Alisertib for Small Cell Lung Cancer

(ALISCA-Lung1 Trial)

Recruiting at 26 trial locations

Overseen By Puma Biotechnology, Inc. Clinical Operations Senior Director

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Recruiting

Sponsor: Puma Biotechnology, Inc.

Must not be taking: AURKA inhibitors

Disqualifiers: Prior AURKA treatment, others

No Placebo Group

Prior Safety Data

Approved in 2 Jurisdictions

Trial Summary

What is the purpose of this trial?

PUMA-ALI-4201 is a Phase 2 study evaluating alisertib monotherapy in patients with pathologically-confirmed small cell lung cancer (SCLC) following progression on or after treatment with one platinum-based chemotherapy and anti-PD-L1 immunotherapy agent. Up to one additional systemic anti-cancer therapy for SCLC is allowed, for a total of up to two prior lines of therapy. This study is intended to identify the biomarker-defined subgroup(s) that may benefit most from alisertib treatment and to evaluate the efficacy, safety, and pharmacokinetics of alisertib.

Do I need to stop my current medications to join the trial?

The trial information does not specify if you need to stop taking your current medications. It's best to discuss this with the study center to understand any specific requirements.

What data supports the effectiveness of the drug Alisertib for Small Cell Lung Cancer?

Research shows that Alisertib, when combined with other drugs like paclitaxel, has been studied as a second-line treatment for small cell lung cancer (SCLC). Additionally, Alisertib has demonstrated anti-tumor activity in various solid tumors, supporting its potential effectiveness in treating SCLC. ^{1 2 3 4 5}

Is alisertib (MLN8237) generally safe for humans?

Alisertib (MLN8237) has been tested in several studies for safety in patients with advanced solid tumors. While it has shown a high safety profile compared to similar treatments, some serious side effects have been reported in clinical trials. ^{1 3 4 6 7}

What makes the drug alisertib unique for treating small cell lung cancer?

Alisertib is unique because it is an oral drug that specifically inhibits Aurora A kinase, a protein involved in cell division, which is not a common target for existing small cell lung cancer treatments. This mechanism allows it to be used alone or in combination with other therapies, potentially offering a new approach for patients who have not responded to standard treatments. ^{1 2 3 4 5}

Research Team

Chief Scientific Officer

Principal Investigator

Puma Biotechnology, Inc.

Eligibility Criteria

This trial is for adults over 18 with extensive-stage small cell lung cancer (ES-SCLC) who have already tried platinum-based chemotherapy and an anti-PDL-1 immunotherapy agent but the cancer has progressed. People can't join if they've previously been treated with AURKA or pan-Aurora-targeted agents, including alisertib.

Inclusion Criteria

My cancer is a type of small cell lung cancer confirmed by a lab test.

My cancer progressed after first-line platinum chemotherapy and I've had anti-PDL-1 treatment.

I am 18 years old or older.

Exclusion Criteria

I have been treated with a drug targeting AURKA or Aurora kinases, like alisertib.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive 50 mg of alisertib PO BID on days 1-7 of each 21-day cycle

21-day cycles, assessed up to 36 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

28 days after last dose

Treatment Details

Interventions

• Alisertib (Anti-mitotic agent)

Trial Overview The study is testing the effectiveness of a drug called Alisertib in patients whose ES-SCLC has worsened despite initial treatments. It aims to understand how safe Alisertib is, how it affects the body, and which specific patient groups might benefit most from it.

Participant Groups

Group I: Alisertib Experimental Treatment 1 Intervention

50 mg of alisertib PO BID on days 1-7 of each 21-day cycle

Who Is Running the Clinical Trial?

Puma Biotechnology, Inc.

Lead Sponsor

Trials

58

Recruited

10,100+

Findings from Research

The phase I study of MLN8237 (alisertib) in 87 adult patients with advanced solid tumors demonstrated that the drug is generally well-tolerated, with common side effects including fatigue, nausea, and neutropenia.

At the maximum tolerated dose of 50 mg twice daily, MLN8237 effectively inhibited Aurora A kinase activity, leading to a partial response in 1% of patients and stable disease in 23% for at least 3 months, suggesting potential efficacy in treating solid tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I study of aurora A kinase inhibitor MLN8237 in advanced solid tumors: safety, pharmacokinetics, pharmacodynamics, and bioavailability of two oral formulations. Dees, EC., Cohen, RB., von Mehren, M., et al.[2021]

In a study of 178 patients with relapsed or refractory small cell lung cancer (SCLC), the combination of alisertib and paclitaxel showed a median progression-free survival (PFS) of 3.32 months, compared to 2.17 months with placebo and paclitaxel, indicating a potential benefit of the treatment.

Patients with specific genetic alterations in cell cycle regulators experienced significantly improved PFS and overall survival when treated with alisertib/paclitaxel, suggesting that these genetic markers could help predict who will benefit most from this therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Randomized Phase II Study of Paclitaxel plus Alisertib versus Paclitaxel plus Placebo as Second-Line Therapy for SCLC: Primary and Correlative Biomarker Analyses. Owonikoko, TK., Niu, H., Nackaerts, K., et al.[2021]

Alisertib, an investigational cancer treatment, showed a 26% increase in total systemic exposure when administered as an oral solution compared to its powder-in-capsule formulation, indicating better bioavailability.

The oral solution of alisertib was absorbed faster than the capsule form, with a quicker peak concentration reached in the bloodstream, suggesting it may be a more effective option for patients who have difficulty swallowing solid medications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Relative bioavailability of a prototype oral solution of the Aurora A kinase inhibitor alisertib (MLN8237) in patients with advanced solid tumors. Falchook, GS., Venkatakrishnan, K., Sarantopoulos, J., et al.[2015]

The combination of alisertib (20 mg twice daily) and docetaxel (75 mg/m²) was found to be safe and well-tolerated in a study involving 41 patients with metastatic cancer, with the recommended phase 2 dose established for future research.

Out of 28 patients evaluated for efficacy, 29% showed objective responses, including one complete response in bladder cancer and several partial responses in prostate cancer and angiosarcoma, indicating potential antitumor activity of the combination.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Open-label, multicenter, phase 1 study of alisertib (MLN8237), an aurora A kinase inhibitor, with docetaxel in patients with solid tumors. Graff, JN., Higano, CS., Hahn, NM., et al.[2018]

Alisertib (MLN8237) is a selective inhibitor of Aurora A kinase, showing promise in treating various cancers, including neuroblastoma and small cell lung cancer, based on its role in cell division and potential non-mitotic functions.

The development of alisertib is guided by scientific insights into Aurora A biology, leading to its evaluation in combination with other therapies like taxanes and EGFR inhibitors to enhance its antitumor activity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Scientific Rationale Supporting the Clinical Development Strategy for the Investigational Aurora A Kinase Inhibitor Alisertib in Cancer. Niu, H., Manfredi, M., Ecsedy, JA.[2023]

Alisertib, a potent Aurora A kinase inhibitor, shows promising anti-cancer effects by improving time to disease progression and progression-free survival in a review of seven studies involving 630 patients.

Despite its efficacy, Alisertib is associated with serious hematological side effects in a significant number of patients, suggesting the need for careful management and consideration of more targeted administration routes to minimize these risks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Critical risk-benefit assessment of the novel anti-cancer aurora a kinase inhibitor alisertib (MLN8237): A comprehensive review of the clinical data. Tayyar, Y., Jubair, L., Fallaha, S., et al.[2018]

The maximum tolerated dose (MTD) of alisertib for East Asian patients with advanced solid tumors or lymphomas was determined to be 30 mg twice daily, which is lower than the 50 mg dose established for Western patients, likely due to higher systemic exposure in this population.

Alisertib was generally well tolerated, with common side effects including neutropenia and stomatitis, and it demonstrated preliminary efficacy, with one patient achieving a partial response and over half of the participants maintaining stable disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase 1 study of the investigational Aurora A kinase inhibitor alisertib (MLN8237) in East Asian cancer patients: pharmacokinetics and recommended phase 2 dose. Venkatakrishnan, K., Kim, TM., Lin, CC., et al.[2022]

References

1. United States pubmed.ncbi.nlm.nih.gov

Phase I study of aurora A kinase inhibitor MLN8237 in advanced solid tumors: safety, pharmacokinetics, pharmacodynamics, and bioavailability of two oral formulations. [2021]

2. United States pubmed.ncbi.nlm.nih.gov

Randomized Phase II Study of Paclitaxel plus Alisertib versus Paclitaxel plus Placebo as Second-Line Therapy for SCLC: Primary and Correlative Biomarker Analyses. [2021]

3. Germany pubmed.ncbi.nlm.nih.gov

Relative bioavailability of a prototype oral solution of the Aurora A kinase inhibitor alisertib (MLN8237) in patients with advanced solid tumors. [2015]

4. United States pubmed.ncbi.nlm.nih.gov

Open-label, multicenter, phase 1 study of alisertib (MLN8237), an aurora A kinase inhibitor, with docetaxel in patients with solid tumors. [2018]

5. Switzerland pubmed.ncbi.nlm.nih.gov

Scientific Rationale Supporting the Clinical Development Strategy for the Investigational Aurora A Kinase Inhibitor Alisertib in Cancer. [2023]

6. Netherlands pubmed.ncbi.nlm.nih.gov

Critical risk-benefit assessment of the novel anti-cancer aurora a kinase inhibitor alisertib (MLN8237): A comprehensive review of the clinical data. [2018]

7. United States pubmed.ncbi.nlm.nih.gov

Phase 1 study of the investigational Aurora A kinase inhibitor alisertib (MLN8237) in East Asian cancer patients: pharmacokinetics and recommended phase 2 dose. [2022]