Alisertib and Pembrolizumab for the Treatment of Patients With Rb-deficient Head and Neck Squamous Cell Cancer

NCT04555837 | Completed Phase 1 Results DMC FDA Drug

• 2 other identifiers: 2020-0210NCI-2020-05051
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

Brief Summary

This phase I/II trial investigates the best dose and effect of alisertib in combination with pembrolizumab in treating patients with Rb-deficient head and neck squamous cell cancer. Alisertib may help block the growth of cancer.. Immunotherapy with monoclonal antibodies, such as pembrolizumab, may help the body's immune system attack the tumor, and may interfere with the ability of tumor cells to grow and spread. 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-deficient.

Conditions

Head and Neck Squamous Cell Carcinoma; Malignant Solid Neoplasm

Keywords

head and neck cancer; HPV; Immunotherapy; squamous cancer

Outcome Measures

Primary Outcomes (3)

• Phase I: The Recommended Phase II Dose Determenation. Phase II: Overall Response Rate (ORR) and Progression Free Survival (PFS)

  Phase I: To determine the recommend phase II dose of the combination of alisertib and pembrolizumab

  Approximately 33 months

• Phase II: Overall Response Rate (ORR)

  Phase II: To determine the overall response rate (ORR) of patients with recurrent or metastatic Rb-deficient head and neck squamous cell carcinoma (HNSCC) treated with the combination of pembrolizumab and alisertib.

  Approximately 33 months

• Phase II: Progression Free Survival (PFS)

  Phase II: To determine the progression free survival (PFS) of patients with recurrent or metastatic Rb-deficient head and neck squamous cell carcinoma (HNSCC) treated with the combination of pembrolizumab and alisertib.

  Approximately 33 months

Secondary Outcomes (5)

• The Safety of the Combination of Pembrolizumab and Alisertib

  Adverse events were monitored until off study due to disease progression, death, unacceptable toxicity, consent withdrawal, or physician's discretion, approximately 33 months.

• The Overall Survival in HNSCC Patients

  28 patients (4 patients were screen failures) enrolled from September 2020 to June 2023, 24 were treated and evaluable for response. Patients were followed for overall survial for approximately 33 months

• The Relationship Between Pharmacokinetics, Pharmacodynamics, Baseline Immune and Tumor Biomarkers and Clinical Responses

  The trial design dictated that if there were no objective responses in thefirst cohort of the phase II study, the trial would close after the first cohort.

• Correlations Between Clinical Responses and the Effect of the Treatment on Human Papilloma Virus (HPV)-Reactive T Cells in HPV+ Cancers.

  The trial design dictated that if there were no objective responses in the first cohort of the phase II study, the trial would close after the first cohort.

• Correlations Between Clinical Responses and Tumor Infiltrating Lymphocyte Function and T Cell Repertoire.

  The trial design dictated that if there were no objective responses in the first cohort of the phase II study, the trial would close after the first cohort.

Study Arms (1)

Treatment (alisertib, pembrolizumab)

EXPERIMENTAL

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.

Drug: Alisertib; Biological: Pembrolizumab

Interventions

Alisertib DRUG

Given PO

Also known as: Aurora A Kinase Inhibitor MLN8237, MLN-8237, MLN8237

Treatment (alisertib, pembrolizumab)

Pembrolizumab BIOLOGICAL

Given IV

Also known as: Keytruda, Lambrolizumab, MK-3475, SCH 900475

Treatment (alisertib, pembrolizumab)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologically or cytological confirmed diagnosis of Rb-deficient HNSCC for which no standard curative therapy is available.
• Rb deficient HNSCC includes CLIA-certified testing confirming one of the following:
• A. HPV positive as determined by any one of the following: p16 immunohistochemistry (IHC), HPV RNA in situ hybridization (ISH), RNAscope (mRNA ISH), DNA ISH, DNA PCR, or qRT PCR.
• B. No Rb protein expression in the tumor as determined by IHC.41, 48 3. Progression on prior treatment with an anti-PD-1 antibody or an anti-PD-L1 antibody.
• A. Has received at least 2 doses of a PD-1/PD-L1 checkpoint blockade therapy. B. Clinical or radiographical progression has been documented within 12 weeks from the last dose of PD-1/PD-L1 checkpoint blockade therapy.
• \. Histologically or cytological confirmed diagnosis of an invasive solid tumor malignancy, for which no standard curative or life prolonging therapy is available.
• Male or female patients ≥ 18 years of age.
• ECOG performance status of ≤ 2 (see section 7.4).
• Clinical laboratory values as specified below within 22 days before the first dose of study drug
• Absolute neutrophil count (ANC) \> 1500/mm³
• Platelets \> 100,000/mm³
• Hgb \> 9 g/dL. Values must be obtained without need for myeloid growth factor or platelet transfusion support within 14 days, however, erythrocyte growth factor is allowed as per published ASCO guidelines.
• Total bilirubin ≤ 1.5 x upper limit of normal (ULN)
• SGOT (AST) and SGPT (ALT)\< 2.5 x ULN. AST and/or ALT may be up to 5X ULN if with known liver mets or total 3 x ULN with direct bilirubin ≤ ULN in patients with well-documented Gilbert syndrome.
• Adequate renal function as defined by calculated creatinine clearance ≥30 ml/min (Cockroft-Gault Formula, see Section 7.5).

You may not qualify if:

• Radiation therapy to more than 25% of the bone marrow. Whole pelvic radiation is considered to be over 25%.
• Prior allogeneic bone marrow or organ transplantation.
• Known gastrointestinal (GI) disease or GI procedures that could interfere with the oral absorption or tolerance of alisertib. Examples include, but are not limited to partial gastrectomy, history of small intestine surgery, and celiac disease.
• Inability to swallow (or use a feeding tube to administer) oral medication or inability or unwillingness to comply with the administration requirements related to alisertib.
• Known history of uncontrolled sleep apnea syndrome and other conditions that could result in excessive daytime sleepiness, such as severe chronic obstructive pulmonary disease; requirement for supplemental oxygen.
• Requirement for constant administration of proton pump inhibitor, H2 antagonist, or pancreatic enzymes throughout the study. The intermittent use of H2-antagonists and antacids (including carafate) is only allowed within these guidelines:
• H2 antagonists until D-1 and after the dosing of alisertib is done
• Antacid formulations until 2 hours before doing and after 2 hours following dosing.
• PPI is allowed until D-5 of first alisertib dose. PPIs are prohibited throughout the study
• Myocardial infarction within 6 months prior to enrollment or has New York Heart Association (NYHA) Class III or IV heart failure (see Section 7.3), uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities. Prior to study entry, any ECG abnormality at Screening has to be documented by the investigator as not medically relevant.
• Female subject who is pregnant or breast-feeding. Confirmation that the subject is not pregnant must be established by a negative urine or serum β-human chorionic gonadotropin (β-hCG) pregnancy test result obtained during screening. Pregnancy testing is not required for post-menopausal or surgically sterilized women.
• Female patient who intend to donate eggs (ova) during the course of this study or 120 days after receiving their last dose of study drug(s).
• Male patients who intend to donate sperm during the course of this study or 120 days after receiving their last dose of study drug(s).
• Other severe acute or chronic medical or psychiatric condition, including uncontrolled diabetes, malabsorption, resection of the pancreas or upper small bowel, requirement for pancreatic enzymes, any condition that would modify small bowel absorption of oral medications, or laboratory abnormality that may increase the risk associated with study participation or investigational product administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the patient inappropriate for enrollment in this study.
• Diagnosed or treated for another invasive malignancy within 2 years of enrollment, with the exception of complete resection of basal cell carcinoma or squamous cell carcinoma of the skin, an in situ malignancy, or low-risk prostate cancer after curative therapy.

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

M D Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Related Links

• MD Anderson Cancer Center

MeSH Terms

Conditions

Squamous Cell Carcinoma of Head and Neck; Head and Neck Neoplasms

Interventions

MLN 8237; pembrolizumab

Condition Hierarchy (Ancestors)

Carcinoma, Squamous Cell; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site

Results Point of Contact

• Title: Faye Johnson, MD
• Organization: The University of Texas MD Anderson Cancer Center

fmjohns@mdanderson.org

(713) 792-6363

Study Officials

• Faye M Johnson, MD

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 14, 2020
• First Posted: September 21, 2020
• Study Start: September 15, 2020
• Primary Completion: April 8, 2025
• Study Completion: April 8, 2025
• Last Updated: May 20, 2025
• Results First Posted: December 16, 2024

Record last verified: 2025-04

Locations

US (1)