Alisertib Phase 2 Combo Trial Launches in Small Cell Lung Cancer

Puma Biotechnology has launched the phase 2 ALISCA-Lung2 trial (PUMA-ALI-4202; NCT07465757) evaluating the investigational aurora kinase A inhibitor alisertib in combination with paclitaxel in patients with small cell lung cancer (SCLC) whose disease has progressed following platinum-based chemotherapy and immunotherapy.¹

The trial is investigating the safety and clinical activity of escalating doses of alisertib in combination with paclitaxel. The target enrollment goal for the study is 50 patients and the estimated primary completion date is March 2028.^1,2

Rationale for the ALISCA-Lung2 Trial

The rationale for the combination is supported by prior clinical findings with alisertib in relapsed SCLC. In a randomized phase 2 study of 178 patients, treatment with alisertib plus paclitaxel produced a median progression-free survival (PFS) of 3.32 months compared with 2.17 months with placebo plus paclitaxel. The hazard ratio (HR) for PFS was 0.77 (95% CI, 0.557-1.067; P = .113) using the original analysis and 0.71 (95% CI, 0.509-0.985; P = .038) following correction of the relapse definition. The objective response rates were 22% and 18%, respectively.³

“Treatment options for patients with small cell lung cancer that has progressed following platinum-based chemotherapy and immunotherapy remain limited, and there is an urgent need for new treatment approaches for these patients. I am pleased to see further evaluation of alisertib in these patients,” Taofeek K. Owonikoko, MD, PhD, chair of the ALISCA-Lung2 Steering Committee, said in a statement.¹

The earlier randomized study also demonstrated a higher incidence of treatment-related grade 3 or higher adverse events with the alisertib combination, occurring in 67% of patients compared with 22% with placebo plus paclitaxel. Neutropenia, anemia, and decreased neutrophil counts occurred more frequently at grade 3 or higher in the alisertib-containing arm. Twelve patients receiving alisertib plus paclitaxel and 11 receiving placebo plus paclitaxel died during the study, including 4 treatment-related deaths in the alisertib arm and none in the placebo arm.³

Alisertib also demonstrated single-agent activity in an earlier phase 2 study of relapsed or refractory SCLC. Among 48 response-evaluable patients, the objective response rate was 21% (95% CI, 10%-35%), with a median PFS of 2.1 months (95% CI, 1.4-3.4).⁴

ALISCA-Lung2 Study Design

ALISCA-Lung2 is an open-label, nonrandomized study consisting of sequential dose-escalation cohorts. Approximately 10 patients will be enrolled at each of 5 planned alisertib dose levels: 30, 40, 50, 60, and 70 mg twice daily. Alisertib is administered orally on days 1 through 7 of each 21-day cycle, while paclitaxel is administered intravenously at 60 mg/m² on days 1 and 8.²

Dose escalation is based on safety during the first 21-day cycle. If 3 or fewer patients experience a protocol-defined event during cycle 1, the alisertib dose may increase by 10 mg twice daily in the subsequent cohort. The planned dose is not expected to exceed 70 mg twice daily. Granulocyte colony-stimulating factor is administered following the final alisertib or paclitaxel dose of each treatment cycle.²

Eligible patients must be at least 18 years old, have pathologically confirmed SCLC with measurable disease according to RECIST 1.1, and have received a platinum-based chemotherapy regimen and an anti–PD-1 or anti–PD-L1 immunotherapy. Up to 1 additional systemic anticancer regimen for SCLC is permitted, for a maximum of 2 prior treatment regimens. Patients previously treated with an aurora kinase A-specific or pan-aurora kinase inhibitor, including alisertib, are excluded.²

The primary end point is the incidence of treatment-emergent adverse events and serious adverse events from the first dose through 28 days after the last dose. Secondary end points include objective response rate, duration of response, disease control rate, PFS, and OS. Exploratory analyses will assess biomarkers in tumor and liquid biopsy samples.^1,2

“The results from previous clinical trials of alisertib in small cell lung cancer, including those in combination with paclitaxel, 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,” Owonikoko stated.¹

References

1. Puma Biotechnology. Puma Biotechnology Initiates ALISCA-Lung2, a Phase II Trial of Alisertib in Combination With Paclitaxel for the Treatment of Patients With Advanced Small Cell Lung Cancer. Published September 17, 2026. Accessed September 28, 2026. https://tinyurl.com/4mmunpc9

2. ClinicalTrials.gov. A Study of Alisertib and Paclitaxel in Patients With Small Cell Lung Cancer (SCLC). NCT07465757. Updated September 24, 2026. Accessed September 28, 2026.

3. Owonikoko TK, Niu H, Nackaerts K, et al. Randomized phase II study of paclitaxel plus alisertib versus paclitaxel plus placebo as second-line therapy for SCLC: primary and correlative biomarker analyses. J Thorac Oncol. 2020;15(2):274-287. doi:10.1016/j.jtho.2019.10.013

4. Melichar B, Adenis A, Lockhart AC, 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)70058-4