Biopharmaceutical company Puma Biotechnology Inc (NASDAQ: PBYI) announced on Wednesday that it has commenced the ALISCA-Breast1 Phase II trial to evaluate alisertib in combination with endocrine therapy for hormone receptor-positive (HR+), HER2-negative metastatic breast cancer. The study targets patients previously treated with CDK 4/6 inhibitors and at least two lines of endocrine therapy in the metastatic setting.

The trial will enroll up to 150 participants randomised to three dosing regimens of alisertib (30 mg, 40 mg, or 50 mg) alongside endocrine therapy. Biomarker analysis will accompany the clinical evaluation to identify optimal dosing and potential biomarker-driven response patterns. Primary endpoints include objective response rate, disease control, progression-free survival, and overall survival, with interim analyses planned for safety and efficacy assessments.

Positive results may prompt discussions with the U.S. Food and Drug Administration to explore an approval pathway. A pivotal Phase III trial design comparing alisertib plus endocrine therapy to placebo is under consideration following dose optimization.

Alisertib development aligns with Puma's strategic expansion beyond its flagship NERLYNX (neratinib), an FDA-approved treatment for early-stage HER2-positive breast cancer. Licensed in September 2022, alisertib represents Puma's focus on addressing unmet needs in breast and small-cell lung cancer.

The ALISCA-Breast1 trial launch follows the February 2024 initiation of ALISCA-Lung1, a Phase II study of alisertib monotherapy in extensive-stage small cell lung cancer.