Puma Biotechnology Initiates Phase II ALISCA-Lung2 Trial of Alisertib Plus Paclitaxel in Advanced Small Cell Lung Cancer
核心洞察
Puma Biotechnology has initiated the Phase II ALISCA-Lung2 trial (PUMA-ALI-4202; NCT07465757) testing alisertib plus paclitaxel in advanced small cell lung cancer (搜索).
The sequential dose escalation study will enroll approximately 50 patients whose disease progressed on or after platinum-based chemotherapy and immunotherapy.
The primary endpoint is safety and tolerability of alisertib with paclitaxel, with objective response rate, duration of response and survival as secondary endpoints.
Puma Biotechnology, Inc. (NASDAQ: PBYI) announced the initiation of the ALISertib in CAncer (ALISCA®-Lung2) Phase II trial (PUMA-ALI-4202; NCT07465757), evaluating alisertib in combination with paclitaxel for the treatment of patients with advanced small cell lung cancer (搜索). The trial is a sequential dose escalation study that will enroll approximately 50 patients with small cell lung cancer who have progressed on or after treatment with platinum-based chemotherapy and immunotherapy.
Trial Design and Endpoints
The primary endpoint of ALISCA®-Lung2 is the safety and tolerability of alisertib when administered with paclitaxel. Secondary endpoints include objective response rate, duration of response, disease control rate, progression-free survival and overall survival. Puma will also evaluate clinical biomarkers to help identify which patients have the greatest benefit to guide the future development of alisertib.
Alisertib is a selective, small molecule, orally administered inhibitor of aurora kinase A (搜索). Puma entered into an exclusive license agreement for the development and commercialization of the anti-cancer drug in September 2022, and initially intends to focus its development on the treatment of small cell lung cancer (搜索) and breast cancer (搜索).
Rationale in a Setting of Limited Options
Taofeek K. Owonikoko, MD, PhD, Chair of the trial's Steering Committee, framed the study against the current treatment gap. "Treatment options for patients with small cell lung cancer (搜索) 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," said Dr. Owonikoko, Executive Director of the University of Maryland Marlene and Stewart Greenebaum Comprehensive Cancer Center and the Kevin J. Cullen, MD Distinguished Professor of Oncology at the University of Maryland School of Medicine.
He added that prior data support continued evaluation: "The results from previous clinical trials of alisertib in small cell lung cancer (搜索), 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 (搜索) inhibitor such as alisertib."
Positioning Within the Alisertib Program
Alan H. Auerbach, Chief Executive Officer, President and Founder of Puma, said, "We are pleased to initiate this Phase II trial, and we hope that the study will provide important insight into the safety and clinical activity of alisertib in combination with paclitaxel in patients with small cell lung cancer (搜索). We are continuing to advance alisertib monotherapy in the ALISCA®-Lung1 trial as well, and we view the ALISCA®-Lung2 trial as additive to the clinical development of alisertib in small cell lung cancer. We look forward to the progress of both the ALISCA®-Lung1 and ALISCA®-Lung2 trials, as well as our other ongoing clinical programs, in the months ahead."
The company's alisertib development plan includes ALISCA®-Lung1, a Phase II trial of alisertib monotherapy initiated in February 2024 for patients with extensive stage small cell lung cancer (搜索), and ALISCA®-Breast1, a Phase II trial initiated in November 2024 of alisertib in combination with endocrine therapy for patients with HER2 (搜索)-negative, HR-positive metastatic breast cancer (搜索). ALISCA®-Lung2 was initiated in September 2026.
Company Context
Puma Biotechnology is a biopharmaceutical company focused on the development and commercialization of innovative products to enhance cancer care. The company in-licensed the global development and commercialization rights to PB272 (neratinib, oral) in 2011. Neratinib was approved by the U.S. Food and Drug Administration in 2017 for the extended adjuvant treatment of adult patients with early stage HER2 (搜索)-overexpressed/amplified breast cancer (搜索) following adjuvant trastuzumab-based therapy, and is marketed in the United States as NERLYNX® (neratinib) tablets. In February 2020, NERLYNX was also approved by the FDA in combination with capecitabine for the treatment of adult patients with advanced or metastatic HER2-positive breast cancer who have received two or more prior anti-HER2-based regimens in the metastatic setting. NERLYNX was granted marketing authorization by the European Commission in 2018 for the extended adjuvant treatment of adult patients with early stage hormone receptor-positive HER2-overexpressed/amplified breast cancer who are less than one year from completion of prior adjuvant trastuzumab-based therapy.