Primary Outcome Measures: | |
1. |
Dose-limiting toxicity and Maximum tolerated dose [ Time Frame: Approximately 42 Days. ]
Dose-limiting toxicity and Maximum tolerated dose in patients with advanced tumors treated by SHR-1501 combined with SHR-1316. |
2. |
Recommended Phase 2 dose (RP2D) [ Time Frame: Approximately 2 years ]
Recommended Phase 2 dose (RP2D) based on comprehensive evaluation |
3. |
Adverse event/Serious adverse event [ Time Frame: Approximately 2 years ]
Incidence/severity of adverse events/serious adverse events (rated based on CTC AE v5.0) |
Secondary Outcome Measures: | |
1. |
Pharmacokinetic (PK) [ Time Frame: Approximately 2 years ]
Single dose: maximum concentration (Cmax) |
2. |
Pharmacokinetic (PK) [ Time Frame: Approximately 2 years ]
Single dose: time to maximum concentration (Tmax) |
3. |
Pharmacokinetic (PK) [ Time Frame: Approximately 2 years ]
Single dose: areas under the concentration-time curve (AUClast and AUCinf) |
4. |
Pharmacokinetic (PK) [ Time Frame: Approximately 2 years ]
Single dose: half-life (t1/2) |
5. |
Pharmacokinetic (PK) [ Time Frame: Approximately 2 years ]
Single dose: clearance (CL) |
6. |
Pharmacokinetic (PK) [ Time Frame: Approximately 2 years ]
Single dose: mean residence time (MRT) |
7. |
Pharmacokinetic (PK) [ Time Frame: Approximately 2 years ]
Single dose: volume at steady state (Vss) |
8. |
Pharmacokinetic (PK) [ Time Frame: Approximately 2 years ]
Multiple doses (at steady state, if applicable): maximum concentration at steady state (Css_max) |
9. |
Pharmacokinetic (PK) [ Time Frame: Approximately 2 years ]
Multiple doses (at steady state, if applicable): time to maximum concentration (Tss_max) |
10. |
Pharmacokinetic (PK) [ Time Frame: Approximately 2 years ]
Multiple doses (at steady state, if applicable): area under the concentration-time curve at steady state (AUCss) |
11. |
Pharmacokinetic (PK) [ Time Frame: Approximately 2 years ]
Multiple doses (at steady state, if applicable): t1/2 |
12. |
Pharmacokinetic (PK) [ Time Frame: Approximately 2 years ]
Multiple doses (at steady state, if applicable):steady-state minimum concentration at steady state (Css_min) |
13. |
Pharmacokinetic (PK) [ Time Frame: Approximately 2 years ]
Multiple doses (at steady state, if applicable): average concentration at steady state(Css_av) |
14. |
Pharmacokinetic (PK) [ Time Frame: Approximately 2 years ]
Multiple doses (at steady state, if applicable): accumulation ratio (Rac) |
15. |
Immune related features [ Time Frame: Approximately 2 years ]
indicated by the count of CD8+ T-lymphocytes in peripheral blood at scheduled post-dose time points. |
16. |
Immune related features [ Time Frame: Approximately 2 years ]
indicated by the percentage of CD8+ T-lymphocytes in peripheral blood at scheduled post-dose time points. |
17. |
Immune related features [ Time Frame: Approximately 2 years ]
indicated by the count of natural killer (NK) cells in peripheral blood at scheduled post-dose time points. |
18. |
Immune related features [ Time Frame: Approximately 2 years ]
indicated by the percentage of natural killer (NK) cells in peripheral blood at scheduled post-dose time points. |
19. |
Objective response rate [ Time Frame: Approximately 2 years ]
Percentage of participants with CR or PR. |
20. |
Disease control rate [ Time Frame: Approximately 2 years ]
Percentage of participants with CR or PR or SD. |
21. |
Duration of response [ Time Frame: Approximately 2 years ]
Duration of time of tumor remission. |
22. |
progression-free survival [ Time Frame: Approximately 2 years ]
Progression-free survival time. |
23. |
12 months overall survival [ Time Frame: Approximately 2 years ]
12-month survival rate. |
24. |
Durable clinical benefit rate at 6 month [ Time Frame: Approximately 2 years ]
Percentage of participants with CR or PR or SD lasts over six months. |
25. |
Immunogenicity [ Time Frame: Approximately 2 years ]
The immunogenicity of SHR-1501 single drug and the immunogenicity of SHR-1316 combined with SHR-1501. The indicator includes number of participants with anti-drug antibody positive or neutralizing antibody positive. |