Clinical trial NCT04220866: 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)
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
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
Lead sponsor: Merck Sharp & Dohme LLC
Sponsor class: INDUSTRY
First posted: 2020-01-07
Enrollment: 18
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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. 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.


Eligibility criteria: Inclusion Criteria:

* 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:

  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 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
* 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

Primary outcomes:
measure: Objective Response Rate (ORR) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1)
timeFrame: Up to 913.0 days
Secondary outcomes:
measure: Progression-free Survival (PFS) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1)
timeFrame: Up to 913.0 days
measure: Duration of Response (DOR) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1)
timeFrame: Up to 913.0 days
measure: Overall Survival (OS)
timeFrame: Up to 913.0 days
measure: Number of Participants Who Experienced an Adverse Event (AE)
timeFrame: Up to 913.0 days
measure: Number of Participants Discontinuing Study Treatment Due to an AE
timeFrame: Up to approximately 715.0 days
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: UCLA Hematology & Oncology ( Site 0005)
state: California
city: San Francisco
country: United States
facility: University of California at San Francisco ( Site 0006)
state: California
city: Detroit
country: United States
facility: Henry Ford Hospital ( Site 0012)
state: Michigan
city: Saint Louis
country: United States
facility: Washington University ( Site 0021)
state: Missouri
city: Sioux Falls
country: United States
facility: Sanford Cancer Center Oncology Clinic ( Site 0014)
state: South Dakota
city: Salt Lake City
country: United States
facility: Huntsman Cancer Institute ( Site 0004)
state: Utah
city: Camperdown
country: Australia
facility: Chris OBrien Lifehouse ( Site 0040)
state: New South Wales
city: Elizabeth Vale
country: Australia
facility: Calvary Central Districts Hospital ( Site 0042)
state: South Australia
city: Clayton
country: Australia
facility: Monash Health-Monash Medical Centre ( Site 0041)
state: Victoria
city: Linz
country: Austria
facility: Ordensklinikum Linz Gmbh - Barmherzige Schwestern ( Site 0051)
state: Oberosterreich
city: Vienna/Wien
country: Austria
facility: Allgemeines Krankenhaus der Stadt Wien ( Site 0049)
state: Wien
city: Salzburg
country: Austria
facility: SCRI-CCCIT GesmbH ( Site 0050)
city: Fortaleza
country: Brazil
facility: Centro Regional Integrado de Oncologia ( Site 0062)
state: Ceara
city: Ijui
country: Brazil
facility: Hospital de Caridade de Ijui ( Site 0061)
state: Rio Grande Do Sul
city: Sao Paulo
country: Brazil
facility: Instituto do Cancer do Estado de Sao Paulo - ICESP ( Site 0058)
city: Sao Paulo
country: Brazil
facility: Real e Benemerita Associacao Portuguesa de Beneficencia ( Site 0064)
city: Nice
country: France
facility: Centre Antoine Lacassagne ( Site 0070)
state: Alpes-Maritimes
city: Lyon
country: France
facility: Centre Leon Berard ( Site 0072)
state: Auvergne
city: Toulouse
country: France
facility: IUCT - Oncopole ( Site 0069)
state: Haute-Garonne
city: Lille
country: France
facility: Centre Oscar Lambret ( Site 0071)
state: Nord
city: Villejuif
country: France
facility: Gustave Roussy ( Site 0068)
state: Val-de-Marne
city: Ramat Gan
country: Israel
facility: Chaim Sheba Medical Center ( Site 0076)
state: Tel Aviv
city: Haifa
country: Israel
facility: Rambam Medical Center ( Site 0077)
city: Jerusalem
country: Israel
facility: Hadassah Medical Center. Ein Kerem ( Site 0078)
city: Seoul
country: Korea, Republic of
facility: Severance Hospital ( Site 0103)
city: Seoul
country: Korea, Republic of
facility: Asan Medical Center ( Site 0104)
city: Bergen
country: Norway
facility: Haukeland Universitetssykehus, Klinisk forskningspost voksne ( Site 0086)
state: Hordaland
city: Oslo
country: Norway
facility: Oslo Universitetssykehus Radiumhospitalet ( Site 0085)
city: Barcelona
country: Spain
facility: H.U. Vall de Hebron ( Site 0112)
city: Barcelona
country: Spain
facility: Hospital Clinico de Barcelona ( Site 0116)
city: Madrid
country: Spain
facility: Hospital Universitario Ramon y Cajal ( Site 0115)
city: Malaga
country: Spain
facility: Hospital Universitario Virgen de la Victoria ( Site 0114)
city: London
country: United Kingdom
facility: Royal Marsden NHS Foundation Trust ( Site 0031)
state: London, City Of
city: Sutton
country: United Kingdom
facility: Royal Marsden Hospital Sutton-Surrey ( Site 0032)
state: Surrey
Study officials:
affiliation: Merck Sharp & Dohme LLC
name: Medical Director
role: STUDY_DIRECTOR
References:
citation: 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.