This is a Phase I, open-label, repeat-dose, non-randomized, multicenter study to evaluate the safety, tolerability, and preliminary clinical activity and establish a recommended dose of HG146 administered orally (PO) alone (Part 1) or co-administered (Part 2) with PD-(L)1 inhibitor in subjects with refractory/relapsed solid tumors or Lymphoma. Part 1 consists of a dose escalation phae,Part2 consists of a dose escalation phase and a cohort expansion phase. In Part 1, escalating doses of HG146 will be evaluated as guided by the "3+3" approach. In Part 2A, escalating doses of HG146 in combination with PD-(L)1 inhibitor will be evaluated as guided by the "3+3" approach. In Part 2B, subjects will receive a single dose level of HG146 as identified based on data from Part 2, in combination with PD-(L)1 inhibitor . A total of approximately 96 subjects will be enrolled in this study, approximately 36 for dose escalation cohorts, and approximately 60 in the expansion cohorts.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
24
HG146 is available as Capsule at a unit dose strength of 5 mg and 10 mg.
PD-(L)1 Antibody is available as solution for infusion or lyophilized powder for reconstitution to be administered Q3W. It will be administered as an IV infusion for 30 minutes.
National Cancer Center/Cancer Hospital
Beijing, China
Part I:Dose-Limiting Toxicities (DLTs)
Number of participants experiencing Dose-Limiting Toxicities (DLTs) According to National Cancer Institute Common Terminology Criteria for Adverse Events Version 5.0 (NCI-CTCAE V5.0)
Time frame: Up to 26 Days in Cycle 0 and Cycle 1
Part I:Serious Adverse Events (SAEs) and Adverse Events (AE)
Number of participants experiencing Serious Adverse Events (SAEs) and Adverse Events (AE) According to Safety performance.
Time frame: Up to 2 years
Part I:Maximum tolerated dose or Recommended Phase Ib dose (RP2D) of HG146
Maximum tolerated dose or Recommended Phase II dose of HG146 will be decided according to safety and effective results.
Time frame: Up to 2 years
Part 2A: Dose-Limiting Toxicities (DLTs) According to National Cancer Institute Common Terminology Criteria for Adverse Events Version 5.0 (NCI-CTCAE v.5.0)
Number of participants experiencing Dose-Limiting Toxicities (DLTs) According to National Cancer Institute Common Terminology Criteria for Adverse Events Version 5.0 (NCI-CTCAE V5.0)
Time frame: Up to 21 Days in Cycle 1
Part 2A: Serious Adverse Events (SAEs) and Adverse Events (AE)
Number of participants experiencing Serious Adverse Events (SAEs) and Adverse Events (AE) According to Safety performance.
Time frame: Up to 2 years
Part 2A:Maximum tolerated dose or Recommended Phase II dose (RP2D) of HG146 in combination with PD-(L)1 antibody
Maximum tolerated dose or Recommended Phase II dose of HG146 will be decided according to safety and effective results.
Time frame: Up to 2 years
Part 1:Area under the concentration versus time curve (AUC) of HG146
Plasma concentration of HG146 will be measured following single dose and multiple dose administration
Time frame: At the end of Cycle 0 Day 5 (Cycle 0 is 5 days);At the end of Cycle 1 Day15 (Except for cycle 0, each cycle is 21 days)
Part 1:Peak plasma concentration (Cmax) of HG146
Plasma concentration of HG146 will be measured following single dose and multiple dose administration
Time frame: At the end of Cycle 0 Day 5 (Cycle 0 is 5 days);At the end of Cycle 1 Day15 (Except for cycle 0, each cycle is 21 days)
Part 1:Time of Cmax (Tmax) of HG146
Plasma concentration of HG146 will be measured following single dose and multiple dose administration
Time frame: At the end of Cycle 0 Day 5 (Cycle 0 is 5 days);At the end of Cycle 1 Day15(Except for cycle 0, each cycle is 21 days)
Part 1:Apparent terminal half-life (T1/2) of HG146
Plasma concentration of HG146 will be measured following single dose and multiple dose administration
Time frame: At the end of Cycle 0 Day 5 (Cycle 0 is 5 days);At the end of Cycle 1 Day15 (Except for cycle 0, each cycle is 21 days)
Part1: objective response rate (ORR)
ORR will be assessed by the Investigators using RECIST v. 1.1 or Lugano 2014( If applicable)
Time frame: Up to 2 years
Part1: Best overall response (BOR)
BOR will be assessed by the Investigators using RECIST v. 1.1 or Lugano 2014( If applicable)
Time frame: Up to 2 years
Part1: Duration of response (DOR)
DOR will be assessed by the Investigators using RECIST v. 1.1 or Lugano 2014( If applicable)
Time frame: Up to 2 years
Part 1:Time-to-response (TTR)
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.
TTR will be assessed by the Investigators using RECIST v. 1.1 or Lugano 2014( If applicable)
Time frame: Up to 2 years
Part 1:Progression-Free Survival (PFS)
PFS will be assessed by the Investigators using RECIST v. 1.1 or Lugano 2014( If applicable)
Time frame: Up to 2 years
Part 2:Area under the concentration versus time curve (AUC) of HG146
Plasma concentration of HG146 will be measured following multiple dose administration in combination with PD-(L)1 antibody
Time frame: At the end of Cycle 1 Day 15 (each cycle is 21 days)
Part 2:maximum observed plasma concentration (Cmax) of HG146
Plasma concentration of HG146 will be measured following multiple dose administration in combination with PD-(L)1 antibody
Time frame: At the end of Cycle 1 Day 15 (each cycle is 21 days)
Part 2:time of maximum observed plasma concentration (Tmax) of HG146
Plasma concentration of HG146 will be measured following multiple dose administration in combination with PD-(L)1 antibody
Time frame: At the end of Cycle 1 Day 15 (each cycle is 21 days)
Part 2:apparent terminal half-life (T1/2) of HG146
Plasma concentration of HG146 will be measured following multiple dose administration in combination with PD-(L)1 antibody
Time frame: At the end of Cycle 1 Day 15 (each cycle is 21 days)
Part2: objective response rate (ORR)
ORR will be assessed by the Investigators using RECIST v. 1.1 or Lugano 2014( If applicable)
Time frame: Up to 2 years
Part2: Best overall response (BOR)
BOR will be assessed by the Investigators using RECIST v. 1.1 or Lugano 2014( If applicable)
Time frame: Up to 2 years
Part2: Duration of response (DOR)
DOR will be assessed by the Investigators using RECIST v. 1.1 or Lugano 2014( If applicable)
Time frame: Up to 2 years
Part 2:Time-to-response (TTR)
TTR will be assessed by the Investigators using RECIST v. 1.1 or Lugano 2014( If applicable)
Time frame: Up to 2 years
Part 2:Progression-Free Survival (PFS)
PFS will be assessed by the Investigators using RECIST v. 1.1 or Lugano 2014( If applicable)
Time frame: Up to 2 years
Overall survival (OS)
OS will be assessed by the investigators
Time frame: Up to 2 years