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Nivolumab plus chemoradiotherapy in locally-advanced cervical cancer: the NICOL phase 1 trial

Author

Listed:
  • Manuel Rodrigues

    (Institut Curie)

  • Giulia Vanoni

    (INSERM U932, PSL Research University, Institut Curie)

  • Pierre Loap

    (Institut Curie)

  • Coraline Dubot

    (Institut Curie)

  • Eleonora Timperi

    (INSERM U932, PSL Research University, Institut Curie)

  • Mathieu Minsat

    (Institut Curie)

  • Louis Bazire

    (Institut Curie)

  • Catherine Durdux

    (Hôpital Européen Georges Pompidou, Department of Radiation Oncology)

  • Virginie Fourchotte

    (Service of Breast and Gynecologic Surgery, Institut Curie)

  • Enora Laas

    (Service of Breast and Gynecologic Surgery, Institut Curie)

  • Nicolas Pouget

    (Service of Breast and Gynecologic Surgery, Institut Curie)

  • Zahra Castel-Ajgal

    (Department of Drug Development and Innovation, Institut Curie)

  • Gregoire Marret

    (Department of Drug Development and Innovation, Institut Curie)

  • Laetitia Lesage

    (Department of Pathology Institut Curie
    Centre d’Investigation Clinique Biothérapie, Institut Curie)

  • Didier Meseure

    (Department of Pathology Institut Curie
    Centre d’Investigation Clinique Biothérapie, Institut Curie)

  • Anne Vincent-Salomon

    (Department of Pathology Institut Curie
    Centre d’Investigation Clinique Biothérapie, Institut Curie)

  • Lolita Lecompte

    (Institut Curie Bioinformatics Platform, INSERM U900, Mines ParisTech)

  • Nicolas Servant

    (Institut Curie Bioinformatics Platform, INSERM U900, Mines ParisTech)

  • Sophie Vacher

    (Pharmacogenomics Unit, Service of Genetics, Institut Curie)

  • Ivan Bieche

    (Pharmacogenomics Unit, Service of Genetics, Institut Curie)

  • Caroline Malhaire

    (Department of Radiology, Institut Curie)

  • Virginie Huchet

    (Department of Nuclear Medicine, Institut Curie)

  • Laurence Champion

    (Department of Nuclear Medicine, Institut Curie)

  • Maud Kamal

    (Department of Drug Development and Innovation, Institut Curie)

  • Sebastian Amigorena

    (INSERM U932, PSL Research University, Institut Curie)

  • Olivier Lantz

    (INSERM U932, PSL Research University, Institut Curie)

  • Marion Chevrier

    (Service of Biostatistics, Institut Curie)

  • Emanuela Romano

    (Institut Curie
    INSERM U932, PSL Research University, Institut Curie)

Abstract

Concurrent chemoradiotherapy (CRT) with blockade of the PD-1 pathway may enhance immune-mediated tumor control through increased phagocytosis, cell death, and antigen presentation. The NiCOL phase 1 trial (NCT03298893) is designed to determine the safety/tolerance profile and the recommended phase-II dose of nivolumab with and following concurrent CRT in 16 women with locally advanced cervical cancer. Secondary endpoints include objective response rate (ORR), progression free survival (PFS), disease free survival, and immune correlates of response. Three patients experience grade 3 dose-limiting toxicities. The pre-specified endpoints are met, and overall response rate is 93.8% [95%CI: 69.8–99.8%] with a 2-year PFS of 75% [95% CI: 56.5–99.5%]. Compared to patients with progressive disease (PD), progression-free (PF) subjects show a brisker stromal immune infiltrate, higher proximity of tumor-infiltrating CD3+ T cells to PD-L1+ tumor cells and of FOXP3+ T cells to proliferating CD11c+ myeloid cells. PF show higher baseline levels of PD-1 and ICOS-L on tumor-infiltrating EMRA CD4+ T cells and tumor-associated macrophages, respectively; PD instead, display enhanced PD-L1 expression on TAMs, higher peripheral frequencies of proliferating Tregs at baseline and higher PD-1 levels at week 6 post-treatment initiation on CD4 and CD8 T cell subsets. Concomitant nivolumab plus definitive CRT is safe and associated with encouraging PFS rates. Further validation in the subset of locally advanced cervical cancer displaying pre-existing, adaptive immune activation is warranted.

Suggested Citation

  • Manuel Rodrigues & Giulia Vanoni & Pierre Loap & Coraline Dubot & Eleonora Timperi & Mathieu Minsat & Louis Bazire & Catherine Durdux & Virginie Fourchotte & Enora Laas & Nicolas Pouget & Zahra Castel, 2023. "Nivolumab plus chemoradiotherapy in locally-advanced cervical cancer: the NICOL phase 1 trial," Nature Communications, Nature, vol. 14(1), pages 1-15, December.
  • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-39383-8
    DOI: 10.1038/s41467-023-39383-8
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