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Head and Neck Squamous Cell Carcinoma (HNSCC)Phase 2NCT04220866

Study of Intratumoral (IT) Ulevostinag (MK-1454) in Combination With Intravenous (IV) Pembrolizumab (MK-3475) Compared to IV Pembrolizumab Alone as the First Line Treatment of Metastatic or Unresectable, Recurrent Head and Neck Squamous Cell Carcinoma (HNSCC) (MK-1454-002)

A Phase 2 study testing Ulevostinag and Pembrolizumab in people with Head and Neck Squamous Cell Carcinoma (HNSCC), run by Merck Sharp & Dohme LLC at 34 sites in 10 countries.

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

The purpose of this study is to assess the efficacy and safety of intratumoral (IT) ulevostinag PLUS pembrolizumab (MK-3475) compared to pembrolizumab alone as a first line treatment of adults with metastatic or unresectable, recurrent head and neck squamous cell carcinoma (HNSCC). Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Ulevostinag and Pembrolizumab
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
18 participants
Where
34 sitesin 10 countries
Study dates
4 Mar 2020to 30 Sep 2022
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

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

  • Has histologically or cytologically confirmed diagnosis of metastatic or unresectable, recurrent head and neck squamous cell carcinoma (HNSCC) that is considered incurable by local therapies
  • Has not had prior systemic therapy administered in the recurrent or metastatic setting
  • Has tumor PD-L1 expression of CPS ≥1. Tumor tissue must be provided for PD-L1 biomarker analysis
  • Has measurable disease per RECIST 1.1, as assessed by BICR
  • Has at least 1 measurable lesion which is amenable to injection
  • Has an Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1
Show all 12Show fewer
  • Demonstrates adequate organ function within 7 days prior to treatment initiation
  • Male participants of reproductive potential must agree to refrain from donating sperm and use a male condom plus partner use of an additional contraceptive method during sexual contact with females of childbearing potential during the intervention period with ulevostinag and for at least 120 days after the last dose of ulevostinag
  • Female participants of childbearing potential who are not pregnant or breastfeeding must be willing to use a highly effective method of birth control or be surgically sterile or abstain from heterosexual activity during the intervention period and for at least 120 days after the last dose of study intervention, and agree not to donate eggs (ova, oocytes) to others or freeze/store for personal use
  • Human immunodeficiency virus (HIV)-infected participants must meet these additional criteria:
  • Has HIV-1 infection documented by using any licensed rapid HIV test or HIV enzyme or chemiluminescence immunoassay (E/CIA) test kit at any time prior to study entry (Day 1)
  • Has well-controlled HIV on anti-retroviral therapy (ART)

Who cannot join

  • Has disease that is suitable for local therapy administered with curative intent
  • Has progressive disease (PD) within 6 months of completion of curatively intended systemic treatment for locoregionally advanced HNSCC
  • Has had chemotherapy or biological cancer therapy in the recurrent or metastatic setting for the treatment of HNSCC
  • Has had radiation therapy (or other non-systemic therapy) within 2 weeks prior to randomization or participant has not fully recovered from adverse events (AEs) due to a previously administered treatment
  • Is expected to require any other form of antineoplastic therapy while on study
  • Has a history of a second malignancy, unless potentially curative treatment has been completed, with no evidence of malignancy for at least 2 years
Show all 26Show fewer
  • Has clinically active central nervous system (CNS) metastases and/or carcinomatous meningitis
  • Has an active autoimmune disease that has required systemic treatment in the past 2 years
  • Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of study treatment
  • Has had an allogenic tissue/solid organ transplant
  • Has a history of vasculitis
  • Has a history of interstitial lung disease
  • Has an active infection requiring systemic therapy
  • Has a known history of active tuberculosis (TB; Bacillus tuberculosis)
  • Has a history of (non-infectious) pneumonitis that required steroids or current pneumonitis
  • Has had a severe hypersensitivity reaction to treatment a monoclonal antibody/components of the study treatment
  • Has known Hepatitis B virus or Hepatitis C virus infections
  • Has received prior therapy with an anti-programmed cell death 1 (anti-PD-1), anti-programmed cell death-ligand 1 (anti-PD-L1), or anti-programmed cell death-ligand 2 (anti-PD-L2) agent or if the participant has previously participated in Merck Sharp \& Dohme (MSD) MK-3475 clinical trials
  • HIV infected participant who has had an HIV-related opportunistic infection within 6 months
  • HIV infected participants who have a history of Kaposi's sarcoma and/or Multicentric Castleman's Disease
  • Is pregnant, breastfeeding, or expecting to conceive or father children within the projected duration of the study, starting with the screening visit through 120 days after the last dose of study treatment
  • Has not fully recovered from any effects of major surgery without significant detectable infection
  • Has a history of re-irradiation for HNSCC at the projected injection site in the head and neck
  • Has received a live-virus vaccine within 30 days of planned study treatment start
  • Has been treated with a stimulator of interferon genes (STING) agonist (e.g. ulevostinag, ADU-S100)
  • Is currently participating and receiving study therapy or has participated in a study of an investigational agent and received study therapy, or used an investigational device, any of which occurred within 4 weeks of the first dose of study treatment

Trial locations and contacts

34 sites in 10 countries.

34 sites in 10 countries

United States6 sites
  • Henry Ford Hospital ( Site 0012)

    Detroit, Michigan, 48202

  • UCLA Hematology & Oncology ( Site 0005)

    Los Angeles, California, 90095

  • Huntsman Cancer Institute ( Site 0004)

    Salt Lake City, Utah, 84112

  • University of California at San Francisco ( Site 0006)

    San Francisco, California, 94158

  • Sanford Cancer Center Oncology Clinic ( Site 0014)

    Sioux Falls, South Dakota, 57104

  • Washington University ( Site 0021)

    St Louis, Missouri, 63110

Other trials in United States

France5 sites
  • Centre Oscar Lambret ( Site 0071)

    Lille, Nord, 59000

  • Centre Leon Berard ( Site 0072)

    Lyon, Auvergne, 69373

  • Centre Antoine Lacassagne ( Site 0070)

    Nice, Alpes-Maritimes, 06189

  • IUCT - Oncopole ( Site 0069)

    Toulouse, Haute-Garonne, 31059

  • Gustave Roussy ( Site 0068)

    Villejuif, Val-de-Marne, 94800

Other trials in France

Brazil4 sites
  • Centro Regional Integrado de Oncologia ( Site 0062)

    Fortaleza, Ceará, 60336-232

  • Hospital de Caridade de Ijui ( Site 0061)

    Ijuí, Rio Grande do Sul, 98700-000

  • Instituto do Cancer do Estado de Sao Paulo - ICESP ( Site 0058)

    São Paulo, 01246-000

  • Real e Benemerita Associacao Portuguesa de Beneficencia ( Site 0064)

    São Paulo, 01321-001

Other trials in Brazil

Spain4 sites
  • H.U. Vall de Hebron ( Site 0112)

    Barcelona, 08035

  • Hospital Clinico de Barcelona ( Site 0116)

    Barcelona, 08036

  • Hospital Universitario Ramon y Cajal ( Site 0115)

    Madrid, 28034

  • Hospital Universitario Virgen de la Victoria ( Site 0114)

    Málaga, 29010

Other trials in Spain

Australia3 sites
  • Chris OBrien Lifehouse ( Site 0040)

    Camperdown, New South Wales, 2050

  • Monash Health-Monash Medical Centre ( Site 0041)

    Clayton, Victoria, 3168

  • Calvary Central Districts Hospital ( Site 0042)

    Elizabeth Vale, South Australia, 5112

Other trials in Australia

Austria3 sites
  • Ordensklinikum Linz Gmbh - Barmherzige Schwestern ( Site 0051)

    Linz, Upper Austria, 4010

  • SCRI-CCCIT GesmbH ( Site 0050)

    Salzburg, 5020

  • Allgemeines Krankenhaus der Stadt Wien ( Site 0049)

    Vienna/Wien, State of Vienna, 1090

Other trials in Austria

Israel3 sites
  • Rambam Medical Center ( Site 0077)

    Haifa, 3109601

  • Hadassah Medical Center. Ein Kerem ( Site 0078)

    Jerusalem, 9112001

  • Chaim Sheba Medical Center ( Site 0076)

    Ramat Gan, Tel Aviv, 5265601

Other trials in Israel

Norway2 sites
  • Haukeland Universitetssykehus, Klinisk forskningspost voksne ( Site 0086)

    Bergen, Hordaland, 5021

  • Oslo Universitetssykehus Radiumhospitalet ( Site 0085)

    Oslo, 0379

Other trials in Norway

South Korea2 sites
  • Severance Hospital ( Site 0103)

    Seoul, 03722

  • Asan Medical Center ( Site 0104)

    Seoul, 05505

Other trials in South Korea

United Kingdom2 sites
  • Royal Marsden NHS Foundation Trust ( Site 0031)

    London, London, City of, SW3 6JJ

  • Royal Marsden Hospital Sutton-Surrey ( Site 0032)

    Sutton, Surrey, SM2 5PT

Other trials in United Kingdom

About this study

Official title: A Phase 2 Study in First Line Metastatic or Unresectable, Recurrent Head and Neck Squamous Cell Carcinoma to Evaluate Intratumoral MK-1454 in Combination With IV Pembrolizumab vs IV Pembrolizumab Monotherapy

The purpose of this study is to assess the efficacy and safety of intratumoral (IT) ulevostinag PLUS pembrolizumab (MK-3475) compared to pembrolizumab alone as a first line treatment of adults with metastatic or unresectable, recurrent head and neck squamous cell carcinoma (HNSCC).

The primary study hypotheses are that IT ulevostinag in combination with pembrolizumab results in a superior Objective Response Rate (ORR), per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1), compared to pembrolizumab alone:

  1. In participants with a tumor that has a programmed cell death-ligand 1 (PD-L1) Combined Positive Scoring (CPS) ≥ 1, and
  2. In participants with a tumor that has a PD-L1 CPS ≥ 20.
Being tested
Ulevostinag, Pembrolizumab
Keywords
Programmed Cell Death-1 (PD1, PD-1), Programmed Death-Ligand 1 (PDL1, PD-L1), intratumoral (IT), metastatic, unresectable, recurrent, ulevostinag, pembrolizumab
Medical subject headings
Squamous Cell Carcinoma of Head and Neck, Parkinson Disease 4, Autosomal Dominant Lewy Body, Neoplasm Metastasis, Recurrence

What participants receive

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

  • UlevostinagDrug

    Also called MK-1454

    IT injection

  • PembrolizumabBiological

    Also called MK-3475, KEYTRUDA®

    IV infusion

Study groups in NCT04220866
Study groupRoleWhat they receive
Ulevostinag+PembrolizumabExperimentalParticipants receive ulevostinag 540 ug via intratumoral (IT) injection on Day 1 of every week for two 3-week cycles (Cycles 1-2), then on Day 1 of each 3-week cycle for up 33 cycles (Cycles 3-35), for a total of 35 cycles PLUS pembrolizumab 200 mg via intravenous (IV) infusion on Day 1 of each 3-week cycle for up to 35 cycles. The total duration of treatment is up to approximately 2 years.
Receives: Drug: Ulevostinag; Biological: Pembrolizumab
PembrolizumabActive comparatorParticipants receive pembrolizumab 200 mg via IV infusion on Day 1 of each 3-week cycle for up to 35 cycles. The total duration of treatment is up to approximately 2 years.
Receives: Biological: Pembrolizumab

What is being measured

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

  1. Objective Response Rate (ORR) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1)

    ORR was defined as the percentage of participants in the analysis population who have a Complete Response (CR: Disappearance of all target lesions) or a Partial Response (PR: At least a 30% decrease in the sum of diameters of target lesions) per RECIST 1.1. ORR was assessed by blinded independent central review (BICR), and the 95% confidence interval (CI) was based on the exact method for binomial data.

    Measured: Up to 913.0 days

Secondary outcomes (5)
  1. Progression-free Survival (PFS) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1)

    PFS was defined as the time from randomization to the first documented progressive disease (PD) or death from any cause, whichever occurs first. Per RECIST 1.1, PD was defined as at least a 20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. The appearance of one or more new lesions was also considered PD. PFS was assessed by BICR and was based on the product-limit (Kaplan-Meier) method for censored data.

    Measured: Up to 913.0 days

  2. Duration of Response (DOR) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1)

    DOR was defined as the time from the first documented evidence of a Complete Response (CR: Disappearance of all target lesions) or a Partial Response (PR: At least a 30% decrease in the sum of diameters of target lesions) per RECIST 1.1 until Progressive Disease (PD) or death due to any cause, whichever occurs first, in participants demonstrating a CR or PR. Per RECIST 1.1, PD is defined as at least a 20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. The appearance of one or more new lesions is also considered PD. DOR was based on the product-limit (Kaplan-Meier) method for censored data.

    Measured: Up to 913.0 days

  3. Overall Survival (OS)

    OS is defined as the time from randomization to the date of death from any cause, and is based on the product-limit (Kaplan-Meier) method for censored data.

    Measured: Up to 913.0 days

  4. Number of Participants Who Experienced an Adverse Event (AE)

    An AE is any untoward medical occurrence in a participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment.

    Measured: Up to 913.0 days

  5. Number of Participants Discontinuing Study Treatment Due to an AE

    An AE is any untoward medical occurrence in a participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment.

    Measured: Up to approximately 715.0 days

Timeline

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

  1. First posted7 Jan 2020
  2. Study start4 Mar 2020
  3. Primary completion30 Sep 2022
  4. Study completion30 Sep 2022

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
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
18 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04220866
Sponsor's protocol ID
1454-002
Other IDs
MK-1454-002, 2019-003060-42, 2019
Status last verified
Oct 2025
First submitted
6 Jan 2020
Last updated
29 Oct 2025
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf

Publications

  • Harrington KJ, Champiat S, Brody JD, Cho BC, Romano E, Golan T, Hyngstrom JR, Strauss J, Oh DY, Popovtzer A, Gomez-Roca C, Perets R, Kim SB, Wong DJ, Powell SF, Khilnani A, Jemielita T, Zhao Q, Zhao R, Ingham M. Phase I and II Clinical Studies of the STING Agonist Ulevostinag with and without Pembrolizumab in Participants with Advanced or Metastatic Solid Tumors or Lymphomas. Clin Cancer Res. 2025 Aug 14;31(16):3400-3411. doi: 10.1158/1078-0432.CCR-24-3630.

    PubMed 40499147
  • McIntosh JA, Liu Z, Andresen BM, Marzijarani NS, Moore JC, Marshall NM, Borra-Garske M, Obligacion JV, Fier PS, Peng F, Forstater JH, Winston MS, An C, Chang W, Lim J, Huffman MA, Miller SP, Tsay FR, Altman MD, Lesburg CA, Steinhuebel D, Trotter BW, Cumming JN, Northrup A, Bu X, Mann BF, Biba M, Hiraga K, Murphy GS, Kolev JN, Makarewicz A, Pan W, Farasat I, Bade RS, Stone K, Duan D, Alvizo O, Adpressa D, Guetschow E, Hoyt E, Regalado EL, Castro S, Rivera N, Smith JP, Wang F, Crespo A, Verma D, Axnanda S, Dance ZEX, Devine PN, Tschaen D, Canada KA, Bulger PG, Sherry BD, Truppo MD, Ruck RT, Campeau LC, Bennett DJ, Humphrey GR, Campos KR, Maddess ML. A kinase-cGAS cascade to synthesize a therapeutic STING activator. Nature. 2022 Mar;603(7901):439-444. doi: 10.1038/s41586-022-04422-9. Epub 2022 Mar 16.

    PubMed 35296845

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Ulevostinag and Pembrolizumab in people with Head and Neck Squamous Cell Carcinoma (HNSCC), run by Merck Sharp & Dohme LLC at 34 sites in 10 countries.

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 12 inclusion and 26 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 29 Oct 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 34 sites in United States, France, Brazil, Spain, Australia and 5 more countries. 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?

Yes. Results are posted in the registry (first posted 27 Oct 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

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) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) (time frame: Up to 913.0 days). 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 NCT04220866, 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 29 Oct 2025.

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