A First-in-Human Study of YL217 in Patients With Advanced Solid Tumors

Lead sponsor

MediLink Therapeutics (Suzhou) Co., Ltd. is the lead sponsor of 23 studies on the registry; 18 are open to participants now.

Study arms

• Experimental
  Combo-Dose Escalation,Backfill and Expansion

  Participants will receive YL217 in combination of bevacizumab with or without 5-FU/LV

  Drug: YL217 · Drug: Bevacizumab · Drug: 5-FU with leucovorin

• Experimental
  Mono-Dose Escalation,Backfill and Expansion

  Participants will receive YL217 monotherapy

  Drug: YL217

Interventions

• DrugYL217

  Patients will receive specific dose of YL217 administered via intravenous(IV)infusion.

• DrugBevacizumab

  Participants will receive bevacizumab administered via intravenous(IV) infusion,at 5mg/kg,Q2W.

• Drug5-FU with leucovorin

  Participants will receive 5 fluorouracil 2400mg/m2 and leucovorin 400mg/m2, administered via intravenous (IV) infusion, Q2W

Primary outcomes

1. Nature and frequency of dose-limiting toxicity(DLT)

   The purpose of DLT is to find maximum tolerated dose (MTD).

   Time frame: Up to approximately 3 years

2. Nature and frequency of adverse events (AEs) with severity

   Nature and frequency of AEs with severity is aim to evaluate the safety of YL217.

   Time frame: Up to approximately 3 years

3. objective response rate (ORR)

   ORR: defined as the proportion of patients who achieved a best overall response of complete response (CR) or partial response (PR).

   Time frame: Up to approximately 3 years

Secondary outcomes

1. Eastern Cooperative Oncology Group performance status (ECOG PS)

   Deterioration of Eastern Cooperative Oncology Group performance status (ECOG PS)

   Time frame: Up to approximately 3 years

2. To evaluate safety endpoint of peripheral oxygen saturation (SpO2)

   Time frame: Up to approximately 3 years

3. Characterize Pharmacokinetics(PK) parameter AUC

   The area under curve: AUC is the total amount of YL217 in bloodstream after drug administration.

   Time frame: Up to approximately 3 years

4. Characterize Pharmacokinetics(PK) parameter Cmax

   Maximum concentration：The highest measured concentration of YL217 in the bloodstream.

   Time frame: Up to approximately 3 years

5. Characterize Pharmacokinetics(PK) parameter Ctrough

   Trough concentration

   Time frame: Up to approximately 3 years

6. Characterize Pharmacokinetics(PK) parameter Tmax

   Time to maximum observed concentration

   Time frame: Up to approximately 3 years

7. Characterize Pharmacokinetics(PK) parameter CL

   Clearance： defined as the amount of drug removed from the bloodstream by the body per unit of time.

   Time frame: Up to approximately 3 years

8. Characterize Pharmacokinetics(PK) parameter Vd

   volume of distribution

   Time frame: Up to approximately 3 years

9. Characterize Pharmacokinetics(PK) parameter t1/2

   Half-life time：defined as the time it takes for the concentration of the drug in plasma or serum to be reduced by 50%.

   Time frame: Up to approximately 3 years

10. Immunogenicity endpoint: Incidence of anti-YL217 antibody (ADAs).

    The presence of ADAs in patients treated with YL217 will be assessed to evaluate immunogenicity.

    Time frame: Up to approximately 3 years

11. Disease control rate (DCR)

    DCR: defined as the proportion of patients who achieved a best overall response of complete response (CR), partial response (PR) or stable disease (SD).

    Time frame: Up to approximately 3 years

12. Duration of response (DoR)

    DoR: defined as the time interval from the date of the first documentation of objective response (CR or PR) to the date of the first documentation of progressive disease (PD).

    Time frame: Up to approximately 3 years

13. Time to response (TTR)

    TTR: defined as the time interval from the date of the first dose of study drug to the date of the first documentation of objective response (CR or PR).

    Time frame: Up to approximately 3 years

14. Depth of response (DpR)

    DpR: defined as the proportion of target lesion shrinkage from baseline to maximum tumor size.

    Time frame: Up to approximately 3 years

15. Progression-free survival (PFS)

    PFS: defined as the time interval from the date of the first dose of study drug to the date of first documentation of PD or death due to any cause, whichever occurs first.

    Time frame: Up to approximately 3 years

16. Overall survival (OS)

    OS: defined as the time interval from the date of the first dose of study drug to the date of death due to any cause.

    Time frame: Up to approximately 3 years

Individual participant data

Plan to share: No