APG-2449 in Patients With Advanced Solid Tumors

NCT03917043 | Recruiting Phase 1

• 1 other identifier: APG2449XC101
• Study Type: interventional
• Target: 165
• Locations: 1 country
• Sites: 9

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.

Conditions

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

Outcome Measures

Primary Outcomes (2)

• Maximum Tolerated Dose (MTD)

  To determine the maximum tolerated dose (MTD) of APG-2449 in subjects with advanced solid tumors

  28 days

• Recommended Phase 2 dose (RP2D)

  To determine the tentative recommended Phase 2 dose (RP2D) of APG-2449 in subjects with advanced solid tumors

  28 days

Secondary Outcomes (4)

• Maximum plasma concentration (Cmax)

  28 days

• Area under the plasma concentration versus time curve (AUC)

  28 days

• Phosphorylation of FAK protein

  28 days

• Preliminary efficacy assessment: Response Evaluation Criteria In Solid Tumors (RECIST) 1.1

  4 weeks

Study Arms (1)

APG-2449

EXPERIMENTAL

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

Interventions

APG-2449 DRUG

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

Also known as: APG-2449 Capsule

APG-2449

Eligibility Criteria

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

You may qualify if:

• 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.
• ECOG Performance Status ≤ 1.
• Expectation of life ≥ 3 months.
• According to RECIST version 1.1, there is at least 1 measurable lesion.
• Adequate hematologic and bone marrow functions.
• Adequate renal and liver function.
• Normal cardiac function.
• Brain metastases with clinically controlled neurologic symptoms.
• Serum pregnancy test results of women of childbearing age were negative within 7 days before taking the first dose of study drug.
• 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
• Ability to understand and willingness to sign a written informed consent form
• Subjects must be willing and able to complete the research procedures and follow-up inspections.
• 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.
• Subjects should provide fresh biopsy tumor tissue specimens prior to treatment.

You may not qualify if:

• 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.
• Receiving TKI therapy within 8 days prior to the first dose of study drug.
• Continuance of toxicities due to prior therapy that do not recover (CTCAE V5.0 Grade\> 1).
• Has difficulty in swallowing, absorbing barrier, or other diseases blocking APG-2449' taken.
• Obvious cardiovascular disease history.
• 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.
• Active symptomatic fungal, bacterial and/or viral infection including, but not limited to, active human immunodeficiency virus (HIV) or viral hepatitis (B or C).
• Known allergies to study drug ingredients or their analogs.
• Female subjects who are pregnant or breastfeeding, or expecting to become pregnant during the study period.
• 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.
• 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.
• Subjects who used CYP3A4 substrates and narrow treatment window 1 week before the first study drug.

Sponsors & Collaborators

• Ascentage Pharma Group Inc.: lead
• Suzhou Yasheng Pharmaceutical Co., Ltd.: collaborator

Study Sites (9)

Beijing Cancer Hospital

Beijing, Beijing Municipality, 100142, China

RECRUITING

Fujian Medical University Union Hospital

Fuzhou, Fujian, 350001, China

NOT YET RECRUITING

Fujian Cancer Hospital

Fuzhou, Fujian, 350014, China

NOT YET RECRUITING

Sun-Yat Sen University Cancer Center

Guangzhou, Guangdong, 510060, China

RECRUITING

The First affiliated hospital, Sun Yat-sen University

Guangzhou, Guangdong, China

RECRUITING

Henan Provincial Oncology Hospital

Zhengzhou, Henan, China

RECRUITING

Union Hospital medical college Huazhong University of Science and Technology

Wuhan, Hubei, China

RECRUITING

Hunan Provincial Oncology Hospital

Changsha, Hunan, China

RECRUITING

Zhejiang Provincial Oncology Hospital

Hangzhou, Zhejiang, China

RECRUITING

Related Publications (2)

• 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.

  PMID: 41146927 DERIVED

• 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.

  PMID: 35820889 DERIVED

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung; Esophageal Neoplasms; Ovarian Neoplasms; Mesothelioma, Malignant

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases; Gastrointestinal Neoplasms; Digestive System Neoplasms; Head and Neck Neoplasms; Digestive System Diseases; Esophageal Diseases; Gastrointestinal Diseases; Endocrine Gland Neoplasms; Ovarian Diseases; Adnexal Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Neoplasms, Female; Urogenital Neoplasms; Genital Diseases; Endocrine System Diseases; Gonadal Disorders; Mesothelioma; Adenoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms, Mesothelial; Pleural Neoplasms

Study Officials

• Li Zhang, Professor

  Sun Yat-sen University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

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

CONTACT

+86-20-28069260; yzhai@ascentage.com

Study Design

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

Model Details: 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.

Study Record Dates

• First Submitted: March 25, 2019
• First Posted: April 16, 2019
• Study Start: May 27, 2019
• Primary Completion (Estimated): December 1, 2027
• Study Completion (Estimated): January 1, 2028
• Last Updated: June 18, 2025

Record last verified: 2025-06

Locations

CN (9)