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Trial details imported from ClinicalTrials.gov
For full trial details, please see the original record at
https://clinicaltrials.gov/ct2/show/NCT03693612
Additional trial details provided through ANZCTR are available at the end of this record.
Registration number
NCT03693612
Ethics application status
Date submitted
1/10/2018
Date registered
3/10/2018
Date last updated
22/08/2022
Titles & IDs
Public title
GSK3359609 Plus Tremelimumab for the Treatment of Advanced Solid Tumors
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Scientific title
A Phase I/II, Open-label, Two Part Study of GSK3359609 in Combination With Tremelimumab in Participants With Selected, Advanced Solid Tumors
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Secondary ID [1]
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207871
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Universal Trial Number (UTN)
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Trial acronym
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Linked study record
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Health condition
Health condition(s) or problem(s) studied:
Neoplasms
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0
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Condition category
Condition code
Intervention/exposure
Study type
Interventional
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Description of intervention(s) / exposure
Treatment: Drugs - feladilimab
Treatment: Drugs - Tremelimumab
Treatment: Drugs - Docetaxel
Treatment: Drugs - Paclitaxel
Treatment: Drugs - Cetuximab
Experimental: Part 1: feladilimab +tremelimumab - In Part 1, subjects with advanced selected solid tumors will be enrolled. Subjects will be administered escalating doses of feladilimab and tremelimumab in combination. feladilimab will be administered every 3 weeks and tremelimumab will be administered every 3 weeks for 6 doses and every 12 weeks thereafter.
Experimental: Part 2: feladilimab +tremelimumab - In Part 2, subjects with R/R HNSCC who have disease progression after receiving at least one platinum-based chemotherapy and at least one anti-PD-1/PD-L1 will be enrolled. Subjects will be administered feladilimab in combination with tremelimumab at recommended Phase 2 dose as determined from Part 1.
Active Comparator: Part 2: SOC - In Part 2, subjects with R/R HNSCC who have disease progression after receiving at least one platinum-based chemotherapy and at least one anti-PD-1/PD-L1 will be enrolled. Subjects will be administered a single agent SOC therapy of either paclitaxel, docetaxel or cetuximab as per the investigators choice.
Treatment: Drugs: feladilimab
feladilimab is humanized anti-ICOS agonist immunoglobulin G (IgG) 4 monoclonal antibody (mAb), which will be administered as an intravenous (IV) infusion once every 3 weeks.
Treatment: Drugs: Tremelimumab
Tremelimumab is humanized anti-CTLA-4 IgG2 mAb, which will be administered as an IV infusion once every 3 weeks for 6 doses, thereafter once every 12 weeks .
Treatment: Drugs: Docetaxel
Docetaxel is a microtubule stabilizer which will be administered as an IV infusion once every 3 weeks at a dose of 75 milligrams per meter square (mg/m^2).
Treatment: Drugs: Paclitaxel
Paclitaxel is a microtubule stabilizer which will be administered as an IV infusion once weekly at a dose of 80 mg/m^2.
Treatment: Drugs: Cetuximab
Cetuximab is a recombinant, human/mouse chimeric anti-estimated glomerular filtration rate (EGFR) mAb. Cetuximab will be administered at a loading dose of 400 mg/m^2 followed by 250 mg/m^2 once weekly.
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Intervention code [1]
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Treatment: Drugs
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Comparator / control treatment
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Control group
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Outcomes
Primary outcome [1]
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Number of Participants With Dose Limiting Toxicities (DLTs)-Part 1
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Assessment method [1]
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A DLT is considered by the investigator to be clinically relevant, attributed event within first 28 days of intervention meeting the following criteria of toxicity, Hematologic: Febrile neutropenia, Grade 4 neutropenia of greater than (>) 7 days in duration or requiring Granulocyte- Colony stimulating factor (G-CSF), Grade 4 anemia and Grade 3 thrombocytopenia with bleeding or Grade 4 thrombocytopenia; Non-hematologic: Grade 4 toxicity, Grade 3 pneumonitis, any greater than or equal to (=) Grade 2 pneumonitis that does not resolve to less than or equal to (= ) Grade 1 within 3 days of the initiation of maximal supportive care, Grade 3 toxicity that does not resolve to Grade 1 or baseline within 3 days despite optimal supportive care and any Grade 2 ocular toxicity requiring systemic steroids, or any = Grade 3 ocular toxicity.
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Timepoint [1]
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Up to 28 days
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Primary outcome [2]
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Number of Participants With DLTs According to Severity-Part 1
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Assessment method [2]
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The severity of all toxicities were graded using the National Cancer Institute- Common Toxicity Criteria for Adverse Events (NCI-CTCAE) version 5.0. Grade 1: Mild reaction; infusion interruption not indicated; intervention not indicated; Grade 2: Requires therapy or infusion interruption but responds promptly to symptomatic treatment or prophylactic medications indicated for =24 hours; Grade 3: Prolonged (i.e., not rapidly responsive to symptomatic medication and/or brief interruption of infusion) or recurrence of symptoms following initial improvement; hospitalization indicated for other clinical sequelae; Grade 4: Life-threatening; pressor or ventilatory support indicated; Grade 5: Death related to AE.
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Timepoint [2]
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Up to 28 days
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Primary outcome [3]
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Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs) and Adverse Events of Special Interest (AESI)-Part 1
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Assessment method [3]
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An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study intervention, whether or not considered related to the study intervention. An SAE is defined as any untoward medical occurrence that, at any dose: results in death; is life-threatening; requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent disability/incapacity; is a congenital anomaly/birth defect and important medical events may jeopardize the subject or may require medical or surgical intervention/SOC to prevent one of the other outcomes mentioned before. AESIs are defined as events of potential immunologic etiology, including immune related AEs.
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Timepoint [3]
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Up to 4 years
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Primary outcome [4]
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Number of Participant With AE/SAE/DLTs Leading to Dose Modifications/Delays/Withdrawals-Part 1
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Assessment method [4]
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The number of participants with AE/SAE/DLTs leading to dose modifications/delays/withdrawals were summarized.
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Timepoint [4]
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Up to 4 years
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Primary outcome [5]
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Number of Participants With AEs, SAEs, AESIs According to Severity - Part 1
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Assessment method [5]
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The severity of all toxicities were graded using the National Cancer Institute- Common Toxicity Criteria for Adverse Events (NCI-CTCAE) version 5.0. Grade 1: Mild reaction; infusion interruption not indicated; intervention not indicated; Grade 2: Requires therapy or infusion interruption but responds promptly to symptomatic treatment or prophylactic medications indicated for =24 hours; Grade 3: Prolonged (i.e., not rapidly responsive to symptomatic medication and/or brief interruption of infusion) or recurrence of symptoms following initial improvement; hospitalization indicated for other clinical sequelae; Grade 4: Life-threatening; pressor or ventilatory support indicated; Grade 5: Death related to AE.
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Timepoint [5]
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Up to 4 years
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Primary outcome [6]
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Number of Participants With Severe- AEs/SAEs/DLTs Leading to Dose Modifications/Delays/Withdrawals-Part 1
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Assessment method [6]
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The number of participants with severe- AE/SAE/DLTs leading to dose modifications/delays/withdrawals were summarized.
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Timepoint [6]
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Up to 4 years
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Primary outcome [7]
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Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP)-Part 1
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Assessment method [7]
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SBP and DBP were measured after 5 minutes of rest for the participant.
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Timepoint [7]
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Baseline (Day 1) and Week 4
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Primary outcome [8]
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Change From Baseline in Temperature-Part 1
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Assessment method [8]
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Temperature was measured after 5 minutes of rest for the participant.
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Timepoint [8]
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Baseline (Day 1) and Week 4
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Primary outcome [9]
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Change From Baseline in Pulse Rate-Part 1
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Assessment method [9]
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Pulse rate was measured after 5 minutes of rest for the participant.
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Timepoint [9]
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Baseline (Day 1) and Week 4
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Primary outcome [10]
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Change From Baseline in Respiratory Rate-Part 1
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Assessment method [10]
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Respiratory rate was measured after 5 minutes of rest for the participant.
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Timepoint [10]
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Baseline (Day 1) and Week 4
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Primary outcome [11]
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Change From Baseline in Oxygen Saturation-Part 1
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Assessment method [11]
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Oxygen saturation was measured using pulse oximeter after 5 minutes of rest for the participant.
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Timepoint [11]
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Baseline (Day 1) and Week 4
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Primary outcome [12]
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Number of Participants With Electrocardiogram (ECG) Findings
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Assessment method [12]
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Single 12-lead ECG was obtained using an automated ECG machine. ECG findings were categorized as: normal, abnormal - clinically significant (CS), or abnormal - not clinically significant (NCS), as determined by the investigator.
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Timepoint [12]
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Baseline (Pre dose, Day 1) and up to 4 Years
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Primary outcome [13]
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Change From Baseline in Neutrophil, Lymphocyte, Monocyte, Eosinophil, Basophil and Platelet Count-Part 1
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Assessment method [13]
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Blood samples were collected to assess change from Baseline in neutrophil, lymphocyte, monocyte, eosinophil, basophil and platelet counts.
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Timepoint [13]
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Baseline (Day 1) and Week 4
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Primary outcome [14]
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Change From Baseline in Hemoglobin Level-Part 1
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Assessment method [14]
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Blood samples were collected to assess change from baseline in hemoglobin level.
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Timepoint [14]
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Baseline (Day 1) and Week 4
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Primary outcome [15]
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Change From Baseline in Hematocrit Level-Part 1
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Assessment method [15]
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Blood samples were collected to assess change from baseline in hematocrit level.
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Timepoint [15]
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Baseline (Day 1) and Week 4
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Primary outcome [16]
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Change From Baseline in Erythrocytes Count-Part 1
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Assessment method [16]
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Blood samples were collected to assess change from baseline in Erythrocytes count.
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Timepoint [16]
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Baseline (Day 1) and Week 4
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Primary outcome [17]
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Change From Baseline in Albumin and Total Protein Levels-Part 1
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Assessment method [17]
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Blood samples were collected to assess change from Baseline in albumin and total protein levels.
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Timepoint [17]
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0
Baseline (Day 1) and Week 4
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Primary outcome [18]
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Change From Baseline in Creatinine and Bilirubin Levels-Part 1
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Assessment method [18]
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Blood samples were collected to assess change from baseline in creatinine and bilirubin levels.
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Timepoint [18]
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Baseline (Day 1) and Week 4
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Primary outcome [19]
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Change From Baseline in Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Alkaline Phosphatase (ALP), Lactate Dehydrogenase (LDH) Levels-Part 1
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Assessment method [19]
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Blood samples were collected to assess change from baseline in ALT, AST ALP, LDH levels.
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Timepoint [19]
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0
Baseline (Day 1) and Week 4
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Primary outcome [20]
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Change From Baseline in Amylase and Lipase Levels-Part 1
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Assessment method [20]
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Blood samples were collected to assess change from baseline in amylase and lipase levels.
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Timepoint [20]
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0
Baseline (Day 1) and week 4
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Primary outcome [21]
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Change From Baseline in Urea, Glucose, Potassium, Sodium and Calcium Levels-Part 1
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Assessment method [21]
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0
Blood samples were collected to assess change in levels of urea, glucose, potassium, sodium and calcium from baseline.
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Timepoint [21]
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0
Baseline (Day 1) and Week 4
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Primary outcome [22]
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Change From Baseline in Specific Gravity of Urine-Part 1
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Assessment method [22]
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Urine samples were collected to assess change from baseline in specific gravity of urine.
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Timepoint [22]
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Baseline (Day 1) and Week 4
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Primary outcome [23]
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Change From Baseline in Potential of Hydrogen (pH) of Urine-Part 1
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Assessment method [23]
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Urine samples were collected to assess change from baseline in pH of urine.
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Timepoint [23]
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0
Baseline (Day 1) and Week 4
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Primary outcome [24]
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Number of Participants With Abnormal Urinalysis Parameters-Part 1
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Assessment method [24]
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The dipstick test gives positive or negative results for protein, ketones, occult blood and glucose in urine. Positive test results were considered as abnormal. Number of participants with positive test results have been summarized.
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Timepoint [24]
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Week 4
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Primary outcome [25]
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Change From Baseline in Thyroid Stimulating Hormone (TSH) or Thyrotropin-Part 1
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Assessment method [25]
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Blood samples were collected to assess change from Baseline in TSH.
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Timepoint [25]
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Baseline (Day 1) and Week 4
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Primary outcome [26]
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Change From Baseline in Free Triiodothyronine (T3)-Part 1
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Assessment method [26]
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Blood samples were collected to assess change from Baseline in free T3.
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Timepoint [26]
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0
Baseline (Day 1) and Week 4
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Primary outcome [27]
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Change From Baseline in Free Thyroxine (T4)-Part 1
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Assessment method [27]
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Blood samples were collected to assess change from baseline in free T4.
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Timepoint [27]
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Baseline (Day 1) and Week 4
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Primary outcome [28]
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Overall Survival-Part 2
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Assessment method [28]
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For participants in Part 2, overall survival is defined as time from the date of randomization to the date of death due to any cause.
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Timepoint [28]
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Up to 4 years
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Secondary outcome [1]
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Overall Response Rate-Part 1
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Assessment method [1]
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Overall response rate is defined as percentage of participants with confirmed complete response (Disappearance of all target lesions. Any pathological lymph nodes [whether target or non-target] must have reduction in short axis to <10 millimeter [mm]) or partial response (At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters) at any time as per response evaluation criteria in solid tumors (RECIST) version 1.1.
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Timepoint [1]
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Up to 4 years
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Secondary outcome [2]
0
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Overall Response Rate-Part 2
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Assessment method [2]
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Overall response rate is defined as percentage of participants with confirmed complete response (Disappearance of all target lesions. Any pathological lymph nodes [whether target or non-target] must have reduction in short axis to <10 mm) or partial response (At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters) at any time as per RECIST version 1.1.
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Timepoint [2]
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Up to 4 years
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Secondary outcome [3]
0
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Disease Control Rate-Part 1
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Assessment method [3]
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Disease control rate is defined as percentage of subjects with confirmed complete response (Disappearance of all target lesions. Any pathological lymph nodes [whether target or non-target] must have reduction in short axis to <10 mm) or partial response (At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters) or at least 18 weeks of stable disease (Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD) as per RECIST version 1.1.
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Timepoint [3]
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0
Up to 4 years
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Secondary outcome [4]
0
0
Disease Control Rate-Part 2
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Assessment method [4]
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Disease control rate is defined as percentage of subjects with confirmed complete response (Disappearance of all target lesions. Any pathological lymph nodes [whether target or non-target] must have reduction in short axis to <10 mm) or partial response (At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters) or at least 18 weeks of stable disease (Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD) as per RECIST version 1.1.
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Timepoint [4]
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Up to 4 years
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Secondary outcome [5]
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Progression Free Survival-Part 2
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Assessment method [5]
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For Part 2, progression free survival duration is defined as the time from the date of randomization to first documented evidence of disease progression (At least a 20% increase in the sum of diameters of target lesions and In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm) or death (regardless of cause of death), whichever comes first as per RECIST version 1.1.
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Timepoint [5]
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Up to 4 years
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Secondary outcome [6]
0
0
Time to Response-Part 2
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Assessment method [6]
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Time to response is defined as the time from the first dose to the first documented evidence of complete response (Disappearance of all target lesions. Any pathological lymph nodes [whether target or non-target] must have reduction in short axis to <10 mm) or partial response (At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters) for participants with a confirmed CR or PR as per RECIST version 1.1.
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Timepoint [6]
0
0
Up to 4 years
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Secondary outcome [7]
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Duration of Response-Part 2
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Assessment method [7]
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Duration of response is defined as time from the first documented evidence of response until the first documented sign of disease progression or death among participants who achieve a response (CR [Disappearance of all target lesions. Any pathological lymph nodes {whether target or non-target} must have reduction in short axis to <10 mm or PR [At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters] as per RECIST version 1.1).
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Timepoint [7]
0
0
Up to 4 years
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Secondary outcome [8]
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0
Maximum Observed Plasma Concentration (Cmax) of Feladilimab-Part 1
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Assessment method [8]
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0
Blood samples were collected at indicated time points for pharmacokinetic assessment.
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Timepoint [8]
0
0
Pre-dose, end of infusion and 4 hours post dose at Day 1
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Secondary outcome [9]
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0
Cmax of Tremelimumab-Part 1
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Assessment method [9]
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0
Blood samples were collected at indicated time points for pharmacokinetic assessment.
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Timepoint [9]
0
0
Pre-dose, end of infusion and 4 hours post dose at Day 1
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Secondary outcome [10]
0
0
Cmax of Feladilimab-Part 2
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Assessment method [10]
0
0
Blood samples were planned to be collected at indicated time points for pharmacokinetic assessment.
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Timepoint [10]
0
0
Pre-dose at Weeks 1, 2, 4, 7, 10, 13, 16, 19, 25, then every 12 weeks for 2 years; end of infusion at Weeks 1, 19 and 25; and 4 hours post-infusion at Week 1
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Secondary outcome [11]
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0
Cmax of Tremelimumab-Part 2
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Assessment method [11]
0
0
Blood samples were planned to be collected at indicated time points for pharmacokinetic assessment.
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Timepoint [11]
0
0
Pre-dose at Weeks 1, 2, 4, 7, 10, 13, 16, 19, 25, then every 12 weeks for 2 years; end of infusion at Weeks 1, 19 and 25; and 4 hours post-infusion at Week 1
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Secondary outcome [12]
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0
Minimum Observed Plasma Concentration (Cmin) of Feladilimab-Part 1
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Assessment method [12]
0
0
Blood samples were collected at indicated time points for pharmacokinetic assessment.
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Timepoint [12]
0
0
Pre-dose, end of infusion and 4 hours post dose at Day 1
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Secondary outcome [13]
0
0
Cmin of Tremelimumab-Part 1
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Assessment method [13]
0
0
Blood samples were collected at indicated time points for pharmacokinetic assessment.
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Timepoint [13]
0
0
Pre-dose, end of infusion and 4 hours post dose at Day 1
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Secondary outcome [14]
0
0
Cmin of Feladilimab-Part 2
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Assessment method [14]
0
0
Blood samples were planned to be collected at indicated time points for pharmacokinetic assessment.
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Timepoint [14]
0
0
Pre-dose at Weeks 1, 2, 4, 7, 10, 13, 16, then every 12 weeks for 2 years; end of infusion; and 4 hours post-infusion at Week 1
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Secondary outcome [15]
0
0
Cmin of Tremelimumab-Part 2
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Assessment method [15]
0
0
Blood samples were planned to be collected at indicated time points for pharmacokinetic assessment.
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Timepoint [15]
0
0
Pre-dose at Weeks 1, 2, 4, 7, 10, 13, 16, then every 12 weeks for 2 years; end of infusion; and 4 hours post-infusion at Week 1
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Secondary outcome [16]
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0
Area Under the Plasma Concentration-time Curve (AUC[0-t]) of Feladilimab-Part 1
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Assessment method [16]
0
0
Blood samples were collected at indicated time points for pharmacokinetic assessment.
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Timepoint [16]
0
0
Pre-dose, end of infusion and 4 hours post dose at Day 1
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Secondary outcome [17]
0
0
AUC(0-t) of Tremelimumab-Part 1
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Assessment method [17]
0
0
Blood samples were collected at indicated time points for pharmacokinetic assessment.
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Timepoint [17]
0
0
Pre-dose, end of infusion and 4 hours post dose at Day 1
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Secondary outcome [18]
0
0
AUC(0-t) of Feladilimab-Part 2
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Assessment method [18]
0
0
Blood samples were planned to be collected at indicated time points for pharmacokinetic assessment.
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Timepoint [18]
0
0
Pre-dose at Weeks 1, 2, 4, 7, 10, 13, 16, 19, 25, then every 12 weeks for 2 years; end of infusion at Weeks 1, 19 and 25, and 4 hours post-infusion at Week 1
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Secondary outcome [19]
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0
AUC(0-t) of Tremelimumab-Part 2
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Assessment method [19]
0
0
Blood samples were planned to be collected at indicated time points for pharmacokinetic assessment
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Timepoint [19]
0
0
Pre-dose at Weeks 1, 2, 4, 7, 10, 13, 16, then every 12 weeks for 2 years; end of infusion; and 4 hours post-infusion at Week 1
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Secondary outcome [20]
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0
Number of Participants With Anti-drug Antibodies Against Feladilimab-Part 1
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Assessment method [20]
0
0
Serum samples were collected and tested for the presence of antibodies to feladilimab.
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Timepoint [20]
0
0
Pre-dose at Week 4, 7, 10 and 13
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Secondary outcome [21]
0
0
Number of Participants With Anti-drug Antibodies Against Tremelimumab-Part 1
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Assessment method [21]
0
0
Serum samples were collected and tested for the presence of antibodies to tremelimumab.
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Timepoint [21]
0
0
Pre-dose at Week 1, 4, 7, 10 and 13
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Secondary outcome [22]
0
0
Number of Participants With Anti-drug Antibodies Against Feladilimab-Part 2
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Assessment method [22]
0
0
Serum samples will be collected and tested for the presence of antibodies to feladilimab.
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Timepoint [22]
0
0
Up to 2.5 years
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Secondary outcome [23]
0
0
Change From Baseline in Free T4-Part 2
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Assessment method [23]
0
0
Blood samples will be collected to assess change from baseline in free T4.
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Timepoint [23]
0
0
Baseline and up to 2 years
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Secondary outcome [24]
0
0
Number of Participants With Anti-drug Antibodies Against Tremelimumab-Part 2
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Assessment method [24]
0
0
Serum samples will be collected and tested for the presence of antibodies to tremelimumab.
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Timepoint [24]
0
0
Up to 2.5 years
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Secondary outcome [25]
0
0
Number of Participants With AEs, SAEs and AESI-Part 2
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Assessment method [25]
0
0
An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study intervention, whether or not considered related to the study intervention. An SAE is defined as any untoward medical occurrence that, at any dose: results in death; is life-threatening; requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent disability/incapacity; is a congenital anomaly/birth defect and important medical events may jeopardize the subject or may require medical or surgical intervention/SOC to prevent one of the other outcomes mentioned before. AESIs are defined as events of potential immunologic etiology, including immune related AEs.
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Timepoint [25]
0
0
Up to 4 years
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Secondary outcome [26]
0
0
Number of Participants With AEs, SAEs, AESIs Based on Severity-Part 2
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Assessment method [26]
0
0
The severity of all toxicities were graded using the National Cancer Institute- Common Toxicity Criteria for Adverse Events (NCI-CTCAE) version 5.0. Grade 1: Mild reaction; infusion interruption not indicated; intervention not indicated; Grade 2: Requires therapy or infusion interruption but responds promptly to symptomatic treatment or prophylactic medications indicated for =24 hours; Grade 3: Prolonged (i.e., not rapidly responsive to symptomatic medication and/or brief interruption of infusion) or recurrence of symptoms following initial improvement; hospitalization indicated for other clinical sequelae; Grade 4: Life-threatening; pressor or ventilatory support indicated; Grade 5: Death related to AE
Query!
Timepoint [26]
0
0
Up to 4 years
Query!
Secondary outcome [27]
0
0
Number of Participants With Severe- AEs/SAEs/DLTs Leading to Dose Modifications/Delays/Withdrawals-Part 2
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Assessment method [27]
0
0
The number of participants with severe- AE/SAE/DLTs leading to dose modifications/delays/withdrawals were planned to be summarized.
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Timepoint [27]
0
0
Up to 4 years
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Secondary outcome [28]
0
0
Change From Baseline in SBP and DBP-Part 2
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Assessment method [28]
0
0
SBP and DBP will be measured after 5 minutes of rest for the participant.
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Timepoint [28]
0
0
Baseline and up to 2 years
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Secondary outcome [29]
0
0
Change From Baseline in Temperature-Part 2
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Assessment method [29]
0
0
Temperature will be measured after 5 minutes of rest for the participant.
Query!
Timepoint [29]
0
0
Baseline and up to 2 years
Query!
Secondary outcome [30]
0
0
Change From Baseline in Pulse Rate-Part 2
Query!
Assessment method [30]
0
0
Pulse rate will be measured after 5 minutes of rest for the participant.
Query!
Timepoint [30]
0
0
Baseline and up to 2 years
Query!
Secondary outcome [31]
0
0
Change From Baseline in Respiratory Rate-Part 2
Query!
Assessment method [31]
0
0
Respiratory rate will be measured after 5 minutes of rest for the participant.
Query!
Timepoint [31]
0
0
Baseline and up to 2 years
Query!
Secondary outcome [32]
0
0
Change From Baseline in Oxygen Saturation-Part 2
Query!
Assessment method [32]
0
0
Oxygen saturation will be measured using pulse oximetry after 5 minutes of rest for the participant.
Query!
Timepoint [32]
0
0
Baseline and up to 2 years
Query!
Secondary outcome [33]
0
0
Change From Baseline in ECG Measurement-Part 2
Query!
Assessment method [33]
0
0
Single 12-lead ECG will be obtained using an automated ECG machine.
Query!
Timepoint [33]
0
0
Baseline (Pre-dose) up to 2 years
Query!
Secondary outcome [34]
0
0
Change From Baseline in Neutrophil, Lymphocyte, Monocyte, Eosinophil, Basophil and Platelet Count-Part 2
Query!
Assessment method [34]
0
0
Blood samples will be collected to assess change from baseline in neutrophil, lymphocyte, monocyte, eosinophil, basophil and platelet count.
Query!
Timepoint [34]
0
0
Baseline and up to 2 years
Query!
Secondary outcome [35]
0
0
Change From Baseline in Hemoglobin Level-Part 2
Query!
Assessment method [35]
0
0
Blood samples will be collected to assess change from baseline in hemoglobin level.
Query!
Timepoint [35]
0
0
Baseline and up to 2 years
Query!
Secondary outcome [36]
0
0
Change From Baseline in Hematocrit Level-Part 2
Query!
Assessment method [36]
0
0
Blood samples will be collected to assess change from baseline in hematocrit level.
Query!
Timepoint [36]
0
0
Baseline and up to 2 years
Query!
Secondary outcome [37]
0
0
Change From Baseline in Erythrocytes Count-Part 2
Query!
Assessment method [37]
0
0
Blood samples will be collected to assess change from Baseline in erythrocytes count.
Query!
Timepoint [37]
0
0
Baseline and up to 2 years
Query!
Secondary outcome [38]
0
0
Change From Baseline in Albumin and Total Protein Levels-Part 2
Query!
Assessment method [38]
0
0
Blood samples will be collected to assess change from baseline in albumin and total protein levels.
Query!
Timepoint [38]
0
0
Baseline and up to 2 years
Query!
Secondary outcome [39]
0
0
Change From Baseline in Creatinine and Bilirubin Levels-Part 2
Query!
Assessment method [39]
0
0
Blood samples will be collected to assess change from baseline in creatinine and bilirubin levels.
Query!
Timepoint [39]
0
0
Baseline and up to 2 years
Query!
Secondary outcome [40]
0
0
Change From Baseline in ALT, AST, ALP, LDH Levels-Part 2
Query!
Assessment method [40]
0
0
Blood samples will be collected to assess change from baseline in ALT, AST ALP, LDH, amylase and lipase levels.
Query!
Timepoint [40]
0
0
Baseline and up to 2 years
Query!
Secondary outcome [41]
0
0
Change From Baseline in Amylase and Lipase Levels-Part 2
Query!
Assessment method [41]
0
0
Blood samples were collected to assess change from baseline in amylase and lipase levels.
Query!
Timepoint [41]
0
0
Baseline and up to 2 years
Query!
Secondary outcome [42]
0
0
Change From Baseline in Urea, Glucose, Potassium, Sodium and Calcium Levels -Part 2
Query!
Assessment method [42]
0
0
Blood samples will be collected to assess change in levels of urea, glucose, potassium, sodium and calcium from baseline.
Query!
Timepoint [42]
0
0
Baseline and up to 2 years
Query!
Secondary outcome [43]
0
0
Change From Baseline in Specific Gravity of Urine-Part 2
Query!
Assessment method [43]
0
0
Urine samples will be collected to assess change from Baseline in specific gravity of urine.
Query!
Timepoint [43]
0
0
Baseline and up to 2 years
Query!
Secondary outcome [44]
0
0
Change From Baseline in pH of Urine-Part 2
Query!
Assessment method [44]
0
0
Urine samples will be collected to assess change from baseline in pH of urine.
Query!
Timepoint [44]
0
0
Baseline and up to 2 years
Query!
Secondary outcome [45]
0
0
Number of Participants With Abnormal Urinalysis Parameters-Part 2
Query!
Assessment method [45]
0
0
The dipstick test gives positive or negative results for protein, ketones, occult blood and glucose. Positive test results were considered as abnormal. Number of participants with positive test results were planned to be summarized.
Query!
Timepoint [45]
0
0
Up to 2 years
Query!
Secondary outcome [46]
0
0
Change From Baseline in TSH-Part 2
Query!
Assessment method [46]
0
0
Blood samples will be collected to assess change from Baseline in TSH.
Query!
Timepoint [46]
0
0
Baseline and up to 2 years
Query!
Secondary outcome [47]
0
0
Change From Baseline in Free T3-Part 2
Query!
Assessment method [47]
0
0
Blood samples will be collected to assess change from baseline in free T3.
Query!
Timepoint [47]
0
0
Baseline and up to 2 years
Query!
Eligibility
Key inclusion criteria
- Capable of giving signed informed consent/assent which includes compliance with the
requirements and restrictions listed in the informed consent form (ICF) and protocol.
- Male or female, aged 18 years or older.
- Body weight >=30 kilograms (kg).
- Histological or cytological documentation of an invasive malignancy that was diagnosed
as locally advanced/metastatic or relapsed/refractory and is of one of the following
tumor types: a) Part 1: cutaneous melanoma; HNSCC (oral cavity, larynx, oropharynx,
hypopharynx, nasal cavity/paranasal sinuses); non-small cell lung cancer (squamous and
non-squamous); urothelial carcinoma of the upper and lower urinary tract; clear cell
renal carcinoma; castrate resistant prostate adenocarcinoma. b) Part 2: HNSCC (oral
cavity, larynx, pharynx, paranasal sinuses).
- Part 1 only: Disease that has progressed after standard therapy for the specific tumor
type, or for which standard therapy has proven to be ineffective, intolerable, or is
considered inappropriate, or if no further standard therapy exists, or where standard
therapy is refused. May be anti-PD-1/anti-PD-L1 experienced or naïve.
- Part 2 only: Disease that has progressed after receiving platinum-based chemotherapy
(unless medically contraindicated or discontinued due to toxicity) and
anti-PD-1/anti-PD-L1 therapy (in combination or as separate lines of therapy in either
sequence).
- Measurable disease per RECIST version 1.1 guidelines. Palpable lesions that are not
measurable by radiographic or photographic evaluations may not be utilized as the only
measurable lesion. Any measurable lesion biopsied at Screening cannot be followed as a
target/index lesion unless agreed upon by GlaxoSmithKline (GSK).
- Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) score of 0 or 1.
- Adequate organ function.
- A female subject is eligible to participate if she is not pregnant, not breastfeeding,
and at least one of the following conditions apply: a) Not a woman of childbearing
potential (WOCBP); or, b) A WOCBP who agrees to follow the contraceptive while
receiving study intervention and for at least 180 days after the last dose of study
intervention.
- A male subject must agree to use a highly effective contraception while receiving
study intervention and for at least 180 days after the last dose of study intervention
and refrain from donating sperm during this period.
- Agree to collection of tumor tissue: a) Part 1 and Part 2: Archival tumor tissue
collected any time from the initial diagnosis of invasive malignancy; a fresh tumor
biopsy will be required if archival specimen is unavailable prior to first dose. b)
Part 1 pharmacokinetic/pharmacodynamic cohort(s): Archival tissue as noted in point
(a) above. Paired tumor biopsies: tumor tissue collected any time after completion of
dosing of the last therapy and prior to first dose and an on-treatment biopsy. c) Part
2: A minimum of 15 subjects from each arm will be required to provide paired tumor
biopsies (in addition to the archival tissues as noted in point (a) above): tumor
tissue collected any time after completion of dosing of the last therapy and prior to
first dose and an on-treatment biopsy.
Query!
Minimum age
18
Years
Query!
Query!
Maximum age
No limit
Query!
Query!
Sex
Both males and females
Query!
Can healthy volunteers participate?
No
Query!
Key exclusion criteria
- Received prior treatment with the following therapies; calculation is based on date of
last therapy to date of first dose of study intervention or SOC: a) Cytotoxic
T-Lymphocyte-Associated Protein 4 (CTLA-4 [including tremelimumab] or Inducible T Cell
Co-Stimulator (ICOS)-directed therapies at any time; b) >=4 lines of prior anticancer
treatment: In subjects that relapse or progress within 1 year from the beginning of
adjuvant or concurrent therapy, the adjuvant/concurrent therapy is considered first
line therapy; c) Systemic anticancer therapy or investigational therapy within 30
days, or 5 half-lives, whichever is shorter; at least 14 days must have elapsed
between the date of the last prior therapy to the date of first dose of study
intervention or SOC.
- Prior radiation therapy: permissible if at least one non-irradiated measurable lesion
is available for assessment per RECIST v1.1 or if a solitary measurable lesion was
irradiated, objective progression is documented. At least 14 days must have elapsed
between the date of the last dosage of radiation and the first dose of study
intervention/SOC.
- Invasive malignancy or history of invasive malignancy other than disease under study
within the last two years, except: a) Any other invasive malignancy for which the
subject was definitively treated, has been disease-free for <=2 years and in the
opinion of the Investigator and Medical Monitor will not affect the evaluation of the
effects of the study intervention or SOC on the currently targeted malignancy, may be
included in this clinical study; Curatively treated non-melanoma skin cancer or
successfully treated in-situ carcinoma.
- Toxicity from previous anticancer treatment that includes: a) >=Grade 3 toxicity
considered related to prior immunotherapy and that led to treatment discontinuation;
b) Toxicity related to prior treatment that has not resolved to <=Grade 1 (except
alopecia, vitiligo, hearing loss, endocrinopathy managed with replacement therapy, and
peripheral neuropathy which must be <=Grade 2).
- Central nervous system (CNS) metastases, with the following exception: Subjects with
previously treated CNS metastases who are clinically stable and had no requirement for
steroids during at least 14 days prior to first dose of study intervention or SOC.
- Major surgery <=28 days of first dose of study intervention or SOC.
- Autoimmune disease (current or history) or syndrome that required systemic treatment
within the past 2 years. Replacement therapies which include physiological doses of
corticosteroids for treatment of endocrinopathies (i.e., adrenal insufficiency) are
not considered systemic treatments.
- Recent history (within 24 weeks) of gastrointestinal obstruction that required
surgery, acute diverticulitis, inflammatory bowel disease, or intra-abdominal abscess.
- Receiving systemic steroids (>=10 milligrams [mg] oral prednisone or equivalent) or
other immunosuppressive agents within 7 days prior to first dose of study intervention
or SOC.
- Prior allogeneic/autologous bone marrow or solid organ transplantation.
- Received live-virus vaccine within 30 days from start of study intervention or SOC.
- Current or history of idiopathic pulmonary fibrosis, pneumonitis (for past, subject is
excluded if steroids were required), interstitial lung disease or organizing
pneumonia.
- Recent history (within 24 weeks) of uncontrolled, symptomatic ascites, pleural or
pericardial effusions.
- History or evidence of cardiac abnormalities within the 24 weeks prior to enrollment
which include: a) Serious uncontrolled cardiac arrhythmia or clinically significant
electrocardiogram 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. c) Symptomatic pericarditis.
- 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.
- Active infection requiring systemic therapy.
- Known human immunodeficiency virus infection; positive test for hepatitis B active
infection (presence of hepatitis B surface antigen) or hepatitis C active infection.
- History of severe hypersensitivity to monoclonal antibodies, the Standard of Care
agents, including any ingredient used in the formulation, based on which treatment the
subject is to receive.
- Any serious and/or unstable pre-existing medical (aside from malignancy), psychiatric
disorder, or other conditions that could interfere with subject's safety, obtaining
informed consent or compliance to the study procedures, in the opinion of the
Investigator.
- For subjects receiving SOC: Requires therapy with a medication that may alter the PK
of the SOC agent (e.g., strong inducers or inhibitors of cytochrome P (CYP)3A4 for
subjects receiving docetaxel or paclitaxel) during the study treatment period. Please
refer to the package insert for the agent the subject is to receive.
- For subjects receiving SOC: Any contraindication, per the package insert and/or
Institutional guidelines, to the treatment the subject is to receive.
Query!
Study design
Purpose of the study
Treatment
Query!
Allocation to intervention
Randomised controlled trial
Query!
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Query!
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Query!
Masking / blinding
Open (masking not used)
Query!
Who is / are masked / blinded?
Query!
Query!
Query!
Query!
Intervention assignment
Parallel
Query!
Other design features
Query!
Phase
Phase 1/Phase 2
Query!
Type of endpoint/s
Query!
Statistical methods / analysis
Query!
Recruitment
Recruitment status
Completed
Query!
Data analysis
Query!
Reason for early stopping/withdrawal
Query!
Other reasons
Query!
Date of first participant enrolment
Anticipated
Query!
Actual
26/11/2018
Query!
Date of last participant enrolment
Anticipated
Query!
Actual
Query!
Date of last data collection
Anticipated
Query!
Actual
16/09/2021
Query!
Sample size
Target
Query!
Accrual to date
Query!
Final
26
Query!
Recruitment in Australia
Recruitment state(s)
VIC
Query!
Recruitment hospital [1]
0
0
GSK Investigational Site - Melbourne
Query!
Recruitment postcode(s) [1]
0
0
3000 - Melbourne
Query!
Recruitment outside Australia
Country [1]
0
0
United States of America
Query!
State/province [1]
0
0
Massachusetts
Query!
Country [2]
0
0
United States of America
Query!
State/province [2]
0
0
New York
Query!
Country [3]
0
0
United States of America
Query!
State/province [3]
0
0
Pennsylvania
Query!
Country [4]
0
0
United States of America
Query!
State/province [4]
0
0
Texas
Query!
Country [5]
0
0
Canada
Query!
State/province [5]
0
0
Ontario
Query!
Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Query!
Name
GlaxoSmithKline
Query!
Address
Query!
Country
Query!
Other collaborator category [1]
0
0
Commercial sector/Industry
Query!
Name [1]
0
0
MedImmune LLC
Query!
Address [1]
0
0
Query!
Country [1]
0
0
Query!
Ethics approval
Ethics application status
Query!
Summary
Brief summary
The purpose of this study is to evaluate if the combination of GSK3359609 and tremelimumab is
safe and tolerable (Part 1) and provides significant survival benefit to subjects with
relapsed/refractory (R/R) Head and Neck Squamous Cell Carcinomas (HNSCC) to warrant further
clinical investigation (Part 2). Part 1 (dose escalation) will enroll subjects with advanced,
selected solid tumors. Subjects will receive escalating doses of GSK3359609 and tremelimumab
in combination in Part 1. Part 2 is randomized expansion and will enroll subjects with R/R
HNSCC who have disease progression after receiving at least 1 platinum-based chemotherapy and
at least 1 anti-programmed death receptor protein-1 (PD-1)/anti-programmed death-ligand 1
(PD-L1) therapy, whether in combination or separately. In Part 2, subjects will be randomized
in a ratio of 2:1 to receive either GSK3359609 in combination with tremelimumab at the
recommended Phase 2 dose or investigators choice of a single-agent standard of care (SOC)
therapy including paclitaxel, docetaxel or cetuximab. The total duration of subjects in the
study will be approximately 4 years.
Query!
Trial website
https://clinicaltrials.gov/ct2/show/NCT03693612
Query!
Trial related presentations / publications
Query!
Public notes
Query!
Contacts
Principal investigator
Name
0
0
GSK Clinical Trials
Query!
Address
0
0
GlaxoSmithKline
Query!
Country
0
0
Query!
Phone
0
0
Query!
Fax
0
0
Query!
Email
0
0
Query!
Contact person for public queries
Name
0
0
Query!
Address
0
0
Query!
Country
0
0
Query!
Phone
0
0
Query!
Fax
0
0
Query!
Email
0
0
Query!
Contact person for scientific queries
Summary Results
For IPD and results data, please see
https://clinicaltrials.gov/ct2/show/NCT03693612
Additional trial details provided through ANZCTR
Accrual to date
Recruiting in Australia
Recruitment state(s)
VIC
Funding & Sponsors
Primary sponsor
Commercial sector/Industry
Primary sponsor name
GlaxoSmithKline
Primary sponsor address
Primary sponsor country
Ethics approval
Ethics application status
Approved
Public notes
Contacts
Principal investigator
Title
61
0
Prof
Query!
Name
61
0
Danny Rischin
Query!
Address
61
0
Peter MacCallum Cancer Centre Melbourne VIC 3000
Query!
Country
61
0
Australia
Query!
Phone
61
0
Query!
Fax
61
0
Query!
Email
61
0
Query!
Contact person for public queries
Title
62
0
Query!
Name
62
0
Query!
Address
62
0
Query!
Country
62
0
Query!
Phone
62
0
Query!
Fax
62
0
Query!
Email
62
0
[email protected]
Query!
Contact person for scientific queries
Title
63
0
Query!
Name
63
0
Query!
Address
63
0
Query!
Country
63
0
Query!
Phone
63
0
Query!
Fax
63
0
Query!
Email
63
0
[email protected]
Query!
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