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)

NCT04220866 | Completed Phase 2 Results FDA Drug

• 3 other identifiers: 1454-002MK-1454-0022019-003060-42
• Study Type: interventional
• Target: 18
• Locations: 9 countries
• Sites: 31

Brief 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). 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. 1.In participants with a tumor that has a programmed cell death-ligand 1 (PD-L1) Combined Positive Scoring (CPS) ≥ 1, and
2. 2.In participants with a tumor that has a PD-L1 CPS ≥ 20.

Conditions

Head and Neck Squamous Cell Carcinoma (HNSCC)

Keywords

Programmed Cell Death-1 (PD1, PD-1); Programmed Death-Ligand 1 (PDL1, PD-L1); intratumoral (IT); metastatic; unresectable; recurrent; ulevostinag; pembrolizumab

Outcome Measures

Primary Outcomes (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.

  Up to 913.0 days

Secondary Outcomes (5)

• Progression-free Survival (PFS) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1)

  Up to 913.0 days

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

  Up to 913.0 days

• Overall Survival (OS)

  Up to 913.0 days

• Number of Participants Who Experienced an Adverse Event (AE)

  Up to 913.0 days

• Number of Participants Discontinuing Study Treatment Due to an AE

  Up to approximately 715.0 days

Study Arms (2)

Ulevostinag+Pembrolizumab

EXPERIMENTAL

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.

Drug: Ulevostinag; Biological: Pembrolizumab

Pembrolizumab

ACTIVE COMPARATOR

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.

Biological: Pembrolizumab

Interventions

Ulevostinag DRUG

IT injection

Also known as: MK-1454

Ulevostinag+Pembrolizumab

Pembrolizumab BIOLOGICAL

IV infusion

Also known as: MK-3475, KEYTRUDA®

Pembrolizumab; Ulevostinag+Pembrolizumab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• 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)

You may not qualify if:

• 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
• 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

Sponsors & Collaborators

• Merck Sharp & Dohme LLC: lead

Study Sites (34)

UCLA Hematology & Oncology ( Site 0005)

Los Angeles, California, 90095, United States

Location

University of California at San Francisco ( Site 0006)

San Francisco, California, 94158, United States

Location

Henry Ford Hospital ( Site 0012)

Detroit, Michigan, 48202, United States

Location

Washington University ( Site 0021)

St Louis, Missouri, 63110, United States

Location

Sanford Cancer Center Oncology Clinic ( Site 0014)

Sioux Falls, South Dakota, 57104, United States

Location

Huntsman Cancer Institute ( Site 0004)

Salt Lake City, Utah, 84112, United States

Location

Chris OBrien Lifehouse ( Site 0040)

Camperdown, New South Wales, 2050, Australia

Location

Calvary Central Districts Hospital ( Site 0042)

Elizabeth Vale, South Australia, 5112, Australia

Location

Monash Health-Monash Medical Centre ( Site 0041)

Clayton, Victoria, 3168, Australia

Location

Ordensklinikum Linz Gmbh - Barmherzige Schwestern ( Site 0051)

Linz, Upper Austria, 4010, Austria

Location

Allgemeines Krankenhaus der Stadt Wien ( Site 0049)

Vienna/Wien, Vienna, 1090, Austria

Location

SCRI-CCCIT GesmbH ( Site 0050)

Salzburg, 5020, Austria

Location

Centro Regional Integrado de Oncologia ( Site 0062)

Fortaleza, Ceará, 60336-232, Brazil

Location

Hospital de Caridade de Ijui ( Site 0061)

Ijuí, Rio Grande do Sul, 98700-000, Brazil

Location

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

São Paulo, 01246-000, Brazil

Location

Real e Benemerita Associacao Portuguesa de Beneficencia ( Site 0064)

São Paulo, 01321-001, Brazil

Location

Centre Antoine Lacassagne ( Site 0070)

Nice, Alpes-Maritimes, 06189, France

Location

Centre Leon Berard ( Site 0072)

Lyon, Auvergne, 69373, France

Location

IUCT - Oncopole ( Site 0069)

Toulouse, Haute-Garonne, 31059, France

Location

Centre Oscar Lambret ( Site 0071)

Lille, Nord, 59000, France

Location

Gustave Roussy ( Site 0068)

Villejuif, Val-de-Marne, 94800, France

Location

Chaim Sheba Medical Center ( Site 0076)

Ramat Gan, Tel Aviv, 5265601, Israel

Location

Rambam Medical Center ( Site 0077)

Haifa, 3109601, Israel

Location

Hadassah Medical Center. Ein Kerem ( Site 0078)

Jerusalem, 9112001, Israel

Location

Haukeland Universitetssykehus, Klinisk forskningspost voksne ( Site 0086)

Bergen, Hordaland, 5021, Norway

Location

Oslo Universitetssykehus Radiumhospitalet ( Site 0085)

Oslo, 0379, Norway

Location

Severance Hospital ( Site 0103)

Seoul, 03722, South Korea

Location

Asan Medical Center ( Site 0104)

Seoul, 05505, South Korea

Location

H.U. Vall de Hebron ( Site 0112)

Barcelona, 08035, Spain

Location

Hospital Clinico de Barcelona ( Site 0116)

Barcelona, 08036, Spain

Location

Hospital Universitario Ramon y Cajal ( Site 0115)

Madrid, 28034, Spain

Location

Hospital Universitario Virgen de la Victoria ( Site 0114)

Málaga, 29010, Spain

Location

Royal Marsden NHS Foundation Trust ( Site 0031)

London, London, City of, SW3 6JJ, United Kingdom

Location

Royal Marsden Hospital Sutton-Surrey ( Site 0032)

Sutton, Surrey, SM2 5PT, United Kingdom

Location

Related Publications (2)

• 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.

  PMID: 40499147 RESULT

• 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.

  PMID: 35296845 DERIVED

Related Links

• Merck Clinical Trials Information

MeSH Terms

Conditions

Squamous Cell Carcinoma of Head and Neck; Parkinson Disease 4, Autosomal Dominant Lewy Body; Neoplasm Metastasis; Recurrence

Interventions

pembrolizumab

Condition Hierarchy (Ancestors)

Carcinoma, Squamous Cell; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Head and Neck Neoplasms; Neoplasms by Site; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Disease Attributes

Results Point of Contact

• Title: Senior Vice President, Global Clinical Development
• Organization: Merck Sharp & Dohme LLC

ClinicalTrialsDisclosure@merck.com

1-800-672-6372

Study Officials

• Medical Director

  Merck Sharp & Dohme LLC

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 6, 2020
• First Posted: January 7, 2020
• Study Start: March 4, 2020
• Primary Completion: September 30, 2022
• Study Completion: September 30, 2022
• Last Updated: October 29, 2025
• Results First Posted: October 27, 2023

Record last verified: 2025-10

Data Sharing

• IPD Sharing: Will share

Locations

KR (2); IL (3); FR (5); ES (4); GB (2); AU (3); NO (2); US (6); BR (4)