We are experiencing 4 week turn-around time in review of submissions and resubmissions. We recommend commencing this process concurrently with your ethics submission and allowing at least 8 weeks for registration to be completed from date of first submission. We currently do not have the capacity to expedite reviews.

Note also there are delays to review of updates. We appreciate your patience.

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this information for consumers
Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT04220866




Registration number
NCT04220866
Ethics application status
Date submitted
6/01/2020
Date registered
7/01/2020
Date last updated
19/04/2021

Titles & IDs
Public title
Study of Intratumoral (IT) 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)
Scientific 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
Secondary ID [1] 0 0
2019-003060-42
Secondary ID [2] 0 0
1454-002
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Head and Neck Squamous Cell Carcinoma (HNSCC) 0 0
Condition category
Condition code
Cancer 0 0 0 0
Non melanoma skin cancer
Cancer 0 0 0 0
Kidney
Cancer 0 0 0 0
Head and neck

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - MK-1454
Other interventions - Pembrolizumab

Experimental: MK-1454+Pembrolizumab - Participants receive MK-1454 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.

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.


Treatment: Drugs: MK-1454
IT injection

Other interventions: Pembrolizumab
IV infusion

Intervention code [1] 0 0
Treatment: Drugs
Intervention code [2] 0 0
Other interventions
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Objective Response Rate (ORR) per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) - 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).
Timepoint [1] 0 0
Up to approximately 2 years
Secondary outcome [1] 0 0
Progression-free Survival (PFS) per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) - 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).
Timepoint [1] 0 0
Up to approximately 2 years
Secondary outcome [2] 0 0
Duration of Response (DOR) per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) - 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.
Timepoint [2] 0 0
Up to approximately 2 years
Secondary outcome [3] 0 0
Overall Survival (OS) - OS is defined as the time from randomization to the date of death from any cause.
Timepoint [3] 0 0
Up to approximately 2 years
Secondary outcome [4] 0 0
Number of participants experiencing 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.
Timepoint [4] 0 0
Up to approximately 2 years
Secondary outcome [5] 0 0
Number of participants discontinuing study treatment due to 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.
Timepoint [5] 0 0
Up to approximately 2 years

Eligibility
Key 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 MK-1454 and for at least 120 days after the last dose of MK-1454

- 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)
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key 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. MK-1454,
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

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Active, not recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,SA,VIC
Recruitment hospital [1] 0 0
Chris OBrien Lifehouse ( Site 0040) - Camperdown
Recruitment hospital [2] 0 0
Calvary Central Districts Hospital ( Site 0042) - Elizabeth Vale
Recruitment hospital [3] 0 0
Monash Health-Monash Medical Centre ( Site 0041) - Clayton
Recruitment postcode(s) [1] 0 0
2050 - Camperdown
Recruitment postcode(s) [2] 0 0
5112 - Elizabeth Vale
Recruitment postcode(s) [3] 0 0
3168 - Clayton
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
Michigan
Country [3] 0 0
United States of America
State/province [3] 0 0
Missouri
Country [4] 0 0
United States of America
State/province [4] 0 0
South Dakota
Country [5] 0 0
United States of America
State/province [5] 0 0
Utah
Country [6] 0 0
Austria
State/province [6] 0 0
Oberosterreich
Country [7] 0 0
Austria
State/province [7] 0 0
Wien
Country [8] 0 0
Austria
State/province [8] 0 0
Salzburg
Country [9] 0 0
Brazil
State/province [9] 0 0
Ceara
Country [10] 0 0
Brazil
State/province [10] 0 0
Rio Grande Do Sul
Country [11] 0 0
Brazil
State/province [11] 0 0
Sao Paulo
Country [12] 0 0
France
State/province [12] 0 0
Alpes-Maritimes
Country [13] 0 0
France
State/province [13] 0 0
Auvergne
Country [14] 0 0
France
State/province [14] 0 0
Haute-Garonne
Country [15] 0 0
France
State/province [15] 0 0
Nord
Country [16] 0 0
France
State/province [16] 0 0
Val-de-Marne
Country [17] 0 0
Israel
State/province [17] 0 0
Tel Aviv
Country [18] 0 0
Israel
State/province [18] 0 0
Haifa
Country [19] 0 0
Israel
State/province [19] 0 0
Jerusalem
Country [20] 0 0
Korea, Republic of
State/province [20] 0 0
Seoul
Country [21] 0 0
Norway
State/province [21] 0 0
Hordaland
Country [22] 0 0
Norway
State/province [22] 0 0
Oslo
Country [23] 0 0
Spain
State/province [23] 0 0
Barcelona
Country [24] 0 0
Spain
State/province [24] 0 0
Madrid
Country [25] 0 0
Spain
State/province [25] 0 0
Malaga
Country [26] 0 0
United Kingdom
State/province [26] 0 0
London, City Of
Country [27] 0 0
United Kingdom
State/province [27] 0 0
Surrey

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Merck Sharp & Dohme Corp.
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
The purpose of this study is to assess the efficacy and safety of intratumoral (IT) MK-1454
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 MK-1454 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.
Trial website
https://clinicaltrials.gov/show/NCT04220866
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Medical Director
Address 0 0
Merck Sharp & Dohme Corp.
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Summary results
Other publications