Alisertib + Pembrolizumab for Head and Neck Cancer

Overseen By Faye M Johnson, MD

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: M.D. Anderson Cancer Center

Must be taking: PD-1/PD-L1 checkpoint blockade

Must not be taking: Proton pump inhibitors

Disqualifiers: Organ transplant, Uncontrolled infection, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

Duration: Approximately 33 months

24 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores the effectiveness of combining two drugs, alisertib and pembrolizumab, for treating head and neck cancer. Alisertib aims to stop cancer cells from growing, while pembrolizumab, an immunotherapy, helps the immune system attack cancer cells. The trial seeks participants with Rb-deficient head and neck cancer, particularly those who have not found success with other treatments. Participants should have previously tried treatments like PD-1 or PD-L1 therapies and experienced cancer progression. As a Phase 1, Phase 2 trial, this research focuses on understanding the treatment's effects in people and measuring its effectiveness in an initial, smaller group, offering participants a chance to contribute to groundbreaking cancer treatment advancements.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that using alisertib with pembrolizumab may help treat certain cancers. Studies have found that this combination is generally well-tolerated, though it can have side effects.

For alisertib, individuals with liver problems might experience higher drug levels in their bodies, potentially leading to more side effects. In other cases, the side effects are manageable. Pembrolizumab, already used for other cancers, is usually safe but can cause immune-related side effects due to increased immune activity.

Overall, past research suggests that the combination is tolerable. It is important to consult a doctor to understand personal risks and benefits. ^{1 2 3 4 5}

Why are researchers excited about this study treatment for head and neck cancer?

Researchers are excited about alisertib combined with pembrolizumab for head and neck cancer because this duo targets cancer in a new way. Alisertib is a unique drug that blocks a protein called Aurora A kinase, which helps cancer cells divide and grow. Pembrolizumab is an immune therapy that boosts the body's ability to fight cancer by targeting a checkpoint protein called PD-1. Together, these treatments could potentially stop cancer growth more effectively than current treatments, which often include chemotherapy and radiation, by both blocking cancer cell growth and enhancing the immune response.

What evidence suggests that alisertib and pembrolizumab might be an effective treatment for head and neck cancer?

This trial will evaluate the combination of alisertib and pembrolizumab for managing Rb-deficient head and neck cancers. Research has shown that this combination might help manage these cancers, which lack a protein that usually controls cell growth. Early tests suggest that alisertib, which blocks a protein called Aurora kinase A, can enhance the effectiveness of immune-based treatments like pembrolizumab. Some patients who no longer responded to other treatments found their cancer stopped growing with this combination. Cancers missing the Rb protein seem to depend on Aurora kinases to survive, so blocking them might be a promising strategy. Overall, this combination holds promise for these difficult-to-treat cancers. ^{2 3 6 7 8}

Who Is on the Research Team?

Faye M. Johnson

Principal Investigator

M.D. Anderson Cancer Center

Are You a Good Fit for This Trial?

This trial is for patients with Rb-deficient head and neck squamous cell cancer, who have no standard curative therapy available. They must not have had prior treatments that target PD-1/PD-L1 or similar immune pathways, should be in a relatively stable condition (ECOG <=2), and able to swallow medication. Women of childbearing potential and men must agree to use contraception.

Inclusion Criteria

My doctor thinks I can't handle chemotherapy as a first treatment.

My treatment is not the first attempt to manage my condition.

My kidney function is good, with a creatinine clearance rate of at least 30 ml/min.

Exclusion Criteria

I will not donate sperm during the study or for 120 days after the last dose.

I have a GI condition or had surgery that may affect medication absorption.

I am on long-term steroids not just for adrenal replacement.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive alisertib orally twice daily on days 1-7 and pembrolizumab intravenously on day 1. Cycles repeat every 21 days.

Approximately 33 months

Follow-up

Participants are monitored for safety and effectiveness after treatment completion every 2-3 months.

Approximately 33 months

What Are the Treatments Tested in This Trial?

Interventions

• Alisertib
• Pembrolizumab

Trial Overview The trial is testing the combination of Alisertib, which may block cancer growth, with Pembrolizumab, an immunotherapy drug that helps the immune system attack tumors. It's designed to see what doses are best and how effective this combo is against head and neck cancers lacking the Rb protein.

How Is the Trial Designed?

Group I: Treatment (alisertib, pembrolizumab) Experimental Treatment 2 Interventions

Patients receive alisertib PO BID on days 1-7 and pembrolizumab IV over 30 minutes on day 1. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity.

Alisertib is already approved in United States, European Union for the following indications:

Approved in United States as Alisertib for:

• Acute myeloid leukemia (AML)

Approved in European Union as Alisertib for:

• None approved; under investigation for various cancers

Who Is Running the Clinical Trial?

M.D. Anderson Cancer Center

Lead Sponsor

Trials

3,107

Recruited

1,813,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39589337/

Phase I/II Study of the Aurora Kinase A Inhibitor Alisertib and ... The combination of alisertib and pembrolizumab was well tolerated and led to prolonged SD in some immunotherapy-resistant patients, ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT04555837

Alisertib and Pembrolizumab for the Treatment of Patients ... Giving alisertib in combination with pembrolizumab may help control Rb-deficient head and neck squamous cell cancer. HPV positive head and neck cancers are Rb- ...

3. aacrjournals.org aacrjournals.org/clincancerres/article/31/3/479/751211/Phase-I-II-Study-of-the-Aurora-Kinase-A-Inhibitor

Phase I/II Study of the Aurora Kinase A Inhibitor Alisertib and ... Data from preclinical models suggest that inhibition of Aurora kinase A (AURKA; Aurora A) may enhance the efficacy of ICI in patients with HPV-positive HNSCC.

4. researchgate.net researchgate.net/publication/386145575_Phase_12_Study_of_the_Aurora_Kinase_A_Inhibitor_Alisertib_and_Pembrolizumab_in_Refractory_Rb-Deficient_Head_and_Neck_Squamous_Cell_Carcinomas

Phase I/II Study of the Aurora Kinase A Inhibitor Alisertib ... Purpose Effective therapy for recurrent head and neck squamous cell carcinoma (HNSCC) that is refractory to chemotherapy and immunotherapy ...

5. aacrjournals.org aacrjournals.org/mct/article/22/12_Supplement/LB_C12/730612/Abstract-LB-C12-Alisertib-and-pembrolizumab-in-Rb

Abstract LB_C12: Alisertib and pembrolizumab in Rb-deficient ... Preclinical studies demonstrate that cancers with retinoblastoma (Rb) loss are dependent upon Aurora kinases for survival.

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11790391/

Phase 1/2 Study of the Aurora Kinase A Inhibitor Alisertib and ... Purpose: Effective therapy for recurrent head and neck squamous cell carcinoma (HNSCC) that is refractory to chemotherapy and immunotherapy is a ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9274904/

Population Pharmacokinetics and Exposure‐Safety ... Adult patients with moderate or severe hepatic impairment have ≈150% higher unbound alisertib exposures compared with patients with normal hepatic function. A ...

8. cdn.clinicaltrials.gov cdn.clinicaltrials.gov/large-docs/37/NCT04555837/Prot_SAP_000.pdf

Alisertib MDACC Subsequently, flat dose-exposure response relationships were also observed in other tumor types including head and neck cancer, bladder cancer, ...