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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)

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ClinicalTrials.gov Identifier: NCT04220866
Recruitment Status : Active, not recruiting
First Posted : January 7, 2020
Last Update Posted : October 11, 2021
Sponsor:
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.

Tracking Information
First Submitted Date  ICMJE January 6, 2020
First Posted Date  ICMJE January 7, 2020
Last Update Posted Date October 11, 2021
Actual Study Start Date  ICMJE March 4, 2020
Estimated Primary Completion Date April 17, 2023   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: January 6, 2020)
Objective Response Rate (ORR) per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) [ Time Frame: Up to approximately 2 years ]
ORR is 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 will be assessed by blinded independent central review (BICR).
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: January 6, 2020)
  • Progression-free Survival (PFS) per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) [ Time Frame: Up to approximately 2 years ]
    PFS is 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 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. PFS will be assessed by blinded independent central review (BICR).
  • Duration of Response (DOR) per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) [ Time Frame: Up to approximately 2 years ]
    DOR is 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.
  • Overall Survival (OS) [ Time Frame: Up to approximately 2 years ]
    OS is defined as the time from randomization to the date of death from any cause.
  • Number of participants experiencing an Adverse Event (AE) [ Time Frame: Up to approximately 2 years ]
    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.
  • Number of participants discontinuing study treatment due to an Adverse Event (AE) [ Time Frame: Up to approximately 2 years ]
    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.
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE 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  ICMJE 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
Brief Summary

The purpose of this study is to assess the efficacy and safety of intratumoral (IT) ulevostinag in 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.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Head and Neck Squamous Cell Carcinoma (HNSCC)
Intervention  ICMJE
  • Drug: Ulevostinag
    IT injection
    Other Name: MK-1454
  • Biological: Pembrolizumab
    IV infusion
    Other Names:
    • MK-3475
    • KEYTRUDA®
Study Arms  ICMJE
  • Experimental: 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.
    Interventions:
    • Drug: Ulevostinag
    • Biological: Pembrolizumab
  • Active Comparator: 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.
    Intervention: Biological: Pembrolizumab
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Estimated Enrollment  ICMJE
 (submitted: January 6, 2020)
200
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE April 17, 2023
Estimated Primary Completion Date April 17, 2023   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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 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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Australia,   Austria,   Brazil,   France,   Israel,   Korea, Republic of,   Norway,   Spain,   United Kingdom,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04220866
Other Study ID Numbers  ICMJE 1454-002
2019-003060-42 ( EudraCT Number )
MK-1454-002 ( Other Identifier: Merck )
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Yes
Plan Description: http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf
URL: http://engagezone.msd.com/ds_documentation.php
Responsible Party Merck Sharp & Dohme Corp.
Study Sponsor  ICMJE Merck Sharp & Dohme Corp.
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Medical Director Merck Sharp & Dohme Corp.
PRS Account Merck Sharp & Dohme Corp.
Verification Date October 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP