APG-2449 in Patients With Advanced Solid Tumors

November 20, 2023 updated by: Ascentage Pharma Group Inc.

A Phase I Study of the Safety, Pharmacokinetic and Pharmacodynamic Properties of Orally Administered APG-2449 in Patients With Advanced Solid Tumors

APG-2449 is a novel, orally active, multi-targeted tyrosine kinase inhibitor, which inhibits FAK, ALK, and ROS1 with nanomolar potencies. In preclinical studies, APG-2449 demonstrated potent antiproliferative activity in various cancer cell lines as a single agent. In combination treatment, APG-2449 enhanced anti-proliferative activities of several chemotherapeutic and targeted agents. It is indicated that APG-2449 may have a broad therapeutic potential for the treatment of human cancer as a single agent and in combination with other classes of anticancer drugs. APG-2449 is intended for the treatment of patients with advanced solid tumors. Upon completion of the Phase 1 dose escalation study to establish the maximum tolerated dose (MTD), dose-limiting toxicities (DLTs), and/or recommended phase 2 dose (RP2D), several phase Ib/II studies will be implemented accordingly.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Estimated)

150

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • China
    • Beijing
      • Beijing, Beijing, China, 100142
        • Recruiting
        • Beijing Cancer Hospital
        • Contact:
        • Contact:
        • Principal Investigator:
          • Jun Zhao, M.D.
        • Principal Investigator:
          • Jian Fang, Ph.D.
    • Fujian
      • Fuzhou, Fujian, China, 350014
        • Not yet recruiting
        • Fujian cancer hospital
        • Contact:
          • Wu Zhuang, Ph.D
        • Principal Investigator:
          • Wu Zhuang, Ph.D
      • Fuzhou, Fujian, China, 350001
        • Not yet recruiting
        • Fujian Medical University Union Hospital
        • Contact:
          • Xiaoyan Lin, Ph.D
        • Principal Investigator:
          • Xiaoyan Lin, Ph.D
    • Guangdong
      • Guangzhou, Guangdong, China, 510060
        • Recruiting
        • Sun-Yat Sen University Cancer Center
        • Contact:
      • Guangzhou, Guangdong, China
        • Recruiting
        • The First Affiliated Hospital, Sun Yat-sen University
        • Contact:
          • Yubiao Guo, Professor
    • Henan
      • Zhengzhou, Henan, China
        • Recruiting
        • Henan Provincial Oncology Hospital
        • Contact:
          • Yanqiu Zhao, Professor
    • Hubei
      • Wuhan, Hubei, China
        • Recruiting
        • Union Hospital medical college Huazhong University of Science and Technology
        • Contact:
          • Gang Wu, Professor
    • Hunan
      • Changsha, Hunan, China
        • Recruiting
        • Hunan Provincial Oncology Hospital
        • Contact:
          • Jianhua Chen, Professor
    • Sichuan
      • Chengdu, Sichuan, China
        • Not yet recruiting
        • West China Hospital of Sichuan University
        • Contact:
          • Youling Gong, Professor
    • Zhejiang
      • Hangzhou, Zhejiang, China
        • Recruiting
        • Zhejiang Provincial Oncology Hospital
        • Contact:
          • Yiping Zhang, Professor

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

16 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  1. Dose exploration stage: non-small cell lung cancer diagnosed by histology and/or cytology and positive for ALK/ROS1 gene fusion (molecular diagnosis confirmed by the investigator) and malignant pleural mesothelioma, esophageal cancer and ovarian cancer. Kind of patients with advanced tumors.

    Expansion stage: cohort one, Patients with non-small cell lung cancer who have progressed or are not tolerated on second-generation ALK TKI therapy or any ROS1 TKI therapy treatment ; cohort two, ALK/ROS1 fusion gene positive without TKI treatment Patients with non-small cell lung cancer. The molecular diagnosis results of the above patients can be confirmed by the investigator.

  2. ECOG Performance Status ≤ 1.
  3. Expectation of life ≥ 3 months.
  4. According to RECIST version 1.1, there is at least 1 measurable lesion.
  5. Adequate hematologic and bone marrow functions.
  6. Adequate renal and liver function.
  7. Normal cardiac function.
  8. Brain metastases with clinically controlled neurologic symptoms.
  9. Serum pregnancy test results of women of childbearing age were negative within 7 days before taking the first dose of study drug.
  10. Men, women of childbearing age (postmenopausal women must have been menopausal for at least 12 months before they can be considered infertile) and their partners voluntarily take the study drug for at least 30 days after signing the informed consent form and taking the study drug as deemed effective by the investigator Contraceptive measures
  11. Ability to understand and willingness to sign a written informed consent form
  12. Subjects must be willing and able to complete the research procedures and follow-up inspections.
  13. Subjects are required to provide fresh (for recurrent subjects only) or archived tumor tissue samples from within 28 days prior to treatment. If none of these specimens are available, they may be included after consultation with the sponsor.

Exclusion Criteria:

  1. Receiving concurrent anti-cancer therapy (chemotherapy, radiotherapy, immunotherapy, biologic therapy); or any investigational therapy within 28 days prior to the first dose of study drug.
  2. Receiving TKI therapy within 8 days prior to the first dose of study drug.
  3. Continuance of toxicities due to prior therapy that do not recover (CTCAE V5.0 Grade> 1).
  4. Has difficulty in swallowing, absorbing barrier, or other diseases blocking APG-2449' taken.
  5. Obvious cardiovascular disease history.
  6. Failure to recover adequately, as judged by the investigator, from prior surgical procedures. Patients who have had major surgery within 28 days from study entry, and patients who have had minor surgery within 14 days of study entry.
  7. Active symptomatic fungal, bacterial and/or viral infection including, but not limited to, active human immunodeficiency virus (HIV) or viral hepatitis (B or C).
  8. Known allergies to study drug ingredients or their analogs.
  9. Female subjects who are pregnant or breastfeeding, or expecting to become pregnant during the study period.
  10. According to the judgment of the investigator or sponsor, any symptoms or disease of the subject may endanger its safety or interfere with the safety assessment of the study drug.
  11. Subjects who have used CYP3A4, CYP2C9, or CYP2C19 moderately potent inhibitors or moderately potent inducers 1 week before receiving the study drug for the first time.
  12. Subjects who used CYP3A4 substrates and narrow treatment window 1 week before the first study drug.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Sequential Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: APG-2449
APG-2449 will be explored sequentially using a standard 3+3 escalation scheme at the dose escalation phase and up to 30-40 patient at the MTD/RP2D dose level.
Drug: APG-2449
Capsule, multiple dose cohorts, oral administration every day (QD) of a 28-day cycle
Other Names:
  • APG-2449 Capsule

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Maximum Tolerated Dose (MTD)
Time Frame: 28 days
To determine the maximum tolerated dose (MTD) of APG-2449 in subjects with advanced solid tumors
28 days
Recommended Phase 2 dose (RP2D)
Time Frame: 28 days
To determine the tentative recommended Phase 2 dose (RP2D) of APG-2449 in subjects with advanced solid tumors
28 days

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Maximum plasma concentration (Cmax)
Time Frame: 28 days
Maximum plasma concentration (Cmax) will be assessed on all participants with APG-2449 treatments
28 days
Area under the plasma concentration versus time curve (AUC)
Time Frame: 28 days
Area under the plasma concentration versus time curve (AUC) will be assessed on all participants with APG-2449 treatments
28 days
Phosphorylation of FAK protein
Time Frame: 28 days
Phosphorylation of FAK protein will be assessed in peripheral blood mononuclear cells on all participants with APG-2449 treatments
28 days
Preliminary efficacy assessment: Response Evaluation Criteria In Solid Tumors (RECIST) 1.1
Time Frame: 4 weeks
To assess preliminary efficacy in subjects with solid tumors using Response Evaluation Criteria In Solid Tumors (RECIST) 1.1
4 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Ascentage Pharma Group Inc.

Collaborators

Suzhou Yasheng Pharmaceutical Co., Ltd.

Investigators

  • Principal Investigator: Li Zhang, Professor, Sun Yat-sen University

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

May 27, 2019

Primary Completion (Estimated)

January 1, 2025

Study Completion (Estimated)

February 1, 2025

Study Registration Dates

First Submitted

March 25, 2019

First Submitted That Met QC Criteria

April 15, 2019

First Posted (Actual)

April 16, 2019

Study Record Updates

Last Update Posted (Estimated)

November 21, 2023

Last Update Submitted That Met QC Criteria

November 20, 2023

Last Verified

November 1, 2023

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • APG2449XC101

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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