The purpose of this phase 2 study is to evaluate the efficacy and safety of NIR178 in combination with PDR001 in multiple solid tumors and diffuse large B-cell lymphoma (DLBCL) and further explore schedule variations of NIR178 to optimize immune activation through inhibition of A2aR.
Name: NIR178
Name: PDR001
Description: Response assessed by RECIST v1.1 (for solid tumors) or Cheson (for DLBCL)
Measure: Determine the overall response rate Time: Every 8 weeks for first 40 weeksDescription: Response assessed by RECIST v1.1 (for solid tumors) or Cheson (for DLBCL)
Measure: Determine the overall response rate Time: Every 12 weeks after the first 40 weeks until disease progression or study discontinuation (an average of 6 months)Description: Response assessed by RECIST v1.1 (for solid tumors) or Cheson (for DLBCL)
Measure: Determine the overall response rate Time: BaselineDescription: Proportion of patients with a best overall response of CR or PR or SD
Measure: Determine the disease control rate (DCR) Time: BaselineDescription: Time from first documented response to disease progression
Measure: Determine the duration of response (DoR) Time: BaselineDescription: Time from start of treatment to date of death due to any reason
Measure: Determine the overall survival rate (OR) Time: Every 12 weeks until end of study for at least 24 months from the start date of the study treatmentDescription: Time from start of treatment to date of the first documented progression or death in months
Measure: Progression free survival (PFS) Time: BaselineDescription: Type, frequency, and severity of AEs and SAEs; Frequency of dose interruptions, reductions and discontinuation, Dose intensity
Measure: Safety and tolerability of the NIR178 and PDR001 combination Time: Date of consent to end of study (An average of 24 months)Description: Change from baseline in TILs by immunohistochemistry (IHC) (such as CD8)
Measure: Characterize changes in the immune infiltrate in tumors Time: ScreeningDescription: Presence and/or concentration of anti-PDR001 antibodies
Measure: Presence and/or concentration of anti-PDR001 antibodies Time: Starting from the first dose of study treatment to Cycle 6 Day 1Description: Plasma concentration time profiles of NIR178 and its metabolites
Measure: Pharmacokinetics: Area under plasma concentration versus time curve (AUC) (NIR178) Time: Starting from the first dose of study treatment to Cycle 6 Day 1Description: Plasma concentration time profiles of PDR001
Measure: Pharmacokinetics: Area under the plasma concentration versus time curve (AUC) (PDR001) Time: End of treatment and as needed (an average of 6 months)Description: Plasma concentration time profiles of NIR178
Measure: Plasma concentration Vs Time profiles (NIR178) Time: End of treatment and as needed (an average of 6 months)Description: Plasma concentration time profiles of PDR001
Measure: Plasma concentration Vs Time profiles (PDR001) Time: End of treatment and as needed (an average of 6 months)Description: Plasma concentration time profiles of NIR178
Measure: Peak plasma concentration- Cmax (NIR178) Time: End of treatment and as needed (an average of 6 months)Description: Plasma concentration time profiles of PDR001
Measure: Peak plasma concentration- Cmax (PDR001) Time: End of treatment and as needed (an average of 6 months)Description: Plasma concentration time profiles of NIR178
Measure: Time of maximum concentration observed- Tmax (NIR178) Time: End of treatment and as needed (an average of 6 months)Description: Plasma concentration time profiles of PDR001
Measure: Time of maximum concentration observed- Tmax (PDR001) Time: End of treatment and as needed (an average of 6 months)Description: Proportion of patients with a best overall response of CR or PR or SD
Measure: Determine the disease control rate (DCR) Time: Every 8 weeks for first 40 weeksDescription: Proportion of patients with a best overall response of CR or PR or SD
Measure: Determine the disease control rate (DCR) Time: Every 12 weeks after the first 40 weeks until disease progressionDescription: Time from first documented response to disease progression
Measure: Determine the duration of response (DoR) Time: Until study discontinuation (an average of 6 months)Description: Time from first documented response to disease progression
Measure: Determine the duration of response (DoR) Time: Every 8 weeks for first 40 weeksDescription: Time from start of treatment to date of the first documented progression or death in months
Measure: Progression free survival (PFS) Time: Until study discontinuation (an average of 6 months)Description: Time from start of treatment to date of the first documented progression or death in months
Measure: Progression free survival (PFS) Time: Every 8 weeks for first 40 weeksDescription: Change from baseline in TILs by immunohistochemistry (IHC) (such as CD8)
Measure: Characterize changes in the immune infiltrate in tumors Time: Cycle 6 Day 1Description: Change from baseline in TILs by immunohistochemistry (IHC) (such as CD8)
Measure: Characterize changes in the immune infiltrate in tumors Time: Cycle 1 Day 8Description: Change from baseline in TILs by immunohistochemistry (IHC) (such as CD8)
Measure: Characterize changes in the immune infiltrate in tumors Time: Cycle 3 Day 1Description: Presence and/or concentration of anti-PDR001 antibodies
Measure: Presence and/or concentration of anti-PDR001 antibodies Time: End of treatment and as needed (an average of 6 months)Description: Plasma concentration time profiles of NIR178 and its metabolites
Measure: Pharmacokinetics: Area under plasma concentration versus time curve (AUC) (NIR178) Time: End of treatment and as needed (an average of 6 months)Description: Plasma concentration time profiles of NIR178
Measure: Plasma concentration Vs Time profiles (NIR178) Time: Starting from the first dose of study treatment to Cycle 6 Day 1Description: Plasma concentration time profiles of PDR001
Measure: Plasma concentration Vs Time profiles (PDR001) Time: Starting from the first dose of study treatment to Cycle 6 Day 1Description: Plasma concentration time profiles of NIR178
Measure: Peak plasma concentration- Cmax (NIR178) Time: Starting from the first dose of study treatment to Cycle 6 Day 1Description: Plasma concentration time profiles of PDR001
Measure: Peak plasma concentration- Cmax (PDR001) Time: Starting from the first dose of study treatment to Cycle 6 Day 1Description: Plasma concentration time profiles of NIR178
Measure: Time of maximum concentration observed- Tmax (NIR178) Time: Starting from the first dose of study treatment to Cycle 6 Day 1Description: Plasma concentration time profiles of PDR001
Measure: Time of maximum concentration observed- Tmax (PDR001) Time: Starting from the first dose of study treatment to Cycle 6 Day 1Description: Proportion of patients with a best overall response of CR or PR or SD
Measure: Determine the disease control rate (DCR) Time: Until study discontinuation (an average of 6 months)Description: Proportion of patients with a best overall response of CR or PR or SD
Measure: Determine the duration of response (DoR) Time: Every 12 weeks after the first 40 weeks until disease progressionDescription: Time from start of treatment to date of the first documented progression or death in months
Measure: Progression free survival (PFS) Time: Every 12 weeks after the first 40 weeks until disease progressionAllocation: Non-Randomized
Parallel Assignment
There is one SNP
- Patients with EGFR positive NSCLC with a T790M mutation must have progressed on osimertinib or discontinued due to toxicity. --- T790M ---