FDA Grants Fast Track Designation to Neoadjuvant APG-157 for Head and Neck Cancer

FDA

The FDA has granted fast track designation to APG-157 for the neoadjuvant treatment of head and neck cancer.¹

APG-157 is a first-in-class botanical drug developed through the FDA's Botanical Drug Development, and is designed to deliver its active components to oromucosal tissues near the tumor target in patients with head and neck cancer.² The dual mechanism of the agents is intended to induce selective apoptosis of cancer cells and reprogram the immune environment.¹

“There is an urgent need for new treatments for [patients with] head and neck cancer, many of whom face poor survival odds and considerable morbidities following current standard-of-care treatments, including surgery, radiotherapy, and chemotherapy/targeted treatments,” Parag Mehta, PhD, chief executive officer of Aveta Biomics, stated in a news release. “The rare grant of fast track designation for neoadjuvant treatment in head and neck cancer underscores the FDA’s recognition of the potential role of APG-157 in providing meaningful treatment benefits to these patients.”

Previous findings from a phase 1 trial that evaluated APG-157 at 100 mg or 200 mg in healthy participants (n = 13) and patients with oral cancer (n = 12) showed that treatment with APG-157 led to circulating concentrations of curcumin and analogs that peaked 3 hours following treatment, and reductions in interleukin (IL)-1β, IL-6, and IL-8 concentrations in the salivary supernatant fluid of those with cancer. Findings from this study suggested that APG-157 could have a role in combination with immunotherapy.²

An ongoing phase 2 trial (NCT05312710) is evaluating APG-157 as neoadjuvant/induction therapy for patients with newly diagnosed, locally advanced head and neck cancer of the oral cavity and/or oropharynx.³

The open-label, single-arm study is enrolling patients at least 18 years of age with biopsy-proven oral cavity or oropharyngeal squamous cell carcinoma. Patients need to have newly diagnosed, treatment-naive stage I to IV head and neck squamous cell carcinoma per the

International Union Against Cancer’s classification system. Acceptable TNM staging includes T1 to T4, N0 to N2, and M0.

Following treatment with APG-157, patients are required to be scheduled to receive one of the following: local therapy with curative-intent surgery alone or surgery followed by radiation; or therapy with palliative-intent radiation alone. Patients who refuse surgery or are unfit for any local therapy are also allowed to enroll.

Key exclusion criteria include the availability of definitive, local treatment less than 4 weeks from initial diagnosis; prior chemotherapy or radiation within the last 8 weeks; recurrent or metastatic disease; tooth abscesses; bleeding gums or cracked teeth; surgery of the oral cavity, teeth, or gums within 8 weeks of enrollment; and a fracture of the mandible or maxilla within 8 weeks of enrollment.

All patients are receiving oral APG-157 at 100 mg 3 times per day before meals. Dosing is planned to continue for 4 weeks, and it is extendable to up to 6 weeks.

The effect of APG-157 on tumor size is serving as the study’s primary end point. Secondary end points include change in immunohistochemistry profile from baseline to end of dosing; changes in cytokine levels and the oral microbiome in saliva from baseline to end of dosing; and changes in cell-free RNA biomarkers in blood and saliva from baseline to end of dosing.

“This fast track designation, based on our comprehensive phase 1 and phase 2 data, accelerates our ability to bring our promising first-line therapy to all newly diagnosed [patients with] locally advanced head and neck cancer in a frontline setting,” Karim Malek, MD, MTh, MBA, chief medical officer of Aveta Biomics, added in a news release.¹

References

1. FDA grants fast track designation to Aveta Biomics’ drug APG-157 for neoadjuvant treatment of head and neck cancer. News release. Aveta Biomics. August 22, 2024. Accessed August 23, 2024. https://avetabiomics.com/2024/08/22/fda-grants-fast-track-designation-to-aveta-biomics-drug-apg-157-for-neoadjuvant-treatment-of-head-and-neck-cancer/
2. Basak SK, Bera A, Yoon AJ, et al. A randomized, phase 1, placebo-controlled trial of APG-157 in oral cancer demonstrates systemic absorption and an inhibitory effect on cytokines and tumor-associated microbes. Cancer. 2020;126(8):1668-1682. doi:10.1002/cncr.32644
3. Safety and efficacy of APG-157 in head and neck cancer. ClinicalTrials.gov. Updated August 14, 2024. Accessed August 23, 2024. https://clinicaltrials.gov/study/NCT05312710