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)
NCT ID: NCT04220866
Last Updated: 2025-10-29
Study Results
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View full resultsBasic Information
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COMPLETED
PHASE2
18 participants
INTERVENTIONAL
2020-03-04
2022-09-30
Brief Summary
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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.
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Detailed Description
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Conditions
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Study Design
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RANDOMIZED
PARALLEL
TREATMENT
NONE
Study Groups
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Ulevostinag+Pembrolizumab
Participants 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.
Ulevostinag
IT injection
Pembrolizumab
IV infusion
Pembrolizumab
Participants 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.
Pembrolizumab
IV infusion
Interventions
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Ulevostinag
IT injection
Pembrolizumab
IV infusion
Other Intervention Names
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Eligibility Criteria
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Inclusion Criteria
* 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
* 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:
1. 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)
2. Has well-controlled HIV on anti-retroviral therapy (ART)
Exclusion Criteria
* 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
* 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
18 Years
ALL
No
Sponsors
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Merck Sharp & Dohme LLC
INDUSTRY
Responsible Party
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Principal Investigators
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Medical Director
Role: STUDY_DIRECTOR
Merck Sharp & Dohme LLC
Locations
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UCLA Hematology & Oncology ( Site 0005)
Los Angeles, California, United States
University of California at San Francisco ( Site 0006)
San Francisco, California, United States
Henry Ford Hospital ( Site 0012)
Detroit, Michigan, United States
Washington University ( Site 0021)
St Louis, Missouri, United States
Sanford Cancer Center Oncology Clinic ( Site 0014)
Sioux Falls, South Dakota, United States
Huntsman Cancer Institute ( Site 0004)
Salt Lake City, Utah, United States
Chris OBrien Lifehouse ( Site 0040)
Camperdown, New South Wales, Australia
Calvary Central Districts Hospital ( Site 0042)
Elizabeth Vale, South Australia, Australia
Monash Health-Monash Medical Centre ( Site 0041)
Clayton, Victoria, Australia
Ordensklinikum Linz Gmbh - Barmherzige Schwestern ( Site 0051)
Linz, Upper Austria, Austria
Allgemeines Krankenhaus der Stadt Wien ( Site 0049)
Vienna/Wien, Vienna, Austria
SCRI-CCCIT GesmbH ( Site 0050)
Salzburg, , Austria
Centro Regional Integrado de Oncologia ( Site 0062)
Fortaleza, Ceará, Brazil
Hospital de Caridade de Ijui ( Site 0061)
Ijuí, Rio Grande do Sul, Brazil
Instituto do Cancer do Estado de Sao Paulo - ICESP ( Site 0058)
São Paulo, , Brazil
Real e Benemerita Associacao Portuguesa de Beneficencia ( Site 0064)
São Paulo, , Brazil
Centre Antoine Lacassagne ( Site 0070)
Nice, Alpes-Maritimes, France
Centre Leon Berard ( Site 0072)
Lyon, Auvergne, France
IUCT - Oncopole ( Site 0069)
Toulouse, Haute-Garonne, France
Centre Oscar Lambret ( Site 0071)
Lille, Nord, France
Gustave Roussy ( Site 0068)
Villejuif, Val-de-Marne, France
Chaim Sheba Medical Center ( Site 0076)
Ramat Gan, Tel Aviv, Israel
Rambam Medical Center ( Site 0077)
Haifa, , Israel
Hadassah Medical Center. Ein Kerem ( Site 0078)
Jerusalem, , Israel
Haukeland Universitetssykehus, Klinisk forskningspost voksne ( Site 0086)
Bergen, Hordaland, Norway
Oslo Universitetssykehus Radiumhospitalet ( Site 0085)
Oslo, , Norway
Severance Hospital ( Site 0103)
Seoul, , South Korea
Asan Medical Center ( Site 0104)
Seoul, , South Korea
H.U. Vall de Hebron ( Site 0112)
Barcelona, , Spain
Hospital Clinico de Barcelona ( Site 0116)
Barcelona, , Spain
Hospital Universitario Ramon y Cajal ( Site 0115)
Madrid, , Spain
Hospital Universitario Virgen de la Victoria ( Site 0114)
Málaga, , Spain
Royal Marsden NHS Foundation Trust ( Site 0031)
London, London, City of, United Kingdom
Royal Marsden Hospital Sutton-Surrey ( Site 0032)
Sutton, Surrey, United Kingdom
Countries
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References
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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.
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.
Provided Documents
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Document Type: Study Protocol and Statistical Analysis Plan
Related Links
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Merck Clinical Trials Information
Other Identifiers
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MK-1454-002
Identifier Type: OTHER
Identifier Source: secondary_id
2019-003060-42
Identifier Type: EUDRACT_NUMBER
Identifier Source: secondary_id
1454-002
Identifier Type: -
Identifier Source: org_study_id
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