APG-2449 in Patients With Advanced Solid Tumors

Ovarian Cancer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03917043
• Other study ID #: APG2449XC101
• Status: Recruiting
• Phase: Phase 1
• Start date: May 27, 2019
• Est. completion date: February 2025

Study information

• Verified date: November 2023
• Source: Ascentage Pharma Group Inc.
• Contact: Yifan Zhai, M.D., Ph.D.
• Phone: +86-20-28069260
• Email: yzhai[@]ascentage.com
• Is FDA regulated: No
• Study type: Interventional

Clinical 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. 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 150
• Est. completion date: February 2025
• Est. primary completion date: January 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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 one, Patients with non-small cell lung cancer who have progressed or are not tolerated on second-generation ALK TKI therapy or any ROS1 TKI therapy treatment ; cohort two, ALK/ROS1 fusion gene positive without TKI treatment Patients with non-small cell lung cancer. 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.

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.

Related Conditions & MeSH terms

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

Intervention

Drug:
• APG-2449
Capsule, multiple dose cohorts, oral administration every day (QD) of a 28-day cycle

Locations

Country	Name	City	State
China	Beijing Cancer Hospital	Beijing	Beijing
China	Hunan Provincial Oncology Hospital	Changsha	Hunan
China	West China hospital of Sichuan University	Chengdu	Sichuan
China	Fujian Cancer Hospital	Fuzhou	Fujian
China	Fujian Medical University Union Hospital	Fuzhou	Fujian
China	Sun-Yat Sen University Cancer Center	Guangzhou	Guangdong
China	The First affiliated hospital, Sun Yat-sen University	Guangzhou	Guangdong
China	Zhejiang Provincial Oncology Hospital	Hangzhou	Zhejiang
China	Union Hospital medical college Huazhong University of Science and Technology	Wuhan	Hubei
China	Henan Provincial Oncology Hospital	Zhengzhou	Henan

Sponsors (2)

Lead Sponsor	Collaborator
Ascentage Pharma Group Inc.	Suzhou Yasheng Pharmaceutical Co., Ltd.

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Maximum Tolerated Dose (MTD)	To determine the maximum tolerated dose (MTD) of APG-2449 in subjects with advanced solid tumors	28 days
Primary	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	Maximum plasma concentration (Cmax)	Maximum plasma concentration (Cmax) will be assessed on all participants with APG-2449 treatments	28 days
Secondary	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	28 days
Secondary	Phosphorylation of FAK protein	Phosphorylation of FAK protein will be assessed in peripheral blood mononuclear cells on all participants with APG-2449 treatments	28 days
Secondary	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	4 weeks