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Advanced Solid CancerPhase 1NCT03917043

APG-2449 in Patients With Advanced Solid Tumors

A Phase 1 study testing APG-2449 in people with Advanced Solid Cancer and Non Small Cell Lung Cancer, run by Ascentage Pharma Group Inc. at 9 sites in China.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
APG-2449
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
165 participants
Where
9 sitesChina
Study dates
27 May 2019to Jan 2028
Phase
Phase 1
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.
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  • 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.

Who cannot join

  • 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.
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  • 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.

Trial locations and contacts

9 sites in 1 country. Contact the study team or a site near you to ask about taking part.

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

+86-20-28069260

yzhai@ascentage.com

9 sites in 1 country

China9 sites, 9 recruiting

  • Beijing Cancer Hospital

    Beijing, Beijing Municipality, 100142

    Jun Zhao, M.D., ohjerry@163.com

    Jian Fang, Ph.D., fangjian5555@163.com

    Recruiting

  • Hunan Provincial Oncology Hospital

    Changsha, Hunan

    Jianhua Chen, Professor

    Recruiting

  • Fujian Medical University Union Hospital

    Fuzhou, Fujian, 350001

    Xiaoyan Lin, Ph.D

    Xiaoyan Lin, Ph.D

    Not yet recruiting

  • Fujian Cancer Hospital

    Fuzhou, Fujian, 350014

    Wu Zhuang, Ph.D

    Wu Zhuang, Ph.D

    Not yet recruiting

  • Sun-Yat Sen University Cancer Center

    Guangzhou, Guangdong, 510060

    LI ZHANG, Professor, +86-20-87343560, Zhangli@sysucc.cn

    Recruiting

  • The First affiliated hospital, Sun Yat-sen University

    Guangzhou, Guangdong

    Yubiao Guo, Professor

    Recruiting

  • Zhejiang Provincial Oncology Hospital

    Hangzhou, Zhejiang

    Yiping Zhang, Professor

    Recruiting

  • Union Hospital medical college Huazhong University of Science and Technology

    Wuhan, Hubei

    Gang Wu, Professor

    Recruiting

  • Henan Provincial Oncology Hospital

    Zhengzhou, Henan

    Yanqiu Zhao, Professor

    Recruiting

Other trials in China

About this study

Official title: 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.

Being tested
APG-2449
Medical subject headings
Carcinoma, Non-Small-Cell Lung, Esophageal Neoplasms, Ovarian Neoplasms, Mesothelioma, Malignant

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • APG-2449Drug

    Also called APG-2449 Capsule

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

Study groups in NCT03917043
Study groupRoleWhat they receive
APG-2449ExperimentalAPG-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.
Receives: Drug: APG-2449

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Maximum Tolerated Dose (MTD)

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

    Measured: 28 days

  2. Recommended Phase 2 dose (RP2D)

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

    Measured: 28 days

Secondary outcomes (4)

  1. Maximum plasma concentration (Cmax)

    Maximum plasma concentration (Cmax) will be assessed on all participants with APG-2449 treatments

    Measured: 28 days

  2. Area under the plasma concentration versus time curve (AUC)

    Area under the plasma concentration versus time curve (AUC) will be assessed on all participants with APG-2449 treatments

    Measured: 28 days

  3. Phosphorylation of FAK protein

    Phosphorylation of FAK protein will be assessed in peripheral blood mononuclear cells on all participants with APG-2449 treatments

    Measured: 28 days

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

    To assess preliminary efficacy in subjects with solid tumors using Response Evaluation Criteria In Solid Tumors (RECIST) 1.1

    Measured: 4 weeks

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted16 Apr 2019
  2. Study start27 May 2019
  3. Primary completionDec 2027 (estimated)
  4. Study completionJan 2028 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Sequential
Model description
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.
Masking
None (open label)
Enrolment
165 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03917043
Sponsor's protocol ID
APG2449XC101
Status last verified
Jul 2026
First submitted
25 Mar 2019
Last updated
23 Jul 2026
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No

Publications

  • 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.

    PubMed 41146927

  • 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.

    PubMed 35820889

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing APG-2449 in people with Advanced Solid Cancer and Non Small Cell Lung Cancer, run by Ascentage Pharma Group Inc. at 9 sites in China.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 15 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: looking for participants now, as of the sponsor's last update on 23 Jul 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 9 sites in China. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact Yifan Zhai, M.D., Ph.D. (+86-20-28069260, yzhai@ascentage.com), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Maximum Tolerated Dose (MTD) (time frame: 28 days). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03917043, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 Jul 2026.

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