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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/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
12/06/2019

Titles & IDs
Public title
GSK3359609 Plus Tremelimumab for the Treatment of Advanced Solid Tumors
Scientific title
A Phase I/II, Open-label, Two Part Study of GSK3359609 in Combination With Tremelimumab in Participants With Selected, Advanced Solid Tumors
Secondary ID [1] 0 0
207871
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Neoplasms 0 0
Condition category
Condition code

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - GSK3359609
Treatment: Drugs - Tremelimumab
Treatment: Drugs - Docetaxel
Treatment: Drugs - Paclitaxel
Treatment: Drugs - Cetuximab

Experimental: Part 1: GSK3359609+tremelimumab - In Part 1, subjects with advanced selected solid tumors will be enrolled. Subjects will be administered escalating doses of GSK3359609 and tremelimumab in combination. GSK3359609 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: GSK3359609+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 GSK3359609 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: GSK3359609
GSK3359609 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.

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Number of subjects with dose limiting toxicities (DLTs)-Part 1 - An adverse event (AE) is considered to be a DLT if it is considered by the investigator to be clinically relevant and is attributed to the study treatment during the 28-day DLT observation period and meets at least 1 of the pre-specified criteria.
Timepoint [1] 0 0
Up to 28 days
Primary outcome [2] 0 0
Severity of DLTs-Part 1 - The severity of all toxicities will be graded using the National Cancer Institute- Common Toxicity Criteria for Adverse Events (NCI-CTCAE) version 5.0.
Timepoint [2] 0 0
Up to 28 days
Primary outcome [3] 0 0
Number of subjects with AEs, serious adverse events (SAEs) and adverse events of significant importance (AESI)-Part 1 - An AE is any untoward medical occurrence in a clinical study subject, temporally associated with the use of a study intervention/SOC, whether or not considered related to the study intervention/SOC. 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.
Timepoint [3] 0 0
Up to 4 years
Primary outcome [4] 0 0
Number of subjects with AE/SAE/DLTs leading to dose modifications/delays/withdrawals-Part 1 - The number of subjects with AE/SAE/DLTs leading to dose modifications/delays/withdrawals will be summarized.
Timepoint [4] 0 0
Up to 4 years
Primary outcome [5] 0 0
Severity of AEs, SAEs, AESI and AE/SAE/DLTs leading to dose modifications/delays/withdrawals-Part 1 - The severity of all toxicities will be graded using the NCI-CTCAE (version 5.0).
Timepoint [5] 0 0
Up to 4 years
Primary outcome [6] 0 0
Change from Baseline in systolic blood pressure (SBP) and diastolic blood pressure (DBP)-Part 1 - SBP and DBP will be measured after 5 minutes of rest for the subject.
Timepoint [6] 0 0
Baseline and up to 2 years
Primary outcome [7] 0 0
Change from Baseline in temperature-Part 1 - Temperature will be measured after 5 minutes of rest for the subject.
Timepoint [7] 0 0
Baseline and up to 2 years
Primary outcome [8] 0 0
Change from Baseline in pulse rate-Part 1 - Pulse rate will be measured after 5 minutes of rest for the subject.
Timepoint [8] 0 0
Baseline and up to 2 years
Primary outcome [9] 0 0
Change from Baseline in respiratory rate-Part 1 - Respiratory rate will be measured after 5 minutes of rest for the subject.
Timepoint [9] 0 0
Baseline and up to 2 years
Primary outcome [10] 0 0
Change from Baseline in oxygen saturation-Part 1 - Oxygen saturation will be measured using pulse oximetry after 5 minutes of rest for the subject.
Timepoint [10] 0 0
Baseline and up to 2 years
Primary outcome [11] 0 0
Change from Baseline in electrocardiogram (ECG) measurement-Part 1 - Single 12-lead ECG will be obtained using an automated ECG machine.
Timepoint [11] 0 0
Baseline and Day 1
Primary outcome [12] 0 0
Change from Baseline in neutrophil, lymphocyte, monocyte, eosinophil, basophil and platelet count-Part 1 - Blood samples will be collected to assess change from Baseline in neutrophil, lymphocyte, monocyte, eosinophil, basophil and platelet count.
Timepoint [12] 0 0
Baseline and up to 2 years
Primary outcome [13] 0 0
Change from Baseline in hemoglobin level-Part 1 - Blood samples will be collected to assess change from Baseline in hemoglobin level.
Timepoint [13] 0 0
Baseline and up to 2 years
Primary outcome [14] 0 0
Change from Baseline in hematocrit level-Part 1 - Blood samples will be collected to assess change from Baseline in hematocrit level.
Timepoint [14] 0 0
Baseline and up to 2 years
Primary outcome [15] 0 0
Change from Baseline in red blood cell (RBC) count-Part 1 - Blood samples will be collected to assess change from Baseline in RBC count.
Timepoint [15] 0 0
Baseline and up to 2 years
Primary outcome [16] 0 0
Change from Baseline in albumin and total protein levels-Part 1 - Blood samples will be collected to assess change from Baseline in albumin and total protein levels.
Timepoint [16] 0 0
Baseline and up to 2 years
Primary outcome [17] 0 0
Change from Baseline in creatinine and bilirubin levels-Part 1 - Blood samples will be collected to assess change from Baseline in creatinine and bilirubin levels.
Timepoint [17] 0 0
Baseline and up to 2 years
Primary outcome [18] 0 0
Change from Baseline in alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), lactate dehydrogenase (LDH), amylase and lipase levels-Part 1 - Blood samples will be collected to assess change from Baseline in ALT, AST ALP, LDH, amylase and lipase levels.
Timepoint [18] 0 0
Baseline and up to 2 years
Primary outcome [19] 0 0
Change from Baseline in blood urea nitrogen (BUN), glucose, potassium, sodium and calcium-Part 1 - Blood samples will be collected to assess change in levels of BUN, glucose, potassium, sodium and calcium from Baseline.
Timepoint [19] 0 0
Baseline and up to 2 years
Primary outcome [20] 0 0
Change from Baseline in specific gravity of urine-Part 1 - Urine samples will be collected to assess change from Baseline in specific gravity of urine.
Timepoint [20] 0 0
Baseline and up to 2 years
Primary outcome [21] 0 0
Change from Baseline in potential of hydrogen (pH) of urine-Part 1 - Urine samples will be collected to assess change from Baseline in pH of urine.
Timepoint [21] 0 0
Baseline and up to 2 years
Primary outcome [22] 0 0
Change from Baseline in glucose, protein, blood and ketone levels in urine-Part 1 - Urine samples will be collected to assess change from Baseline in glucose, protein, blood and ketone levels in urine .
Timepoint [22] 0 0
Baseline and up to 2 years
Primary outcome [23] 0 0
Change from Baseline in thyroxine stimulating hormone (TSH)-Part 1 - Blood samples will be collected to assess change from Baseline in TSH.
Timepoint [23] 0 0
Baseline and up to 2 years
Primary outcome [24] 0 0
Change from Baseline in free triiodothyronine (T3)-Part 1 - Blood samples will be collected to assess change from Baseline in free T3.
Timepoint [24] 0 0
Baseline and up to 2 years
Primary outcome [25] 0 0
Change from Baseline in free thyroxine (T4)-Part 1 - Blood samples will be collected to assess change from Baseline in free T4.
Timepoint [25] 0 0
Baseline and up to 2 years
Primary outcome [26] 0 0
Overall survival-Part 2 - For subjects in Part 2, overall survival is defined as time from the date of randomization to the date of death due to any cause.
Timepoint [26] 0 0
Up to 4 years
Secondary outcome [1] 0 0
Overall response rate-Part 1 - Overall response rate is defined as percentage of subjects with confirmed complete response or partial response at any time as per response evaluation criteria in solid tumors (RECIST) version 1.1.
Timepoint [1] 0 0
Up to 4 years
Secondary outcome [2] 0 0
Overall response rate-Part 2 - Overall response rate is defined as percentage of subjects with confirmed complete response or partial response at any time as per RECIST version 1.1.
Timepoint [2] 0 0
Up to 4 years
Secondary outcome [3] 0 0
Disease control rate-Part 1 - Disease control rate is defined as percentage of subjects with confirmed complete response or partial response or at least 18 weeks of stable disease.
Timepoint [3] 0 0
Up to 4 years
Secondary outcome [4] 0 0
Disease control rate-Part 2 - Disease control rate is defined as percentage of subjects with confirmed complete response or partial response or at least 18 weeks of stable disease.
Timepoint [4] 0 0
Up to 4 years
Secondary outcome [5] 0 0
Progression free survival-Part 2 - For Part 2, progression free survival duration is defined as the time from the date of randomization to first documented evidence of disease progression or death (regardless of cause of death), whichever comes first.
Timepoint [5] 0 0
Up to 4 years
Secondary outcome [6] 0 0
Time to response-Part 2 - Time to response is defined as the time from the first dose to the first documented evidence of complete response (CR) or partial response (PR) for subjects with a confirmed CR or PR.
Timepoint [6] 0 0
Up to 4 years
Secondary outcome [7] 0 0
Duration of response-Part 2 - 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 subjects who achieve a response (CR or PR).
Timepoint [7] 0 0
Up to 4 years
Secondary outcome [8] 0 0
Maximum observed plasma concentration (Cmax) of GSK3359609-Part 1 - Blood samples will be collected at indicated time points for pharmacokinetic assessment.
Timepoint [8] 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
Secondary outcome [9] 0 0
Cmax of tremelimumab-Part 1 - Blood samples will be collected at indicated time points for pharmacokinetic assessment.
Timepoint [9] 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
Secondary outcome [10] 0 0
Cmax of GSK3359609-Part 2 - Blood samples will be collected at indicated time points for pharmacokinetic assessment.
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
Secondary outcome [11] 0 0
Cmax of tremelimumab-Part 2 - Blood samples will be collected at indicated time points for pharmacokinetic assessment.
Timepoint [11] 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
Secondary outcome [12] 0 0
Minimum observed plasma concentration (Cmin) of GSK3359609-Part 1 - Blood samples will be collected at indicated time points for pharmacokinetic assessment.
Timepoint [12] 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
Secondary outcome [13] 0 0
Cmin of tremelimumab-Part 1 - Blood samples will be collected at indicated time points for pharmacokinetic assessment.
Timepoint [13] 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
Secondary outcome [14] 0 0
Cmin of GSK3359609-Part 2 - Blood samples will be collected at indicated time points for pharmacokinetic assessment.
Timepoint [14] 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
Secondary outcome [15] 0 0
Cmin of tremelimumab-Part 2 - Blood samples will be collected at indicated time points for pharmacokinetic assessment.
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
Secondary outcome [16] 0 0
Area under the plasma concentration-time curve AUC(0-t) of GSK3359609-Part 1 - Blood samples will be collected at indicated time points for pharmacokinetic assessment.
Timepoint [16] 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
Secondary outcome [17] 0 0
AUC(0-t) of GSK3359609-Part 2 - Blood samples will be collected at indicated time points for pharmacokinetic assessment.
Timepoint [17] 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
Secondary outcome [18] 0 0
AUC(0-t) of tremelimumab-Part 1 - Blood samples will be collected at indicated time points for pharmacokinetic assessment.
Timepoint [18] 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
Secondary outcome [19] 0 0
AUC(0-t) of tremelimumab-Part 2 - Blood samples will be collected at indicated time points for pharmacokinetic assessment.
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
Secondary outcome [20] 0 0
Number of subjects with anti-drug antibodies against GSK3359609-Part 1 - Serum samples will be collected and tested for the presence of antibodies to GSK3359609.
Timepoint [20] 0 0
Up to 2.5 years
Secondary outcome [21] 0 0
Number of subjects with anti-drug antibodies against GSK3359609-Part 2 - Serum samples will be collected and tested for the presence of antibodies to GSK3359609.
Timepoint [21] 0 0
Up to 2.5 years
Secondary outcome [22] 0 0
Number of subjects with anti-drug antibodies against tremelimumab-Part 1 - Serum samples will be collected and tested for the presence of antibodies to tremelimumab.
Timepoint [22] 0 0
Up to 2.5 years
Secondary outcome [23] 0 0
Number of subjects with anti-drug antibodies against tremelimumab-Part 2 - Serum samples will be collected and tested for the presence of antibodies to tremelimumab.
Timepoint [23] 0 0
Up to 2.5 years
Secondary outcome [24] 0 0
Number of subjects with AEs, SAEs and AESI-Part 2 - An AE is any untoward medical occurrence in a clinical study subject, temporally associated with the use of a study intervention/SOC, whether or not considered related to the study intervention/SOC. 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.
Timepoint [24] 0 0
Up to 4 years
Secondary outcome [25] 0 0
Severity of AEs, SAEs, AESI and AE/SAEs leading to dose modifications/delays/withdrawals-Part 2 - The severity of all toxicities will be graded using the NCI-CTCAE (version 5.0).
Timepoint [25] 0 0
Up to 4 years
Secondary outcome [26] 0 0
Change from Baseline in SBP and DBP-Part 2 - SBP and DBP will be measured after 5 minutes of rest for the subject.
Timepoint [26] 0 0
Baseline and up to 2 years
Secondary outcome [27] 0 0
Change from Baseline in temperature-Part 2 - Temperature will be measured after 5 minutes of rest for the subject.
Timepoint [27] 0 0
Baseline and up to 2 years
Secondary outcome [28] 0 0
Change from Baseline in pulse rate-Part 2 - Pulse rate will be measured after 5 minutes of rest for the subject.
Timepoint [28] 0 0
Baseline and up to 2 years
Secondary outcome [29] 0 0
Change from Baseline in respiratory rate-Part 2 - Respiratory rate will be measured after 5 minutes of rest for the subject.
Timepoint [29] 0 0
Baseline and up to 2 years
Secondary outcome [30] 0 0
Change from Baseline in oxygen saturation-Part 2 - Oxygen saturation will be measured using pulse oximetry after 5 minutes of rest for the subject.
Timepoint [30] 0 0
Baseline and up to 2 years
Secondary outcome [31] 0 0
Change from Baseline in ECG measurement-Part 2 - Single 12-lead ECG will be obtained using an automated ECG machine.
Timepoint [31] 0 0
Baseline and Day 1
Secondary outcome [32] 0 0
Change from Baseline in neutrophil, lymphocyte, monocyte, eosinophil, basophil and platelet count-Part 2 - Blood samples will be collected to assess change from Baseline in neutrophil, lymphocyte, monocyte, eosinophil, basophil and platelet count.
Timepoint [32] 0 0
Baseline and up to 2 years
Secondary outcome [33] 0 0
Change from Baseline in hemoglobin level-Part 2 - Blood samples will be collected to assess change from Baseline in hemoglobin level.
Timepoint [33] 0 0
Baseline and up to 2 years
Secondary outcome [34] 0 0
Change from Baseline in hematocrit level-Part 2 - Blood samples will be collected to assess change from Baseline in hematocrit level.
Timepoint [34] 0 0
Baseline and up to 2 years
Secondary outcome [35] 0 0
Change from Baseline in RBC count-Part 2 - Blood samples will be collected to assess change from Baseline in RBC count.
Timepoint [35] 0 0
Baseline and up to 2 years
Secondary outcome [36] 0 0
Change from Baseline in albumin and total protein levels-Part 2 - Blood samples will be collected to assess change from Baseline in albumin and total protein levels.
Timepoint [36] 0 0
Baseline and up to 2 years
Secondary outcome [37] 0 0
Change from Baseline in creatinine and bilirubin levels-Part 2 - Blood samples will be collected to assess change from Baseline in creatinine and bilirubin levels.
Timepoint [37] 0 0
Baseline and up to 2 years
Secondary outcome [38] 0 0
Change from Baseline in ALT, AST, ALP, LDH, amylase and lipase levels-Part 2 - Blood samples will be collected to assess change from Baseline in ALT, AST ALP, LDH, amylase and lipase levels.
Timepoint [38] 0 0
Baseline and up to 2 years
Secondary outcome [39] 0 0
Change from Baseline in BUN, glucose, potassium, sodium and calcium-Part 2 - Blood samples will be collected to assess change in levels of BUN, glucose, potassium, sodium and calcium from Baseline.
Timepoint [39] 0 0
Baseline and up to 2 years
Secondary outcome [40] 0 0
Change from Baseline in specific gravity of urine-Part 2 - Urine samples will be collected to assess change from Baseline in specific gravity of urine.
Timepoint [40] 0 0
Baseline and up to 2 years
Secondary outcome [41] 0 0
Change from Baseline in pH of urine-Part 2 - Urine samples will be collected to assess change from Baseline in pH of urine.
Timepoint [41] 0 0
Baseline and up to 2 years
Secondary outcome [42] 0 0
Change from Baseline in glucose, protein, blood and ketone levels in urine-Part 2 - Urine samples will be collected to assess change from Baseline in glucose, protein, blood and ketone levels in urine.
Timepoint [42] 0 0
Baseline and up to 2 years
Secondary outcome [43] 0 0
Change from Baseline in TSH-Part 2 - Blood samples will be collected to assess change from Baseline in TSH.
Timepoint [43] 0 0
Baseline and up to 2 years
Secondary outcome [44] 0 0
Change from Baseline in free T3-Part 2 - Blood samples will be collected to assess change from Baseline in free T3.
Timepoint [44] 0 0
Baseline and up to 2 years
Secondary outcome [45] 0 0
Change from Baseline in free T4-Part 2 - Blood samples will be collected to assess change from Baseline in free T4.
Timepoint [45] 0 0
Baseline and up to 2 years

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.
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
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.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 0 0
GSK Investigational Site - Melbourne
Recruitment postcode(s) [1] 0 0
3000 - Melbourne
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Massachusetts
Country [2] 0 0
United States of America
State/province [2] 0 0
New York
Country [3] 0 0
United States of America
State/province [3] 0 0
Pennsylvania
Country [4] 0 0
United States of America
State/province [4] 0 0
Texas
Country [5] 0 0
Canada
State/province [5] 0 0
Ontario

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
GlaxoSmithKline
Address
Country
Other collaborator category [1] 0 0
Commercial sector/Industry
Name [1] 0 0
MedImmune LLC
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

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.
Trial website
https://clinicaltrials.gov/show/NCT03693612
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
GSK Clinical Trials
Address 0 0
GlaxoSmithKline
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
US GSK Clinical Trials Call Center
Address 0 0
Country 0 0
Phone 0 0
877-379-3718
Fax 0 0
Email 0 0
GSKClinicalSupportHD@gsk.com
Contact person for scientific queries

Summary results
For IPD and results data, please see https://clinicaltrials.gov/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
Name 61 0
Danny Rischin
Address 61 0
Peter MacCallum Cancer Centre Melbourne VIC 3000
Country 61 0
Australia
Phone 61 0
Fax 61 0
Email 61 0
Contact person for public queries
Title 62 0
Name 62 0
Address 62 0
Country 62 0
Phone 62 0
Fax 62 0
Email 62 0
GSKClinicalSupportHD@gsk.com
Contact person for scientific queries
Title 63 0
Name 63 0
Address 63 0
Country 63 0
Phone 63 0
Fax 63 0
Email 63 0
GSKClinicalSupportHD@gsk.com