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

NCT04281420 | Terminated Phase 1

• 1 other identifier: ATG-019-STL-001
• Study Type: interventional
• Target: 20
• Locations: 2 countries
• Sites: 8

Brief Summary

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).

Conditions

Solid Tumor, Non-Hodgkin's Lymphoma

Outcome Measures

Primary Outcomes (3)

• 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 Outcomes (8)

• Peak Plasma Concentration (Cmax)

  18 months

• Time to Reach Cmax （Tmax）

  18 months

• To determine RP2D*

  18 months

• Duration of response (DOR)

  18 months

• Disease control rate (DCR)

  18 months

Study Arms (2)

ATG-019 Alone

EXPERIMENTAL

A starting does of 30 mg QoD×3 ATG-019

Drug: ATG-019

ATG-019 + Niacin ER

EXPERIMENTAL

A starting dose of 60 mg ATG-019 and 500 mg niacin ER

Combination Product: ATG-019 + Niacin ER

Interventions

ATG-019 DRUG

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.

Also known as: KPT-9274

ATG-019 Alone

ATG-019 + Niacin ER COMBINATION_PRODUCT

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.

ATG-019 + Niacin ER

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Written informed consent obtained prior to any screening procedures and in accordance with local and institutional guidelines.
• Age ≥18 years.
• 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.
• Patients must have objective evidence of PD on study entry:
• Advanced solid tumors: Measureable disease as defined by RECIST 1.11.
• NHL: Measureable disease including target lesion(s) as defined by the Cheson 2014 Classification2 for initial evaluation and staging.
• Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 1.
• Adequate hepatic function.
• Adequate renal function.
• Life expectancy of ≥ 3 months.
• Adequate hematopoietic function.
• 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.

You may not qualify if:

• Female patients who are pregnant or lactating.
• Time since the last prior therapy for treatment of advanced solid tumors or NHL\*\*:
• Radiation, chemotherapy, immunotherapy or any other anticancer therapy, including investigational anti-cancer therapy ≤ 4 weeks prior to C1D1.
• Palliative steroids for disease related symptoms within 7 days prior to C1D1.
• Known central nervous system metastases.
• Major surgery within 4 weeks before C1D1.
• Impaired cardiac function or clinically significant cardiac diseases.
• Active infection with completion of therapeutic antibiotics, antivirals, or antifungals within 1 week prior to C1D1.
• Patients diagnosed with tuberculosis and had received treatment.
• Patients with a known history of human immunodeficiency virus (HIV).
• Known, active hepatitis A, B, or C infection.
• Serious psychiatric or medical conditions that, in the opinion of the Investigator, could interfere with treatment, compliance, or the ability to give consent.

Sponsors & Collaborators

• Antengene Therapeutics Limited: lead

Study Sites (8)

Jiangsu Province Hospital

Nanjing, Jiangsu, 210029, China

Location

Fudan University Zhongshan Hospital

Shanghai, Shanghai Municipality, 200032, China

Location

Xinhua Hospital Affiliated To Shanghai Jiaotong University School of Medicine

Shanghai, Shanghai Municipality, 200092, China

Location

Kaohsiung Medical University Chung-Ho Memorial Hospital (KMUH)

Kaohsiung City, 807, Taiwan

Location

Kaohsiung Chang Gung Memorial Hospital (CGMHKS)

Kaohsiung City, 83301, Taiwan

Location

China Medical University Hospital (CMUH)

Taichang, 40447, Taiwan

Location

National Cheng Kung University Hospital (NCKUH)

Tainan, 70457, Taiwan

Location

Tri-Service General Hospital (TSGH)

Taipei, 114, Taiwan

Location

MeSH Terms

Conditions

Lymphoma, Non-Hodgkin

Interventions

KPT-9274

Condition Hierarchy (Ancestors)

Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Study Officials

• Stephen Xie, MD; PhD

  Medical Monitor

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: ATG-019 ATG-019+Niacin ER

Study Record Dates

• First Submitted: February 18, 2020
• First Posted: February 24, 2020
• Study Start: April 13, 2020
• Primary Completion: October 2, 2023
• Study Completion: October 2, 2023
• Last Updated: April 30, 2024

Record last verified: 2022-07

Locations

CN (3); TW (5)