FDA Grants Orphan Drug Designation to Apatinib in Adenoid Cystic Carcinoma

The FDA has granted Orphan Drug Designation to the small-molecule tyrosine kinase inhibitor apatinib for the treatment of the rare malignancy, adenoid cystic carcinoma.

The FDA has granted Orphan Drug Designation to the small molecule tyrosine kinase inhibitor apatinib (Rivoceranib) for the treatment of the rare cancer adenoid cystic carcinoma, announced Elevar Therapeutics, Inc, in a press release.1

"With no approved treatments for adenoid cystic carcinoma, a significant unmet need remains for therapies that slow or stop this relentless disease," said Mark Gelder, MD, chief medical officer of Elevar, in a statement. "The orphan drug designation from the FDA reinforces the urgency of Elevar's work with [apatinib] in ACC and our commitment to improving treatment experiences and outcomes for patients who have limited or inadequate therapeutic options."

An open-label, multicenter phase 2 clinical trial (NCT04119453) of apatinib in patients with recurrent or metastatic adenoid cystic carcinoma is already underway. The study is exploring treatment with oral apatinib at 700 mg daily in patients with metastatic or recurrent disease that is not amenable to potentially curative surgery or radiation therapy.

The primary end point of the study is objective response rate by investigator assessment per RECIST 1.1 criteria, and secondary end points include overall survival (OS), duration of response, progression-free survival (PFS), time to progression, and safety.

In results reported in 2018 from 59 patients treated in an earlier phase 2 study (NCT02775370), findings confirmed that apatinib was effective and safe in patients with adenoid cystic carcinoma after the agent achieved the best response rate ever reported.2

The analysis was performed on patients who were treated with 500 mg daily apatinib between April of 2016 and December of 2017. The cohort was 37.3% male and 62.7% female. Patients enrolled had a median age of 47.5 years. Notably, 61.0% of the population had metastases. The primary end point evaluated in these patients was PFS. The study also assessed the OS rate, response rate, and the number of patients with treatment-related adverse events (AEs) as secondary end points.

At the data cutoff, the median PFS and OS had not been reached, but patients had received apatinib for a median of 6.4 months (interquartile range, 3.8-9.9). The 6-month PFS rate observed with apatinib in patients with adenoid cystic carcinoma was 87.9% (95% CI, 76.6%-99.1%), and the 12-month PFS rate was 50.7% (95% CI 21.8%-79.7%). Also, at 12 months, the OS rate achieved was 96.3% (95% CI, 91.3%-101.3%).

Treatment with apatinib led to a response rate of 47.1% in the study and the disease control rate was 98.1%.

Apatinib demonstrated a good safety profile in patients with adenoid cystic carcinoma. Drug-related AEs occurred in 88.1%, and 22.0% of patients experienced grade 3 AEs. The most common AEs observed included hypertension (54.2%), hand-foot syndrome (33.9%), and proteinuria (23.7%). Overall, 57.6% of patients required dose reductions.

Considering that apatinib showed encouraging early results in the original cohort and that the trial gained high interest from physicians of and patients with adenoid cystic carcinoma, Elevar Therapeutics announced in November 2020 that the target enrollment for the open-label, multicenter study would be increased to 77 patients.3

To be eligible for enrollment, patients must have histologically or cytologically confirmed adenoid cystic carcinoma, documented recurrent or metastatic disease, a measurable target lesion, be ineligible for surgery and radiation therapy, have received prior chemotherapy, and be at least 18 years of age. In terms of disease status at screening, patients are required to present with a Karnofsky score over 60, and adequate organ function.

"We are pleased by the FDA's recognition of the critical need to develop treatments for adenoid cystic carcinoma given the progressive nature of the disease," said Alex Kim, CEO of Elevar, in a statement. "The orphan drug designation provides further momentum for the [apatinib] development program, which we are committed to advancing as quickly as possible for patients in need."


1. Elevar Therapeutics announces Orphan Drug Designation for Rivoceranib (apatinib) for the treatment of adenoid cystic carcinoma (ACC). News release. February 8, 2021. Accessed February 8, 2021. https://bit.ly/36RCCOE

2. Zhu G, Zhang L, Li R, et al. Phase II trial of apatinib in patients with recurrent and/or metastatic adenoid cystic carcinoma of the head and neck: Updated analysis. J Clin Oncol. 2018;36(suppl 15): 6026. doi:10.1200/JCO.2018.36.15_suppl.6026

3. Elevar Therapeutics announces early completion of initial target enrollment in pivotal phase 2 study evaluating Rivoceranib (apatinib) in adenoid cystic cancer (ACC). News release. Elevar Therapeutics, Inc. November 17, 2020. Accessed February 8, 2021. https://bit.ly/36QDoeA