A Study of Alisertib and Paclitaxel in Patients With Small Cell Lung Cancer (SCLC) (ALISCA-Lung2)

A Phase 2 Study of Alisertib in Combination With Paclitaxel in Patients With Small Cell Lung Cancer

The goal of this clinical trial is to determine how well people tolerate treatment with alisertib at different doses when it is used together with paclitaxel to treat people with SCLC. The main question it aims to answer is:

• What percentage of side effects, both mild and serious, do participants experience when being treated with alisertib and paclitaxel based on the National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0 (NCI CTCAE v.5.0)?

The study will consist of different groups, called cohorts, in which alisertib will be studied at increasing doses. Participants in the first group, Cohort 1, will take 30 mg of alisertib by mouth 2 times a day. The dose will increase by 10 mg 2 times a day for each new cohort of participants joining the study. Side effects will be checked during the study, and the decision to increase the dose of alisertib will be based on the specific side effects experienced during the first 21 days of treatment for each cohort.

Participants will:

• take alisertib by mouth on their own 2 times a day from Day 1 through Day 7 of each 21-day cycle and will be given paclitaxel intravenously at a dose of 60 mg/m2 on Day 1 and Day 8 of each 21-day cycle.
• be given a preventive treatment to increase their body defenses, called granulocyte-colony stimulating factor (G-CSF). Study staff will give G-CSF after the last dose of alisertib or paclitaxel of each 21-day cycle in which alisertib was given.
• provide blood samples to evaluate the different levels of alisertib in the blood at different times. Blood samples will be collected on Days 1 and 7 of the first and second 21-day cycles of treatment.
• be treated with alisertib and paclitaxel until death, worsening of the disease, unacceptable toxicity, unwillingness to continue participating in the trial, or other criteria that requires participants to stop treatment and participation in the study.
• be contacted every 8 weeks after stopping alisertib and paclitaxel treatment as part of a specific study phase called the long-term follow-up period. This will last until death, unwillingness to continue participating in the trial, or until the end of the study.

Study Overview

• Status: Not yet recruiting
• Conditions: Small Cell Lung Cancer ( SCLC )
• Intervention / Treatment: Drug: Alisertib; Drug: Alisertib; Drug: Alisertib; Drug: Alisertib; Drug: Alisertib; Drug: Paclitaxel

Detailed Description

This is a Phase 2 open label study evaluating increasing doses of alisertib administered in combination with paclitaxel in patients with pathologically confirmed small cell lung cancer (SCLC) following progression on or after treatment with up to 2 prior treatment regimens. Patients must have received treatment with platinum-based chemotherapy and an anti-programmed death receptor 1 (PD-1) or anti-programmed death-ligand 1 (PD-L1) immunotherapy agent. Patients must have measurable disease as defined by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1.

Starting with alisertib 30 mg twice a day (BID) in Cohort 1 and increasing in each successive cohort by 10 mg BID, each dosing cohort will enroll approximately 10 safety-evaluable patients to assess safety. Toxicity will be assessed throughout the study using NCI CTCAE v5.0, and decisions regarding escalating the alisertib dose will be based on the occurrence of Events during Cycle 1 (Days 1-21) of each dose level. If 3 or fewer patients experience an Event during Cycle 1, then the alisertib dose may be increased by 10 mg BID at the next dose level. It is not anticipated that the planned dosage of alisertib would exceed 70 mg BID. At the time 10 patients have completed Cycle 1 or the maximum number (4) of Events has been reached, whichever is sooner, the Sponsor will hold enrollment until a decision on moving to the next dose level is made.

• Study Type: Interventional
• Enrollment (Estimated): 50
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Puma Biotechnology, Inc. Clinical Operations Senior Director; Phone Number: 424-248-6500; Email: ClinicalTrials@pumabiotechnology.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Aged ≥18 years at signing of informed consent
• Pathologically confirmed SCLC
• Prior treatment with one platinum-based chemotherapy and an anti-PD-1/PD-L1 immunotherapy. Up to one additional systemic anti-cancer therapy for SCLC is allowed, for a total of up to 2 prior treatment regimens
• Measurable disease as defined by RECIST v1.1

Exclusion Criteria:

• Prior treatment with an aurora kinase A (AURKA) specific-targeted or pan-Aurora- targeted agent, including alisertib, in any setting

There are additional inclusion and exclusion criteria. The study center will determine if you meet all of the criteria.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cohort 1: Alisertib 30 mg BID + Paclitaxel; Approximately ten participants will be enrolled in the cohort. Alisertib dose may be increased by 10 mg BID in the next cohort if 3 or fewer participants experience an Event during Cycle 1.	Drug: Alisertib; Alisertib enteric-coated tablets, 30 mg BID self-administered orally on Days 1-7 of every 21-day cycle; Other Names: MLN8237; PB-8237; Drug: Alisertib; Alisertib enteric-coated tablets, 40 mg BID self-administered orally on Days 1-7 of every 21-day cycle; Other Names: MLN8237; PB-8237; Drug: Alisertib; Alisertib enteric-coated tablets, 50 mg BID self-administered orally on Days 1-7 of every 21-day cycle; Other Names: MLN8237; PB-8237; Drug: Alisertib; Alisertib enteric-coated tablets, 60 mg BID self-administered orally on Days 1-7 of every 21-day cycle; Other Names: MLN8237; PB-8237; Drug: Alisertib; Alisertib enteric-coated tablets, 70 mg BID self-administered orally on Days 1-7 of every 21-day cycle; Other Names: MLN8237; PB-8237; Drug: Paclitaxel; 60 mg/m^2 IV on Days 1 and 8 of every 21-day cycle
Experimental: Cohort 2: Alisertib 40 mg BID + Paclitaxel; Approximately ten participants will be enrolled in the cohort. Alisertib dose may be increased by 10 mg BID in the next cohort if 3 or fewer participants experience an Event during Cycle 1.	Drug: Alisertib; Alisertib enteric-coated tablets, 30 mg BID self-administered orally on Days 1-7 of every 21-day cycle; Other Names: MLN8237; PB-8237; Drug: Alisertib; Alisertib enteric-coated tablets, 40 mg BID self-administered orally on Days 1-7 of every 21-day cycle; Other Names: MLN8237; PB-8237; Drug: Alisertib; Alisertib enteric-coated tablets, 50 mg BID self-administered orally on Days 1-7 of every 21-day cycle; Other Names: MLN8237; PB-8237; Drug: Alisertib; Alisertib enteric-coated tablets, 60 mg BID self-administered orally on Days 1-7 of every 21-day cycle; Other Names: MLN8237; PB-8237; Drug: Alisertib; Alisertib enteric-coated tablets, 70 mg BID self-administered orally on Days 1-7 of every 21-day cycle; Other Names: MLN8237; PB-8237; Drug: Paclitaxel; 60 mg/m^2 IV on Days 1 and 8 of every 21-day cycle
Experimental: Cohort 3: Alisertib 50 mg BID + Paclitaxel; Approximately ten participants will be enrolled in the cohort. Alisertib dose may be increased by 10 mg BID in the next cohort if 3 or fewer participants experience an Event during Cycle 1.	Drug: Alisertib; Alisertib enteric-coated tablets, 30 mg BID self-administered orally on Days 1-7 of every 21-day cycle; Other Names: MLN8237; PB-8237; Drug: Alisertib; Alisertib enteric-coated tablets, 40 mg BID self-administered orally on Days 1-7 of every 21-day cycle; Other Names: MLN8237; PB-8237; Drug: Alisertib; Alisertib enteric-coated tablets, 50 mg BID self-administered orally on Days 1-7 of every 21-day cycle; Other Names: MLN8237; PB-8237; Drug: Alisertib; Alisertib enteric-coated tablets, 60 mg BID self-administered orally on Days 1-7 of every 21-day cycle; Other Names: MLN8237; PB-8237; Drug: Alisertib; Alisertib enteric-coated tablets, 70 mg BID self-administered orally on Days 1-7 of every 21-day cycle; Other Names: MLN8237; PB-8237; Drug: Paclitaxel; 60 mg/m^2 IV on Days 1 and 8 of every 21-day cycle
Experimental: Cohort 4: Alisertib 60 mg BID + Paclitaxel; Approximately ten participants will be enrolled in the cohort. Alisertib dose may be increased by 10 mg BID in the next cohort if 3 or fewer participants experience an Event during Cycle 1.	Drug: Alisertib; Alisertib enteric-coated tablets, 30 mg BID self-administered orally on Days 1-7 of every 21-day cycle; Other Names: MLN8237; PB-8237; Drug: Alisertib; Alisertib enteric-coated tablets, 40 mg BID self-administered orally on Days 1-7 of every 21-day cycle; Other Names: MLN8237; PB-8237; Drug: Alisertib; Alisertib enteric-coated tablets, 50 mg BID self-administered orally on Days 1-7 of every 21-day cycle; Other Names: MLN8237; PB-8237; Drug: Alisertib; Alisertib enteric-coated tablets, 60 mg BID self-administered orally on Days 1-7 of every 21-day cycle; Other Names: MLN8237; PB-8237; Drug: Alisertib; Alisertib enteric-coated tablets, 70 mg BID self-administered orally on Days 1-7 of every 21-day cycle; Other Names: MLN8237; PB-8237; Drug: Paclitaxel; 60 mg/m^2 IV on Days 1 and 8 of every 21-day cycle
Experimental: Cohort 5: Alisertib 70 mg BID + Paclitaxel; Approximately ten participants will be enrolled in the cohort.	Drug: Alisertib; Alisertib enteric-coated tablets, 30 mg BID self-administered orally on Days 1-7 of every 21-day cycle; Other Names: MLN8237; PB-8237; Drug: Alisertib; Alisertib enteric-coated tablets, 40 mg BID self-administered orally on Days 1-7 of every 21-day cycle; Other Names: MLN8237; PB-8237; Drug: Alisertib; Alisertib enteric-coated tablets, 50 mg BID self-administered orally on Days 1-7 of every 21-day cycle; Other Names: MLN8237; PB-8237; Drug: Alisertib; Alisertib enteric-coated tablets, 60 mg BID self-administered orally on Days 1-7 of every 21-day cycle; Other Names: MLN8237; PB-8237; Drug: Alisertib; Alisertib enteric-coated tablets, 70 mg BID self-administered orally on Days 1-7 of every 21-day cycle; Other Names: MLN8237; PB-8237; Drug: Paclitaxel; 60 mg/m^2 IV on Days 1 and 8 of every 21-day cycle

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants with Treatment-Emergent Adverse Events (Adverse Events and Serious Adverse Events)	Treatment emergent adverse events are those events reported on or after the first dose of investigational product and up to 28 days after the last dose.	From date of first dose through last dose plus 28 days, assessed up to 24 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective Response Rate (ORR)	ORR is defined as the proportion of participants demonstrating a confirmed Complete or Partial Response during the treatment phase of the study.	From date of first dose to first confirmed Complete or Partial Response, assessed up to 24 months
Duration of response (DOR)	DOR is measured from the time at which measurement criteria are first met for confirmed Complete or Partial Response (whichever status is recorded first) until the first date of recurrence or progressive disease (PD) or death is objectively documented.	From start date of response to first PD or death, assessed up to 24 months
Disease Control Rate (DCR)	DCR is defined as the proportion of patients who achieve overall tumor response (confirmed Complete or Partial Response) or Stable Disease lasting for at least 12 weeks from first dose of investigational product.	From date of first dose to first confirmed Complete or Partial Response, whichever came earlier, assessed up to 24 months
Progression Free Survival (PFS)	PFS is measured in months and based on the local tumor assessment. The time interval from the date of first dose until the first date on which recurrence, progression, or death due to any cause, is documented.	From date of first dose to date of recurrence, progression or death, assessed up to 24 months
Overall Survival (OS)	OS is defined as the time from date of first dose to death due to any cause, censored at the last date known alive on or prior to the data cutoff employed for the analysis, whichever was earlier.	From date of first dose to death, assessed up to 24 months

Collaborators and Investigators

• Sponsor: Puma Biotechnology, Inc.
• Investigators: Study Director: Chief Reg Affairs, Med Affairs, Pharmacovigilance Officer, Puma Biotechnology, Inc.

Study record dates

Study Major Dates

• Study Start (Estimated): September 30, 2026
• Primary Completion (Estimated): March 31, 2028
• Study Completion (Estimated): September 30, 2028

Study Registration Dates

• First Submitted: March 6, 2026
• First Submitted That Met QC Criteria: March 6, 2026
• First Posted (Actual): March 12, 2026

Study Record Updates

• Last Update Posted (Actual): March 12, 2026
• Last Update Submitted That Met QC Criteria: March 6, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: SCLC; alisertib
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Respiratory Tract Diseases; Lung Diseases; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Small Cell Lung Carcinoma; Organic Chemicals; Hydrocarbons; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Terpenes; Taxoids; Cyclodecanes; Diterpenes; Paclitaxel; MLN 8237
• Other Study ID Numbers: PUMA-ALI-4202; 2026-525382-47-00 (Ctis)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD Plan Description

Puma Biotechnology is committed to sharing clinical trial data and information to help physicians and patients make informed treatment decisions, and to help qualified researchers advance scientific knowledge.

In accordance with legal and regulatory requirements, Puma publishes study protocol information and clinical study results on clinical trial registries, including ClinicalTrials.gov and EU Clinical Trials Register. Puma also publishes information about clinical studies in peer-reviewed scientific journals and shares data in scientific meetings.

Puma commits to safeguarding confidentiality and patient privacy throughout the clinical trial data and information sharing process. Any patient-level data will be anonymized to protect personally identifiable information.

Qualified researchers and study participants may submit requests for other study documentation and clinical trial data to clinicaltrials@pumabiotechnology.com for consideration.

• IPD Sharing Time Frame: Clinical study documents and clinical trial data may be requested by qualified researchers and study participants for studies that have been completed for at least 18 months, and for which the indication of the drug has been approved in the US and/or EU, as applicable. Requests will be accepted for up to 24 months after the criteria described in this section are met.

IPD Sharing Access Criteria

Requestors must provide organizational contact information; a detailed research plan, including outcomes; timeline for completion of the research; qualifications of the research team; funding source; and potential conflicts of interest.

Puma will not provide access to patient-level data if there is a reasonable likelihood that individual patients could be identified, or in cases where confidentiality or consent provisions prohibit transfer of data or information to third parties. Additionally, Puma will not disclose information that jeopardizes intellectual property rights or divulges confidential commercial information.

• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No