Efficacy of pembrolizumab and vorinostat combination in patients with recurrent and/or metastatic squamous cell carcinomas: a phase 2 basket trial
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 .
Authors
- Fabrice André (ORCID: https://orcid.org/0000-0001-5795-8357)
- Carlos Gomez‐Roca (ORCID: https://orcid.org/0000-0002-8043-2529)
- Thomas Filleron (ORCID: https://orcid.org/0000-0003-0724-0659)
- F. Legrand
- Christian Borel (ORCID: https://orcid.org/0000-0002-7710-2086)
- Elena Guerini‐Rocco (ORCID: https://orcid.org/0000-0003-2001-7582)
- Emmanuelle Jeannot (ORCID: https://orcid.org/0000-0002-4851-7450)
- Maral Halladjian (ORCID: https://orcid.org/0000-0001-6126-0031)
- Xavier Durando (ORCID: https://orcid.org/0000-0001-6035-3172)
- Zahra Castel-Ajgal
- Bastien Cabarrou (ORCID: https://orcid.org/0000-0003-1477-6013)
- Damien Vansteene (ORCID: https://orcid.org/0000-0002-4440-0626)
- Ivan Bièche (ORCID: https://orcid.org/0000-0002-2430-5429)
- Luca Mazzarella (ORCID: https://orcid.org/0000-0002-4043-3279)
- Maria Manuela Tonini
- Gianmaria Frigè (ORCID: https://orcid.org/0000-0003-3253-7091)
- François Ghiringhelli (ORCID: https://orcid.org/0000-0002-5465-8305)
- Grégoire Marret (ORCID: https://orcid.org/0000-0003-4525-7777)
- Nicolas Servant (ORCID: https://orcid.org/0000-0003-1678-7410)
- Maud Kamal (ORCID: https://orcid.org/0000-0003-1466-0950)
- Clélia Coutzac (ORCID: https://orcid.org/0000-0002-8347-6957)
- Elodie Coquan (ORCID: https://orcid.org/0000-0002-9497-0424)
- Christophe Le Tourneau (ORCID: https://orcid.org/0000-0001-9772-4686)
- Mathilde Saint‐Ghislain (ORCID: https://orcid.org/0000-0001-9432-6762)
- Olivia Le Saux (ORCID: https://orcid.org/0000-0002-7815-323X)
- R. Chaltiel
- Benoît You (ORCID: https://orcid.org/0000-0002-3177-8857)
- Marta Jimenez (ORCID: https://orcid.org/0000-0002-4233-8478)
- Frédéric Bigot (ORCID: https://orcid.org/0000-0001-5890-107X)
- Aurélien Lambert (ORCID: https://orcid.org/0000-0001-9990-1201)
- Miguel Francisco
- Célia Dupain (ORCID: https://orcid.org/0000-0001-6248-140X)
- Édith Borcoman (ORCID: https://orcid.org/0000-0002-5393-5657)
- Sophie Cousin
- Marie-Paule Sablin
- Esma Saâda-Bouzid
Institutions
- Université Claude Bernard Lyon 1 (FR)
- Inserm (FR)
- Université Paris Sciences et Lettres (FR)
- Université Paris-Saclay (FR)
- Institut Gustave Roussy (FR)
- Centre Georges François Leclerc (FR)
- Institut de Cancérologie de Lorraine (FR)
- Hospices Civils de Lyon (FR)
- Luxembourg Institute of Health (LU)
- Centre Léon Bérard (FR)
- Institut de Cancérologie de l'Ouest (FR)
- Immunité et Cancer (FR)
- Translational Research in Oncology (FR)
- European School of Oncology (IT)
- Centre François Baclesse (FR)
- Centre Jean Perrin (FR)
- Institut Claudius Regaud (FR)
- Institut Bergonié (FR)
- UniCancer Group (FR)
- Centre Antoine Lacassagne (FR)
- Institut Jean Godinot (FR)
- European Institute of Oncology (IT)
- École Nationale Supérieure des Mines de Paris (FR)
- Institut Curie (FR)
- HCL Technologies (India) (IN)
Publication Details
- Journal
- Nature Cancer
- Published
- 2025-06-30
- DOI
- https://doi.org/10.1038/s43018-025-01004-2
- Citations
- 5
- Primary Topic
- Cancer Immunotherapy and Biomarkers
- Type
- article
- Field-Weighted Citation Impact
- 5.23
Funders
- Amgen
- Bristol-Myers Squibb
- Eli Lilly and Company
- Pfizer
- AstraZeneca
- Sanofi
- Celgene
- F. Hoffmann-La Roche
- Les Laboratories Pierre Fabre
- European Commission
- Agence Nationale de la Recherche
- Fonds National de la Recherche Luxembourg
- Ministero della Salute
- Eisai
- Fondation ARC pour la Recherche sur le Cancer
- Servier
- PharmaMar
- Unicancer
- Genentech
- Foundation Medicine
- Daiichi Sankyo Europe