FDA Awards Orphan Drug Designation to Alisertib in ES-SCLC

The FDA has granted an orphan drug designation to alisertib (MLN8237) for the treatment of patients with extensive-stage small cell lung cancer (ES-SCLC), according to an announcement from Puma Biotechnology.¹

Alisertib is a selective, small-molecule inhibitor of aurora kinase A, and it will be evaluated in the phase 2 PUMA-ALI-4201 trial in patients with ES-SCLC whose disease has progressed following first-line platinum-based chemotherapy and immunotherapy.²

“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, stated in a press release.¹ “There is an urgent need for new treatments for patients with SCLC, and we look forward to the initiation of our phase 2 [PUMA-ALI-4201] trial of alisertib in SCLC.”

In August 2023, Puma Biotechnology obtained FDA approval for an investigative new drug application of alisertib, prompting the continued clinical development of the agent as a monotherapy for patients with ES-SCLC. The phase 2 study will enroll up to 60 patients, and enrollment is expected to begin in the second half of 2023.²

Patients with ES-SCLC included in the study will be required to provide tissue-based biopsies for the biomarker analysis. Investigators will analyze specific predefined biomarker subgroups to better understand any efficacy outcomes or differences in responses between patient subsets.

Enrolled patients will receive alisertib monotherapy at 50 mg twice daily on days 1 to 7 of every 21-day cycle.

The primary end point of the study will be objective response rate (ORR), and secondary end points will include duration of response, disease control rate, progression-free survival, and overall survival.

Previously, the safety and activity of alisertib was evaluated for in a phase 2 trial (NCT01045421) in patients with predefined types of advanced solid tumors, including SCLC (n = 60), non–small cell lung cancer (n = 26), breast cancer (n = 53), head and neck squamous cell carcinoma (n = 55), and gastroesophageal adenocarcinoma (n = 55).³ Data from the global, multicenter trial showed that patients with SCLC evaluable for efficacy (n = 48) experienced an ORR of 21% (95% CI, 10%-35%), and all responses were partial responses.

All patients treated during the study received alisertib at 50 mg twice per day on days 1 to 7 of each 21-day cycle.

Regarding safety, findings were consistent across all tumor types. The most common grade 3/4 treatment-related adverse effects (TRAEs) included neutropenia (43%), leukopenia (21%), and anemia (10%). Additionally, 43% of patients experienced serious TRAEs.

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 September 28, 2023. https://investor.pumabiotechnology.com/news-releases/news-details/2023/Puma-Biotechnology-Receives-FDA-Orphan-Drug-Designation-for-Alisertib-for-the-Treatment-of-Small-Cell-Lung-Cancer/
2. Puma Biotechnology Announces FDA Clearance of IND for Alisertib in Small Cell Lung Cancer. News Release. Puma Biotechnology. August 8, 2023. Accessed September 28, 2023. https://www.pumabiotechnology.com/
3. Melichar B, Adenis A, Lockhart C, et al. Safety and activity of alisertib, an investigational aurora kinase A inhibitor, in patients with breast cancer, small-cell lung cancer, non-small-cell lung cancer, head and neck squamous-cell carcinoma, and gastro-oesophageal adenocarcinoma: a five-arm phase 2 study. Lancet Oncol. 2015;16(4):395-405. doi:10.1016/S1470-2045(15)70051-3