Antineoplastic Agents

All Drugs and Chemicals

Irinotecan

Fluorouracil

Antimetabolites

Immunosuppressive Agents

Immunologic Factors

Topoisomerase I Inhibitors

Enzyme Inhibitors

The starting dose was 30 mg/m2 IV and the subsequent dose was increased according to the protocol of 60 mg/m2, 90 mg/m2, 120 mg/m2, 150 mg/m2, 180mg/m2. The interval between the first dose and the second dose was 3 weeks, followed by 2 weeks.

According to the subjects' tolerance, appropriate dose will be selected and the safety, PK characteristics and initial efficacy of LY01610 were further evaluated in 6 - 8 patients. The interval between the first dose and the second dose was 3 weeks, followed by 2 weeks.

Dose Escalation:

Based on the results of the first stage, three doses of low, medium and high doses were selected in combination with a fixed dose of 5-Fu to determine the DLT, MTD, PK characteristics and the preliminary efficacy. 5-Fu, 400mg/m2 will be administered intravenously on days 1, followed by 600 mg/m2 given as a 22-hour continuous infusion on day 1 and 2, every 2 weeks.

Similarly, according to the subjects' tolerance, appropriate dose will be selected and the safety, PK characteristics and initial efficacy of LY01610 combined with a fixed dose of 5-Fu were further evaluated in additional 6 - 8 patients.

In dose escalation and dose extension stages, both LY01610 and fixed dose 5-Fu will be given once every 2 weeks.

After receiving the MTD of LY01610, another 8 subjects were enrolled and given Irinotecan Hydrochloride Injection（captol ®） (180mg/m2) once every 2 weeks. Upon completion of the pharmacokinetics study, the sponsor will continue to provide the study drug treatment free of charge, and the researcher will conduct treatment and examination according to the subject's situation, without collecting any safety and efficacy data of the subject.

Part1-Dose Escalation and Part1-Dose Extension : subjects take LY01610;

LY01610 ( Irinotecan hydrochloride liposome injection )

Part2-Dose Escalation and Part2-Dose Extension : subjects take LY01610 with 5-Fu;

LY01610 ( Irinotecan hydrochloride liposome injection ) with 5-Fu（Fluorouracil Injection）

Irinotecan Hydrochloride Injection（CAMPTO®） pharmacokinetics comparative study

Irinotecan Hydrochloride Injection（CAMPTO®）

Huang jing

This is a Phase I, open-label, non-randomized, dose-escalation study to evaluate the safety and tolerability, the maximum tolerated dose (MTD) and the dose limited toxicity(DLT) of LY01610 monotherapy and combine with 5-Fu in patients with advanced solid tumors. Additionally, the pharmacokinetics and preliminary efficacy of LY01610 monotherapy and combine with 5-Fu will be investigated in this study.

This study will be conducted in two stages: In the first stage, ascending doses of LY01610 will be administered as monotherapy in participants with solid tumors. The starting dose was 30 mg/m2 and the subsequent dose was increased according to the protocol of 60 mg/m2, 90 mg/m2, 120 mg/m2, 150 mg/m2, 180mg/m2. Each subject received only one dose of the drug, and the next dose group study could only be performed if the previous dose group was completed 21 days of observation after the first dose and safe tolerance was confirmed. According to the subjects' tolerance, appropriate doses will be selected and the safety, PK characteristics and initial efficacy of LY01610 were further evaluated in additional 6 - 8 patients. The interval between the first dose and the second dose was 3 weeks, followed by 2 weeks.Another 8 subjects were enrolled and given CAMPTO® (180 mg/m2) once every 2 weeks to perform the pharmacokinetic profiles.

The second stage is a dose escalation study of LY01610 combined with 5-Fu. Based on the results of the first stage, three doses of low, medium and high doses were selected in combination with a fixed dose of 5-Fu to determine the DLT and MTD. Similarly, according to the subjects' tolerance, appropriate dose will be selected and the safety, PK characteristics and initial efficacy of LY01610 combined with a fixed dose of 5-Fu were further evaluated in 6 - 8 patients. The drug was administered every 2 weeks.

Irinotecan Hydrochloride Liposome Injection (LY01610) For Advanced Solid Tumors

PhaseⅠStudy of Irinotecan Hydrochloride Liposome Injection (LY01610) About the Safety, Tolerability, Pharmacokinetics (PK)and Preliminary Efficacy in Patients With Advanced Solid Tumors

The DLT of LY01610 monotherapy was obtained through the dose-increasing study of LY01610

The DLT of combination of LY01610 and 5-fu was obtained through the dose-increasing study of LY01610 and 5-Fu

The MTD of LY01610 monotherapy was obtained through the single-drug dose increase study

The MTD of combination of LY01610 and 5-fu was obtained through the combined dose increase study

The AUC of LY01610 monotherapy was obtained through the dose escalation and extension study，the AUC of active comparator CAMPTO® was obtained through the study，and the AUC of LY01610 combined with 5-fu was obtained through the dose escalation and extension study.

The t1/2 of LY01610 monotherapy was obtained through the dose escalation and extension study，the t1/2 of active comparator CAMPTO® was obtained through the study，and the t1/2 of LY01610 combined with 5-fu was obtained through the dose escalation and extension study.

The Cmax of LY01610 monotherapy was obtained through the dose escalation and extension study，the Cmax of active comparator CAMPTO® was obtained through the study，and the Cmax of LY01610 combined with 5-fu was obtained through the dose escalation and extension study.

The tmax of LY01610 monotherapy was obtained through the dose escalation and extension study，the tmax of active comparator CAMPTO® was obtained through the study，and the tmax of LY01610 combined with 5-fu was obtained through the dose escalation and extension study.

The Vd of LY01610 monotherapy was obtained through the dose escalation and extension study，the Vd of active comparator CAMPTO® was obtained through the study，and the Vd of LY01610 combined with 5-fu was obtained through the dose escalation and extension study.

The CL of LY01610 monotherapy was obtained through the dose escalation and extension study，the CL of active comparator CAMPTO® was obtained through the study，and the CL of LY01610 combined with 5-fu was obtained through the dose escalation and extension study.

The MRT of LY01610 monotherapy was obtained through the dose escalation and extension study，the MRT of active comparator CAMPTO® was obtained through the study，and the MRT of LY01610 combined with 5-fu was obtained through the dose escalation and extension study.

The Kel of LY01610 monotherapy was obtained through the dose escalation and extension study，the Kel of active comparator CAMPTO® was obtained through the study，and the Kel of LY01610 combined with 5-fu was obtained through the dose escalation and extension study.

Preliminary efficacy evaluation of LY01610 and LY01610 combined with 5-fu

Spots Global Cancer Trial Database for ly01610 ( irinotecan hydrochloride liposome injection )