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APG-2449 in Patients With Advanced Solid Tumors

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ClinicalTrials.gov Identifier: NCT03917043
Recruitment Status : Recruiting
First Posted : April 16, 2019
Last Update Posted : October 19, 2020
Sponsor:
Collaborator:
Suzhou Yasheng Pharmaceutical Co., Ltd
Information provided by (Responsible Party):
Ascentage Pharma Group Inc.

Study Description
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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.

Condition or disease Intervention/treatment Phase
Advanced Solid Cancer Non Small Cell Lung Cancer Esophageal Cancer Ovarian Cancer Malignant Pleural Mesothelioma Drug: APG-2449 Phase 1

Study Design
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 40 participants
Allocation: N/A
Intervention Model: Sequential Assignment
Intervention Model Description: Beginning with 150 mg dose level, and escalating to 300mg, 450mg, 600mg, 750mg, and 900mg dose level sequentially under "3+3" design
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase I Study of the Safety, Pharmacokinetic and Pharmacodynamic Properties of Orally Administered APG-2449 in Patients With Advanced Solid Tumors
Actual Study Start Date : May 27, 2019
Estimated Primary Completion Date : May 2021
Estimated Study Completion Date : May 2022

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Arms and Interventions
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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 15 patient at the MTD dose level.
 Drug: APG-2449
Capsule, multiple dose cohorts, oral administration every day (QD) of a 28-day cycle
Other Name: APG-2449 Capsule


Outcome Measures
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Primary Outcome Measures :
  1. Maximum Tolerated Dose (MTD) [ Time Frame: 28 days ]
    To determine the maximum tolerated dose (MTD) of APG-2449 in subjects with advanced solid tumors

  2. 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


Secondary Outcome Measures :
  1. Maximum plasma concentration (Cmax) [ Time Frame: 28 days ]
    Maximum plasma concentration (Cmax) will be assessed on all participants with APG-2449 treatments

  2. 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

  3. 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

  4. 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


Eligibility Criteria
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Ages Eligible for Study:   18 Years to 75 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03917043


Contacts
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Contact: Yifan Zhai, M.D., Ph.D. +86-20-28069260 yzhai@ascentagepharma.com

Locations
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China, Guangdong
Sun-Yat Sen University Cancer Center Recruiting
Guangzhou, Guangdong, China, 510060
Contact: LI ZHANG, Professor    +86-20-87343560    Zhangli@sysucc.cn   
Sponsors and Collaborators
Ascentage Pharma Group Inc.
Suzhou Yasheng Pharmaceutical Co., Ltd
Investigators
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Principal Investigator: Li Zhang, Professor Sun Yat-sen University
More Information
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Responsible Party: Ascentage Pharma Group Inc.
ClinicalTrials.gov Identifier: NCT03917043    
Other Study ID Numbers: APG2449XC101
First Posted: April 16, 2019    Key Record Dates
Last Update Posted: October 19, 2020
Last Verified: October 2020

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Mesothelioma
Neoplasms
Adenoma
 Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms, Mesothelial