APG-5918 for Cancer

Recruiting in Palo Alto (17 mi)

+1 other location

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 1

Recruiting

Sponsor: Ascentage Pharma Group Inc.

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

Disqualifiers: Severe cardiac conditions, Active infections, others

No Placebo Group

Approved in 2 Jurisdictions

Trial Summary

What is the purpose of this trial?

This trial tests a new oral drug, APG-5918, for patients with advanced solid tumors or non-Hodgkin's lymphoma who have no other treatment options. The goal is to find the safest and most effective dose by adjusting it over time and monitoring the patients.

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.

What safety data exists for APG-5918 (apatinib) in humans?

Apatinib has been studied for various cancers and is generally considered safe, but it can cause side effects like high blood pressure, hand-foot syndrome (redness and swelling of the hands and feet), and proteinuria (protein in urine). Serious side effects are less common but can include severe high blood pressure and hand-foot syndrome. ^{1 2 3 4 5}

Research Team

Yifan Zhai, MD, PhD

Principal Investigator

Ascentage Pharma Group Inc.

Eligibility Criteria

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.

Trial Timeline

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

Treatment Details

Interventions

• APG-5918 (Other)

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.

Participant Groups

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 for the following indications:

Approved in China 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+

Findings from Research

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]

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 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]

References

1. China pubmed.ncbi.nlm.nih.gov

[Clinical study of apatinib combined with chemotherapy for advanced non-small cell lung cancer with negative driving genes]. [2020]

2. England pubmed.ncbi.nlm.nih.gov

The safety of apatinib for the treatment of gastric cancer. [2018]

3. Singapore pubmed.ncbi.nlm.nih.gov

Apatinib monotherapy for advanced non-small cell lung cancer after the failure of chemotherapy or other targeted therapy. [2019]

4. New Zealand pubmed.ncbi.nlm.nih.gov

Anorexia, Hypertension, Pneumothorax, and Hypothyroidism: Potential Signs of Improved Clinical Outcome Following Apatinib in Advanced Osteosarcoma. [2022]

5. United States 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. [2020]