Apatinib Clinical Trials

What Is Apatinib?

Apatinib is a medication that has received approval from the China Food and Drug Administration (CFDA) for treating certain advanced cancers. It is approved for advanced gastric cancer, gastroesophageal junction adenocarcinoma, hepatocellular carcinoma, advanced osteosarcoma, metastatic nasopharyngeal carcinoma, and advanced non-squamous head and neck cancer.

Apatinib works as a multi-targeted tyrosine kinase inhibitor. Specifically, it is a highly selective inhibitor of Vascular Endothelial Growth Factor Receptor 2 (VEGFR-2). By blocking VEGFR-2, apatinib interferes with signals that help cancer cells grow and form new blood vessels, which are essential for tumor survival and spread.

Beyond its approved uses, apatinib is also being studied in numerous clinical trials for a wide range of other cancers. These investigations aim to understand its effectiveness and safety in treating additional types of tumors.

Uses and Conditions Under Study

Apatinib is being extensively studied across many types of cancer, with a total of 787 trials involving 96,131 participants. The earliest trial began in 2002, and new studies are planned through 2026. Many of these trials are sponsored by industry leaders like GlaxoSmithKline and Jiangsu HengRui Medicine Co., Ltd., as well as academic and government institutions.

The conditions most frequently investigated with apatinib include:

• Breast Cancers: Apatinib is being studied in 74 trials for breast cancer, 45 trials for neoplasms of the breast, 31 trials for metastatic breast cancer, and 11 trials for breast neoplasms. These studies explore its potential in various breast cancer subtypes, including those that have spread to other parts of the body.
• Gastric and Esophageal Cancers: Apatinib is a mainstream systemic treatment option in China for advanced gastric cancer, with 43 trials focusing on this condition. It is also being investigated for esophageal cancer, including esophageal squamous cell carcinoma (ESCC), and gastroesophageal junction adenocarcinoma.
• Liver Cancer: For hepatocellular carcinoma (HCC), a common and aggressive liver cancer, apatinib is approved in China as a second-line treatment and is being studied in 35 trials. Research explores its use alone or in combination with other therapies like transcatheter arterial chemoembolization (TACE) and immunotherapies.
• Sarcomas: Apatinib is a recognized treatment option in China for advanced osteosarcoma, a type of bone cancer where traditional chemotherapy has failed. It is also being evaluated for soft tissue sarcomas, with studies exploring its effectiveness in these rare and aggressive cancers.
• Lung Cancers: Apatinib is under investigation for both small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC), particularly in patients who have relapsed or developed resistance to initial treatments.
• Head and Neck Cancers: Apatinib has been approved in China for advanced non-squamous head and neck cancer and metastatic nasopharyngeal carcinoma. Studies continue to assess its role in these cancers, which are prevalent in certain regions.
• Ovarian and Colorectal Cancers: Apatinib is being explored in 19 trials for ovarian cancer, a gynecologic malignancy with a high recurrence rate, and in 11 trials for colorectal cancer, often in combination with other agents to improve outcomes for advanced disease.
• Other Cancers: Additional conditions under study include thyroid cancer (specifically radioactive iodine-refractory differentiated thyroid cancer), gliomas, bladder cancer, and endometrial cancer.

Dosing

Apatinib is available in oral forms, primarily as apatinib mesylate tablets and apatinib-etoposide capsules. The dosage and administration schedule can vary depending on the specific cancer being treated and whether it's used alone or in combination with other medications.

Commonly studied dosages for apatinib include:

• 250 mg taken orally once daily, often in combination with other drugs like camrelizumab.
• 500 mg taken orally once daily. One regimen involves continuous administration for 5 days, followed by a 2-day break, with a 28-day cycle. Imaging evaluations are typically performed every 2 to 3 cycles to monitor treatment response.
• 750 mg taken orally once daily, also being investigated in various treatment combinations.

These dosages are used in adult patients for various advanced cancers. Clinical trials continue to explore optimal dosing strategies and combinations to maximize effectiveness and manage potential side effects.

Side Effects

In clinical trials involving over 4,000 patients, Apatinib was associated with several side effects. The most common side effect was diarrhea, affecting 54.1% of patients taking Apatinib, compared to 18.4% of patients on placebo. Rash was also frequently reported, occurring in 43.7% of Apatinib patients versus 15.5% on placebo.

Other common side effects included:

• Neutropenia (a decrease in white blood cells): 27.9% with Apatinib versus 25.1% with placebo.
• Nausea: 27.5% with Apatinib versus 21.3% with placebo.
• Fatigue: 18.7% with Apatinib versus 16.6% with placebo.
• Vomiting: 18.4% with Apatinib versus 13.0% with placebo.
• Asthenia (lack of energy or strength): 15.5% with Apatinib versus 11.6% with placebo.
• Decreased appetite: 15.3% with Apatinib versus 9.6% with placebo.
• Alopecia (hair loss): 15.1% with Apatinib versus 12.5% with placebo.
• Dry skin: 10.9% with Apatinib versus 2.8% with placebo.

Headache was reported in 10.2% of Apatinib patients, which was slightly lower than the 10.7% reported in patients taking placebo.

Clinical Trial Results

Clinical trials have investigated Apatinib in various cancer types, demonstrating its effects on disease progression and patient outcomes.

Non-Small Cell Lung Cancer (NSCLC)

In a study (NCT00073008) of advanced or metastatic NSCLC, patients received Apatinib at different daily doses. For patients in the non-targeted population, 27.1% of those taking Apatinib 1500 mg once daily achieved progression-free survival (PFS) at four months, compared to 18.3% of those taking Apatinib 500 mg twice daily. In the targeted patient population, 34.5% on Apatinib 1500 mg once daily achieved PFS at four months, versus 19.7% on Apatinib 500 mg twice daily.

Advanced or Metastatic Breast Cancer

A study (NCT00073528) compared Apatinib plus letrozole to placebo plus letrozole in patients with advanced or metastatic breast cancer. In patients with HER2-positive disease, the overall tumor response rate was 27.9% for those receiving Apatinib plus letrozole, compared to 14.8% for those on placebo plus letrozole. The median progression-free survival (PFS) in the HER2-positive population was significantly longer for patients on Apatinib plus letrozole, at 35.4 weeks, versus 13.0 weeks for the placebo group. Across the entire study population (ITT), 55.8% of patients on Apatinib plus letrozole showed clinical benefit, compared to 50.6% on placebo plus letrozole.

Another trial (NCT00075270) examined Apatinib with paclitaxel as a first-line therapy for advanced or metastatic breast cancer. Patients receiving Apatinib plus paclitaxel had a median overall survival of 23.82 months, compared to 20.17 months for those on placebo plus paclitaxel. The median progression-free survival was 25.1 weeks with Apatinib plus paclitaxel, versus 22.6 weeks with placebo plus paclitaxel. Clinical benefit was observed in 40.5% of patients receiving Apatinib plus paclitaxel, compared to 31.9% in the placebo group.

In a separate study (NCT00089999) for chemotherapy-naive or metastatic breast cancer, two different Apatinib dosing regimens were compared. The median progression-free survival (as assessed by an independent review committee) was 24.4 weeks for Apatinib 500 mg twice daily, versus 17.6 weeks for Apatinib 1500 mg once daily. Clinical benefit was achieved by 40.6% of patients on Apatinib 500 mg twice daily, compared to 29.0% on Apatinib 1500 mg once daily.

Recurrent and/or Metastatic Salivary Gland Cancers

A study (NCT00095563) investigating Apatinib in recurrent and/or metastatic adenoid cystic cancer or other salivary gland cancers reported that 0 participants achieved an objective response (complete or partial response). The median progression-free survival ranged from 2.1 to 3.6 months. Stable disease was observed in 9 participants and 4 participants in different assessments.

Currently Recruiting Trials

Apatinib is currently being investigated in numerous clinical trials, exploring its potential to treat a wide range of cancers, often in combination with other therapies. These studies aim to improve outcomes for patients with various advanced or difficult-to-treat conditions.

One such study, NCT07479732, is a Phase 1/Phase 2 trial led by Peking University People's Hospital. It is recruiting 56 participants with refractory or metastatic osteosarcoma to evaluate apatinib combined with liposomal irinotecan. For advanced osteosarcoma patients whose traditional chemotherapy has failed, this combination seeks to overcome secondary resistance.

For patients with advanced hepatocellular carcinoma (HCC), Linhui Peng is sponsoring a Phase 3 study, NCT07267806, targeting an enrollment of 326. This trial investigates camrelizumab and apatinib with or without FOLFOX chemotherapy as a first-line treatment. Another Phase 3 trial, NCT06925243, sponsored by Zuoyi Jiao, is enrolling 682 participants with locally advanced gastric/gastroesophageal junction adenocarcinoma. It compares neoadjuvant apatinib combined with sintilimab and perioperative SOX chemotherapy against neoadjuvant sintilimab with perioperative SOX.

In the realm of breast cancer, Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University is conducting two Phase 3 studies. NCT06889688 is recruiting 246 patients with advanced triple-negative breast cancer to compare camrelizumab, apatinib, and eribulin against physician's choice chemotherapy. Similarly, NCT06255392 aims for 200 participants with HRD-positive/HER2-negative advanced breast cancer, evaluating fluzoparib in combination with apatinib versus investigator-selected chemotherapy.

Further studies include NCT07569679, a Phase 2 trial enrolling 124 patients with unresectable biliary tract cancer, exploring alternating hepatic arterial infusion chemotherapy (HAIC) and systemic chemotherapy with or without adebrelimab and apatinib. Apatinib is also being studied in pediatric populations, such as in NCT05027386, a Phase 1/Phase 2 trial for 125 children with recurrent or refractory neuroblastoma, combining apatinib mesylate with an IT regimen.

Where to Participate

Clinical trials for Apatinib are actively recruiting participants across a broad geographic area, spanning 33 cities and 19 states. This widespread availability allows more patients to potentially access investigational treatments.

Key locations with recruiting sites include:

• New York, New York
• Los Angeles, California
• St Louis, Missouri
• Ann Arbor, Michigan
• Fullerton, California
• Irvine, California
• Newport Beach, California
• Santa Rosa, California
• Washington D.C., District of Columbia
• Fleming Island, Florida

Eligibility for these studies is inclusive, welcoming participants of all genders aged between 2 and 130 years. Healthy volunteers and children are also eligible for specific trials, broadening the scope of research and potential benefit.

Development Timeline

The journey of Apatinib in clinical development began on August 28, 2002, with its first trial. Since then, its research pipeline has expanded significantly, encompassing a total of 787 trials and enrolling over 96,131 participants. Initially, studies explored conditions like IBS-C and hyperphosphatemia, but the focus quickly shifted and broadened to various oncology indications.

Leading the development efforts are prominent sponsors such as GlaxoSmithKline and Jiangsu HengRui Medicine Co., Ltd., alongside institutions like the National Cancer Institute and Sun Yat-sen University. These organizations have driven Apatinib's progression through all phases of clinical research.

The majority of studies, 476, are in Phase 2, indicating a robust exploration of efficacy across multiple cancer types. There are also 84 Phase 3 trials, signifying advanced stages of investigation aimed at confirming effectiveness and safety. Apatinib's development has expanded to address a wide array of cancers, including gastric cancer, hepatocellular carcinoma, metastatic breast cancer, ovarian cancer, and small cell lung cancer, demonstrating its versatile potential as a multi-targeted tyrosine kinase inhibitor.