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Squamous Cell Lung CancerPhase 2PEVOsqNCT04357873

Efficacy of Immunotherapy Plus a Drug in Patients With Progressive Advanced Mucosal Cancer of Different Locations

A Phase 2 study testing pembrolizumab; vorinostat in people with Squamous Cell Lung Cancer and Vulvar Cancer, run by UNICANCER at 14 sites in France.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial summary

Interventional study evaluating the efficacy of an immunotherapy (pembrolizumab) in combination with a targeted therapy (vorinostat) in patient with recurrent and/or metastatic squamous cell carcinoma (localisations : head and neck, lung, cervix, anus, vulva, and penis) Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
pembrolizumab; vorinostat
Could I receive a placebo?
No, everyone receives an active treatment
How many people
112 participants
Where
14 sitesFrance
Study dates
28 Oct 2020to 26 Nov 2024
Phase
Phase 2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Aged ≥18 years old.
  • Patients with Eastern Cooperative Oncology Group (ECOG) performance status ≤1.
  • Patients must have histologically confirmed recurrent and/or metastatic squamous cell carcinoma of the head and neck, cervix, lung, anus, vulva, or penis.
  • Patients must have radiologically confirmed progressive recurrent and/or metastatic disease.
  • Patients naive or previously treated for recurrent and/or metastatic disease for which a treatment with an anti-PD1/PD-L1 agents and vorinostat is an acceptable option according to investigator.
  • Disease amenable to biopsy for study purpose.
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  • Measurable disease according to RECIST v1.1.
  • Adequate renal function: serum creatinine ≤1.5 x upper limit of normal (ULN) (OR creatinine clearance [Cockcroft and Gault] ≥30 mL/min for participant with creatinine levels >1.5 × ULN) within 14 days prior inclusion.
  • Adequate liver function: aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels ≤3 × ULN (≤5 ULN when documented liver metastases) and total bilirubin level ≤1.5 × ULN, within 14 days prior inclusion.
  • Adequate bone marrow function: absolute neutrophil count (ANC) ≥1,000/mm³, platelet count ≥100,000/mm³, and hemoglobin ≥9 g/dL, within 14 days prior inclusion.
  • Adequate coagulation: prothrombin time (PT)/international normalized ratio (INR) ≤1.5 × ULN within 14 days prior inclusion If participant is receiving anticoagulant therapy then the PT or activated partial thromboplastin time (aPTT) should be within the therapeutic range of intended use of anticoagulant.
  • Female of child-bearing potential must have a negative serum pregnancy test within 72 h before starting study treatment.
  • Female of childbearing potential, must use "highly effective" methods of contraception for the study duration and for 4 months following the last dose of pembrolizumab and 6 months following the last dose of vorinostat.
  • Male participants must agree to use an effective contraceptive for the duration of the trial and for at least 4 months after the last the last dose of pembrolizumab and 6 months following the last dose of vorinostat (to allow for effective elimination of the study drugs). Also, they should refrain from donating sperm during this period.
  • Patients must be willing and able to comply with the protocol for the duration of the study including scheduled visits, treatment plan, and laboratory tests.
  • Patients must be willing and able to comply with other study procedures, including a baseline tumor biopsy and a series of blood samples throughout the study.
  • Patients able to swallow oral medications.
  • Patients must be affiliated to a Social Security System (or equivalent).
  • Patients must have signed a written informed consent prior to any trial-specific procedures. When the patient is physically unable to give their written consent, a trusted person of their choice, independent from the investigator or the sponsor, can confirm in writing the patient's consent.

Who cannot join

  • Prior treatment with anti-PD-1/PD-L1 agents or histone deacetylases (HDAC) inhibitors.
  • Patients with central nervous system involvement that has not been controlled for >3 months.
  • Patients with no other site for biopsy than bone lesions.
  • Patients with other concurrent severe and/or uncontrolled medical disease which could compromise participation in the study, including uncontrolled diabetes, cardiac disease, uncontrolled hypertension, congestive cardiac failure, ventricular arrhythmias, active ischemic heart disease, myocardial infection within one year, chronic liver or renal disease, active gastrointestinal tract ulceration, severely impaired lung function.
  • Known history of human immunodeficiency virus (HIV), Hepatitis B virus (HBV; defined as Hepatitis B surface antigen [HBsAg] reactive) or known active Hepatitis C virus (HCV; defined as HCV RNA detected) virus infection.
  • History of autoimmune disease with the exception of:
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  • (1) Patients with a history of autoimmune hypothyroidism on a stable dose of thyroid replacement hormone,
  • (2) Patients with controlled Type 1 diabetes mellitus on a stable insulin regimen,
  • (3) Patients with eczema, psoriasis, lichen simplex chronicus, or vitiligo with dermatologic manifestations only (e.g., patients with psoriatic arthritis would be excluded) provided that they meet the following conditions: (i) Rash must cover less than 10% of body surface area; (ii) Disease is well controlled at baseline and only requiring low potency topical steroids; (iii) No acute exacerbations of underlying condition within the previous 12 months (not requiring psoralen plus ultraviolet A radiation [PUVA], methotrexate, retinoid, biologic agents, oral calcineurin inhibitors, high-potency or oral steroids).
  • History of allogeneic organ or bone marrow transplantation.
  • History of non-infectious pneumonitis that required steroids or has current pneumonitis.
  • Has an active infection requiring systemic therapy.
  • Has received a live vaccine within 30 days prior to the first dose of study drug. Examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, varicella/zoster (chicken pox), yellow fever, rabies, Bacillus Calmette-Guérin (BCG), and typhoid vaccine. Seasonal influenza vaccines for injection are generally killed virus vaccines and are allowed; however, intranasal influenza vaccines (eg, FluMist®) are live attenuated vaccines and are not allowed.
  • Known prior severe hypersensitivity to investigational products or its excipients,
  • Has received prior systemic anti-cancer therapy including investigational agents within 4 weeks [could consider shorter interval for kinase inhibitors or other short half-life drugs] prior to first dose of study treatments.
  • Note: Participants must have recovered from all adverse events due to previous therapies to ≤Grade 1 or baseline. Participants with ≤Grade 2 neuropathy may be eligible.
  • Has received prior radiotherapy within 2 weeks of start of study treatment. Participants must have recovered from all radiation-related toxicities, not require corticosteroids, and not have had radiation pneumonitis. A 1-week washout is permitted for palliative radiation (≤2 weeks of radiotherapy) to non-central nervous system disease.
  • Major surgery within 28 days prior to the first dose of study treatments. Note: Local surgery of isolated lesions for palliative intent is acceptable.
  • Current or prior use of immunosuppressive medication within 7 days before the first dose of pembrolizumab. The following are exceptions to this criterion:
  • Intranasal, inhaled, topical steroids, or local steroid injections (e.g., intra articular injection),
  • Systemic corticosteroids at physiologic doses ≤10 mg/day of prednisone or its equivalent,
  • Steroids as premedication for hypersensitivity reactions (e.g., CT scan premedication).
  • Patients using drugs that could have pharmacokinetics interaction with investigational drugs. This includes, but is not limited to, valproic acid, coumarin-derivative anticoagulants, drugs that disrupt electrolyte levels, drugs that may prolong QT.
  • Pregnant women or women who are breast-feeding.
  • Patients enrolled in another therapeutic study within 30 days prior to inclusion and during the treatment period. Patients can participate in an independent approved non-interventional studies.
  • Patients unwilling or unable to comply with the medical follow-up required by the trial because of geographic, familial, social, or psychological reasons.
  • Persons deprived of their liberty or under protective custody or guardianship

Trial locations and contacts

14 sites in 1 country.

14 sites in 1 country

France14 sites

  • Institut de Cancérologie de l'Ouest - Site Paul Papin

    Angers

  • Institut Bergonié

    Bordeaux

  • Centre François Baclesse

    Caen

  • Centre Jean Perrin

    Clermont-Ferrand

  • Centre George François Leclerc

    Dijon

  • Centre Oscar Lambret

    Lille

  • Centre Léon Bérard

    Lyon

  • Institut de Cancérologie de Lorraine

    Nancy

  • Institut de Cancérologie de l'Ouest (site René Gauducheau)

    Nantes

  • Institut Curie

    Paris

  • Centre Hospitalier Lyon Sud - Hospices Civils de Lyon

    Pierre-Bénite

  • Institut Godinot

    Reims

  • Centre Paul Strauss

    Strasbourg

  • Institut Claudius Regaud

    Toulouse

Other trials in France

About this study

Official title: Phase II Basket Trial Evaluating the Efficacy of a Combination of Pembrolizumab and Vorinostat in Patients With Recurrent and/or Metastatic Squamous Cell Carcinoma

Interventional study evaluating the efficacy of an immunotherapy (pembrolizumab) in combination with a targeted therapy (vorinostat) in patient with recurrent and/or metastatic squamous cell carcinoma (localisations : head and neck, lung, cervix, anus, vulva, and penis)

Read the detailed description

Open-label, non-randomized, multi-center, basket phase II trial, evaluating the efficacy of pembrolizumab in combination with vorinostat in adult patients with recurrent and/or metastatic squamous cell carcinoma of different locations.

Antitumor activity of the combination will be evaluated using the objective response rate (ORR) during treatment (investigator assessment).

Being tested
pembrolizumab; vorinostat
Keywords
squamous cell carcinoma, squamous cell cancer
Medical subject headings
Vulvar Neoplasms, Penile Neoplasms, Uterine Cervical Neoplasms, Squamous Cell Carcinoma of Head and Neck, Anus Neoplasms, Carcinoma, Squamous Cell, Neoplasms, Squamous Cell

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • pembrolizumab; vorinostatDrug

    Also called KEYTRUDA; ZOLINZA

    Pembrolizumab: 200 mg every 3 weeks, up to 35 administrations

    Vorinostat: 400 mg once daily, until progression

Study groups in NCT04357873
Study groupRoleWhat they receive
pembrolizumab + vorinostatExperimentalPembrolizumab: 200 mg every 3 weeks, up to 35 administrations Vorinostat: 400 mg once daily, until progression
Receives: Drug: pembrolizumab; vorinostat

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Objective Response Rate (ORR), investigator assessment

    Investigators will assess the ORR. The ORR is defined in each cohort as the percentage of evaluable patients for ORR, designate as the proportion of patients with best response of complete response (CR) or a partial response (PR) during treatment according to response evaluation criteria in solid tumors version 1.1 (RECIST v1.1).

    Measured: From inclusion to first and subsequent tumor assesment or progression, up to 24 months

Secondary outcomes (6)

  1. Objective Response Rate (ORR), central assessment

    ORR defined as the proportion of patients with best response of CR or PR during treatment, as assessed by a central radiological panel according to RECIST v1.1.

    Measured: From inclusion to first and subsequent tumor assesment or progression, up to 36 months

  2. immune Objective Response Rate (iORR), central assessment

    ORR defined as the proportion of patients with best response of CR or PR during treatment, as assessed by a central radiological panel according to immune-specific response criteria.

    Measured: From inclusion to first and subsequent tumor assesment or progression, up to 36 months

  3. Duration Of Response (DOR)

    DOR will be evaluated in patients with either CR or PR. DOR is defined as the time from the first assessment of a CR or PR until the date of the first occurrence of progressive disease (PD) or death from any cause (if death occurred within predefined period), whichever occurs first.

    Measured: From the first assessment of a CR or PR until the date of the first occurrence of PD or death from any cause

  4. Progression Free Survival (PFS)

    PFS is defined per RECIST v1.1 as the time from inclusion until disease progression (per RECIST v1.1) or death from any cause, whichever occurs first. At the time of analysis, a patient alive and without disease progression will be censored at the date of the last tumor assessment. Patients alive without disease progression who started a new anticancer therapy will be censored at the date of the last tumor assessment prior to the start of the new anticancer therapy.

    Measured: From inclusion to disease progression or death, up to 36 months

  5. immune Progression Free Survival (iPFS)

    iPFS is defined per immune-specific response evaluation criteria in solid tumors (iRECIST) as the time from inclusion until confirmed disease progression (per iRECIST), or death from any cause, whichever occurs first. At the time of analysis, a patient alive and without progression will be censored at the date of the last tumor assessment. Patients alive without disease progression who started a new anti-cancer therapy will be censored at the date of the last tumor assessment prior to the start of the new anticancer therapy.

    Measured: From inclusion to disease progression or death, up to 36 months

  6. Overall Survival (OS)

    OS is defined as the time from inclusion until death from any cause. Patients who are alive at last follow-up news will be censored at this date.

    Measured: From inclusion to death from any cause, up to 36 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted22 Apr 2020
  2. Study start28 Oct 2020
  3. Primary completion15 Dec 2022
  4. Study completion26 Nov 2024

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Model description
6 independent cohorts (head and neck, cervix, lung, anus, vulva, and penis) evaluating the association of pembrolizumab and vorinostat
Masking
None (open label)
Enrolment
112 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04357873
Sponsor's protocol ID
UC-GMP-1908
Other IDs
2019-003839-33, 2019
Acronym
PEVOsq
Status last verified
Feb 2024
First submitted
20 Apr 2020
Last updated
19 Feb 2025
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No: Individual Participant Data will not be shared at an individual level. Those data will be part of the study database including all enrolled patients.

Publications

  • Filippini DM, Cabarrou B, Dupain C, Halladjian M, Coquan E, Sablin MP, Mazzarella L, Francisco M, Servant N, Tonini MM, Hundt AF, Castel-Ajgal Z, You B, Bigot F, Ghiringhelli F, Vansteene D, Gomez-Roca C, Cousin S, Lambert A, Saada-Bouzid E, Durando X, Abdeddaim C, Borel C, Chaltiel R, Borcoman E, Legrand F, Bernhart S, Jimenez M, Bieche I, Filleron T, Le Tourneau C, Kamal M, Jeannot E. HPV circulating tumor DNA to monitor response to pembrolizumab and vorinostat combination in patients with advanced HPV-related squamous-cell carcinomas. ESMO Open. 2026 Jan;11(1):106024. doi: 10.1016/j.esmoop.2025.106024. Epub 2025 Dec 29.

    PubMed 41468684

  • Borcoman E, Cabarrou B, Francisco M, Bigot F, Ghiringhelli F, Vansteene D, Legrand F, Halladjian M, Dupain C, Le Saux O, Coutzac C, Borel C, Chaltiel R, You B, Gomez-Roca C, Cousin S, Coquan E, Lambert A, Saada-Bouzid E, Durando X, Saint-Ghislain M, Frige G, Guerini-Rocco E, Tonini MM, Bieche I, Castel-Ajgal Z, Marret G, Sablin MP, Jeannot E, Andre F, Filleron T, Jimenez M, Mazzarella L, Servant N, Kamal M, Le Tourneau C. Efficacy of pembrolizumab and vorinostat combination in patients with recurrent and/or metastatic squamous cell carcinomas: a phase 2 basket trial. Nat Cancer. 2025 Aug;6(8):1370-1383. doi: 10.1038/s43018-025-01004-2. Epub 2025 Jun 30.

    PubMed 40588522

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing pembrolizumab; vorinostat in people with Squamous Cell Lung Cancer and Vulvar Cancer, run by UNICANCER at 14 sites in France.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 19 inclusion and 27 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 19 Feb 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 14 sites in France. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Objective Response Rate (ORR), investigator assessment (time frame: From inclusion to first and subsequent tumor assesment or progression, up to 24 months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04357873, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Feb 2025.

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