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 |
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Recruitment Status :
Completed
First Posted : January 7, 2020
Results First Posted : October 27, 2023
Last Update Posted : October 27, 2023
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Sponsor:
Merck Sharp & Dohme LLC
Information provided by (Responsible Party):
Merck Sharp & Dohme LLC
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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:
- In participants with a tumor that has a programmed cell death-ligand 1 (PD-L1) Combined Positive Scoring (CPS) ≥ 1, and
- In participants with a tumor that has a PD-L1 CPS ≥ 20.
| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Head and Neck Squamous Cell Carcinoma (HNSCC) | Drug: Ulevostinag Biological: Pembrolizumab | Phase 2 |
| Study Type : | Interventional (Clinical Trial) |
| Actual Enrollment : | 18 participants |
| Allocation: | Randomized |
| Intervention Model: | Parallel Assignment |
| Masking: | None (Open Label) |
| Primary Purpose: | Treatment |
| 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 |
| Actual Study Start Date : | March 4, 2020 |
| Actual Primary Completion Date : | September 30, 2022 |
| Actual Study Completion Date : | September 30, 2022 |
Resource links provided by the National Library of Medicine
MedlinePlus Genetics related topics:
Head and neck squamous cell carcinoma
Drug Information
available for:
Pembrolizumab
| Arm | Intervention/treatment |
|---|---|
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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.
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Drug: Ulevostinag
IT injection
Other Name: MK-1454 Biological: Pembrolizumab IV infusion
Other Names:
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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.
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Biological: Pembrolizumab
IV infusion
Other Names:
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Primary Outcome Measures :
- Objective Response Rate (ORR) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) [ Time Frame: Up to 913.0 days ]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.
Secondary Outcome Measures :
- Progression-free Survival (PFS) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) [ Time Frame: Up to 913.0 days ]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.
- Duration of Response (DOR) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) [ Time Frame: Up to 913.0 days ]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.
- Overall Survival (OS) [ Time Frame: Up to 913.0 days ]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.
- Number of Participants Who Experienced an Adverse Event (AE) [ Time Frame: Up to 913.0 days ]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 AE [ Time Frame: Up to approximately 715.0 days ]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.
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| Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
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
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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)
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
Information from the National Library of Medicine
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04220866
Locations
Show 34 study locations
Sponsors and Collaborators
Merck Sharp & Dohme LLC
Investigators
| Study Director: | Medical Director | Merck Sharp & Dohme LLC |
Study Documents (Full-Text)
Documents provided by Merck Sharp & Dohme LLC:
Documents provided by Merck Sharp & Dohme LLC:
Study Protocol and Statistical Analysis Plan [PDF] October 20, 2022
Additional Information:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
| Responsible Party: | Merck Sharp & Dohme LLC |
| ClinicalTrials.gov Identifier: | NCT04220866 |
| Other Study ID Numbers: |
1454-002 MK-1454-002 ( Other Identifier: Merck ) 2019-003060-42 ( EudraCT Number ) |
| First Posted: | January 7, 2020 Key Record Dates |
| Results First Posted: | October 27, 2023 |
| Last Update Posted: | October 27, 2023 |
| Last Verified: | October 2023 |
| Individual Participant Data (IPD) Sharing Statement: | |
| Plan to Share IPD: | Yes |
| Plan Description: | http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf |
| URL: | http://engagezone.msd.com/ds_documentation.php |
| Studies a U.S. FDA-regulated Drug Product: | Yes |
| Studies a U.S. FDA-regulated Device Product: | No |
Keywords provided by Merck Sharp & Dohme LLC:
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Programmed Cell Death-1 (PD1, PD-1) Programmed Death-Ligand 1 (PDL1, PD-L1) intratumoral (IT) metastatic |
unresectable recurrent ulevostinag pembrolizumab |
Additional relevant MeSH terms:
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Carcinoma Carcinoma, Squamous Cell Squamous Cell Carcinoma of Head and Neck Neoplasms, Glandular and Epithelial Neoplasms by Histologic Type Neoplasms Neoplasms, Squamous Cell |
Head and Neck Neoplasms Neoplasms by Site Pembrolizumab Antineoplastic Agents, Immunological Antineoplastic Agents Immune Checkpoint Inhibitors Molecular Mechanisms of Pharmacological Action |