Dose Escalation and Expansion Study of GSK3359609 in Participants With Selected Advanced Solid Tumors (INDUCE-1)

An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study treatment, whether or not considered related to the study treatment. 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 or Is a congenital anomaly/birth defect, Other situations which involve medical or scientific judgment or is associated with liver injury and impaired liver function. SAEs are subset of AEs. A summary of number of participants with any AEs and SAEs is presented. AEs were coded using the MedDRA dictionary.

Blood samples were collected for analysis of clinical chemistry parameters. Laboratory parameters were graded according to CTCAE v4.03. Grade (G) 0: None; G1: mild; G2: moderate; G3: severe or medically significant; G4: life-threatening consequences. Higher grade indicates greater severity and increase in grade was defined relative to Baseline grade. Baseline (Day 1) was defined as latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Only grade change data is presented for Baseline (B) and Worst-Case Post-Baseline (WCPB) as G0, G1, G2, G3, G4, and missing (M) here as "Parameter name, B GX, WCPB GX" where X=grade digit.

Normal ranges were 6 to 8.3 grams/L (protein); 100 to 250 international units (IU)/L (Lactate Dehydrogenase(LDH)); 2.3 - 4.1 picomoles/L (Free Triiodothyronine(T3)); 4.6 to 11.2 picomoles/L (Free Thyroxine(T4)); 0 and 0.04 microgram (ug)/L (Troponin I); 0 - 0.01 ug/L (Troponin T); 0.45 to 4.5 milliunits (Mu)/L (Thyrotropin(TSH)); and 6 to 24 millimoles/L (Urea). Participants were counted in worst case category that their value changes to low, normal or no change [NC] or high), unless there is NC in their category. Participants whose laboratory value category was unchanged (e.g. High to High) or whose value became normal, were recorded in "To Normal or No Change" category. Participants were counted twice if participant had values that changed To Low and To High, so percentages may not add to 100%

Blood samples were collected for analysis of hematology parameters. Laboratory parameters were graded according to CTCAE v4.03. Grade (G) 0: None; G1: mild; G2: moderate; G3: severe or medically significant; G4: life-threatening consequences. Higher grade indicates greater severity and increase in grade was defined relative to Baseline grade. Baseline (Day 1) was defined as latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Only grade change data is presented for Baseline (B) and Worst-Case Post-Baseline (WCPB) as G0, G1, G2, G3, G4, and missing (M) here as "Parameter name, B GX, WCPB GX" where X=grade digit.

Normal ranges were 0.01 to 0.3*10^9 cells/L (basophils), 0 to 500 cells /L (eosinophils), 41 to 50 percentage of RBC in blood (hematocrit), 2 to 8 percentage of WBC (monocytes), and Women: 4.2 to 5.4 million RBC/ mcL of blood and Men: 4.7 to 6.1 million RBC/ mcL (erythrocyte count). Participants were counted in worst case category that their value changes to low, normal or no change [NC] or high), unless there is NC in their category. Participants whose laboratory value category was unchanged (e.g. High to High) or whose value became normal, were recorded in "To Normal or No Change" category. Participants were counted twice if participant had values that changed To Low and To High, so percentages may not add to 100%.

Urine samples were collected to assess urine glucose, ketones and occult blood using dipstick method. The dipstick test gave results in a semi-quantitative manner, and results for urinalysis parameters were recorded as negative, trace, 1+, 2+, 3+ indicating proportional concentrations in the urine sample. Baseline (Day 1) was defined as the most recent, non-missing value prior to or on the first study treatment dose date. Result for urinalysis parameters were recorded as no change/decreased and any increase.

Number of participants with dose modifications (including dose delays, dose escalation and infusion interruptions) were reported for Feladilimab.

An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study treatment, whether or not considered related to the study treatment. 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 or is a congenital anomaly/birth defect, other situations which involve medical or scientific judgment or is associated with liver injury and impaired liver function. SAEs are subset of AEs. A summary of number of participants with any AEs and SAEs is presented. AEs were coded using the MedDRA dictionary.

Blood samples were collected for analysis of clinical chemistry parameters. Laboratory parameters were graded according to CTCAE v4.03. Grade (G) 0: None; G1: mild; G2: moderate; G3: severe or medically significant; G4: life-threatening consequences. Higher grade indicates greater severity and increase in grade was defined relative to Baseline grade. Baseline (Day 1) was defined as latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Only grade change data is presented for Baseline (B) and Worst-Case Post-Baseline (WCPB) as G0, G1, G2, G3, G4, and missing (M) here as "Parameter name, B GX, WCPB GX" where X=grade digit.

Normal ranges were 0.1 to 0.3 micromoles (umol)/liter (L) (direct bilirubin); 6 to 8.3 grams/L (protein); 100 to 250 international units (IU)/L (Lactate Dehydrogenase(LDH)); 2.3 - 4.1 picomoles/L (Free Triiodothyronine(T3)); 4.6 to 11.2 picomoles/L (Free Thyroxine(T4)); 0 and 0.04 microgram (ug)/L (Troponin I); 0 - 0.01 ug/L (Troponin T); 0.45 to 4.5 milliunits (Mu)/L (Thyrotropin(TSH)); 24-204 ug/L (creatine kinase); and 6 to 24 millimoles/L (Urea). Participants were counted in worst case category that their value changes to low, normal or no change [NC] or high), unless there is NC in their category. Participants whose laboratory value category was unchanged (e.g. High to High) or whose value became normal, were recorded in "To Normal or No Change" category. Participants were counted twice if participant had values that changed To Low and To High, so percentages may not add to 100%.

Blood samples were collected for analysis of hematology parameters. Laboratory parameters were graded according to CTCAE v4.03. Grade (G) 0: None; G1: mild; G2: moderate; G3: severe or medically significant; G4: life-threatening consequences. Higher grade indicates greater severity and increase in grade was defined relative to Baseline grade. Baseline (Day 1) was defined as latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Only grade change data is presented for Baseline (B) and Worst-Case Post-Baseline (WCPB) as G0, G1, G2, G3, G4, and missing (M) here as "Parameter name, B GX, WCPB GX" where X=grade digit.

Normal ranges were 0.01 to 0.3*10^9 cells/L (basophils), 0 to 500 cells/L(eosinophils), 41 to 50 percentage of RBC in blood (hematocrit), 1,000 - 4,800 lymphocytes per microliter (µL) of blood (lymphocytes), 80-100 fl (erythrocytes, mean corpuscular volume), 2 to 8 percentage of WBC (monocytes), 40 to 60 cells/mcL (neutrophils) and Women: 4.2 to 5.4 million RBC/ mcL of blood and Men: 4.7 to 6.1 million RBC/ mcL (erythrocytes count). Participants were counted in worst case category that their value changes to low, normal or no change [NC] or high), unless there is NC in their category. Participants whose laboratory value category was unchanged (e.g. High to High) or whose value became normal, were recorded in "To Normal or No Change" category. Participants were counted twice if participant had values that changed To Low and To High, so percentages may not add to 100%.

Urine samples were collected to assess urine glucose, ketones and occult blood using dipstick method. The dipstick test gave results in a semi-quantitative manner, and results for urinalysis parameters were recorded as negative, trace, 1+, 2+, 3+ indicating proportional concentrations in the urine sample. Baseline (Day 1) was defined as the most recent, non-missing value prior to or on the first study treatment dose date. Result for urinalysis parameters were recorded as no change/decreased and any increase.

Number of participants with dose modifications (including dose delays, dose escalations, and infusion interruptions) were reported for Feladilimab.

ORR was defined as the percentage of participants with immune-related confirmed complete response (irCR) or ir confirmed partial response (irPR) per Immune-related Response Evaluation Criteria in Solid Tumors Criteria (irRECIST). irCR is defined as disappearance of all target lesions and any pathological lymph nodes (whether target or non-target) must have reduction in short axis to less than (<)10 millimeters (mm). irPR is defined as at least a 30% decrease in the sum of the diameters of target lesions, taking as a reference, the baseline sum of the diameters.

DCR was defined as percentage of participants with best overall response of irCR or irPR at any time + ir stable disease (irSD) meeting the minimum time criteria from the start of treatment until ir disease progression (irPD) or death due to any cause or the start of new anticancer therapy/crossover. irCR is defined as disappearance of all target lesions. Any pathological lymph nodes must have reduction in short axis to <10 mm. irPR defined as at least 30% decrease in the sum of diameters of target lesions, taking as a reference, the baseline sum of the diameters. irSD defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease. IrPD defined as the date of radiological disease progression based on imaging data per irRECIST. A one-week visit window was considered in the duration of irSD, i.e. a minimum of 8 weeks (irSD>=9 weeks) and 17 weeks (irSD>=18 weeks) were considered.

OS was defined as the interval between the date of first assigned study therapy/randomization and date of death due to any cause.

PFS was defined as the interval between the date of first dose of study treatment (or date of randomization for randomized cohorts) and the date of disease progression according to radiological response from investigator assessment, or death due to any cause, whichever occurs earlier. Disease progression was defined as the date of radiological disease progression based on imaging data per RECIST v1.1

TTR was defined as the time from date of first dose of study treatment/randomization to the date of first documented confirmed (=4 weeks) CR or PR. CR is defined as disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to less than (<)10 mm. PR is defined as at least a 30% decrease in the sum of the diameters of target lesions, taking as a reference, the baseline sum of the diameters.

DOR was defined as the interval of time in months from the date of the first documented evidence of a response (confirmed CR or PR) to the date of first documented evidence of disease progression according to radiological response from investigator assessment per RECIST v1.1, or date of last adequate assessment of response or the date of death due to any cause (whichever occurs earlier). CR is defined as disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to less than (<)10 mm. PR is defined as at least a 30% decrease in the sum of the diameters of target lesions, taking as a reference, the baseline sum of the diameters. Disease progression was defined as the date of radiological disease progression based on imaging data per RECIST v1.1.

ORR was defined as the percentage of participants with irCR or irPR per irRECIST. irCR is defined as disappearance of all target lesions and any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 millimeters (mm). irPR is defined as at least a 30% decrease in the sum of the diameters of target lesions, taking as a reference, the baseline sum of the diameters.

DCR was defined as percentage of participants with best overall response of irCR or irPR at any time + irSD meeting the minimum time criteria from the start of treatment until irPD or death due to any cause or the start of new anticancer therapy/crossover. irCR defined as disappearance of all target lesions. Any pathological lymph nodes must have reduction in short axis to <10 mm. irPR defined as at least 30% decrease in the sum of diameters of target lesions, taking as a reference, the baseline sum of the diameters. irSD defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease. IrPD defined as the date of radiological disease progression based on imaging data per irRECIST. A one-week visit window was considered in the duration of irSD, i.e. a minimum of 8 weeks (irSD>=9 weeks) and 17 weeks (irSD>=18 weeks) were considered.

OS was defined as the interval between the date of first assigned study therapy/randomization and date of death due to any cause.

PFS was defined as the interval between the date of first dose of study treatment (or date of randomization for randomized cohorts) and the date of disease progression according to radiological response from investigator assessment, or death due to any cause, whichever occurs earlier. Disease Progression was defined as the date of radiological disease progression based on imaging data per RECIST v1.1.

TTR was defined as the time from date of first dose of study treatment/randomization to the date of first documented confirmed (=4 weeks) CR or PR. CR is defined as disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to less than (<)10 mm. PR is defined as at least a 30% decrease in the sum of the diameters of target lesions, taking as a reference, the baseline sum of the diameters.

DOR was defined as the interval of time in months from the date of the first documented evidence of a response (confirmed CR or PR) to the date of first documented evidence of disease progression according to radiological response from investigator assessment per RECIST v1.1, or date of last adequate assessment of response or the date of death due to any cause (whichever occurs earlier). CR is defined as disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to less than (<)10 mm. PR is defined as at least a 30% decrease in the sum of the diameters of target lesions, taking as a reference, the baseline sum of the diameters. Disease progression is defined as the date of radiological disease progression based on imaging data per RECIST v1.1.

ORR was defined as the percentage of participants with a confirmed irCR or confirmed irPR per irRECIST. irCR is defined as disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. irPR is defined as at least a 30% decrease in the sum of the diameters of target lesions, taking as a reference, the baseline sum of the diameters.

DCR was defined as percentage of participants with best overall response of irCR or irPR at any time + irSD meeting the minimum time criteria from the start of treatment until irPD or death due to any cause or the start of new anticancer therapy/crossover. irCR is defined as disappearance of all target lesions. Any pathological lymph nodes must have reduction in short axis to <10 mm. irPR defined as at least 30% decrease in the sum of diameters of target lesions, taking as a reference, the baseline sum of the diameters. irSD defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease. IrPD defined as the date of radiological disease progression based on imaging data per irRECIST. A one-week visit window was considered in the duration of irSD, i.e. a minimum of 8 weeks (irSD>=9 weeks) and 17 weeks (irSD>=18 weeks) were considered.

OS was defined as the interval between the date of first assigned study therapy/randomization and date of death due to any cause.

PFS was defined as the interval between the date of first dose of study treatment (or date of randomization for randomized cohorts) and the date of disease progression according to radiological response from investigator assessment, or death due to any cause, whichever occurs earlier. Disease progression was defined as the date of radiological disease progression based on imaging data per RECIST v1.1.

TTR was defined as the time from date of first dose of study treatment/randomization to the date of first documented confirmed (=4 weeks) CR or PR. CR is defined as disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to less than (<)10 mm. PR is defined as at least a 30% decrease in the sum of the diameters of target lesions, taking as a reference, the baseline sum of the diameters.

DOR was defined as the interval of time in months from the date of the first documented evidence of a response (confirmed CR or PR) to the date of first documented evidence of disease progression according to radiological response from investigator assessment per RECIST v1.1, or date of last adequate assessment of response or the date of death due to any cause (whichever occurs earlier). CR is defined as disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to less than (<)10 mm. PR is defined as at least a 30% decrease in the sum of the diameters of target lesions, taking as a reference, the baseline sum of the diameters. Disease progression is defined as the date of radiological disease progression based on imaging data per RECIST v1.1.

ORR was defined as the percentage of participants with a confirmed irCR or confirmed irPR per irRECIST. irCR is defined as disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. irPR is defined as at least a 30% decrease in the sum of the diameters of target lesions, taking as a reference, the baseline sum of the diameters.

DCR was defined as the percentage of participants with a best overall response of irCR or irPR at any time plus irSD meeting the minimum time criteria from the start of treatment until irPD or death due to any cause or the start of new anticancer therapy/crossover. irCR is defined as disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. irPR is defined as at least a 30% decrease in the sum of the diameters of target lesions, taking as a reference, the baseline sum of the diameters. irSD is defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease. irPD is defined as the date of radiological disease progression based on imaging data per irRECIST. A one-week visit window was considered in the duration of irSD, i.e. a minimum of 8 weeks (irSD>=9 weeks) and 17 weeks (irSD>=18 weeks) were considered.

OS was defined as the interval between the date of first assigned study therapy/randomization and date of death due to any cause.

PFS was defined as the interval between the date of first dose of study treatment (or date of randomization for randomized cohorts) and the date of disease progression according to radiological response from investigator assessment, or death due to any cause, whichever occurs earlier. Disease progression was defined as the date of radiological disease progression based on imaging data per RECIST v1.1.

TTR was defined as the time from date of first dose of study treatment/randomization to the date of first documented confirmed (=4 weeks) CR or PR. CR is defined as disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to less than (<)10 mm. PR is defined as at least a 30% decrease in the sum of the diameters of target lesions, taking as a reference, the baseline sum of the diameters.

DOR was defined as the interval of time in months from the date of the first documented evidence of a response (confirmed CR or PR) to the date of first documented evidence of disease progression according to radiological response from investigator assessment per RECIST v1.1, or date of last adequate assessment of response or the date of death due to any cause (whichever occurs earlier). CR is defined as disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. PR is defined as at least a 30% decrease in the sum of the diameters of target lesions, taking as a reference, the baseline sum of the diameters. Disease progression is defined as the date of radiological disease progression based on imaging data per RECIST v1.1

Blood samples were collected for Pharmacokinetic (PK) analysis. PK analysis was calculated based on standard non-compartmental method.

Blood samples were collected for PK analysis. PK analysis was calculated based on standard non-compartmental method.

Blood samples were collected for PK analysis. PK analysis was calculated based on standard non-compartmental method.

Blood samples were collected for PK analysis. PK analysis was calculated based on standard non-compartmental method.

Blood samples were collected for PK analysis. PK analysis was calculated based on standard non-compartmental method.

Blood samples were collected for PK analysis. PK analysis was calculated based on standard non-compartmental method.

Blood samples were collected for PK analysis. PK analysis was calculated based on standard non-compartmental method.

Blood samples were collected for PK analysis. PK analysis was calculated based on standard non-compartmental method.

Blood samples were collected for PK analysis. PK analysis was calculated based on standard non-compartmental method.

Blood samples were collected for PK analysis. PK analysis was calculated based on standard non-compartmental method.

Blood samples were collected for PK analysis. PK analysis was calculated based on standard non-compartmental method.

Blood samples were collected for PK analysis. PK analysis was calculated based on standard non-compartmental method.

Blood samples were collected for PK analysis. PK analysis was calculated based on standard non-compartmental method.

Serum samples collected and tested for the presence of ADA with a screening assay.

Serum samples collected and tested for the presence of ADA with a screening assay.

Serum samples collected and tested for the presence of ADA with a screening assay.

Serum samples collected and tested for the presence of ADA with a screening assay.

Serum samples collected and tested for the presence of ADA with a screening assay.

Serum samples collected and tested for the presence of ADA with a screening assay.

Serum samples collected and tested for the presence of ADA with a screening assay.

Serum samples collected and tested for the presence of ADA with a screening assay.

Serum samples collected and tested for the presence of ADA with a screening assay.

Blood samples were collected to assess the cluster of differentiation 4 (CD4+) and cluster of differentiation 8 (CD8+) receptor occupancy by Feladilimab as a pharmacodynamic analysis. It was assessed using validated flow cytometry assay.

Blood samples were collected to assess the cluster of differentiation 4 (CD4+) and cluster of differentiation 8 (CD8+) receptor occupancy by Feladilimab as a pharmacodynamic analysis. It was assessed using validated flow cytometry assay.

Blood samples were collected to assess the cluster of differentiation 4 (CD4+) and cluster of differentiation 8 (CD8+) receptor occupancy by Feladilimab as a pharmacodynamic analysis. It was assessed using validated flow cytometry assay.

Blood samples were collected to assess the cluster of differentiation 4 (CD4+) and cluster of differentiation 8 (CD8+) receptor occupancy by Feladilimab as a pharmacodynamic analysis. It was assessed using validated flow cytometry assay.