T-cell co-stimulator (ICOS) agonist at any time. b) Prior systemic or intratumoral therapy with TLR agonist. c) Anticancer therapy or investigational therapy within 30 days or 5 half-lives of the drug, whichever is shorter. d) Prior radiation therapy: permissible if at least 1 non-irradiated measurable lesion is available for assessment according to RECIST version 1.1 or if a solitary measurable lesion was irradiated, objective progression is documented. A wash out of at least 14 days before start of study treatment for radiation of any intended use to the extremities for bone metastases and 28 days for radiation to the chest, brain, or visceral organs is required.
- Prior allogeneic or autologous bone marrow transplantation or other solid organ transplantation.
- Toxicity from previous treatment including: a) Toxicity Grade >=3 related to prior immunotherapy and that lead to study treatment discontinuation. b) Toxicity related to prior treatment has not resolved to Grade <=1 (except alopecia, or endocrinopathy managed with replacement therapy).
- Received transfusion of blood products (including platelets or red blood cells) or administration of colony stimulating factors (including granulocyte colony-stimulating factor [G-CSF], granulocyte macrophage colony-stimulating factor, and recombinant erythropoietin) within 2 weeks before the first dose of study treatment.
- Major surgery <=4 weeks before the first dose of study treatment. Subjects must have also fully recovered from any surgery (major or minor) and/or its complications before initiating study treatment.
- Known drug or alcohol abuse.
- Receipt of any live vaccine within 4 weeks. Additional Exclusion Criteria for Subjects in Part 2c
- Received prior anti-PD-1/PD-L1 therapy.
Trial location(s)
Location
GSK Investigational Site
St. Louis, Missouri, United States, 63110
Status
Study Complete
Location
GSK Investigational Site
Tacoma, Washington, United States, 98405
Status
Study Complete
Showing 1 - 6 of 8 Results
Study documents
Study report synopsis
Available language(s): English
Protocol
Available language(s): English
Statistical analysis plan
Available language(s): English
If you wish to request for full study report, please contact - [email protected]
Results overview
Results posted on ClinicalTrials.gov
Recruitment status
Study complete
Actual primary completion date
2020-01-07
Actual study completion date
2022-11-03
Plain language summaries
Plain language summaries of clinical trial results for Phase 2-4 clinical trials that were initiated on or after January 2022 will be posted by GSK within one year following study completion.
Additional information about the trial
Additional information
Not applicable
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