GSK3359609 Plus Tremelimumab for the Treatment of Advanced Solid Tumors

• ClinicalTrials.gov Identifier: NCT03693612
• Recruitment Status: Completed
• First Posted: October 3, 2018
• Results First Posted: August 22, 2022
• Last Update Posted: August 22, 2022
• Sponsor: GlaxoSmithKline
• Collaborator: MedImmune LLC
• Information provided by (Responsible Party): GlaxoSmithKline

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Neoplasms	Drug: feladilimab; Drug: Tremelimumab; Drug: Docetaxel; Drug: Paclitaxel; Drug: Cetuximab	Phase 1; Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 26 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Intervention Model Description: In Part 1, dose escalation will occur using a zone based approach. Part 2 will be randomized, parallel group study wherein the subjects will be randomized in a ratio of 2:1 to either recommended Phase 2 dose combination of GSK3359609 and tremelimumab or SOC (paclitaxel, docetaxel or cetuximab).
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase I/II, Open-label, Two Part Study of GSK3359609 in Combination With Tremelimumab in Participants With Selected, Advanced Solid Tumors
• Actual Study Start Date: November 26, 2018
• Actual Primary Completion Date: June 25, 2021
• Actual Study Completion Date: September 16, 2021

Arms and Interventions

Arm	Intervention/treatment
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.	Drug: 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.; Drug: 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 .
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.	Drug: 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.; Drug: 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 .
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.	Drug: 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).; Drug: Paclitaxel; Paclitaxel is a microtubule stabilizer which will be administered as an IV infusion once weekly at a dose of 80 mg/m^2.; Drug: 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.

Outcome Measures

Primary Outcome Measures :

1. Number of Participants With Dose Limiting Toxicities (DLTs)-Part 1 [ Time Frame: Up to 28 days ]
   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.
2. Number of Participants With DLTs According to Severity-Part 1 [ Time Frame: Up to 28 days ]
   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.
3. Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs) and Adverse Events of Special Interest (AESI)-Part 1 [ Time Frame: Up to 4 years ]
   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.
4. Number of Participant With AE/SAE/DLTs Leading to Dose Modifications/Delays/Withdrawals-Part 1 [ Time Frame: Up to 4 years ]
   The number of participants with AE/SAE/DLTs leading to dose modifications/delays/withdrawals were summarized.
5. Number of Participants With AEs, SAEs, AESIs According to Severity - Part 1 [ Time Frame: Up to 4 years ]
   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.
6. Number of Participants With Severe- AEs/SAEs/DLTs Leading to Dose Modifications/Delays/Withdrawals-Part 1 [ Time Frame: Up to 4 years ]
   The number of participants with severe- AE/SAE/DLTs leading to dose modifications/delays/withdrawals were summarized.
7. Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP)-Part 1 [ Time Frame: Baseline (Day 1) and Week 4 ]
   SBP and DBP were measured after 5 minutes of rest for the participant.
8. Change From Baseline in Temperature-Part 1 [ Time Frame: Baseline (Day 1) and Week 4 ]
   Temperature was measured after 5 minutes of rest for the participant.
9. Change From Baseline in Pulse Rate-Part 1 [ Time Frame: Baseline (Day 1) and Week 4 ]
   Pulse rate was measured after 5 minutes of rest for the participant.
10. Change From Baseline in Respiratory Rate-Part 1 [ Time Frame: Baseline (Day 1) and Week 4 ]
    Respiratory rate was measured after 5 minutes of rest for the participant.
11. Change From Baseline in Oxygen Saturation-Part 1 [ Time Frame: Baseline (Day 1) and Week 4 ]
    Oxygen saturation was measured using pulse oximeter after 5 minutes of rest for the participant.
12. Number of Participants With Electrocardiogram (ECG) Findings [ Time Frame: Baseline (Pre dose, Day 1) and up to 4 Years ]
    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.
13. Change From Baseline in Neutrophil, Lymphocyte, Monocyte, Eosinophil, Basophil and Platelet Count-Part 1 [ Time Frame: Baseline (Day 1) and Week 4 ]
    Blood samples were collected to assess change from Baseline in neutrophil, lymphocyte, monocyte, eosinophil, basophil and platelet counts.
14. Change From Baseline in Hemoglobin Level-Part 1 [ Time Frame: Baseline (Day 1) and Week 4 ]
    Blood samples were collected to assess change from baseline in hemoglobin level.
15. Change From Baseline in Hematocrit Level-Part 1 [ Time Frame: Baseline (Day 1) and Week 4 ]
    Blood samples were collected to assess change from baseline in hematocrit level.
16. Change From Baseline in Erythrocytes Count-Part 1 [ Time Frame: Baseline (Day 1) and Week 4 ]
    Blood samples were collected to assess change from baseline in Erythrocytes count.
17. Change From Baseline in Albumin and Total Protein Levels-Part 1 [ Time Frame: Baseline (Day 1) and Week 4 ]
    Blood samples were collected to assess change from Baseline in albumin and total protein levels.
18. Change From Baseline in Creatinine and Bilirubin Levels-Part 1 [ Time Frame: Baseline (Day 1) and Week 4 ]
    Blood samples were collected to assess change from baseline in creatinine and bilirubin levels.
19. Change From Baseline in Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Alkaline Phosphatase (ALP), Lactate Dehydrogenase (LDH) Levels-Part 1 [ Time Frame: Baseline (Day 1) and Week 4 ]
    Blood samples were collected to assess change from baseline in ALT, AST ALP, LDH levels.
20. Change From Baseline in Amylase and Lipase Levels-Part 1 [ Time Frame: Baseline (Day 1) and week 4 ]
    Blood samples were collected to assess change from baseline in amylase and lipase levels.
21. Change From Baseline in Urea, Glucose, Potassium, Sodium and Calcium Levels-Part 1 [ Time Frame: Baseline (Day 1) and Week 4 ]
    Blood samples were collected to assess change in levels of urea, glucose, potassium, sodium and calcium from baseline.
22. Change From Baseline in Specific Gravity of Urine-Part 1 [ Time Frame: Baseline (Day 1) and Week 4 ]
    Urine samples were collected to assess change from baseline in specific gravity of urine.
23. Change From Baseline in Potential of Hydrogen (pH) of Urine-Part 1 [ Time Frame: Baseline (Day 1) and Week 4 ]
    Urine samples were collected to assess change from baseline in pH of urine.
24. Number of Participants With Abnormal Urinalysis Parameters-Part 1 [ Time Frame: Week 4 ]
    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.
25. Change From Baseline in Thyroid Stimulating Hormone (TSH) or Thyrotropin-Part 1 [ Time Frame: Baseline (Day 1) and Week 4 ]
    Blood samples were collected to assess change from Baseline in TSH.
26. Change From Baseline in Free Triiodothyronine (T3)-Part 1 [ Time Frame: Baseline (Day 1) and Week 4 ]
    Blood samples were collected to assess change from Baseline in free T3.
27. Change From Baseline in Free Thyroxine (T4)-Part 1 [ Time Frame: Baseline (Day 1) and Week 4 ]
    Blood samples were collected to assess change from baseline in free T4.
28. Overall Survival-Part 2 [ Time Frame: Up to 4 years ]
    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.

Secondary Outcome Measures :

1. Overall Response Rate-Part 1 [ Time Frame: Up to 4 years ]
   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.
2. Overall Response Rate-Part 2 [ Time Frame: Up to 4 years ]
   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.
3. Disease Control Rate-Part 1 [ Time Frame: Up to 4 years ]
   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.
4. Disease Control Rate-Part 2 [ Time Frame: Up to 4 years ]
   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.
5. Progression Free Survival-Part 2 [ Time Frame: Up to 4 years ]
   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.
6. Time to Response-Part 2 [ Time Frame: Up to 4 years ]
   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.
7. Duration of Response-Part 2 [ Time Frame: Up to 4 years ]
   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).
8. Maximum Observed Plasma Concentration (Cmax) of Feladilimab-Part 1 [ Time Frame: Pre-dose, end of infusion and 4 hours post dose at Day 1 ]
   Blood samples were collected at indicated time points for pharmacokinetic assessment.
9. Cmax of Tremelimumab-Part 1 [ Time Frame: Pre-dose, end of infusion and 4 hours post dose at Day 1 ]
   Blood samples were collected at indicated time points for pharmacokinetic assessment.
10. Cmax of Feladilimab-Part 2 [ Time Frame: 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 ]
    Blood samples were planned to be collected at indicated time points for pharmacokinetic assessment.
11. Cmax of Tremelimumab-Part 2 [ Time Frame: 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 ]
    Blood samples were planned to be collected at indicated time points for pharmacokinetic assessment.
12. Minimum Observed Plasma Concentration (Cmin) of Feladilimab-Part 1 [ Time Frame: Pre-dose, end of infusion and 4 hours post dose at Day 1 ]
    Blood samples were collected at indicated time points for pharmacokinetic assessment.
13. Cmin of Tremelimumab-Part 1 [ Time Frame: Pre-dose, end of infusion and 4 hours post dose at Day 1 ]
    Blood samples were collected at indicated time points for pharmacokinetic assessment.
14. Cmin of Feladilimab-Part 2 [ Time Frame: 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 ]
    Blood samples were planned to be collected at indicated time points for pharmacokinetic assessment.
15. Cmin of Tremelimumab-Part 2 [ Time Frame: 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 ]
    Blood samples were planned to be collected at indicated time points for pharmacokinetic assessment.
16. Area Under the Plasma Concentration-time Curve (AUC[0-t]) of Feladilimab-Part 1 [ Time Frame: Pre-dose, end of infusion and 4 hours post dose at Day 1 ]
    Blood samples were collected at indicated time points for pharmacokinetic assessment.
17. AUC(0-t) of Tremelimumab-Part 1 [ Time Frame: Pre-dose, end of infusion and 4 hours post dose at Day 1 ]
    Blood samples were collected at indicated time points for pharmacokinetic assessment.
18. AUC(0-t) of Feladilimab-Part 2 [ Time Frame: 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 ]
    Blood samples were planned to be collected at indicated time points for pharmacokinetic assessment.
19. AUC(0-t) of Tremelimumab-Part 2 [ Time Frame: 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 ]
    Blood samples were planned to be collected at indicated time points for pharmacokinetic assessment
20. Number of Participants With Anti-drug Antibodies Against Feladilimab-Part 1 [ Time Frame: Pre-dose at Week 4, 7, 10 and 13 ]
    Serum samples were collected and tested for the presence of antibodies to feladilimab.
21. Number of Participants With Anti-drug Antibodies Against Tremelimumab-Part 1 [ Time Frame: Pre-dose at Week 1, 4, 7, 10 and 13 ]
    Serum samples were collected and tested for the presence of antibodies to tremelimumab.
22. Number of Participants With Anti-drug Antibodies Against Feladilimab-Part 2 [ Time Frame: Up to 2.5 years ]
    Serum samples will be collected and tested for the presence of antibodies to feladilimab.
23. Change From Baseline in Free T4-Part 2 [ Time Frame: Baseline and up to 2 years ]
    Blood samples will be collected to assess change from baseline in free T4.
24. Number of Participants With Anti-drug Antibodies Against Tremelimumab-Part 2 [ Time Frame: Up to 2.5 years ]
    Serum samples will be collected and tested for the presence of antibodies to tremelimumab.
25. Number of Participants With AEs, SAEs and AESI-Part 2 [ Time Frame: Up to 4 years ]
    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.
26. Number of Participants With AEs, SAEs, AESIs Based on Severity-Part 2 [ Time Frame: Up to 4 years ]
    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
27. Number of Participants With Severe- AEs/SAEs/DLTs Leading to Dose Modifications/Delays/Withdrawals-Part 2 [ Time Frame: Up to 4 years ]
    The number of participants with severe- AE/SAE/DLTs leading to dose modifications/delays/withdrawals were planned to be summarized.
28. Change From Baseline in SBP and DBP-Part 2 [ Time Frame: Baseline and up to 2 years ]
    SBP and DBP will be measured after 5 minutes of rest for the participant.
29. Change From Baseline in Temperature-Part 2 [ Time Frame: Baseline and up to 2 years ]
    Temperature will be measured after 5 minutes of rest for the participant.
30. Change From Baseline in Pulse Rate-Part 2 [ Time Frame: Baseline and up to 2 years ]
    Pulse rate will be measured after 5 minutes of rest for the participant.
31. Change From Baseline in Respiratory Rate-Part 2 [ Time Frame: Baseline and up to 2 years ]
    Respiratory rate will be measured after 5 minutes of rest for the participant.
32. Change From Baseline in Oxygen Saturation-Part 2 [ Time Frame: Baseline and up to 2 years ]
    Oxygen saturation will be measured using pulse oximetry after 5 minutes of rest for the participant.
33. Change From Baseline in ECG Measurement-Part 2 [ Time Frame: Baseline (Pre-dose) up to 2 years ]
    Single 12-lead ECG will be obtained using an automated ECG machine.
34. Change From Baseline in Neutrophil, Lymphocyte, Monocyte, Eosinophil, Basophil and Platelet Count-Part 2 [ Time Frame: Baseline and up to 2 years ]
    Blood samples will be collected to assess change from baseline in neutrophil, lymphocyte, monocyte, eosinophil, basophil and platelet count.
35. Change From Baseline in Hemoglobin Level-Part 2 [ Time Frame: Baseline and up to 2 years ]
    Blood samples will be collected to assess change from baseline in hemoglobin level.
36. Change From Baseline in Hematocrit Level-Part 2 [ Time Frame: Baseline and up to 2 years ]
    Blood samples will be collected to assess change from baseline in hematocrit level.
37. Change From Baseline in Erythrocytes Count-Part 2 [ Time Frame: Baseline and up to 2 years ]
    Blood samples will be collected to assess change from Baseline in erythrocytes count.
38. Change From Baseline in Albumin and Total Protein Levels-Part 2 [ Time Frame: Baseline and up to 2 years ]
    Blood samples will be collected to assess change from baseline in albumin and total protein levels.
39. Change From Baseline in Creatinine and Bilirubin Levels-Part 2 [ Time Frame: Baseline and up to 2 years ]
    Blood samples will be collected to assess change from baseline in creatinine and bilirubin levels.
40. Change From Baseline in ALT, AST, ALP, LDH Levels-Part 2 [ Time Frame: Baseline and up to 2 years ]
    Blood samples will be collected to assess change from baseline in ALT, AST ALP, LDH, amylase and lipase levels.
41. Change From Baseline in Amylase and Lipase Levels-Part 2 [ Time Frame: Baseline and up to 2 years ]
    Blood samples were collected to assess change from baseline in amylase and lipase levels.
42. Change From Baseline in Urea, Glucose, Potassium, Sodium and Calcium Levels -Part 2 [ Time Frame: Baseline and up to 2 years ]
    Blood samples will be collected to assess change in levels of urea, glucose, potassium, sodium and calcium from baseline.
43. Change From Baseline in Specific Gravity of Urine-Part 2 [ Time Frame: Baseline and up to 2 years ]
    Urine samples will be collected to assess change from Baseline in specific gravity of urine.
44. Change From Baseline in pH of Urine-Part 2 [ Time Frame: Baseline and up to 2 years ]
    Urine samples will be collected to assess change from baseline in pH of urine.
45. Number of Participants With Abnormal Urinalysis Parameters-Part 2 [ Time Frame: Up to 2 years ]
    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.
46. Change From Baseline in TSH-Part 2 [ Time Frame: Baseline and up to 2 years ]
    Blood samples will be collected to assess change from Baseline in TSH.
47. Change From Baseline in Free T3-Part 2 [ Time Frame: Baseline and up to 2 years ]
    Blood samples will be collected to assess change from baseline in free T3.

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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.

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.

Contacts and Locations

Locations

United States, Massachusetts

GSK Investigational Site

Boston, Massachusetts, United States, 02215

United States, New York

GSK Investigational Site

New York, New York, United States, 10016-4744

GSK Investigational Site

New York, New York, United States, 10032

United States, Pennsylvania

GSK Investigational Site

Pittsburgh, Pennsylvania, United States, 15232

United States, Texas

GSK Investigational Site

San Antonio, Texas, United States, 78229

Australia, Victoria

GSK Investigational Site

Melbourne, Victoria, Australia, 3000

Canada, Ontario

GSK Investigational Site

Ottawa, Ontario, Canada, K1H 8L6

GSK Investigational Site

Toronto, Ontario, Canada, M5G 2M9

Sponsors and Collaborators

GlaxoSmithKline

MedImmune LLC

Investigators

• Study Director: GSK Clinical Trials; GlaxoSmithKline

  Study Documents (Full-Text)

Documents provided by GlaxoSmithKline:

Study Protocol  [PDF] September 20, 2018

Statistical Analysis Plan  [PDF] December 16, 2020

More Information

• Responsible Party: GlaxoSmithKline
• ClinicalTrials.gov Identifier: NCT03693612
• Other Study ID Numbers: 207871
• First Posted: October 3, 2018
• Results First Posted: August 22, 2022
• Last Update Posted: August 22, 2022
• Last Verified: July 2022

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes
• Plan Description: IPD for this study will be made available via the Clinical Study Data Request site.
• Supporting Materials: Study Protocol; Statistical Analysis Plan (SAP); Informed Consent Form (ICF); Clinical Study Report (CSR)
• Time Frame: IPD will be made available within 6 months of publishing the results of the primary endpoints, key secondary endpoints and safety data of the study.
• Access Criteria: Access is provided after a research proposal is submitted and has received approval from the Independent Review Panel and after a Data Sharing Agreement is in place. Access is provided for an initial period of 12 months but an extension can be granted, when justified, for up to another 12 months.
• URL: http://clinicalstudydatarequest.com

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by GlaxoSmithKline:

advanced solid tumor; Head and Neck Squamous Cell Carcinoma; standard of care; GSK3359609; urothelial carcinoma of the upper and lower urinary tract; non-small cell lung cancer; cutaneous melanoma; Tremelimumab; clear cell renal carcinoma; castrate resistant prostate adenocarcinoma

Additional relevant MeSH terms:

Paclitaxel; Docetaxel; Cetuximab; Tremelimumab; Antineoplastic Agents, Phytogenic; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents, Immunological