APG-2449 in Patients With Advanced Solid Tumors

Brief Title

APG-2449 in Patients With Advanced Solid Tumors

Official Title

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

Brief Summary

      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 Phase

Phase 1

Study Type

Interventional

Primary Outcome

Maximum Tolerated Dose (MTD)

Secondary Outcome

 Maximum plasma concentration (Cmax)

Condition

Advanced Solid Cancer

Intervention

APG-2449

Study Arms / Comparison Groups

 APG-2449

Description:  APG-2449 will be explored sequentially using a standard 3+3 escalation scheme at the dose escalation phase and up to 15 patient at the MTD dose level.

Publications

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Status

Drug

Estimated Enrollment

40

Start Date

May 27, 2019

Completion Date

May 2022

Primary Completion Date

May 2021

Eligibility Criteria

        Inclusion Criteria:

          1. Histologically or cytologically confirmed advanced solid tumors that has relapsed from
             or is refractory to standard treatment, including NSCLC, malignant pleural
             mesothelioma, esophageal cancer, ovarian cancer, et al.

          2. ECOG Performance Status ≤ 1.

          3. Expectation of life ≥ 3 months.

          4. Adequate hematologic and bone marrow functions.

          5. Adequate renal and liver function.

          6. Normal cardiac function.

          7. Brain metastases with clinically controlled neurologic symptoms.

          8. Ability to understand and willingness to sign a written informed consent form.

          9. Willingness to provide tumor samples for testing FAK and p-FAK expression.

        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 14 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. History of SAE due to prior TKI therapy.

          7. 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.

          8. Active symptomatic fungal, bacterial and/or viral infection including, but not limited
             to, active human immunodeficiency virus (HIV) or viral hepatitis (B or C).

          9. Any other condition or circumstance of that would, in the opinion of the investigator,
             make the patient unsuitable for participation in the study.

         10. Receiving inhibitors or inducers of CYP3A4, CYP2C9 or CYP2C19 within 7 days prior to
             the first dose of study drug or during the study.

         11. Receiving substrates of CYP3A4 with narrow therapy window within 7 days prior to the
             first dose of study drug or during the study.
      

Gender

All

Ages

18 Years - 75 Years

Accepts Healthy Volunteers

No

Contacts

Li Zhang, Professor, +86-20-28069260, [email protected]

Location Countries

China

Location Countries

China

NCT ID

NCT03917043

Organization ID

APG2449XC101

Responsible Party

Sponsor

Study Sponsor

Ascentage Pharma Group Inc.

Collaborators

 Suzhou Yasheng Pharmaceutical Co., Ltd

Study Sponsor

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

Verification Date

October 2020