Efficacy of pembrolizumab and vorinostat combination in patients with recurrent and/or metastatic squamous cell carcinomas: a phase 2 basket trial

被引：0

作者：

Borcoman, Edith ^{[1
,2
,3
,4
]}

Cabarrou, Bastien ^{[5
]}

Francisco, Miguel ^{[6
,7
]}

Bigot, Frederic ^{[8
]}

Ghiringhelli, Francois ^{[9
]}

Vansteene, Damien ^{[10
]}

Legrand, Francois ^{[11
]}

Halladjian, Maral ^{[1
]}

Dupain, Celia ^{[1
]}

Le Saux, Olivia ^{[12
]}

Coutzac, Clelia ^{[12
]}

Borel, Christian ^{[13
]}

Chaltiel, Raphael ^{[14
]}

You, Benoit ^{[15
]}

Gomez-Roca, Carlos ^{[16
]}

Cousin, Sophie ^{[17
]}

Coquan, Elodie ^{[18
]}

Lambert, Aurelien ^{[19
]}

Saada-Bouzid, Esma ^{[20
,21
]}

Durando, Xavier ^{[22
]}

Saint-Ghislain, Mathilde ^{[1
]}

Frige, Gianmaria ^{[23
]}

Guerini-Rocco, Elena ^{[24
,25
]}

Tonini, Maria Manuela ^{[26
]}

Bieche, Ivan ^{[27
]}

Castel-Ajgal, Zahra ^{[1
]}

Marret, Gregoire ^{[1
]}

Sablin, Marie-Paule ^{[1
]}

Jeannot, Emmanuelle ^{[28
]}

Andre, Fabrice ^{[29
]}

Filleron, Thomas ^{[5
]}

Jimenez, Marta ^{[11
]}

Mazzarella, Luca ^{[30
,31
,32
]}

Servant, Nicolas ^{[6
]}

Kamal, Maud ^{[1
]}

Le Tourneau, Christophe ^{[1
,6
,7
]}

机构：

[1] Inst Curie, Dept Drug Dev & Innovat D3i, Paris, France

[2] Inst Curie, INSERM, U932, Immun & Canc, Paris, France

[3] Inst Curie, Translat Res Dept, Translat Immunotherapy Team, Paris, France

[4] Univ Paris Sci Lettres PSL, Paris, France

[5] Oncopole Claudius Regaud, Biostat & Hlth Data Sci Unit, Toulouse, France

[6] Mines Paris Tech, INSERM, U900, Inst Curie, Paris, France

[7] Paris Saclay Univ, Paris, France

[8] Inst Cancerol Ouest, Angers, France

[9] Ctr Georges Francois Leclerc, Dijon, France

[10] Inst Cancerol Ouest, St Herblain, France

[11] Unicancer, Paris, France

[12] Ctr Leon Berard, Med Oncol, Lyon, France

[13] Ctr Paul Strauss, Strasbourg, France

[14] Inst Godinot, Reims, France

[15] Univ Lyon 1, Lyon Univ Hosp HCL, Med Oncol, CITOHL,EPSILYON,IC HCL, Lyon, France

[16] IUCT Oncopole, Inst Claudius Regaud, Toulouse, France

[17] Inst Bergonie, Bordeaux, France

[18] Ctr Francois Baclesse, Caen, France

[19] Inst Cancerol Lorraine, Vandoeuvre Les Nancy, France

[20] Ctr Antoine Lacassagne, Med Oncol Dept, Nice, France

[21] Cote DAzur Univ, Lab Translat Res Oncol, Nice, France

[22] Ctr Jean Perrin, Dept Med Oncol, Clermont Ferrand, France

[23] Ist Europeo Oncol, Expt Oncol, Milan, Italy

[24] European Inst Oncol IRCCS, Div Pathol, Milan, Italy

[25] European Univ Milan, Dept Oncol & Hematooncol, Milan, Italy

[26] Luxembourg Inst Hlth, Translat Med Operat Hub, Strassen, Luxembourg

[27] Inst Curie, Dept Genet, Paris, France

[28] Inst Curie, Dept Pathol, Paris, France

[29] Gustave Roussy, Villejuif, France

[30] European Inst Oncol IRCCS, Lab Translat Oncol, Milan, Italy

[31] European Inst Oncol IRCCS, Div Gatrointestinal Oncol, Milan, Italy

[32] European Inst Oncol IRCCS, Div Adv Mol Diagnost DIMA, Milan, Italy

来源：

NATURE CANCER | 2025年 / 6卷 / 08期

关键词：

INVASIVE CERVICAL-CANCER; DROSOPHILA-MELANOGASTER; HUMAN-PAPILLOMAVIRUS; ELDERLY-PATIENTS; SOLID TUMORS; OPEN-LABEL; HEAD; CHEMOTHERAPY; NIVOLUMAB; INHIBITORS;

D O I：

10.1038/s43018-025-01004-2

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Immune checkpoint inhibitors improve the treatment of many solid tumors and have shown encouraging results in advanced squamous cell carcinoma (SCC), yet only a minority of patients respond to immune checkpoint inhibitor monotherapy. We conducted the PEVOsq trial, an open-label, nonrandomized, multicenter, basket phase 2 trial to evaluate the combination of pembrolizumab and vorinostat in recurrent/metastatic SCC of various origins. The primary endpoint was the objective response rate (ORR) in each tumor cohort during treatment as per the investigators' assessment. Secondary endpoints included safety and antitumor activity evaluation in terms of centrally confirmed ORR, progression-free survival, overall survival and duration of response. In the efficacy population (n = 107), the ORR was met in cervical (39%), anal (31%) and vulvar/vaginal (19%) cancer cohorts, but not in head and neck SCC (19%) or penile (18%) cancer cohorts (overall ORR = 26%). Median progression-free survival was 4.0 months (95% confidence interval: 2.6-4.3), and median overall survival was 11.1 months (95% confidence interval: 9.2-17.4). In the safety population, 101 (91%) of 111 patients developed at least one treatment-related adverse event, with 39% and 5.4% of patients experiencing at least one grade 3 and grade 4 treatment-related adverse event, respectively. Vorinostat-related toxicity prompted a dose reduction/interruption in 66% of patients. Whole-exome sequencing analyses revealed several potential predictive biomarkers of response to treatment. Further studies in a larger number of patients are required to validate these findings. ClinicalTrials.gov identifier: NCT04357873.

引用

页码：1370 / 1383

页数：22

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