This is a multi-center, open-label clinical study with separate Dose Escalation and Expansion Phases to assess preliminary safety, tolerability, and efficacy of ATG-019, a dual inhibitor of PAK4 and NAMPT, alone or co-administered with starting dose of 500 mg niacin ER in patients with advanced solid tumors or non-Hodgkin's lymphoma (NHL).
This is a multi-center, open-label clinical study with separate Dose Escalation and Expansion Phases to assess preliminary safety, tolerability, and efficacy of ATG-019, a dual inhibitor of PAK4 and NAMPT, alone or co-administered with starting dose of 500 mg niacin ER (may be titrated to 1,000 mg of daily dose, per label), in patients with advanced solid tumors or non-Hodgkin's lymphoma (NHL) for which all standard therapeutic options considered useful by the investigator have been exhausted and with PD at study entry. The MTD and RP2D will be determined.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
20
ATG-019 30 mg QoD×3 is selected as the staring dose. Oral ATG-019 will be taken three times a week every other day (Days 1, 3, 5, 8, 10, 12, 15, 17, 19, 22, 24, and 26) during each 28-day cycle.
ATG-019 60 mg is selected as starting dose. Oral ATG-019 will be taken three times a week every other day (Days 1, 3, 5, 8, 10, 12, 15, 17, 19, 22, 24, and 26) during each 28-day cycle. And a starting dose of 500 mg niacin ER (may be titrated up to 1,000 mg of daily dose, per label) co-administered with each dose of ATG-019.
Jiangsu Province Hospital
Nanjing, Jiangsu, China
Fudan University Zhongshan Hospital
Shanghai, Shanghai Municipality, China
Xinhua Hospital Affiliated To Shanghai Jiaotong University School of Medicine
Shanghai, Shanghai Municipality, China
Kaohsiung Medical University Chung-Ho Memorial Hospital (KMUH)
To determine MTD* or RP2D*
MTD will be evaluated using the NCI-CTCAE, Version 5.0; RP2D will be determined by SMC for dose escalation phase.
Time frame: 18 months
To evaluate the Dose-Limiting Toxicity (DLT) for dose escalation phase
DLTs will be evaluated using the CTCAE, Version 5.0 for grading.
Time frame: 18 months
Overall Response Rate (ORR)
ORR analysis will be performed for both study phases by calculating the point estimate of the percentage of patients who have either CR or PR, presented as the number and percentage of patients, including a two-sided 95% CI.
Time frame: 18 months
Peak Plasma Concentration (Cmax)
To determine the maximum plasma concentration (Cmax) for dose escalation phase.
Time frame: 18 months
Time to Reach Cmax (Tmax)
To evaluate the time to reach Cmax after single and multiple doses for dose escalation phase.
Time frame: 18 months
To determine RP2D*
RP2D will be determined by SMC for dose escalation phase.
Time frame: 18 months
Duration of response (DOR)
The duration of time from first meeting CR or PR measurement criteria (whichever occurs first) until the first date that PD recurrence is objectively documented.
Time frame: 18 months
Disease control rate (DCR)
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Kaohsiung City, Taiwan
Kaohsiung Chang Gung Memorial Hospital (CGMHKS)
Kaohsiung City, Taiwan
China Medical University Hospital (CMUH)
Taichang, Taiwan
National Cheng Kung University Hospital (NCKUH)
Tainan, Taiwan
Tri-Service General Hospital (TSGH)
Taipei, Taiwan
The analysis of DCR will be similar to that described for ORR, for patients who achieve CR, PR, or SD for ≥ 8 weeks.
Time frame: 18 months
Progression-free survival (PFS)
The duration of time from date of first dose of study treatment until the first date that PD is objectively documented or death due to any cause.
Time frame: 18 months
Overall Survival (OS)
The duration of time from date of first dose of study treatment until death from any cause.
Time frame: 18 months
Time to progression (TTP)
The duration of time from date of first dose of study treatment to date of PD.
Time frame: 18 months