This study is a Phase Ib, multi-center, open-label study of TNO155 in combination with spartalizumab or ribociclib with a dose escalation part followed by a dose expansion part in adult subjects with advanced solid tumors. These two treatment arms will enroll subjects in parallel to characterize the safety, tolerability, PK, PD and preliminary antitumor activity. The study treatment will be administered until the subject experiences unacceptable toxicity, progressive disease, and/or has treatment discontinued at the discretion of the Investigator or the subject, or due to withdrawal of consent.
Name: TNO155
Description: CapsuleType: DrugTNO155 in combination with spartalizumab TNO155 in combination with ribociclib
Name: Spartalizumab
Description: Concentrate for solution for infusionType: DrugTNO155 in combination with spartalizumab
Name: Ribociclib
Description: Capsule and tabletType: DrugTNO155 in combination with ribociclib
Description: Incidence of dose limiting toxicities (DLTs) during the first cycle of combination treatment during the dose escalation part
Measure: DLT incidence Time: 1 yearDescription: Incidence and severity of adverse events (AEs) and serious adverse events (SAEs) as per CTCAE v5.0, by treatment
Measure: AE and SAE incidence Time: 3 yearsDescription: Dose tolerability
Measure: Dose interruptions, reductions and dose intensity, by treatment Time: 3 yearsDescription: Cmax for TNO155, spartalizumab, and ribociclib
Measure: Pharmacokinetics (PK): Cmax Time: 3 yearsDescription: Tmax for TNO155, spartalizumab, and ribociclib
Measure: Pharmacokinetics (PK): Tmax Time: 3 yearsDescription: AUClast for TNO155, spartalizumab, and ribociclib
Measure: Pharmacokinetics (PK): AUClast Time: 3 yearsDescription: AUCtau for TNO155, spartalizumab, and ribociclib
Measure: Pharmacokinetics (PK): AUCtau Time: 3 yearsDescription: Overall response rate (ORR) per RECIST v1.1, by treatment
Measure: Efficacy measurements per RECIST v1.1: ORR Time: 3 yearsDescription: Disease control rate (DCR) per RECIST v1.1, by treatment
Measure: Efficacy measurements per RECIST v1.1: DCR Time: 3 yearsDescription: Progression-free survival (PFS) per RECIST v1.1, by treatment
Measure: Efficacy measurements per RECIST v1.1: PFS Time: 3 yearsDescription: Duration of response (DOR) per RECIST v1.1, by treatment
Measure: Efficacy measurements per RECIST v1.1: DOR Time: 3 yearsDescription: Overall response rate (ORR) per iRECIST for TNO155 in combination with spartalizumab
Measure: Efficacy measurements per iRECIST: ORR Time: 3 yearsDescription: Disease control rate (DCR) per iRECIST for TNO155 in combination with spartalizumab
Measure: Efficacy measurements per iRECIST: DCR Time: 3 yearsDescription: Progression-free survival (PFS) per iRECIST for TNO155 in combination with spartalizumab
Measure: Efficacy measurements per iRECIST: PFS Time: 3 yearsDescription: Duration of response (DOR) per iRECIST for TNO155 in combination with spartalizumab
Measure: Efficacy measurements per iRECIST: DOR Time: 3 yearsDescription: Overall survival (OS) by treatment
Measure: Overall Survival Time: 3 yearsAllocation: Non-Randomized
Parallel Assignment
There is one SNP
For TNO155 plus spartalizumab combination: i. Advanced EGFR WT, ALK WT, KRAS G12C NSCLC after progression on or intolerance to platinum-containing combination chemotherapy and after progression on anti-PD-1 or anti-PD-L1 therapy. --- G12C ---