APG-2449 for advanced solid tumors

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

This study is testing a new oral medication called APG-2449 to see how well it works and what the safe dosage is for people with advanced solid tumors like non-small cell lung cancer.

Quick facts

• Phase: PHASE1
• Study type: Interventional
• Enrollment: 165 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Ascentage Pharma Group Inc. (industry)
• Drugs / interventions: lorlatinib, chemotherapy, immunotherapy
• Locations: 9 sites (Beijing, Beijing Municipality and 8 other locations)
• Trial ID: NCT03917043 on ClinicalTrials.gov

What this trial studies

This clinical trial evaluates APG-2449, a novel oral tyrosine kinase inhibitor targeting FAK, ALK, and ROS1, in patients with advanced solid tumors. The study aims to determine the maximum tolerated dose and assess dose-limiting toxicities in a Phase 1 dose escalation format. Following this, additional Phase Ib/II studies will explore its efficacy in combination with other anticancer agents. The trial includes patients with specific types of advanced cancers, including non-small cell lung cancer and malignant pleural mesothelioma.

Who should consider this trial

Good fit: Ideal candidates include patients with advanced non-small cell lung cancer or other specified cancers who have specific genetic markers and have either progressed on or are intolerant to previous treatments.

Not a fit: Patients with early-stage cancers or those without the required genetic markers may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could provide a new therapeutic option for patients with advanced solid tumors that are resistant to current therapies.

How similar studies have performed: Other studies involving multi-targeted tyrosine kinase inhibitors have shown promise, suggesting potential for success with this novel approach.

Eligibility criteria

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.

Where this trial is running

Beijing, Beijing Municipality and 8 other locations

• Beijing Cancer Hospital — Beijing, Beijing Municipality, China (RECRUITING)
• Fujian Medical University Union Hospital — Fuzhou, Fujian, China (NOT_YET_RECRUITING)
• Fujian Cancer Hospital — Fuzhou, Fujian, China (NOT_YET_RECRUITING)
• Sun-Yat Sen University Cancer Center — Guangzhou, Guangdong, 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)

Study contacts

• Principal investigator: Li Zhang, Professor — Sun Yat-Sen University Cancer Center
• Study coordinator: Yifan Zhai, M.D., Ph.D.

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