Phase 2 Study Evaluating Safety and Tolerability of Alisertib Combined with Paclitaxel in Patients with Small Cell Lung Cancer

The primary objective is to evaluate safety and tolerability of escalating doses of alisertib administered on days 1‑7 combined with paclitaxel given on days 1 and 8 of a 21‑day cycle in patients with small cell lung cancer, providing critical information on the acceptability of this regimen for further clinical development. The secondary objective is to determine investigator‑assessed efficacy of the combination therapy within the study population, generating data on antitumor activity that may inform therapeutic benefit.

Twenty participants were enrolled, comprising both male and female adults aged ≥18 years. All subjects had a confirmed diagnosis of Small Cell Lung Cancer that was the primary malignancy, with measurable disease outside the central nervous system per RECIST v1.1. Enrollment required prior exposure to at least one platinum‑based chemotherapy regimen and an anti‑PD‑1/PD‑L1 immunotherapy, with progression after these treatments; a maximum of two prior systemic regimens was permitted. Participants were required to provide a recent formalin‑fixed paraffin‑embedded tumor specimen, archival tissue being acceptable. The cohort represented patients who were otherwise eligible for routine clinical care and did not include individuals classified as vulnerable under regulatory definitions. No specific dietary, physical activity, or habit‑related criteria were stipulated for inclusion.

This Phase 2 study evaluates the safety, tolerability, and preliminary efficacy of alisertib (140 mg oral daily on Days 1–7) in combination with paclitaxel (60 mg/m² IV on Days 1 and 8) administered in 21‑day cycles to patients with Small Cell Lung Cancer. The trial follows a single‑arm, open‑label design with scheduled assessments over multiple treatment cycles until disease progression, unacceptable toxicity, withdrawal of consent, or study termination. The visit schedule includes: screening (eligibility verification, baseline laboratory tests, and provision of a formalin‑fixed paraffin‑embedded tissue sample), baseline/pre‑treatment (confirmation of dosing schedule and baseline imaging), cycle visits (clinical evaluation, laboratory safety tests, adverse event monitoring, and drug administration on Days 1 and 8), imaging assessments for tumor response every two cycles, and an end‑of‑study visit (final safety and efficacy evaluations). Participants are expected to remain in the study for the duration of treatment, typically ranging from several weeks to many months depending on response and tolerability. Early termination criteria include occurrence of grade ≥ 3 drug‑related toxicities, disease progression as defined by RECIST v1.1, or patient/physician decision to discontinue therapy. Primary endpoints focus on Adverse Events per NCI CTCAE v5.0, while secondary endpoints include objective response rate, duration of response, disease control rate, progression‑free survival, and overall survival.

The investigational regimen includes Alisertib administered as enteric‑coated tablets containing alisertib sodium. Each tablet delivers a dose of 140 mg and is taken orally once daily on Days 1 through 7 of each 21‑day treatment cycle.

In the same protocol, paclitaxel is provided as a 6 mg/mL solution for infusion. The dose is calculated at 60 mg/m² and is administered intravenously on Days 1 and 8 of each 21‑day cycle.

Both agents are given in combination for patients with Small Cell Lung Cancer. Dosing follows a repeating 21‑day schedule, with alisertib given for a seven‑day consecutive period and paclitaxel given on two separate days. Compliance with oral alisertib administration is monitored through patient diaries and pill counts at each study visit, while infusion administration is documented in the clinical record to confirm timing and dose accuracy.

Efficacy will be evaluated using the secondary endpoints of Objective response rate (ORR), duration of response (DOR), disease control rate (DCR), progression‑free survival (PFS), and overall survival (OS). These parameters will be derived from clinical and radiographic assessments performed throughout the study period.