APG-5918 for Cancer

Not currently recruiting at 1 trial location

Overseen By Wendy Chu

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Ascentage Pharma Group Inc.

Must not be taking: Anticoagulants, Antiplatelets, QT-prolonging drugs

Disqualifiers: Severe cardiac conditions, Active infections, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new treatment called APG-5918 for certain types of cancer. The goal is to determine the optimal dose and assess its effectiveness for individuals with advanced or stubborn cancers, such as nasopharyngeal carcinoma and prostate cancer. Participants will take APG-5918 orally in 28-day cycles. It suits those with solid tumors or Non-Hodgkin's Lymphoma who have not responded to other treatments. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new treatment.

Do I need to stop my current medications to join the trial?

The trial requires that you do not take any concurrent anti-cancer therapy or certain other medications, such as therapeutic doses of anti-coagulants and QT interval-prolonging drugs. If you are on these medications, you may need to stop them before joining the trial. Please discuss with the trial team for specific guidance.

Is there any evidence suggesting that APG-5918 is likely to be safe for humans?

Research has shown that APG-5918 is undergoing early testing. These studies aim to determine the right dose and evaluate the treatment's effectiveness against cancer cells. Detailed information about its safety for humans is not yet available. As it is in the first phase of testing, researchers are primarily focused on assessing its safety.

The treatment has shown promise in lab tests by slowing the growth of cancer cells. While this is encouraging, the main goal of these early studies is to ensure the treatment's safety for people. Participants in these studies are closely monitored for any side effects or issues.

In summary, APG-5918 has demonstrated potential in lab settings, but human safety data is still being collected. This phase of testing focuses on ensuring its safety for human use. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

APG-5918 is unique because it targets cancer cells in a novel way compared to traditional treatments like chemotherapy and radiation. While most standard treatments attack both healthy and cancerous cells, APG-5918 aims to specifically inhibit proteins that are essential for cancer cell survival, potentially reducing collateral damage to healthy cells. Researchers are excited about this treatment because it may offer a more targeted approach, which could lead to fewer side effects and better outcomes for patients.

What evidence suggests that APG-5918 might be an effective treatment for cancer?

Research has shown that APG-5918, the investigational treatment in this trial, holds strong potential in fighting cancer. In lab studies, it effectively stopped the growth of several cancer cell types, including prostate cancer cells, even in small amounts. Early data also suggest it works well with other treatments, like PD-1 antibodies, in animal studies of pancreatic cancer. APG-5918 showed promising results when combined with another drug, tucidinostat, in studies of T-cell lymphoma, a type of blood cancer. These early findings suggest that APG-5918 could be a powerful option for treating various cancers. ^{1 2 4 5 6}

Who Is on the Research Team?

Yifan Zhai, MD, PhD

Principal Investigator

Ascentage Pharma Group Inc.

Are You a Good Fit for This Trial?

This trial is for adults with advanced solid tumors or lymphomas, including specific cancers like nasopharyngeal and prostate cancer, who have not responded to existing treatments. Participants must be expected to live more than 3 months, have a certain level of physical fitness (ECOG status), and measurable disease. They should also have adequate organ function and agree to use effective contraception.

Inclusion Criteria

Ability to understand and willingness to sign a written informed consent form (the consent form must be signed by the patient prior to any study-specific procedures)

Adequate hepatic and renal function defined as: AST and ALT ≤ 3 x upper limit of normal (ULN) (≤ 5 x ULN if liver metastases), Calculated creatinine clearance ≥ 50 mL/min using the Cockcroft-Gault formula, Total Bilirubin ≤1.5 x ULN (Except if considered secondary to Gilbert's syndrome and primarily indirect bilirubinemia), PT and aPTT ≤2 x ULN, Troponin ≤ 2 x ULN, QTcF interval ≤470ms for all genders (mean (triplicate) n =3), measured between 2-5 minutes apart, Stable brain metastases with clinically controlled neurologic symptoms

My cancer has spread or returned and doesn't respond to treatment anymore.

Exclusion Criteria

I have not taken any biologic treatments like G-CSF, GM-CSF, or erythropoietin in the last 7 days.

I do not have severe heart issues or uncontrolled brain cancer symptoms.

I am not on any cancer treatments except for thyroid hormones or estrogen replacement.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation

Establish the maximum tolerated dose (MTD) or recommended phase 2 dose (RP2D) of APG-5918

28 days per cycle

Visits as per cycle schedule

Dose Expansion

Evaluate safety and efficacy at established dose levels in two cohorts

28 days per cycle

Visits as per cycle schedule

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• APG-5918

Trial Overview The study tests APG-5918's safety and effectiveness in two parts: dose escalation followed by dose expansion. It involves patients taking the drug orally in cycles lasting 28 days each.

How Is the Trial Designed?

Group I: Cohort 2 in Dose expansion Experimental Treatment 1 Intervention

Group II: Cohort 1 in Dose expansion Experimental Treatment 1 Intervention

APG-5918 is already approved in China, United States for the following indications:

Approved in China as APG-5918 for:

• Advanced solid tumors
• Hematologic malignancies

Approved in United States as APG-5918 for:

• Advanced solid tumors
• Hematologic malignancies

Who Is Running the Clinical Trial?

Ascentage Pharma Group Inc.

Lead Sponsor

Trials

54

Recruited

5,700+

Published Research Related to This Trial

Apatinib, a VEGFR-2 inhibitor, was found to be effective for treating advanced non-small cell lung cancer in 34 patients after chemotherapy failure, with a median progression-free survival of four months.

The treatment was generally safe, with manageable side effects like hypertension and hand-foot syndrome, and no severe adverse reactions were reported, indicating good tolerability.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Apatinib monotherapy for advanced non-small cell lung cancer after the failure of chemotherapy or other targeted therapy. Liu, Z., Ou, W., Li, N., et al.[2019]

Apatinib is an effective and safe oral medication for advanced gastric cancer, particularly after other treatments have failed, with manageable side effects such as hand-foot syndrome and hypertension.

The drug should be avoided in patients with a risk of bleeding or perforation, and early signs of certain adverse events may indicate its effectiveness in treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The safety of apatinib for the treatment of gastric cancer. Geng, R., Song, L., Li, J., et al.[2018]

In a study of 41 patients with advanced osteosarcoma, apatinib treatment showed potential adverse events, with the most common severe side effects being pneumothorax (16.22%) and wound dehiscence (10.81%).

Certain adverse events like hypertension and anorexia were associated with better outcomes, indicating they may serve as markers for clinical benefit in patients treated with apatinib.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Anorexia, Hypertension, Pneumothorax, and Hypothyroidism: Potential Signs of Improved Clinical Outcome Following Apatinib in Advanced Osteosarcoma. Xie, L., Xu, J., Sun, X., et al.[2022]

In a study of 62 advanced non-small cell lung cancer (NSCLC) patients, combining apatinib with standard chemotherapy significantly improved median progression-free survival (PFS) to 6.4 months compared to 4.9 months for chemotherapy alone, and overall survival (OS) was also better at 11.3 months versus 9.2 months.

While the combination treatment showed promising survival benefits, it was associated with a higher incidence of adverse effects, such as hypertension (46.7%) and hand-foot syndrome (53.3%), compared to the control group, indicating a need for careful monitoring of side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Clinical study of apatinib combined with chemotherapy for advanced non-small cell lung cancer with negative driving genes]. Li, YF., Jiang, HY., Li, Q., et al.[2020]

In a phase II trial involving 29 patients with microsatellite stable metastatic colorectal cancer, the combination of SHR-1210 (an anti-PD-1 antibody) and apatinib showed an objective response rate of 0% and a disease control rate of only 22.2%, indicating that this treatment did not improve efficacy for these patients.

All patients experienced treatment-related adverse events, with 100% reporting issues such as hypertension and proteinuria, and 90% experiencing grade 3 adverse events, suggesting that the high toxicity may have contributed to the lack of effectiveness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Anti-PD-1 antibody SHR-1210 plus apatinib for metastatic colorectal cancer: a prospective, single-arm, open-label, phase II trial. Ren, C., Mai, ZJ., Jin, Y., et al.[2020]

Citations

1. aacrjournals.org aacrjournals.org/cancerres/article/85/8_Supplement_1/446/755141/Abstract-446-Embryonic-ectoderm-development

Embryonic ectoderm development protein (EED) inhibitor APG ... APG-5918 showed superior inhibitory effects on cellular proliferation in vitro, with IC50 values of 10.16 nM in LNCaP, 26.32 nM in C4-2B, and ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT05415098

Study of Safety, Pharmacokinetic and Efficacy of APG-5918 ... This is a multicenter, open-label, Phase 1 study that will be conducted in two parts. Part 1 is the dose escalation of APG-5918.

3. ascentage.com ascentage.com/ascentage-pharma-announces-ind-approval-in-china-for-phase-i-study-of-apg-5918-in-patients-with-advanced-solid-tumors-or-hematologic-malignancies/

Ascentage Pharma Announces IND Approval in China for ... Preliminary data showed that APG-5918 has in vitro antiproliferative activity in various tumor cell lines and antitumor activity in patient ...

4. aacrjournals.org aacrjournals.org/cancerres/article/85/8_Supplement_1/7189/759765/Abstract-7189-EED-inhibitor-APG-5918-renders?searchresult=1

Abstract 7189: EED inhibitor APG-5918 renders vulnerability ... Our study demonstrated that the EED inhibitor APG-5918 synergizes with PD-1 antibody to exert anti-tumor effects in immune-competent murine pancreatic cancer ...

5. library.ehaweb.org library.ehaweb.org/eha/2025/eha2025-congress/4161067/eric.liang.embryonic.ectoderm.development.28eed29.inhibitor.apg-5918.exhibits.html?f=listing%3D0%2Abrowseby%3D8%2Asortby%3D2%2Asearch%3Dtazemetostat

EMBRYONIC ECTODERM DEVELOPMENT ... Summary/Conclusion: APG-5918 exhibited potent antitumor activity alone and synergized with tucidinostat in preclinical TCL models.

6. ashpublications.org ashpublications.org/blood/article/144/Supplement%201/1415/531999/Embryonic-Ectoderm-Development-EED-Inhibitor-APG

Embryonic Ectoderm Development (EED) Inhibitor APG-5918 ... Significant and dose-dependent antitumor activities were observed. On day 29, T/C values were 58.98% for 1 mg/kg, 31.80% for 3 mg/kg (p < 0.05 ...