APG-2449 in Patients With Advanced Solid Tumors

NCT ID: NCT03917043

Last Updated: 2025-06-18

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE1

Total Enrollment

165 participants

Study Classification

INTERVENTIONAL

Study Start Date

2019-05-27

Study Completion Date

2028-01-31

Brief Summary

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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.

Detailed Description

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Conditions

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Advanced Solid Cancer Non Small Cell Lung Cancer Esophageal Cancer Ovarian Cancer Malignant Pleural Mesothelioma

Study Design

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Allocation Method

NA

Intervention Model

SEQUENTIAL

Dose escalation of APG-2449 will use standard 3+3 design. The starting dose is 150 mg and will be increased in subsequent cohorts to 300mg, 450mg, 600mg, 750mg, 900mg, 1200mg and 1500mg, accordingly.
Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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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.

Group Type EXPERIMENTAL

APG-2449

Intervention Type DRUG

Capsule, multiple dose cohorts, oral administration every day (QD) of a 28-day cycle

Interventions

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APG-2449

Capsule, multiple dose cohorts, oral administration every day (QD) of a 28-day cycle

Intervention Type DRUG

Other Intervention Names

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APG-2449 Capsule

Eligibility Criteria

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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 1, patients with non-small cell lung cancer who have progressed or are intolerant to TKI therapy, including patients with second-generation ALK TKI, or either ROS1 TKI, or third-generation ALK inhibitor (lorlatinib, etc.) with pFAK expression (pFAK expression is subject to central laboratory results) of about 10 or above; Cohort 2, TKI-naïve patients with ALK/ROS1 fusion gene positive NSCLC. 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.
14. Subjects should provide fresh biopsy tumor tissue specimens prior to treatment.

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.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Suzhou Yasheng Pharmaceutical Co., Ltd.

INDUSTRY

Sponsor Role collaborator

Ascentage Pharma Group Inc.

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Li Zhang, Professor

Role: PRINCIPAL_INVESTIGATOR

Sun Yat-sen University

Locations

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Beijing Cancer Hospital

Beijing, Beijing Municipality, China

Site Status RECRUITING

Fujian Medical University Union Hospital

Fuzhou, Fujian, China

Site Status NOT_YET_RECRUITING

Fujian Cancer Hospital

Fuzhou, Fujian, China

Site Status NOT_YET_RECRUITING

Sun-Yat Sen University Cancer Center

Guangzhou, Guangdong, China

Site Status RECRUITING

The First affiliated hospital, Sun Yat-sen University

Guangzhou, Guangdong, China

Site Status RECRUITING

Henan Provincial Oncology Hospital

Zhengzhou, Henan, China

Site Status RECRUITING

Union Hospital medical college Huazhong University of Science and Technology

Wuhan, Hubei, China

Site Status RECRUITING

Hunan Provincial Oncology Hospital

Changsha, Hunan, China

Site Status RECRUITING

Zhejiang Provincial Oncology Hospital

Hangzhou, Zhejiang, China

Site Status RECRUITING

Countries

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China

Central Contacts

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Yifan Zhai, M.D., Ph.D.

Role: CONTACT

+86-20-28069260

Facility Contacts

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Jun Zhao, M.D.

Role: primary

Jian Fang, Ph.D.

Role: backup

Xiaoyan Lin, Ph.D

Role: primary

Wu Zhuang, Ph.D

Role: primary

LI ZHANG, Professor

Role: primary

+86-20-87343560

Yubiao Guo, Professor

Role: primary

Yanqiu Zhao, Professor

Role: primary

Gang Wu, Professor

Role: primary

Jianhua Chen, Professor

Role: primary

Yiping Zhang, Professor

Role: primary

References

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Ma Y, Song Z, Chen J, Zhao Y, Fang W, Guo Y, Dong Y, Yang Y, Wu G, Fang J, Lin X, Li J, Huang Y, Zhao Y, Hong S, Xue J, Zhang Y, Liu Q, Yang C, Xu L, Yang Y, Xiong D, Yang D, Zhai Y, Zhang L, Zhao H. Safety, pharmacokinetic, pharmacodynamic, and efficacy properties of orally administered APG-2449 in patients with advanced ALK + and ROS1 + non-small-cell lung cancer: a multicentre, open-label, single-arm phase 1 trial. EClinicalMedicine. 2025 Oct 16;89:103556. doi: 10.1016/j.eclinm.2025.103556. eCollection 2025 Nov.

Reference Type DERIVED
PMID: 41146927 (View on PubMed)

Fang DD, Tao R, Wang G, Li Y, Zhang K, Xu C, Zhai G, Wang Q, Wang J, Tang C, Min P, Xiong D, Chen J, Wang S, Yang D, Zhai Y. Discovery of a novel ALK/ROS1/FAK inhibitor, APG-2449, in preclinical non-small cell lung cancer and ovarian cancer models. BMC Cancer. 2022 Jul 11;22(1):752. doi: 10.1186/s12885-022-09799-4.

Reference Type DERIVED
PMID: 35820889 (View on PubMed)

Other Identifiers

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APG2449XC101

Identifier Type: -

Identifier Source: org_study_id

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