Neoplasms

Respiratory Tract (Lung and Bronchial) Diseases

All Conditions

Skin and Connective Tissue Diseases

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Rare Diseases

Lung Neoplasms

Carcinoma, Non-Small-Cell Lung

Carcinoma

Carcinoma, Squamous Cell

Adenocarcinoma

Melanoma

Carcinoma, Renal Cell

Carcinoma, Transitional Cell

Melanoma, Cutaneous Malignant

Kidney Neoplasms

Renal Cell Carcinoma

Clear Cell Renal Cell Carcinoma

Transitional Cell Carcinoma

All Drugs and Chemicals

Antineoplastic Agents

Antibodies

Antibodies, Monoclonal

Paclitaxel

Docetaxel

Cetuximab

Albumin-Bound Paclitaxel

Immunoglobulins

Immunoglobulin G

Immunoglobulins, Intravenous

Tremelimumab

Tubulin Modulators

Antimitotic Agents

Antineoplastic Agents, Immunological

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.

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.

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.

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.

feladilimab

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 .

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).

Paclitaxel is a microtubule stabilizer which will be administered as an IV infusion once weekly at a dose of 80 mg/m\^2.

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.

GSK Clinical Trials

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.

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).

GSK3359609 Plus Tremelimumab for the Treatment of Advanced Solid Tumors

A Phase I/II, Open-label, Two Part Study of GSK3359609 in Combination With Tremelimumab in Participants With Selected, Advanced Solid Tumors

IPD for this study will be made available via the Clinical Study Data Request site.

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.

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.

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.

The number of participants with AE/SAE/DLTs leading to dose modifications/delays/withdrawals were summarized.

The number of participants with severe- AE/SAE/DLTs leading to dose modifications/delays/withdrawals were summarized.

SBP and DBP were measured after 5 minutes of rest for the participant.

Temperature was measured after 5 minutes of rest for the participant.

Pulse rate was measured after 5 minutes of rest for the participant.

Respiratory rate was measured after 5 minutes of rest for the participant.

Oxygen saturation was measured using pulse oximeter after 5 minutes of rest for the participant.

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.

Blood samples were collected to assess change from Baseline in neutrophil, lymphocyte, monocyte, eosinophil, basophil and platelet counts.

Blood samples were collected to assess change from baseline in hemoglobin level.

Blood samples were collected to assess change from baseline in hematocrit level.

Blood samples were collected to assess change from baseline in Erythrocytes count.

Blood samples were collected to assess change from Baseline in albumin and total protein levels.

Blood samples were collected to assess change from baseline in creatinine and bilirubin levels.

Blood samples were collected to assess change from baseline in ALT, AST ALP, LDH levels.

Blood samples were collected to assess change from baseline in amylase and lipase levels.

Blood samples were collected to assess change in levels of urea, glucose, potassium, sodium and calcium from baseline.

Urine samples were collected to assess change from baseline in specific gravity of urine.

Urine samples were collected to assess change from baseline in pH of urine.

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.

Blood samples were collected to assess change from Baseline in TSH.

Blood samples were collected to assess change from Baseline in free T3.

Blood samples were collected to assess change from baseline in free T4.

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.

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.

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.

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.

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.

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.

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).

Blood samples were collected at indicated time points for pharmacokinetic assessment.

Blood samples were planned to be collected at indicated time points for pharmacokinetic assessment.

Blood samples were planned to be collected at indicated time points for pharmacokinetic assessment

Serum samples were collected and tested for the presence of antibodies to feladilimab.

Serum samples were collected and tested for the presence of antibodies to tremelimumab.

Serum samples will be collected and tested for the presence of antibodies to feladilimab.

Blood samples will be collected to assess change from baseline in free T4.

Serum samples will be collected and tested for the presence of antibodies to tremelimumab.

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

The number of participants with severe- AE/SAE/DLTs leading to dose modifications/delays/withdrawals were planned to be summarized.

SBP and DBP will be measured after 5 minutes of rest for the participant.

Temperature will be measured after 5 minutes of rest for the participant.

Pulse rate will be measured after 5 minutes of rest for the participant.

Respiratory rate will be measured after 5 minutes of rest for the participant.

Oxygen saturation will be measured using pulse oximetry after 5 minutes of rest for the participant.

Single 12-lead ECG will be obtained using an automated ECG machine.

Blood samples will be collected to assess change from baseline in neutrophil, lymphocyte, monocyte, eosinophil, basophil and platelet count.

Blood samples will be collected to assess change from baseline in hemoglobin level.

Blood samples will be collected to assess change from baseline in hematocrit level.

Blood samples will be collected to assess change from Baseline in erythrocytes count.

Blood samples will be collected to assess change from baseline in albumin and total protein levels.

Blood samples will be collected to assess change from baseline in creatinine and bilirubin levels.

Blood samples will be collected to assess change from baseline in ALT, AST ALP, LDH, amylase and lipase levels.

Blood samples will be collected to assess change in levels of urea, glucose, potassium, sodium and calcium from baseline.

Urine samples will be collected to assess change from Baseline in specific gravity of urine.

Urine samples will be collected to assess change from baseline in pH of urine.

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.

Blood samples will be collected to assess change from Baseline in TSH.

Blood samples will be collected to assess change from baseline in free T3.

MedImmune LLC

GlaxoSmithKline

All Treated Population included participants who received at least 1 dose of SOC or tremelimumab or feladilimab. The sponsor made the decision to not continue the study at the end of Part 1 based on the totality of available data due to lack of efficacy and not due to safety. Hence Part 2 was not initiated and participants were not enrolled in the same.

In Part 1, participants with advanced, selected solid tumors were enrolled. Participants were administered 8 mg Feladilimab first as a 30-minute IV infusion once Q3W in combination with 75 mg tremelimumab as an IV infusion over 60 minutes beginning at least 1 hour and no more than 2 hours once Q3W for 6 doses followed by once Q12W.

Part 1: Feladilimab (GSK3359609) 8 mg + Tremelimumab 75 mg

In Part 1, participants with advanced, selected solid tumors were enrolled. Participants were administered 24 mg Feladilimab first as a 30-minute IV infusion once Q3W in combination with 75 mg tremelimumab as an IV infusion over 60 minutes beginning at least 1 hour and no more than 2 hours once Q3W for 6 doses followed by once Q12W.

Part 1: Feladilimab 24 mg + Tremelimumab 75 mg

In Part 1, participants with advanced, selected solid tumors were enrolled. Participants were administered 8 mg Feladilimab first as a 30-minute IV infusion once Q3W in combination with 225 mg tremelimumab as an IV infusion over 60 minutes beginning at least 1 hour and no more than 2 hours once Q3W for 6 doses followed by once Q12W.

Part 1: Feladilimab 8 mg + Tremelimumab 225 mg

In Part 1, participants with advanced, selected solid tumors were enrolled. Participants were administered 80 mg Feladilimab first as a 30-minute IV infusion once Q3W in combination with 75 mg tremelimumab as an IV infusion over 60 minutes beginning at least 1 hour and no more than 2 hours once Q3W for 6 doses followed by once Q12W.

Part 1: Feladilimab 80 mg + Tremelimumab 75 mg

In Part 1, participants with advanced, selected solid tumors were enrolled. Participants were administered 24 mg Feladilimab first as a 30-minute IV infusion once Q3W in combination with 225 mg tremelimumab as an IV infusion over 60 minutes beginning at least 1 hour and no more than 2 hours once Q3W for 6 doses followed by once Q12W.

Part 1: Feladilimab 24 mg + Tremelimumab 225 mg

In Part 2, participants with HNSCC who have progressed after receiving at least 1 platinum-based chemotherapy and at least one anti-PD-1/ PD-L1 therapy, whether in combination or separately were planned to be enrolled. Participants were planned to be administered with Feladilimab and Tremelimumab as an IV infusion after the RP2D determination.

Part 2: Feladilimab + Tremelimumab

In Part 2, participants with HNSCC who have progressed after receiving at least 1 platinum-based chemotherapy and at least one anti-PD-1/PD-L1 therapy, whether in combination or separately were planned to be enrolled. Participants were planned to be administered with a single agent SOC therapy of either paclitaxel (as an IV infusion once weekly at a dose of 80 mg/m\^2), docetaxel (as an IV infusion once every 3 weeks at a dose of 75 mg/m\^2) or cetuximab (at a loading dose of 400 mg/m\^2 followed by 250 mg/m\^2 once weekly) as per the investigator's choice.

Part 2: Standard of Care (SOC)

Total

Age, Continuous

Sex: Female, Male

Black or African American

Multiple

White - White/Caucasian/European Heritage

Race/Ethnicity, Customized

The sponsor made the decision to not continue the study at the end of Part 1 based on the totality of available data due to lack of efficacy and not due to safety. Hence Part 2 was not initiated and participants were not enrolled.

The sponsor made the decision to not continue the study at the end of Part 1 based on the totality of available data due to lack of efficacy and not due to safety. Hence Part 2 was not initiated and participants were not enrolled in the same.

GSK Response Center

All Treated Population includes all participants who received at least 1 dose of Tremelimumab or Feladilimab.

Number of Participants With Dose Limiting Toxicities (DLTs)-Part 1

Grade 1

Grade 2

Grade 3

Grade 4

Grade 5

Number of Participants With DLTs According to Severity-Part 1

SAEs

AESIs

Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs) and Adverse Events of Special Interest (AESI)-Part 1

Any Aes-Dose Modification

Any Aes-Dose Delay

Any Aes-Dose Withdrawal

Any SAEs-Dose Modification

Any SAEs-Dose Delay

Any SAEs-Dose Withdrawal

Any DLTs-Dose Modification

Any DLTs-Dose Delay

Any DLTs-Dose Withdrawal

Number of Participant With AE/SAE/DLTs Leading to Dose Modifications/Delays/Withdrawals-Part 1

Grade 1: AEs

Grade 2: AEs

Grade 3: AEs

Grade 4: AEs

Grade 5: AEs

Grade 1: SAEs

Grade 2: SAEs

Grade 3: SAEs

Grade 4: SAEs

Grade 5: SAEs

Grade 1: AESI

Grade 2: AESI

Grade 3: AESI

Grade 4: AESI

Grade 5: AESI

Number of Participants With AEs, SAEs, AESIs According to Severity - Part 1

Any Severe Aes-Dose Modification

Any Severe Aes-Dose Delay

Any Severe Aes-Dose Withdrawal

Any Severe SAEs-Dose Modification

Any Severe SAEs-Dose Delay

Any Severe SAEs-Dose Withdrawal

Any Severe DLTs-Dose Modification

Any Severe DLTs-Dose Delay

Any Severe DLTs-Dose Withdrawal

Number of Participants With Severe- AEs/SAEs/DLTs Leading to Dose Modifications/Delays/Withdrawals-Part 1

SBP, Baseline (Day 1)

SBP, Week 4

DBP, Baseline (Day 1)

DBP, Week 4

All Treated Population. Only those participants with data available at the specified data points were analyzed.

Spots Global Cancer Trial Database for castrate resistant prostate adenocarcinoma