A Phase I First Time in Human Open Label Study of GSK3745417 Administered With and Without Anticancer Agents in Participants With Advanced Solid Tumors

Part 1A: Number of Participants Achieving Dose-limiting Toxicity (DLT) Following Administration of GSK3745417 Alone (Q1W)

Time Frame: Up to 21 Days

AE is DLT if deemed clinically relevant,attributed to study intervention \& met DLT criteria:CytokineReleaseSyndrome (CRS) (Grade(G) 3/4);Liver Toxicity: ALT≥3xULN + bilirubin≥2xULN/INR\>1.5, ALT≥5x ULN+≥2x baseline with liver,metastases/tumor infiltration or HCC;G≥3 non-hematologic exceptions: Transient lab abnormalities, CRS≤G2,Controlled diarrhea,Resolving nausea/vomiting,Alopecia,G3 fatigue\<7 days,G3 headache resolving in 24 hrs;G≥3 immune-related toxicity unresolved in 8 days despite therapy and G≥3 infusion reactions included;Other toxicities: G≥2 uveitis, Unresolved eye pain/blurred vision in 2 wks,Endocrine toxicity needing hormone replacement,Colitis/diarrhea unresolved for ≥7Days despite steroids,ICANS;Hematologic toxicity includes: Neutropenia(G4 ≥7Days or G3/4 with infection/febrile neutropenia),Thrombocytopenia (G4/G3 with bleeding/transfusion),Anemia (G4/G3 needing transfusion);Other events deemed DLTs by the investigator and GSK Medical Monitor per NCI-CTCAE v5.0

Parts 1A: Number of Participants Achieving DLT Following Administration of GSK3745417 Alone (Q3W)

Time Frame: Up to 29 Days

AE is DLT if deemed clinically relevant,attributed to study intervention \& met DLT criteria:CytokineReleaseSyndrome (CRS) (Grade(G) 3/4);Liver Toxicity: ALT≥3xULN + bilirubin≥2xULN/INR\>1.5, ALT≥5x ULN+≥2x baseline with liver,metastases/tumor infiltration or HCC;G≥3 non-hematologic exceptions: Transient lab abnormalities, CRS≤G2,Controlled diarrhea,Resolving nausea/vomiting,Alopecia,G3 fatigue\<7 days,G3 headache resolving in 24 hrs;G≥3 immune-related toxicity unresolved in 8 days despite therapy and G≥3 infusion reactions included;Other toxicities: G≥2 uveitis, Unresolved eye pain/blurred vision in 2 wks,Endocrine toxicity needing hormone replacement,Colitis/diarrhea unresolved for ≥7Days despite steroids,ICANS;Hematologic toxicity includes: Neutropenia(G4 ≥7Days or G3/4 with infection/febrile neutropenia),Thrombocytopenia (G4/G3 with bleeding/transfusion),Anemia (G4/G3 needing transfusion);Other events deemed DLTs by the investigator and GSK Medical Monitor per NCI-CTCAE v5.0

Parts 2A: Number of Participants Achieving DLT Following Administration of GSK3745417 in Combination With Dostarlimab (Q1W)

Time Frame: Up to 29 Days

AE is DLT if deemed clinically relevant,attributed to study intervention \& met DLT criteria:CytokineReleaseSyndrome (CRS) (Grade(G) 3/4);Liver Toxicity: ALT≥3xULN + bilirubin≥2xULN/INR\>1.5, ALT≥5x ULN+≥2x baseline with liver,metastases/tumor infiltration or HCC;G≥3 non-hematologic exceptions: Transient lab abnormalities, CRS≤G2,Controlled diarrhea,Resolving nausea/vomiting,Alopecia,G3 fatigue\<7 days,G3 headache resolving in 24 hrs;G≥3 immune-related toxicity unresolved in 8 days despite therapy and G≥3 infusion reactions included;Other toxicities: G≥2 uveitis, Unresolved eye pain/blurred vision in 2 wks,Endocrine toxicity needing hormone replacement,Colitis/diarrhea unresolved for ≥7Days despite steroids,ICANS;Hematologic toxicity includes: Neutropenia(G4 ≥7Days or G3/4 with infection/febrile neutropenia),Thrombocytopenia (G4/G3 with bleeding/transfusion),Anemia (G4/G3 needing transfusion);Other events deemed DLTs by the investigator and GSK Medical Monitor per NCI-CTCAE v5.0

Parts 2A: Number of Participants Achieving Dose-limiting Toxicity (DLT) Following Administration of GSK3745417 in Combination With Dostarlimab (Q3W)

Time Frame: Up to 29 Days

AE is DLT if deemed clinically relevant,attributed to study intervention \& met DLT criteria:CytokineReleaseSyndrome (CRS) (Grade(G) 3/4);Liver Toxicity: ALT≥3xULN + bilirubin≥2xULN/INR\>1.5, ALT≥5x ULN+≥2x baseline with liver,metastases/tumor infiltration or HCC;G≥3 non-hematologic exceptions: Transient lab abnormalities, CRS≤G2,Controlled diarrhea,Resolving nausea/vomiting,Alopecia,G3 fatigue\<7 days,G3 headache resolving in 24 hrs;G≥3 immune-related toxicity unresolved in 8 days despite therapy and G≥3 infusion reactions included;Other toxicities: G≥2 uveitis, Unresolved eye pain/blurred vision in 2 wks,Endocrine toxicity needing hormone replacement,Colitis/diarrhea unresolved for ≥7Days despite steroids,ICANS;Hematologic toxicity includes: Neutropenia(G4 ≥7Days or G3/4 with infection/febrile neutropenia),Thrombocytopenia (G4/G3 with bleeding/transfusion),Anemia (G4/G3 needing transfusion);Other events deemed DLTs by the investigator and GSK Medical Monitor per NCI-CTCAE v5.0

Parts 1A: Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious Treatment-emergent Adverse Events (STEAEs) by Severity

Time Frame: Up to approximately 62 weeks

AE is any untoward medical occurrence in clinical investigation participant, temporally associated with the use of medicinal product, whether or not considered related to the medicinal product. SAE is defined as 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, is 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. TEAE is an event that emerges during treatment having been absent pretreatment or worsens relative to the pretreatment state. AEs were graded by the investigator according to National Cancer Institute Common Terminology Criteria for AE (NCI-CTCAE) (version 5.0):G1=Mild,G2=Moderate,G3=Severe or medically significant but not immediately life-threatening,G4=Life-threatening consequences,G5=Death related AE.

Parts 2A: Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious Treatment-emergent Adverse Events (STEAEs) by Severity

Time Frame: Up to approximately 93 weeks

AE is any untoward medical occurrence in clinical investigation participant, temporally associated with the use of medicinal product, whether or not considered related to the medicinal product. SAE is defined as 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, is 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. TEAE is an event that emerges during treatment having been absent pretreatment or worsens relative to the pretreatment state. AEs were graded by the investigator according to NCI-CTCAE v5.0: G1=Mild, G2=Moderate, G3=Severe or medically significant but not immediately life-threatening, G4=Life-threatening consequences, G5=Death related AE.

Crossover Phase: Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious Treatment-emergent Adverse Events (STEAEs) by Severity

Time Frame: Up to 30.3 weeks

AE is any untoward medical occurrence in clinical investigation participant, temporally associated with the use of medicinal product, whether or not considered related to the medicinal product. SAE is defined as 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, is 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. TEAE is an event that emerges during treatment having been absent pretreatment or worsens relative to the pretreatment state. AEs were graded by the investigator according to NCI-CTCAE v5.0: G1=Mild, G2=Moderate, G3=Severe or medically significant but not immediately life-threatening, G4=Life-threatening consequences, G5=Death related AE.