A Study of Evaluating Dual Inhibitor of PAK4 and NAMPT ATG-019 in Advanced Solid Tumors or Non-Hodgkin's Lymphoma (TEACH)

A Phase I Open-Label Study of the Safety and Tolerability of ATG-019, a Dual Inhibitor of PAK4 and NAMPT, in Patients With Advanced Solid Tumors or Non-Hodgkin's Lymphoma

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).

Study Overview

• Status: Terminated
• Conditions: Solid Tumor, Non-Hodgkin's Lymphoma
• Intervention / Treatment: Drug: ATG-019; Combination product: ATG-019 + Niacin ER

Detailed Description

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
• Enrollment (Actual): 20
• Phase: Phase 1

Contacts and Locations

Study Locations

• China
  • Jiangsu
    • Nanjing, Jiangsu, China, 210029
      • Jiangsu Province Hospital
  • Shanghai
    • Shanghai, Shanghai, China, 200092
      • Xinhua Hospital Affiliated to Shanghai Jiaotong University School of Medicine
    • Shanghai, Shanghai, China, 200032
      • Fudan University Zhongshan Hospital
• Taiwan
  • Kaohsiung, Taiwan, 807
    • Kaohsiung Medical University Chung-Ho Memorial Hospital (KMUH)
  • Kaohsiung, Taiwan, 83301
    • Kaohsiung Chang Gung Memorial Hospital (CGMHKS)
  • Taichang, Taiwan, 40447
    • China Medical University Hospital (CMUH)
  • Tainan, Taiwan, 70457
    • National Cheng Kung University Hospital (NCKUH)
  • Taipei, Taiwan, 114
    • Tri-Service General Hospital (TSGH)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Written informed consent obtained prior to any screening procedures and in accordance with local and institutional guidelines.
2. Age ≥18 years.
3. Patients with histologically or cytologically confirmed, NHL or advanced solid tumors which have progressed despite standard therapy, for whom no standard therapy exists, or who have refused standard therapy.

4. Patients must have objective evidence of PD on study entry:

   1. Advanced solid tumors: Measureable disease as defined by RECIST 1.11.
   2. NHL: Measureable disease including target lesion(s) as defined by the Cheson 2014 Classification2 for initial evaluation and staging.
5. Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 1.
6. Adequate hepatic function.
7. Adequate renal function.
8. Life expectancy of ≥ 3 months.
9. Adequate hematopoietic function.
10. Female patients of child-bearing potential must agree to use dual methods of contraception (including one highly effective and one effective method of contraception) and have a negative serum pregnancy test at Screening, and male patients must use an effective barrier method of contraception if sexually active with a female of child-bearing potential.

Exclusion Criteria:

1. Female patients who are pregnant or lactating.

2. Time since the last prior therapy for treatment of advanced solid tumors or NHL**:

   1. Radiation, chemotherapy, immunotherapy or any other anticancer therapy, including investigational anti-cancer therapy ≤ 4 weeks prior to C1D1.
   2. Palliative steroids for disease related symptoms within 7 days prior to C1D1.
3. Known central nervous system metastases.
4. Major surgery within 4 weeks before C1D1.
5. Impaired cardiac function or clinically significant cardiac diseases.
6. Active infection with completion of therapeutic antibiotics, antivirals, or antifungals within 1 week prior to C1D1.
7. Patients diagnosed with tuberculosis and had received treatment.
8. Patients with a known history of human immunodeficiency virus (HIV).
9. Known, active hepatitis A, B, or C infection.
10. Serious psychiatric or medical conditions that, in the opinion of the Investigator, could interfere with treatment, compliance, or the ability to give consent.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: ATG-019 Alone; A starting does of 30 mg QoD×3 ATG-019	Drug: ATG-019; 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.; Other Names: KPT-9274
Experimental: ATG-019 + Niacin ER; A starting dose of 60 mg ATG-019 and 500 mg niacin ER	Combination product: ATG-019 + Niacin ER; 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	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.	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.	18 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Peak Plasma Concentration (Cmax)	To determine the maximum plasma concentration (Cmax) for dose escalation phase.	18 months
Time to Reach Cmax （Tmax）	To evaluate the time to reach Cmax after single and multiple doses for dose escalation phase.	18 months
To determine RP2D*	RP2D will be determined by SMC for dose escalation phase.	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.	18 months
Disease control rate (DCR)	The analysis of DCR will be similar to that described for ORR, for patients who achieve CR, PR, or SD for ≥ 8 weeks.	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.	18 months
Overall Survival (OS)	The duration of time from date of first dose of study treatment until death from any cause.	18 months
Time to progression (TTP)	The duration of time from date of first dose of study treatment to date of PD.	18 months

Collaborators and Investigators

• Sponsor: Antengene Therapeutics Limited
• Investigators: Study Director: Stephen Xie, MD; PhD, Medical Monitor

Study record dates

Study Major Dates

• Study Start (Actual): April 13, 2020
• Primary Completion (Actual): October 2, 2023
• Study Completion (Actual): October 2, 2023

Study Registration Dates

• First Submitted: February 18, 2020
• First Submitted That Met QC Criteria: February 21, 2020
• First Posted (Actual): February 24, 2020

Study Record Updates

• Last Update Posted (Actual): April 30, 2024
• Last Update Submitted That Met QC Criteria: April 27, 2024
• Last Verified: July 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Lymphoma; Lymphoma, Non-Hodgkin; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Vasodilator Agents; Antimetabolites; Micronutrients; Hypolipidemic Agents; Lipid Regulating Agents; Vitamins; Vitamin B Complex; Niacin
• Other Study ID Numbers: ATG-019-STL-001

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No