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

Manuel Rodrigues, Giulia Vanoni, Pierre Loap, Coraline Dubot, Eleonora Timperi, Mathieu Minsat, Louis Bazire, Catherine Durdux, Virginie Fourchotte, Enora Laas, Nicolas Pouget, Zahra Castel-Ajgal, Gregoire Marret, Laetitia Lesage, Didier Meseure, Anne Vincent-Salomon, Lolita Lecompte, Nicolas Servant, Sophie Vacher, Ivan Bieche, Caroline Malhaire, Virginie Huchet, Laurence Champion, Maud Kamal, Sebastian Amigorena, Olivier Lantz, Marion Chevrier and Emanuela Romano ()
Additional contact information
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
Didier Meseure: Department of Pathology Institut Curie
Anne Vincent-Salomon: Department of Pathology 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

Nature Communications, 2023, vol. 14, issue 1, 1-15

Abstract: 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.

Date: 2023
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DOI: 10.1038/s41467-023-39383-8

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