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)

Head and Neck Squamous Cell Carcinoma (HNSCC) Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04220866
• Other study ID #: 1454-002
• Secondary ID: MK-1454-0022019-
• Status: Completed
• Phase: Phase 2
• Start date: March 4, 2020
• Est. completion date: September 30, 2022

Study information

• Verified date: October 2023
• Source: Merck Sharp & Dohme LLC
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 18
• Est. completion date: September 30, 2022
• Est. primary completion date: September 30, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Carcinoma
• Carcinoma, Squamous Cell
• Head and Neck Squamous Cell Carcinoma (HNSCC)
• Squamous Cell Carcinoma of Head and Neck

Intervention

Drug:
• Ulevostinag
IT injection

Biological:
• Pembrolizumab
IV infusion

Locations

Country	Name	City	State
Australia	Chris OBrien Lifehouse ( Site 0040)	Camperdown	New South Wales
Australia	Monash Health-Monash Medical Centre ( Site 0041)	Clayton	Victoria
Australia	Calvary Central Districts Hospital ( Site 0042)	Elizabeth Vale	South Australia
Austria	Ordensklinikum Linz Gmbh - Barmherzige Schwestern ( Site 0051)	Linz	Oberosterreich
Austria	SCRI-CCCIT GesmbH ( Site 0050)	Salzburg
Austria	Allgemeines Krankenhaus der Stadt Wien ( Site 0049)	Vienna/Wien	Wien
Brazil	Centro Regional Integrado de Oncologia ( Site 0062)	Fortaleza	Ceara
Brazil	Hospital de Caridade de Ijui ( Site 0061)	Ijui	Rio Grande Do Sul
Brazil	Instituto do Cancer do Estado de Sao Paulo - ICESP ( Site 0058)	Sao Paulo
Brazil	Real e Benemerita Associacao Portuguesa de Beneficencia ( Site 0064)	Sao Paulo
France	Centre Oscar Lambret ( Site 0071)	Lille	Nord
France	Centre Leon Berard ( Site 0072)	Lyon	Auvergne
France	Centre Antoine Lacassagne ( Site 0070)	Nice	Alpes-Maritimes
France	IUCT - Oncopole ( Site 0069)	Toulouse	Haute-Garonne
France	Gustave Roussy ( Site 0068)	Villejuif	Val-de-Marne
Israel	Rambam Medical Center ( Site 0077)	Haifa
Israel	Hadassah Medical Center. Ein Kerem ( Site 0078)	Jerusalem
Israel	Chaim Sheba Medical Center ( Site 0076)	Ramat Gan	Tel Aviv
Korea, Republic of	Asan Medical Center ( Site 0104)	Seoul
Korea, Republic of	Severance Hospital ( Site 0103)	Seoul
Norway	Haukeland Universitetssykehus, Klinisk forskningspost voksne ( Site 0086)	Bergen	Hordaland
Norway	Oslo Universitetssykehus Radiumhospitalet ( Site 0085)	Oslo
Spain	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)	Malaga
United Kingdom	Royal Marsden NHS Foundation Trust ( Site 0031)	London	London, City Of
United Kingdom	Royal Marsden Hospital Sutton-Surrey ( Site 0032)	Sutton	Surrey
United States	Henry Ford Hospital ( Site 0012)	Detroit	Michigan
United States	UCLA Hematology & Oncology ( Site 0005)	Los Angeles	California
United States	Washington University ( Site 0021)	Saint Louis	Missouri
United States	Huntsman Cancer Institute ( Site 0004)	Salt Lake City	Utah
United States	University of California at San Francisco ( Site 0006)	San Francisco	California
United States	Sanford Cancer Center Oncology Clinic ( Site 0014)	Sioux Falls	South Dakota

Sponsors (1)

Lead Sponsor	Collaborator
Merck Sharp & Dohme LLC

Countries where clinical trial is conducted

United States,  Australia,  Austria,  Brazil,  France,  Israel,  Korea, Republic of,  Norway,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Progression-free Survival (PFS) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1)	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.	Up to 913.0 days
Secondary	Duration of Response (DOR) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1)	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.	Up to 913.0 days
Secondary	Overall Survival (OS)	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.	Up to 913.0 days
Secondary	Number of Participants Who Experienced an Adverse Event (AE)	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.	Up to 913.0 days
Secondary	Number of Participants Discontinuing Study Treatment Due to an AE	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.	Up to approximately 715.0 days

External Links

•   Merck Clinical Trials Information