Alisertib Earns FDA Orphan Drug Designation for Small Cell Lung Cancer

An investigational new drug (IND) application for single-agent alisertib was cleared by the FDA for extensive stage small cell lung cancer in August 2023, with a phase 2 study slated for the second half of 2023.

The FDA has granted orphan drug designation to single-agent alisertib for patients with small cell lung cancer (SCLC), according to a press release from Puma Biotechnology.¹

The selective, oral, small molecule, aurora kinase A inhibitor is being evaluated in patients with SCLC who progressed during or following treatment with platinum-based chemotherapy as part of the phase 2 Study PUMA-ALI-4201.

“Obtaining orphan drug designation from the FDA signifies our continued progress and commitment to the development of alisertib for the treatment of [SCLC],” Alan H. Auerbach, chief executive officer, president, and founder of Puma Biotechnology, said in the press release. “There is an urgent need for new treatments for patients with [SCLC], and we look forward to the initiation of our phase 2 trial (Study PUMA-ALI-4201) of alisertib in [SCLC].”

An investigational new drug (IND) application for single-agent alisertib was cleared by the FDA for extensive-stage SCLC (ES-SCLC) in August 2023, with a phase 2 study slated for the second half of 2023.²

“We are pleased to move forward with the clinical development of alisertib in [SCLC],” Auerbach, said in a press release at the time of the IND clearance.² “We are eagerly awaiting the start of this phase 2 trial, and we hope that the study will provide much needed insight into the clinical activity of alisertib in [SCLC] and, more specifically, in patients with molecularly defined tumors that may be targetable with an aurora kinase A inhibitor like alisertib.”

In Study PUMA-ALI-4201, a maximum enrollment of 60 patients with ES-SCLC and disease progression following frontline platinum-based chemotherapy and immunotherapy will receive alisertib at a dose of 50 mg twice a day on days 1 to 7 per 21-day cycle. Additionally, patients will be required to provide tissue from biopsies for biomarker analysis.

The primary end point is objective response rate, with key secondary end points including duration of response, disease control rate, progression-free survival, and overall survival. These end points will also be evaluated across pre-specified biomarker subgroups.

Investigators will look to conduct an initial interim analysis assessing both biomarkers and efficacy as part of Study PUMA-ALI-4201. Additionally, developers plan to discuss the possibility of an accelerated approval pathway for alisertib in SCLC depending on the outcomes observed in the study.

“Treatment options for patients with [SCLC] that has progressed on or after platinum-based chemotherapy are limited, and there is an urgent need for new drugs to treat this patient population,” Taofeek K. Owonikoko, MD, PhD, a professor of medicine, chief of the Division of Hematology/Oncology, associate director for Translational Research, and co-leader of the Cancer Therapeutics Program at the University of Pittsburgh Medical Center Hillman Cancer Center, concluded.² “The results from the previous clinical trials of alisertib in [SCLC] suggest that the drug may represent a potentially promising treatment option for these patients and, more specifically, for patient subsets whose tumors harbor potential molecular markers that are likely associated with the clinical activity of an aurora kinase A inhibitor such as alisertib.”

References

1. Puma Biotechnology receives FDA orphan drug designation for alisertib for the treatment of small cell lung cancer. News release. Puma Biotechnology. September 21, 2023. Accessed October 2, 2023. https://bit.ly/3rD8TXd
2. Puma Biotechnology announces FDA clearance of IND for alisertib in small cell lung cancer. News release. Puma Biotechnology. August 8, 2023. Accessed October 2, 2023. https://bit.ly/3RGFVQG