Puma Biotechnology Initiates Phase II ALISCA®-Lung2 Trial of Alisertib and Paclitaxel in Advanced Small Cell Lung Cancer
Puma Biotechnology, Inc. (NASDAQ: PBYI), a biopharmaceutical company focused on developing innovative cancer therapies, has announced the initiation of its Phase II ALISertib in CAncer (ALISCA®-Lung2) clinical trial evaluating alisertib in combination with paclitaxel for patients with advanced small cell lung cancer (SCLC). The study, designated PUMA-ALI-4202 and registered on ClinicalTrials.gov as NCT07465757, is designed to investigate the safety, tolerability and preliminary clinical activity of the combination in patients whose disease has progressed following treatment with platinum-based chemotherapy and immunotherapy.
The initiation of ALISCA®-Lung2 represents another step in Puma Biotechnology’s clinical development strategy for alisertib in small cell lung cancer. The company is evaluating the investigational therapy both as a monotherapy and in combination with paclitaxel through separate clinical programs.
The ALISCA®-Lung2 study is expected to enroll approximately 50 patients with small cell lung cancer. It will use a sequential dose-escalation design to examine alisertib administered together with paclitaxel. The trial will focus on patients with advanced disease who have experienced progression on or after standard treatment involving platinum-based chemotherapy and immunotherapy.
Phase II Study Targets Patients With Limited Treatment Options
Small cell lung cancer is an aggressive form of lung cancer characterized by rapid tumor growth and a tendency to spread to other parts of the body. Although treatment approaches have advanced, patients whose disease progresses following initial platinum-based chemotherapy and immunotherapy continue to face significant therapeutic challenges.
The ALISCA®-Lung2 trial is therefore designed to explore an additional treatment strategy for patients whose disease has progressed after these commonly used systemic therapies.
The primary objective of the Phase II study is to assess the safety and tolerability of alisertib when administered in combination with paclitaxel. Safety assessments will help investigators characterize the adverse events and other tolerability considerations associated with the treatment combination and determine appropriate dosing as the program progresses.
In addition to its primary safety objective, the study will evaluate several measures of antitumor activity. Secondary endpoints include objective response rate (ORR), duration of response (DOR), disease control rate (DCR), progression-free survival (PFS) and overall survival (OS).
Together, these measures are intended to provide a broader assessment of how patients respond to the combination and how long potential treatment benefits may persist.
Puma also plans to evaluate clinical biomarkers during the trial. The biomarker work is intended to help identify patient populations that may derive greater benefit from alisertib and could provide information for subsequent clinical development.
Investigating Aurora Kinase A Inhibition
Alisertib is being developed as an inhibitor of Aurora kinase A, a protein involved in cell division and other processes that are important for tumor cell proliferation. The rationale for targeting Aurora kinase A in cancer is based on its role in regulating the cell cycle and maintaining proper chromosome segregation.
By inhibiting Aurora kinase A, alisertib is being investigated for its potential to interfere with mechanisms that cancer cells use to continue dividing and growing.
The ALISCA®-Lung2 trial will examine this mechanism in combination with paclitaxel. Paclitaxel is a chemotherapy agent that interferes with microtubule function and cell division. Combining agents that affect different aspects of tumor-cell proliferation is one approach being investigated in oncology to determine whether complementary mechanisms can produce clinically meaningful activity.
According to Puma, earlier clinical studies of alisertib in small cell lung cancer, including studies evaluating the drug in combination with paclitaxel, provide the basis for continued investigation of the regimen.
Expert Highlights Need for New SCLC Treatments
Taofeek K. Owonikoko, MD, PhD, Chair of the ALISCA®-Lung2 trial’s Steering Committee, emphasized the limited treatment options available for patients whose small cell lung cancer has progressed after platinum-based chemotherapy and immunotherapy.
“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,” Dr. Owonikoko said.
Dr. Owonikoko is Executive Director of the University of Maryland Marlene and Stewart Greenebaum Comprehensive Cancer Center and serves as the Kevin J. Cullen, MD Distinguished Professor of Oncology at the University of Maryland School of Medicine.
He also pointed to previous clinical research involving alisertib in small cell lung cancer as part of the rationale for further evaluation.
According to Dr. Owonikoko, previous trials, including studies of alisertib combined with paclitaxel, have generated findings that support continued investigation of the treatment approach. He noted that the potential activity of the therapy may be particularly relevant to subsets of patients whose tumors contain molecular markers that could be associated with sensitivity to Aurora kinase A inhibition.
The biomarker component of ALISCA®-Lung2 is consequently an important element of the study design. By examining clinical biomarkers alongside treatment outcomes, researchers may be able to identify biological characteristics associated with response and use those findings to inform later-stage development.
Multiple Clinical Development Paths for Alisertib
Puma Biotechnology is advancing alisertib through more than one clinical development strategy in small cell lung cancer.
In addition to the newly initiated ALISCA®-Lung2 Phase II trial, the company is continuing to evaluate alisertib as a monotherapy in the ALISCA®-Lung1 trial. Puma described the two studies as complementary components of its broader effort to evaluate the potential role of alisertib in small cell lung cancer.
The ALISCA®-Lung2 study will specifically examine the combination of alisertib and paclitaxel, while the ALISCA®-Lung1 program is evaluating alisertib alone. Data generated from the separate studies could contribute to the company’s understanding of the drug’s activity, safety profile and potential patient populations.
Alan H. Auerbach, Chief Executive Officer, President and Founder of Puma Biotechnology, said the company is pleased to begin the Phase II combination trial.
“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,” Auerbach said.
He added that Puma will continue advancing the alisertib monotherapy program through ALISCA®-Lung1 and views ALISCA®-Lung2 as an additional component of the company’s clinical development efforts in SCLC.
Study Could Provide Biomarker Insights
One of the notable features of ALISCA®-Lung2 is its planned evaluation of clinical biomarkers. Biomarker research has become an increasingly important part of oncology drug development because cancers that appear similar based on their tissue of origin can have substantially different molecular characteristics.
Identifying biomarkers associated with treatment response could potentially help researchers understand which patients are most likely to benefit from a particular targeted therapy. In the case of alisertib, Puma is investigating whether certain molecular characteristics may be associated with activity related to Aurora kinase A inhibition.
The company’s biomarker analysis will therefore be conducted alongside clinical assessments such as response rate, disease control, progression-free survival and overall survival.
However, the Phase II study is primarily intended to generate clinical information regarding safety and activity. Findings from the trial would need to be evaluated together with results from other studies before conclusions could be drawn regarding the drug’s potential role in the treatment of small cell lung cancer.
Advancing the ALISCA Clinical Program
The initiation of ALISCA®-Lung2 adds another clinical study to Puma Biotechnology’s broader development program for alisertib. The company is pursuing the therapy in different treatment settings and is continuing to evaluate how its activity may translate into potential therapeutic options for patients with cancer.
For patients with advanced small cell lung cancer whose disease has progressed following platinum-based chemotherapy and immunotherapy, the ALISCA®-Lung2 population represents a setting in which additional treatment approaches are being investigated.
The approximately 50-patient trial is expected to provide data across several important clinical parameters. Safety and tolerability will be the primary focus, while efficacy-related endpoints and biomarker assessments are intended to provide additional information about the potential clinical activity of the combination.
As enrollment and treatment progress, investigators will assess objective tumor responses and disease control, as well as measures of how long patients remain without disease progression and overall survival. The duration of response endpoint will also help characterize the persistence of responses among patients who experience tumor shrinkage.
Puma said it looks forward to continued progress in both ALISCA®-Lung1 and ALISCA®-Lung2, alongside its other ongoing clinical programs.
The initiation of the Phase II ALISCA®-Lung2 trial marks an important development in the company’s evaluation of alisertib for small cell lung cancer. By studying alisertib together with paclitaxel in patients who have progressed after platinum-based chemotherapy and immunotherapy, Puma aims to generate additional evidence on the combination’s safety and clinical activity while exploring biomarkers that may help define responsive patient populations.
Results from the study, together with data from the ongoing alisertib monotherapy program, are expected to contribute to the company’s understanding of how Aurora kinase A inhibition could be developed as part of the treatment landscape for small cell lung cancer.
About Puma Biotechnology
Puma Biotechnology, Inc. is a biopharmaceutical company with a focus on the development and commercialization of innovative products to enhance cancer care. Puma in-licensed the global development and commercialization rights to PB272 (neratinib, oral) in 2011. Neratinib, oral was approved by the U.S. Food and Drug Administration in 2017 for the extended adjuvant treatment of adult patients with early stage HER2-overexpressed/amplified breast cancer, 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 and who are less than one year from completion of prior adjuvant trastuzumab-based therapy.
NERLYNX® is a registered trademark of Puma Biotechnology, Inc. In September 2022, Puma entered into an exclusive license agreement for the development and commercialization of the anti-cancer drug alisertib, a selective, small molecule, orally administered inhibitor of aurora kinase A. Initially, Puma intends to focus the development of alisertib on the treatment of small cell lung cancer and breast cancer. In February 2024, Puma initiated ALISCA®-Lung1, a Phase II clinical trial of alisertib monotherapy for the treatment of patients with extensive stage small cell lung cancer.
In November 2024, Puma initiated ALISCA®-Breast1, a Phase II clinical trial of alisertib in combination with endocrine therapy for the treatment of patients with HER2-negative, HR-positive metastatic breast cancer. In September 2026, Puma initiated ALISCA®-Lung2, a Phase II clinical trial of alisertib in combination with paclitaxel for the treatment of patients with advanced small cell lung cancer. ALISCA® is a registered trademark of Puma Biotechnology, Inc.