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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT02723955


Additional trial details provided through ANZCTR are available at the end of this record.


Registration number
NCT02723955
Ethics application status
Date submitted
24/03/2016
Date registered
31/03/2016
Date last updated
27/05/2020

Titles & IDs
Public title
Dose Escalation and Expansion Study of GSK3359609 in Participants With Selected Advanced Solid Tumors (INDUCE-1)
Scientific title
A Phase I Open Label Study of GSK3359609 Administered Alone and in Combination With Anticancer Agents in Subjects With Selected Advanced Solid Tumors
Secondary ID [1] 0 0
2016-000148-32
Secondary ID [2] 0 0
204691
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 IV infusion
Treatment: Drugs - GSK3174998 IV infusion
Treatment: Drugs - Pembrolizumab 200 mg IV infusion
Treatment: Drugs - Docetaxel 75 milligrams per square meters (mg/m^2) IV infusion
Treatment: Drugs - Pemetrexed 500 mg/m^2 plus Carboplatin area under the curve (AUC) 4-6 mg/mL per minute IV infusion
Treatment: Drugs - Paclitaxel 200 mg/m^2 plus Carboplatin AUC 4-6 mg/mL per minute IV infusion
Treatment: Drugs - Gemcitabine 1250 mg/m^2 plus Carboplatin AUC 4-6 mg/mL per minute IV infusion
Treatment: Drugs - Fluorouracil (5-FU) 1000 mg/m^2/day plus carboplatin or cisplatin
Treatment: Drugs - Pembrolizumab 400 mg IV infusion
Treatment: Drugs - Dostarlimab
Treatment: Drugs - Cobolimab
Treatment: Drugs - Bintrafusp alfa

Experimental: Part 1A: Dose escalation GSK3359609 - Participants will receive GSK3359609 as an intravenous (IV) infusion administered once every 3 weeks (Q3W) continuously at a dose level dependent on to which dose level the participant is accrued.

Experimental: Part 1B: Expansion GSK3359609 - Participants will receive GSK3359609 as an IV infusion administered Q3W continuously at a dose level chosen for further exploration in dose expansion cohorts.

Experimental: Part 2A: Dose escalation (GSK3359609+pembrolizumab) - Participants will receive GSK3359609 as an IV infusion administered Q3W continuously in combination with 200 milligram (mg) of pembrolizumab as an IV infusion administered once Q3W continuously.

Experimental: Part 2A: Dose escalation (GSK3359609+GSK3174998) - Participants will receive GSK3359609 as an IV infusion administered Q3W continuously in combination with GSK3174998 as an IV infusion administered once Q3W.

Experimental: Part 2A: Safety run-in (GSK3359609+chemotherapy) - Participants participating in Part 2A chemotherapy combination cohorts will receive GSK3359609 in combination with chemotherapy at doses and schedules based on standard of care practice.

Experimental: Part 2A: Dose escalation (GSK3359609+ dostarlimab) - Participants will receive GSK3359609 as an IV infusion administered Q3W continuously in combination with dostarlimab administered as an IV infusion at 500 mg Q3W for 4 cycles followed by 1000 mg Q6W.

Experimental: Part 2A: Dose escalation (GSK3359609+dostarlimab+cobolimab) - Participants will receive GSK3359609 as an IV infusion administered Q3W continuously in combination with dostarlimab administered as an IV infusion at 500 mg Q3W for 4 cycles followed by 1000 mg Q6W plus cobolimab administered as an IV infusion at 300 mg Q3W.

Experimental: Part 2A: Dose escalation (GSK3359609+bintrafusp alfa) - Participants will receive GSK3359609 as an IV infusion administered Q3W continuously in combination with bintrafusp alfa administered as an IV infusion at 2400 mg Q3W.

Experimental: Part 2B: Expansion-GSK3359609 - Participants will receive GSK3359609 as an IV infusion administered Q3W continuously in combination with 200 mg of pembrolizumab as an IV infusion administered once Q3W continuously.

Experimental: Part 2B: Expansion-GSK3359609 (Q6W) - Participants will receive GSK3359609 as an IV infusion administered once every 6 weeks (Q6W) continuously in combination with 400 mg of pembrolizumab as an IV infusion administered Q6W continuously.


Treatment: Drugs: GSK3359609 IV infusion
GSK3359609 diluted product will be administered as an IV infusion to participants Q3W or Q6W.

Treatment: Drugs: GSK3174998 IV infusion
GSK3174998 diluted product will be administered as an IV infusion to participants Q3W.

Treatment: Drugs: Pembrolizumab 200 mg IV infusion
Pembrolizumab 200 mg will be administered as an IV infusion to participants Q3W.

Treatment: Drugs: Docetaxel 75 milligrams per square meters (mg/m^2) IV infusion
Docetaxel 75 mg/m^2 diluted product will be administered as an IV infusion to participants Q3W.

Treatment: Drugs: Pemetrexed 500 mg/m^2 plus Carboplatin area under the curve (AUC) 4-6 mg/mL per minute IV infusion
Pemetrexed 500 mg/m^2 diluted product in combination with Carboplatin AUC 4-6 milligram per milliliter (mg/mL) per minute (diluted product), will be administered as an IV infusion to participants Q3W.

Treatment: Drugs: Paclitaxel 200 mg/m^2 plus Carboplatin AUC 4-6 mg/mL per minute IV infusion
Paclitaxel 200 mg/m^2 diluted product in combination with Carboplatin AUC 4-6 mg/mL per minute (diluted product), will be administered as an IV infusion to participants Q3W.

Treatment: Drugs: Gemcitabine 1250 mg/m^2 plus Carboplatin AUC 4-6 mg/mL per minute IV infusion
Gemcitabine 1250 mg/m^2 diluted product in combination with Carboplatin AUC 4-6 mg/mL per minute (diluted product), will be administered as an IV infusion to participants Q3W.

Treatment: Drugs: Fluorouracil (5-FU) 1000 mg/m^2/day plus carboplatin or cisplatin
Carboplatin AUC 4-6 mg/mL per minute or cisplatin at 100 mg/m^2 will be combined with 5-FU at 1000 mg/m^2/day will be administered as an IV infusion to participants Q3W.

Treatment: Drugs: Pembrolizumab 400 mg IV infusion
Pembrolizumab 400 mg will be administered as an IV infusion to participants Q6W.

Treatment: Drugs: Dostarlimab
Dostarlimab will be administered as an IV infusion at a dose of 500 mg once Q3W for 4 doses followed by a dose of 1000 mg Q6W.

Treatment: Drugs: Cobolimab
Cobolimab will be administered as an IV infusion at a dose of 300 mg Q3W.

Treatment: Drugs: Bintrafusp alfa
Bintrafusp alfa will be administered as an IV infusion at a dose of 2400 mg Q3W.

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

Outcomes
Primary outcome [1] 0 0
Part 1: Number of participants with any adverse event(s) (AE) - AE is any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product.
Timepoint [1] 0 0
Up to 27 months
Primary outcome [2] 0 0
Part 1: Number of participants with serious adverse event(s) (SAE) - An SAE is any untoward medical occurrence that, at any dose results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, or is a congenital anomaly/birth defect or is medically significant or associated with liver injury and impaired liver function.
Timepoint [2] 0 0
Up to 27 months
Primary outcome [3] 0 0
Part 1: Number of participants with dose limiting toxicity (DLT) - A DLT is defined as an AE that meets at least one of the criteria listed in protocol, according to National Cancer Institute (NCI) common terminology criteria for AE (CTCAE) version 4.0, and is considered by the investigator to be clinically relevant and attributed (probably, or possibly) to the study treatment during the first 28 days after the first dose of study treatment.
Timepoint [3] 0 0
Up to 28 days
Primary outcome [4] 0 0
Part 1: Change from Baseline in systolic and diastolic blood pressure (Millimeter of mercury) - Systolic and diastolic blood pressure (Millimeter of mercury) will be measured in semi-supine position after 5 minutes of rest.
Timepoint [4] 0 0
Baseline and up to 24 months
Primary outcome [5] 0 0
Part 1: Change from Baseline in pulse rate (Beats per minute) - Pulse rate (Beats per minute) will be measured in semi-supine position after 5 minutes of rest.
Timepoint [5] 0 0
Baseline and up to 24 months
Primary outcome [6] 0 0
Part 1: Change from Baseline in body temperature (Degrees Celsius) - Body temperature (Degrees Celsius) will be measured in semi-supine position after 5 minutes of rest.
Timepoint [6] 0 0
Baseline and up to 24 months
Primary outcome [7] 0 0
Part 1: Change from Baseline in hemoglobin (Grams per liter) - Blood samples will be collected at indicated time points and change from Baseline in hemoglobin (Grams per liter) will be analyzed.
Timepoint [7] 0 0
Baseline and up to 24 months
Primary outcome [8] 0 0
Part 1: Change from Baseline in hematocrit (Proportion of red blood cells in blood) - Blood samples will be collected at indicated time points and change from Baseline in hematocrit (Proportion of red blood cells in blood) will be analyzed.
Timepoint [8] 0 0
Baseline and up to 24 months
Primary outcome [9] 0 0
Part 1: Change from Baseline in red blood cell (RBC) count (Trillion cells per liter) - Blood samples will be collected at indicated time points and change from Baseline in RBC (Trillion cells per liter) will be analyzed.
Timepoint [9] 0 0
Baseline and up to 24 months
Primary outcome [10] 0 0
Part 1: Change from Baseline in platelet count (Giga cells per Liter) - Blood samples will be collected at indicated time points and change from Baseline in platelet count (Giga cells per Liter) will be analyzed.
Timepoint [10] 0 0
Baseline and up to 24 months
Primary outcome [11] 0 0
Part 1: Change from Baseline in white blood cell (WBC) count (Giga cells per Liter) - Blood samples will be collected at indicated time points and change from Baseline in WBC count (Giga cells per Liter) will be analyzed.
Timepoint [11] 0 0
Baseline and up to 24 months
Primary outcome [12] 0 0
Part 1: Change from Baseline in total neutrophils, eosinophils, monocytes, basophils and lymphocytes (Giga cells per Liter) - Blood samples will be collected at indicated time points and change from Baseline in total neutrophils, eosinophils, monocytes, basophils, and lymphocytes (Giga cells per Liter) will be analyzed.
Timepoint [12] 0 0
Baseline and up to 24 months
Primary outcome [13] 0 0
Part 1: Change from Baseline in blood urea nitrogen (BUN) (Millimoles per Liter) - Blood samples will be collected at indicated time points and change from Baseline in BUN (Millimoles per Liter) will be analyzed.
Timepoint [13] 0 0
Baseline and up to 24 months
Primary outcome [14] 0 0
Part 1: Change from Baseline in creatinine and bilirubin (Micromoles per liter) - Blood samples will be collected at indicated time points and change from Baseline in creatinine and bilirubin (Micromoles per liter) will be analyzed.
Timepoint [14] 0 0
Baseline and up to 24 months
Primary outcome [15] 0 0
Part 1: Change from Baseline in glucose, calcium, sodium and potassium (Millimoles per liter) - Blood samples will be collected at indicated time points and change from Baseline in glucose, calcium, sodium and potassium (Millimoles per liter) will be analyzed.
Timepoint [15] 0 0
Baseline and up to 24 months
Primary outcome [16] 0 0
Part 1: Change from Baseline in total protein and albumin (Grams per liter) - Blood samples will be collected at indicated time points and change from Baseline in total protein and albumin (Grams per liter) will be analyzed.
Timepoint [16] 0 0
Baseline and up to 24 months
Primary outcome [17] 0 0
Part 1: Change from Baseline in aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase (ALP) (International units per liter) - Blood samples will be collected at indicated time points and change from Baseline in AST, ALT and ALP (International units per liter) will be analyzed.
Timepoint [17] 0 0
Baseline and up to 24 months
Primary outcome [18] 0 0
Part 1: Number of participants with any abnormal findings in urine analysis parameters - The following urinalysis parameters will be measured: potential of hydrogen (pH), glucose, protein, blood, ketones by dipstick and specific gravity.
Timepoint [18] 0 0
Up to 24 months
Primary outcome [19] 0 0
Part 1: Change from Baseline in Troponin I or Troponin T (nanograms per liter) - Troponin I or Troponin T will be assessed by echocardiogram or multigated acquisition scans (MUGA) (nanograms per liter).
Timepoint [19] 0 0
Baseline and up to 24 months
Primary outcome [20] 0 0
Part 1: Change from Baseline in thyroid stimulating hormone (TSH) (milliunits per liter) - Blood samples will be collected at indicated time points and change from Baseline in TSH (milliunits per liter) will be analyzed.
Timepoint [20] 0 0
Baseline and up to 24 months
Primary outcome [21] 0 0
Part 1: Change from Baseline in triiodothyronine (T3) and thyroxine (T4) (nanograms per deciliter) - Blood samples will be collected at indicated time points and change from Baseline in T3 and T4 (nanograms per deciliter) will be analyzed.
Timepoint [21] 0 0
Baseline and up to 24 months
Primary outcome [22] 0 0
Part 1: Number of participants requiring dose modifications - All dose modifications due to any reason(s) will be recorded.
Timepoint [22] 0 0
Up to 24 months
Primary outcome [23] 0 0
Part 2: Number of participants with any AEs - AE is any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product.
Timepoint [23] 0 0
Up to 27 months
Primary outcome [24] 0 0
Part 2: Number of participants with serious adverse event(s) (SAE) - An SAE is any untoward medical occurrence that, at any dose results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, or is a congenital anomaly/birth defect or is medically significant or associated with liver injury and impaired liver function.
Timepoint [24] 0 0
Up to 27 months
Primary outcome [25] 0 0
Part 2: Number of participants with DLT - A DLT is defined as an AE that meets at least one of the criteria listed in protocol, according to NCI CTCAE version 4.0, and is considered by the investigator to be clinically relevant and attributed (probably, or possibly) to the study treatment during the first 28 days after the first dose of study treatment.
Timepoint [25] 0 0
Up to 28 days
Primary outcome [26] 0 0
Part 2: Change from Baseline in systolic and diastolic blood pressure (Millimeter of mercury) - Systolic and diastolic blood pressure (Millimeter of mercury) will be measured in semi-supine position after 5 minutes of rest.
Timepoint [26] 0 0
Baseline and up to 24 months
Primary outcome [27] 0 0
Part 2: Change from Baseline in pulse rate (Beats per minute) - Pulse rate (beats per minute) will be measured in semi-supine position after 5 minutes of rest.
Timepoint [27] 0 0
Baseline and up to 24 months
Primary outcome [28] 0 0
Part 2: Change from Baseline in body temperature (Degrees Celsius) - Body temperature (Degrees Celsius) will be measured in semi-supine position after 5 minutes of rest.
Timepoint [28] 0 0
Baseline and up to 24 months
Primary outcome [29] 0 0
Part 2: Change from Baseline in hemoglobin (Grams per liter) - Blood samples will be collected at indicated time points and change from Baseline in haemoglobin (Grams per liter) will be analyzed.
Timepoint [29] 0 0
Baseline and up to 24 months
Primary outcome [30] 0 0
Part 2: Change from Baseline in hematocrit (Proportion of red blood cells in blood) - Blood samples will be collected at indicated time points and change from Baseline in hematocrit (Proportion of red blood cells in blood) will be analyzed.
Timepoint [30] 0 0
Baseline and up to 24 months
Primary outcome [31] 0 0
Part 2: Change from Baseline in RBC count (Trillion cells per liter) - Blood samples will be collected at indicated time points and change from Baseline in RBC (Trillion cells per liter) will be analyzed.
Timepoint [31] 0 0
Baseline and up to 24 months
Primary outcome [32] 0 0
Part 2: Change from Baseline in platelet count (Giga cells per Liter) - Blood samples will be collected at indicated time points and change from Baseline in platelet (Giga cells per Liter) count will be analyzed.
Timepoint [32] 0 0
Baseline and up to 24 months
Primary outcome [33] 0 0
Part 2: Change from Baseline in WBC count (Giga cells per Liter) - Blood samples will be collected at indicated time points and change from Baseline in WBC (Giga cells per Liter) count will be analyzed.
Timepoint [33] 0 0
Baseline and up to 24 months
Primary outcome [34] 0 0
Part 2: Change from Baseline in total neutrophils, eosinophils, monocytes, basophils, and lymphocytes (Giga cells per Liter) - Blood samples will be collected at indicated time points and change from Baseline in total neutrophils, eosinophils, monocytes, basophils, and lymphocytes (Giga cells per Liter) will be analyzed.
Timepoint [34] 0 0
Baseline and up to 24 months
Primary outcome [35] 0 0
Part 2: Change from Baseline in BUN (Millimoles per Liter) - Blood samples will be collected at indicated time points and change from Baseline in BUN (Millimoles per Liter) will be analyzed.
Timepoint [35] 0 0
Baseline and up to 24 months
Primary outcome [36] 0 0
Part 2: Change from Baseline in creatinine and bilirubin (Micromoles per liter) - Blood samples will be collected at indicated time points and change from Baseline in creatinine and bilirubin (Micromoles per liter) will be analyzed.
Timepoint [36] 0 0
Baseline and up to 24 months
Primary outcome [37] 0 0
Part 2: Change from Baseline in glucose, calcium, sodium and potassium (Millimoles per liter) - Blood samples will be collected at indicated time points and change from Baseline in glucose, calcium, sodium and potassium (Millimoles per liter) will be analyzed.
Timepoint [37] 0 0
Baseline and up to 24 months
Primary outcome [38] 0 0
Part 2: Change from Baseline in total protein and albumin (Grams per liter) - Blood samples will be collected at indicated time points and change from Baseline in total protein and albumin (Grams per liter) will be analyzed.
Timepoint [38] 0 0
Baseline and up to 24 months
Primary outcome [39] 0 0
Part 2: Change from Baseline in AST, ALT and ALP (International units per liter) - Blood samples will be collected at indicated time points and change from Baseline in AST, ALT and ALP (International units per liter) will be analyzed.
Timepoint [39] 0 0
Baseline and up to 24 months
Primary outcome [40] 0 0
Part 2: Number of participants with any abnormal findings in urine analysis parameters - The following urinalysis parameters will be measured: pH, glucose, protein, blood, ketones by dipstick and specific gravity.
Timepoint [40] 0 0
Up to 24 months
Primary outcome [41] 0 0
Part 2: Change from Baseline in Troponin I or Troponin T (nanograms per liter) - Troponin I or Troponin T will be assessed by echocardiogram or MUGA (nanograms per liter).
Timepoint [41] 0 0
Baseline and up to 24 months
Primary outcome [42] 0 0
Part 2: Change from Baseline in TSH (milliunits per liter) - Blood samples will be collected at indicated time points and change from Baseline in TSH (milliunits per liter) will be analyzed.
Timepoint [42] 0 0
Baseline and up to 24 months
Primary outcome [43] 0 0
Part 2: Change from Baseline in T3 and T4 (nanograms per deciliter) - Blood samples will be collected at indicated time points and change from Baseline in T3 and T4 (nanograms per deciliter) will be analyzed.
Timepoint [43] 0 0
Baseline and up to 24 months
Primary outcome [44] 0 0
Part 2: Number of participants requiring dose modifications - All dose modifications due to any reason(s) will be recorded.
Timepoint [44] 0 0
Up to 24 months
Secondary outcome [1] 0 0
Part 1: Disease control rate (DCR) - DCR is defined as the percentage of participants with a confirmed complete response (CR) + partial response (PR) at any time, plus stable disease (SD) >=18 weeks.
Timepoint [1] 0 0
Up to 27 months
Secondary outcome [2] 0 0
Part 1: Overall survival (OS) - OS is defined as time from the date of first dose of study treatment to the date of death due to any cause.
Timepoint [2] 0 0
up to 4 years
Secondary outcome [3] 0 0
Part 1: Progression-free survival (PFS) - PFS is defined as time from the date of first dose of study treatment to the date of disease progression according to clinical or radiographic assessment or death due to any cause, whichever occurs earliest.
Timepoint [3] 0 0
Up to 27 months
Secondary outcome [4] 0 0
Part 1: Time to overall response (TTR) - TTR will be summarized for participants with a confirmed CR or PR and is defined as the time from date of first dose of study treatment to date of first documented confirmed CR or PR.
Timepoint [4] 0 0
Up to 27 months
Secondary outcome [5] 0 0
Part 1: Duration of response (DOR) - DOR will be summarized for participants with a confirmed CR or PR and is defined as the time from date of initial confirmed response to the date of disease progression or death due to any cause.
Timepoint [5] 0 0
Up to 27 months
Secondary outcome [6] 0 0
Part 1: Overall response rate (ORR) - ORR is defined as the percentage of participants with a best overall confirmed CR or a PR at any time as per disease-specific criteria.
Timepoint [6] 0 0
Up to 27 months
Secondary outcome [7] 0 0
Part 1: Maximum observed plasma concentration (Cmax) of GSK3359609 - Blood samples will be collected at the indicated time points for evaluation of Cmax.
Timepoint [7] 0 0
Day1:predose,end of infusion(EOI),EOI+30 minutes,+1,+2,+4hours, Day2:EOI+24hours, Day 8 and 15,Day22:pre EOI+4hours,Days29and 36,Days43 to 106:pre EOI+4hours,Day127:pre dose;Week21 then every12weeks postdose(Up to 27months)
Secondary outcome [8] 0 0
Part 1: Minimum observed plasma concentration (Cmin) of GSK3359609 - Blood samples will be collected at the indicated time points for evaluation of Cmin.
Timepoint [8] 0 0
Day1:predose,end of infusion(EOI),EOI+30 minutes,+1,+2,+4hours, Day2:EOI+24hours, Day 8 and 15,Day22:pre EOI+4hours,Days29and 36,Days43 to 106:pre EOI+4hours,Day127:pre dose;Week21 then every12weeks postdose(Up to 27months)
Secondary outcome [9] 0 0
Part 1: Area under the concentration-time curve over the dosing interval (AUC[0-tau]) of GSK3359609 in plasma - Blood samples will be collected at the indicated time points for evaluation of AUC(0-tau).
Timepoint [9] 0 0
Day1:predose,end of infusion(EOI),EOI+30 minutes,+1,+2,+4hours, Day2:EOI+24hours, Day 8 and 15,Day22:pre EOI+4hours,Days29and 36,Days43 to 106:pre EOI+4hours,Day127:pre dose;Week21 then every12weeks postdose(Up to 27months)
Secondary outcome [10] 0 0
Part 1: Number of participants with positive results in Anti-drug antibody (ADA) test by GSK3359609 dose level - Blood samples will be collected up to 27 months for ADA test.
Timepoint [10] 0 0
Up to 27 months
Secondary outcome [11] 0 0
Part 1: Number of participants with positive results in GSK3359609 - Blood samples will be collected up to 27 months for immunogenicity.
Timepoint [11] 0 0
Up to 27 months
Secondary outcome [12] 0 0
Part 2: Number of participants with DLT following administration of GSK3359609 combination with chemotherapies - A DLT is defined as an AE that meets at least one of the criteria listed in protocol, according to NCI CTCAE G version 4.0, and is considered by the investigator to be clinically relevant and attributed (probably, or possibly) to the study treatment during the first 28 days after the first dose of study treatment.
Timepoint [12] 0 0
Up to 28 days
Secondary outcome [13] 0 0
Part 2: Disease control rate (DCR) - DCR is defined as the percentage of participants with a confirmed CR + PR at any time, plus SD >=18 weeks.
Timepoint [13] 0 0
Up to 27 months
Secondary outcome [14] 0 0
Part 2: Overall survival (OS) - OS is defined as time from the date of first dose of study treatment to the date of death due to any cause.
Timepoint [14] 0 0
Up to 4 years
Secondary outcome [15] 0 0
Part 2: Progression-free survival (PFS) - PFS is defined as time from the date of first dose of study treatment to the date of disease progression according to clinical or radiographic assessment or death due to any cause, whichever occurs earliest.
Timepoint [15] 0 0
Up to 27 months
Secondary outcome [16] 0 0
Part 2: Time to overall response (TTR) - TTR will be summarized for participants with a confirmed CR or PR and is defined as the time from date of first dose of study treatment to date of first documented confirmed CR or PR.
Timepoint [16] 0 0
Up to 27 months
Secondary outcome [17] 0 0
Part 2: Duration of response (DOR) - DOR will be summarized for participants with a confirmed CR or PR and is defined as the time from date of initial confirmed response to the date of disease progression or death due to any cause.
Timepoint [17] 0 0
Up to 27 months
Secondary outcome [18] 0 0
Part 2: Overall response rate (ORR) - ORR is defined as the percentage of participants with a best overall confirmed CR or a PR at any time as per disease-specific criteria.
Timepoint [18] 0 0
Up to 27 months
Secondary outcome [19] 0 0
Part 2: Cmax of GSK3359609 (Q3W dosing) - Blood samples will be collected at the indicated time points for evaluation of Cmax.
Timepoint [19] 0 0
Day1:predose,EOI,EOI+30 minutes,+1,+2,+4hours, Day2:EOI+24hours, Day 8 and 15, Day22:pre EOI+4hours,Days29 and 36,Days43 to 106:pre EOI+4hours,Day127:pre dose;Week21 then every 12weeks postdose (Up to 27months)
Secondary outcome [20] 0 0
Part 2: Cmin of GSK3359609 (Q3W dosing) - Blood samples will be collected at the indicated time points for evaluation of Cmin.
Timepoint [20] 0 0
Day1:predose,EOI,EOI+30 minutes,+1,+2,+4hours, Day2:EOI+24hours, Day 8 and 15, Day22:pre EOI+4hours,Days29 and 36,Days43 to 106:pre EOI+4hours,Day127:pre dose;Week21 then every 12weeks postdose (Up to 27months)
Secondary outcome [21] 0 0
Part 2: AUC(0-tau) of GSK3359609 (Q3W dosing) - Blood samples will be collected at the indicated time points for evaluation of AUC(0-tau).
Timepoint [21] 0 0
Day1:predose,EOI,EOI+30 minutes,+1,+2,+4hours, Day2:EOI+24hours, Day 8 and 15, Day22:pre EOI+4hours,Days29 and 36,Days43 to 106:pre EOI+4hours,Day127:pre dose;Week21 then every 12weeks postdose (Up to 27months)
Secondary outcome [22] 0 0
Part 2: Cmax of GSK3174998 - Blood samples will be collected at the indicated time points for evaluation of Cmax.
Timepoint [22] 0 0
Day 1: predose, EOI, EOI+4 hours, EOI+24 hours, Day 8 and 15, Day22: predose, Day 43:predose, EOI,EOI+4hours, Day 64 and 85: predose, EOI+4hours, Day 106: predose,Day127:pre dose;Week21 then every 12weeks postdose (Up to 24months)
Secondary outcome [23] 0 0
Part 2: Cmin of GSK3174998 - Blood samples will be collected at the indicated time points for evaluation of Cmin.
Timepoint [23] 0 0
Day 1: predose, EOI, EOI+4 hours, EOI+24 hours, Day 8 and 15, Day22: predose, Day 43:predose, EOI,EOI+4hours, Day 64 and 85: predose, EOI+4hours, Day 106: predose,Day127:pre dose;Week21 then every 12weeks postdose (Up to 24months)
Secondary outcome [24] 0 0
Part 2: AUC(0-tau) of GSK3174998 - Blood samples will be collected at the indicated time points for evaluation of AUC(0-tau).
Timepoint [24] 0 0
Day 1: predose, EOI, EOI+4 hours, EOI+24 hours, Day 8 and 15, Day22: predose, Day 43:predose, EOI,EOI+4hours, Day 64 and 85: predose, EOI+4hours, Day 106: predose,Day127:pre dose;Week21 then every 12weeks postdose (Up to 24months)
Secondary outcome [25] 0 0
Part 2: Cmax of Pembrolizumab (Q3W dosing) - Blood samples will be collected at the indicated time points for evaluation of Cmax.
Timepoint [25] 0 0
Day 1: pre-dose, EOI + 30 minutes, Day 2: EOI+24 hours, Days 8 and 15, Days 22, 43, 85, and 106: predose, Days 29, 36 and 64, Day 127: predose, and Week 21 then every 12 weeks postdose (Up to 27 months)
Secondary outcome [26] 0 0
Part 2: Cmin of Pembrolizumab (Q3W dosing) - Blood samples will be collected at the indicated time points for evaluation of Cmin.
Timepoint [26] 0 0
Day 1: pre-dose, EOI + 30 minutes, Day 2: EOI+24 hours, Days 8 and 15, Days 22, 43, 85, and 106: predose, Days 29, 36 and 64, Day 127: predose, and Week 21 then every 12 weeks postdose (Up to 27 months)
Secondary outcome [27] 0 0
Part 2: AUC(0-tau) of Pembrolizumab (Q3W dosing) - Blood samples will be collected at the indicated time points for evaluation of AUC(0-tau).
Timepoint [27] 0 0
Day 1: pre-dose, EOI + 30 minutes, Day 2: EOI+24 hours, Days 8 and 15, Days 22, 43, 85, and 106: predose, Days 29, 36 and 64, Day 127: predose, and Week 21 then every 12 weeks postdose (Up to 27 months)
Secondary outcome [28] 0 0
Part 2: Number of participants with positive results in ADA test by GSK3359609 in combination with pembrolizumab or GSK3174998 dose level - Blood samples will be collected up to 27 months for ADA test.
Timepoint [28] 0 0
Up to 27 months
Secondary outcome [29] 0 0
Part 2: Number of participants with positive results in Pembrolizumab - Blood samples will be collected up to 27 months for immunogenicity.
Timepoint [29] 0 0
Up to 27 months
Secondary outcome [30] 0 0
Part 2: Number of participants with positive results in GSK3174998 - Blood samples will be collected up to 27 months for immunogenicity.
Timepoint [30] 0 0
Up to 27 months
Secondary outcome [31] 0 0
Part 2: Cmax of GSK3359609 combination with chemotherapies - Blood samples will be collected at the indicated time points for evaluation of Cmax.
Timepoint [31] 0 0
Day 1: predose, EOI, EOI+2 hours, EOI+4 hours, Days 22, 64, 106, and 127: EOI, EOI+ 2 hours post chemotherapy (Up to 27 months)
Secondary outcome [32] 0 0
Part 2: Cmin of GSK3359609 combination with chemotherapies - Blood samples will be collected at the indicated time points for evaluation of Cmin.
Timepoint [32] 0 0
Day 1: predose, EOI, EOI+2 hours, EOI+4 hours, Days 22, 64, 106, and 127: EOI, EOI+ 2 hours post chemotherapy (Up to 27 months)
Secondary outcome [33] 0 0
Part 2: Number of participants with positive results in ADA test by GSK3359609 combination with chemotherapies dose level - Blood samples will be collected up to 27 months for ADA test.
Timepoint [33] 0 0
Up to 27 months
Secondary outcome [34] 0 0
Part 2: Cmax of GSK3359609 (Q6W dosing) - Blood samples will be collected at the indicated time points for evaluation of Cmax.
Timepoint [34] 0 0
Day1:predose,EOI,EOI+30 minutes,+1,+2,+4hours, Day2:EOI+24hours, Days 8, 15, 22, 29 and 36:pre dose,Days43 and 85:pre EOI+4hours,Days 64,106 and 127:pre dose;Week21 then every12weeks postdose (Up to 27months)
Secondary outcome [35] 0 0
Part 2: Cmin of GSK3359609 (Q6W dosing) - Blood samples will be collected at the indicated time points for evaluation of Cmin.
Timepoint [35] 0 0
Day1:predose,EOI,EOI+30 minutes,+1,+2,+4hours, Day2:EOI+24hours, Days 8, 15, 22, 29 and 36:pre dose,Days43 and 85:pre EOI+4hours,Days 64,106 and 127:pre dose;Week21 then every 12weeks postdose (Up to 27months)
Secondary outcome [36] 0 0
Part 2: AUC(0-tau) of GSK3359609 (Q6W dosing) - Blood samples will be collected at the indicated time points for evaluation of AUC(0-tau).
Timepoint [36] 0 0
Day1:predose,EOI,EOI+30 minutes,+1,+2,+4hours, Day2:EOI+24hours, Days 8, 15, 22, 29 and 36:pre dose,Days43 and 85:pre EOI+4hours,Days 64,106 and 127:pre dose;Week21 then every12weeks postdose (Up to 27months)
Secondary outcome [37] 0 0
Part 2: Cmax of Pembrolizumab (Q6W dosing) - Blood samples will be collected at the indicated time points for evaluation of Cmax.
Timepoint [37] 0 0
Day 1: pre-dose, EOI + 30 minutes, Day 2: EOI+24 hours, Day 8, 15, 22, 29, 36, 64 and 106, Days 43, 85 and 127: predose, and Week 21 then every 12 weeks postdose (Up to 27 months)
Secondary outcome [38] 0 0
Part 2: Cmin of Pembrolizumab (Q6W dosing) - Blood samples will be collected at the indicated time points for evaluation of Cmin.
Timepoint [38] 0 0
Day 1: pre-dose, EOI + 30 minutes, Day 2: EOI+24 hours, Day 8, 15, 22, 29, 36, 64 and 106, Days 43, 85 and 127: predose, and Week 21 then every 12 weeks postdose (Up to 27 months)
Secondary outcome [39] 0 0
Part 2: AUC(0-tau) of Pembrolizumab (Q6W dosing) - Blood samples will be collected at the indicated time points for evaluation of AUC(0-tau).
Timepoint [39] 0 0
Day 1: pre-dose, EOI + 30 minutes, Day 2: EOI+24 hours, Day 8, 15, 22, 29, 36, 64 and 106, Days 43, 85 and 127: predose, and Week 21 then every 12 weeks postdose (Up to 27 months)
Secondary outcome [40] 0 0
Part 2: Cmax of dostarlimab - Blood samples will be collected at the indicated time points for evaluation of Cmax.
Timepoint [40] 0 0
Day 1, 22, 85 and 127: pre-dose, EOI, then pre-dose every 18 weeks (Up to 27 months)
Secondary outcome [41] 0 0
Part 2: Cmin of dostarlimab - Blood samples will be collected at the indicated time points for evaluation of Cmin.
Timepoint [41] 0 0
Day 1, 22, 85 and 127: pre-dose, EOI, then pre-dose every 18 weeks (Up to 27 months)
Secondary outcome [42] 0 0
Part 2: AUC(0-tau) of dostarlimab - Blood samples will be collected at the indicated time points for evaluation of AUC(0-tau).
Timepoint [42] 0 0
Day 1, 22, 85 and 127: pre-dose, EOI, then pre-dose every 18 weeks (Up to 27 months)
Secondary outcome [43] 0 0
Part 2: Cmax of cobolimab - Blood samples will be collected at the indicated time points for evaluation of Cmax
Timepoint [43] 0 0
Days 1, 22, 43, 64, 85, 106 and 127: pre-dose, EOI + 0.5 hours then pre-dose every 18 weeks (Up to 27 months)
Secondary outcome [44] 0 0
Part 2: Cmin of cobolimab - Blood samples will be collected at the indicated time points for evaluation of Cmin.
Timepoint [44] 0 0
Days 1, 22, 43, 64, 85, 106 and 127: pre-dose, EOI + 0.5 hours then pre-dose every 18 weeks (Up to 27 months)
Secondary outcome [45] 0 0
Part 2: AUC(0-tau) of cobolimab - Blood samples will be collected at the indicated time points for evaluation of AUC(0-tau).
Timepoint [45] 0 0
Days 1, 22, 43, 64, 85, 106 and 127: pre-dose, EOI + 0.5 hours then pre-dose every 18 weeks (Up to 27 months)
Secondary outcome [46] 0 0
Part 2: Cmax of bintrafusp alfa - Blood samples will be collected at the indicated time points for evaluation of Cmax.
Timepoint [46] 0 0
Day 1: pre-dose, EOI, EOI + 30 minutes, Day 2: EOI+24 hours, Days 8 and 15, Days 22, 43, 64, 85, 106: pre-dose, EOI; Day 127: pre-dose and pre-dose at Week 21 then every 12 weeks (Up to 27 months)
Secondary outcome [47] 0 0
Part 2: Cmin of bintrafusp alfa - Blood samples will be collected at the indicated time points for evaluation of Cmin.
Timepoint [47] 0 0
Day 1: pre-dose, EOI, EOI + 30 minutes, Day 2: EOI+24 hours, Days 8 and 15, Days 22, 43, 64, 85, 106: pre-dose, EOI; Day 127: pre-dose and pre-dose at Week 21 then every 12 weeks (Up to 27 months)
Secondary outcome [48] 0 0
Part 2: AUC(0-tau) of bintrafusp alfa - Blood samples will be collected at the indicated time points for evaluation of AUC(0-tau).
Timepoint [48] 0 0
Day 1: pre-dose, EOI, EOI + 30 minutes, Day 2: EOI+24 hours, Days 8 and 15, Days 22, 43, 64, 85, 106: pre-dose, EOI; Day 127: pre-dose and pre-dose at Week 21 then every 12 weeks (Up to 27 months)

Eligibility
Key inclusion criteria
Inclusion Criteria

- Capable of giving signed, written informed consent.

- Male or female, age >=18 years (at the time consent is obtained).

- 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: bladder/urothelial cancer of the upper and lower urinary tract; cervical;
colorectal (includes appendix); esophagus, squamous cell; head and neck carcinoma;
melanoma; malignant pleural mesothelioma (MPM); non-small-cell lung cancer (NSCLC),
prostate; Microsatellite Instability-High/deficient mismatch repair (MSI-H/dMMR) tumor
(Part 1B and Part 2B) and Human Papilloma Virus (HPV)-positive or Epstein-Barr
(EBV)-positive tumor (Part 1B and Part 2B).

- 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; exceptions are in these tumor
types in which pembrolizumab single agent may be a standard: NSCLC, head and neck
squamous cell cancer (HNSCC), bladder/urothelial cancer, MSI-H/dMMR cancers and
melanoma and cervical cancer. In Part 2B pembrolizumab combination expansion cohorts,
prior treatment with anti-Programmed cell death protein 1(PD-1)/ Ligand-1 (L1) may not
be required. 1) Participants must not have received more than 5 prior lines of therapy
for advanced disease including both standards of care and investigational therapies.
2) Participants who received prior PD-1/L1 therapy must fulfill the following
requirements (Part 1B [except PK/PD cohort]/ Part 2B):a) Have achieved a CR, PR or SD
and subsequently had disease progression while still on PD-1/L1 therapy; b) Have
received at least 2 doses of an approved PD-1/L1 inhibitor (by any regulatory
authority), c) Have demonstrated disease progression as defined by Response Evaluation
Criteria in Solid Tumors (RECIST) version 1.1 within 18 weeks from the last dose of
the PD-1/L1 inhibitor. The initial evidence of disease progression is to be confirmed
by a second assessment no less than four weeks from the date of the first documented
Progressive Disease (PD) (the confirmatory scan could be the Baseline eligibility scan
for this study). 3) In Part 2A 5-fluorouracil (FU)/platinum combination with
GSK3359609 and pembrolizumab cohort, participants must not have received prior
systemic therapy administered in the recurrent or metastatic setting (with the
exception of systemic therapy given as part of multimodal treatment for locally
advanced disease).

- Archival tumor tissue obtained at any time from the initial diagnosis to study entry;
a fresh tumor biopsy using a procedure that is safe for the participant on a lesion
not previously irradiated unless lesion progressed will be required if archival tissue
is unavailable.

- Agree to undergo a pre-treatment and on treatment biopsy and have disease amenable to
biopsy required in pharmacokinetic (PK) / pharmacodynamics (PD), dose randomized
HNSCC, Melanoma dose expansion and Biomarker cohorts..

- Measurable disease per RECIST version 1.1. 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) 0-1.

- Life expectancy of at least 12 weeks.

- Adequate organ function.

- QT interval corrected for heart rate according to Fridericia's formula (QTcF) <450
milliseconds (msec) or QTcF <480 msec for participants with bundle branch block.

- A female participant is eligible to participate if she is not pregnant (as confirmed
by a negative serum beta-human chorionic gonadotrophin [beta-hCG] test in females of
reproductive potential), and not lactating or reproductive potential agrees to follow
one of the options listed in protocol from 30 days prior to the first dose of study
medication and until 120 days after the last dose of study treatment.

- Male participants with female partners of child bearing potential must agree to use
one of the methods of contraception specified in protocol from time of first dose of
study treatment until 120 days after the last dose of study treatment.

- Documented HPV/ EBV-positive tumor as determined by a local laboratory for Part 1B and
Part 2B pembrolizumab combination viral-positive expansion cohorts only.

- Documented MSI-H or dMMR-positive tumor as determined by local laboratory for Part 1B
and Part 2B pembrolizumab combination MSI-H/dMMR expansion cohorts only.

- Documented ICOS expression using an analytically validated immunohistochemistry (IHC)
assay by central laboratory for Part 1B biomarker cohort only.

- Documented gene expression (GEX) result using an analytically validated method by
central laboratory (Part 1B Biomarker Cohort only).

- PD-L1 combined positive score (CPS) <1 using the Food and Drug Administration (FDA)
approved PD-L1 IHC 22C3 pharmdx assay by central laboratory testing for Part 2B HNSCC
PD-L1 CPS <1 Cohort. Documented test result from FDA approved PD-L1 IHC 22C3 pharmDx
assay in local laboratory, if available, may be accepted in lieu of the central
laboratory test result.

- Defined PD-L1 expression using the Ventana PD-L1 (SP263) IHC assay by central testing
for enrollment in the PK/PD cohort with bintrafusp alfa, dostarlimab, dostarlimab and
cobolimab combination studies (Part 2A).
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Exclusion Criteria

- Prior treatment with the following therapies:

- Anticancer therapy within 30 days or 5 half-lives of the drug, whichever is
shorter. At least 14 days must have elapsed between the last dose of prior
anticancer agent and the first dose of study drug is administered.

- Part 2B (GSK3359609/pembrolizumab combination): prior pembrolizumab washout is
not required.

- Prior radiation therapy: permissible if at least one non-irradiated measurable
lesion is available for assessment according to RECIST version 1.1 or if a
solitary measurable lesion was irradiated, objective progression is documented. A
wash out of at least two weeks before start of study drug for radiation of any
intended use to the extremities for bone metastases and 4 weeks for radiation to
the chest, brain, or visceral organs is required. • Investigational therapy
within 30 days or 5 half-lives of the investigational product (whichever is
shorter). At least 14 days must have elapsed between the last dose of
investigational agent and the first dose of study drug is administered.

- Prior allogeneic or autologous bone marrow transplantation or other solid organ
transplantation.

- Toxicity from previous anticancer treatment

- Invasive malignancy or history of invasive malignancy other than disease under study
within the last two years except: Any other invasive malignancy for which the
participant was definitively treated, has been disease-free for <=2 years and in the
opinion of the principal investigator and GSK Medical Monitor will not affect the
evaluation of the effects of the study treatment on the currently targeted malignancy,
may be included in this clinical trial; and curatively treated non-melanoma skin
cancer.

- Central nervous system (CNS) metastases, with the following exception: • Participants
who have previously-treated CNS metastases, are asymptomatic, and have no requirement
for steroids at least 14 days prior to first dose of study drug. Participants with
carcinomatous meningitis or leptomeningeal spread are excluded regardless of clinical
stability.

- Received transfusion of blood products (including platelets or red blood cells) or
administration of colony stimulating factors (including granulocyte colony-stimulating
factor [G-CSF], granulocyte-macrophage colony-stimulating factor, recombinant
erythropoietin) within 14 days prior to the first dose of GSK3359609.

- Major surgery <=4 weeks before the first dose of study treatment. Participants must
have also fully recovered from any surgery (major or minor) and/or its complications
before initiating study treatment.

- Active autoimmune disease that has required systemic treatment within the last two
years (i.e., with use of disease modifying agents, corticosteroids or
immunosuppressive drugs). Replacement therapy (e.g., thyroxine or physiologic
corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is
not considered a form of systemic treatment.

- Concurrent medical condition requiring the use of systemic immunosuppressive
medications within 7 days before the first dose of study treatment. Physiologic doses
of corticosteroids for treatment of endocrinopathies or steroids with minimal systemic
absorption, including topical, inhaled, or intranasal corticosteroids may be continued
if the participant is on a stable dose.

- Condition requiring treatment with strong inhibitors/inducers of cytochrome (CYP) p450
3A4 within 7 days prior to first dose of chemotherapy (requirement applies to
participants enrolled to Part 2 chemotherapy combination with docetaxel).

- Active infection requiring systemic therapy, known human immunodeficiency virus
infection, or positive test for hepatitis B active infection or hepatitis C active
infection.

- Current active liver or biliary disease (with the exception of Gilbert's syndrome or
asymptomatic gallstones, liver metastases, or otherwise stable chronic liver disease
per investigator assessment).

- Recent history (within the past 6 months) of acute diverticulitis, inflammatory bowel
disease, intra-abdominal abscess, or gastrointestinal obstruction that required
surgery.

- Receipt of any live vaccine within 4 weeks prior to first dose of study treatment.

- Recent history of allergen desensitization therapy within 4 weeks of starting study
treatment.

- History of severe hypersensitivity to monoclonal antibodies or to the chemotherapies
under investigation including any ingredient used in the formulation.

- History or evidence of cardiac abnormalities.

- History of (current and past) idiopathic pulmonary fibrosis, pneumonitis (for past
pneumonitis exclusion only if steroids were required for treatment), interstitial lung
disease, or organizing pneumonia. Note: post-radiation changes in the lung related to
prior radiotherapy and/or asymptomatic radiation-induced pneumonitis not requiring
treatment may be permitted if agreed by the investigator and Medical Monitor.

- Recent history (within 6 months) of uncontrolled symptomatic ascites or pleural
effusions.

- Any serious and/or unstable pre-existing medical, psychiatric disorder, or other
condition that could interfere with the participant's safety, obtaining informed
consent, or compliance to the study procedures.

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised 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
Other
Other design features
Phase
Phase 1
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,WA
Recruitment hospital [1] 0 0
GSK Investigational Site - Heidelberg
Recruitment hospital [2] 0 0
GSK Investigational Site - Melbourne
Recruitment hospital [3] 0 0
GSK Investigational Site - Nedlands
Recruitment postcode(s) [1] 0 0
3084 - Heidelberg
Recruitment postcode(s) [2] 0 0
3000 - Melbourne
Recruitment postcode(s) [3] 0 0
6009 - Nedlands
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
Florida
Country [3] 0 0
United States of America
State/province [3] 0 0
New York
Country [4] 0 0
United States of America
State/province [4] 0 0
Oklahoma
Country [5] 0 0
United States of America
State/province [5] 0 0
Pennsylvania
Country [6] 0 0
United States of America
State/province [6] 0 0
Tennessee
Country [7] 0 0
Canada
State/province [7] 0 0
Ontario
Country [8] 0 0
France
State/province [8] 0 0
Bordeaux Cedex
Country [9] 0 0
France
State/province [9] 0 0
Lyon cedex 08
Country [10] 0 0
France
State/province [10] 0 0
Paris
Country [11] 0 0
France
State/province [11] 0 0
Villejuif cedex
Country [12] 0 0
Italy
State/province [12] 0 0
Toscana
Country [13] 0 0
Japan
State/province [13] 0 0
Chiba
Country [14] 0 0
Japan
State/province [14] 0 0
Osaka
Country [15] 0 0
Japan
State/province [15] 0 0
Tokyo
Country [16] 0 0
Netherlands
State/province [16] 0 0
Amsterdam
Country [17] 0 0
Spain
State/province [17] 0 0
Barcelona
Country [18] 0 0
Spain
State/province [18] 0 0
Madrid
Country [19] 0 0
Spain
State/province [19] 0 0
Málaga
Country [20] 0 0
Spain
State/province [20] 0 0
Sevilla

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
Merck Sharp & Dohme Corp.
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
GSK3359609 is an anti-Inducible T cell Co-Stimulator (ICOS) receptor agonist antibody
intended for the treatment of cancers of different histology. This is a first-time-in-human
(FTIH), open-label, multicenter study designed to investigate the safety, pharmacology, and
preliminary antitumor activity in participants with selected, advanced or recurrent solid
tumors with the aim to establish recommended dose(s) of GSK3359609 for further exploration as
monotherapy and in combination with pembrolizumab, chemotherapy or other immune therapies.
The study is comprised of two primary parts, each composed of two phases: Part 1: GSK3359609
monotherapy with Part 1A as dose escalation phase and Part 1B as cohort expansion phase; Part
2: GSK3359609 combination therapy with Part 2A pembrolizumab or GSK3174998 or dostarlimab or
dostarlimab plus cobolimab or Bintrafusp alfa combination dose escalation phase and Part 2B
expansion phase with pembrolizumab. Part 2A GSK3359609 combinations with chemotherapy will
only consist of safety run-in cohorts. Each part and phase of the study includes a screening
period, a treatment period, and a follow-up period. The primary objective of the study is to
determine the safety, tolerability, maximum tolerated dose or the maximum administered dose
of GSK3359609 alone or in combination.
Trial website
https://clinicaltrials.gov/show/NCT02723955
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/NCT02723955

Additional trial details provided through ANZCTR
Accrual to date
Recruiting in Australia
Recruitment state(s)
WA,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
Investigators:
Michael Millward, Sir Charles Gairdner Hospital, Western Australia, Nedlands, Australia, 6009
Hui Gan, Austin Health, Victoria, Heidelberg, Australia, 3084
Danny Rischin, Peter MacCallum Cancer Institute, Victoria, Melbourne, Australia, 3000

Contacts
Principal investigator
Title 73 0
Name 73 0
Address 73 0
Country 73 0
Phone 73 0
Fax 73 0
Email 73 0
Contact person for public queries
Title 74 0
Name 74 0
Address 74 0
Country 74 0
Phone 74 0
Fax 74 0
Email 74 0
GSKClinicalSupportHD@gsk.com
Contact person for scientific queries
Title 75 0
Name 75 0
Address 75 0
Country 75 0
Phone 75 0
Fax 75 0
Email 75 0
GSKClinicalSupportHD@gsk.com