Evidence map›Paper›PMID 39589337›Full record

Trial reportClinical cancer research : an official journal of the American Association for Cancer Research2025

Phase I/II Study of the Aurora Kinase A Inhibitor Alisertib and Pembrolizumab in Refractory, Rb-Deficient Head and Neck Squamous Cell Carcinomas.

Faye M Johnson, Madison P O'Hara, Lacin Yapindi, Peixin Jiang, Hai T Tran, Alexandre Reuben, Weihong Xiao, Maura L Gillison, Xiaowen Sun, Alexander Khalaf and 3 more

Abstract readClinical Trial, Phase IIClinical Trial, Phase I
In one paragraph

Trial report in Clinical cancer research : an official journal of the American Association for Cancer Research, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

6 citing papers in PubMed.

  1. Dual Inhibition of TRIP13 and Aurora A Induces Mitotic DNA Damage and Concurrent Pyroptotic-Apoptotic Cell Death in Rb-Deficient Cancer Cells.Clinical cancer research : an official journal of the American Association for Cancer Research · 2026
    Article
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

13 authors.

Faye M JohnsonDepartment of Thoracic/Head & Neck Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas.ORCID 0000-0002-2862-4160
Madison P O'HaraDepartment of Thoracic/Head & Neck Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas.ORCID 0009-0009-2435-3410
Lacin YapindiDepartment of Thoracic/Head & Neck Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas.ORCID 0000-0002-9429-7583
Peixin JiangDepartment of Thoracic/Head & Neck Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas.ORCID 0009-0005-8033-1639
Hai T TranDepartment of Thoracic/Head & Neck Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas.ORCID 0000-0003-4065-9355
Alexandre ReubenDepartment of Thoracic/Head & Neck Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas.ORCID 0000-0003-4510-0382
Weihong XiaoDepartment of Thoracic/Head & Neck Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas.ORCID 0000-0003-4132-213X
Maura L GillisonDepartment of Thoracic/Head & Neck Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas.ORCID 0000-0002-8145-5749
Xiaowen SunDepartment of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, Texas.ORCID 0009-0002-2207-6789
Alexander KhalafDepartment of Neuroradiology, The University of Texas MD Anderson Cancer Center, Houston, Texas.ORCID 0000-0001-6366-6318
J Jack LeeDepartment of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, Texas.ORCID 0000-0001-5469-9214
Jagannadha K SastryDepartment of Thoracic/Head & Neck Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas.ORCID 0000-0002-6987-4422
Soma GhoshDepartment of Thoracic/Head & Neck Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas.ORCID 0000-0002-9133-8538

Funding

Tumor Evolution and Metastasis ProgramP30CA016672 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI DIANE BODURKA · 1985 to 2026
$290.8M
Harnessing Aurora kinase inhibition‐induced cell death to enhance immunotherapy in HPV‐driven cancersR01CA248205 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI JOHNSON, FAYE, SASTRY, JAGANNADHA K · 2020 to 2024
$1.8M
Division of Cancer Prevention, National Cancer Institute (DCP, NCI) R01CA248205National Cancer Institute (NCI) P30CA016672NCI NIH HHS P30 CA016672NCI NIH HHS R01 CA248205
6 · The paper itself

Abstract

purposeEffective therapy for recurrent head and neck squamous cell carcinoma (HNSCC) that is refractory to chemotherapy and immunotherapy is a considerable need. Aurora kinase A inhibition leads to apoptosis and immunogenic cell death in preclinical models of human papilloma virus (HPV)-driven cancers. PATIENTS AND

methodsAlisertib was administered orally twice daily on days 1-7 and pembrolizumab on day 1 of a 21-day cycle to adults with advanced solid tumors (phase I) or with immunotherapy- and platinum-resistant, HPV-positive HNSCC (phase II).

resultsThe recommended phase II alisertib dose was 40 mg, which had only the expected toxicity including cytopenia that led to dose reductions in two phase II patients at cycles 13 and 16. We saw no objective responses, but the combination led to prolonged stable disease (SD) in several patients, including two of 10 phase I patients (8 and 27 months). Eight of the 15 HPV-positive patients had SD, of which four (heavily pretreated) had ≥6 months, with median overall and progression-free survival durations of 16.8 and 1.4 months, respectively. In circulating immune cells and plasma, patients with SD had markedly higher levels of HLA de novo resistance-expressing NK cells than did progressive disease patients who demonstrated a more immunosuppressive and inflammatory profile. Pharmacokinetics did not indicate any significant drug-drug interactions between pembrolizumab and alisertib.

conclusionsThe combination of alisertib and pembrolizumab was well tolerated and led to prolonged SD in some immunotherapy-resistant patients, supporting our hypothesis that Aurora kinase A inhibition can reverse immunotherapy resistance of retinoblastoma protein-deficient HNSCC.

Indexed as

Antineoplastic Combined Chemotherapy ProtocolsAurora Kinase AAzepinesHead and Neck NeoplasmsPyrimidinesSquamous Cell Carcinoma of Head and NeckAdultAgedAntibodies, Monoclonal, HumanizedDrug Resistance, NeoplasmFemaleHumansMaleMiddle AgedProtein Kinase InhibitorsAntibodies, Monoclonal, HumanizedAURKA protein, humanAurora Kinase AAzepinesMLN 8237pembrolizumabProtein Kinase InhibitorsPyrimidines

Identifiers

PMID39589337
PMCPMC11790391

What Socratic holds

Textmetadata
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Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.