Trial Review

Technical difficulties have been reported by some users of the search function and is being investigated by technical staff. Thank you for your patience and apologies for any inconvenience caused.

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/ct2/show/NCT03765918




Registration number
NCT03765918
Ethics application status
Date submitted
6/11/2018
Date registered
5/12/2018
Date last updated
16/04/2024

Titles & IDs
Public title
Study of Pembrolizumab Given Prior to Surgery and in Combination With Radiotherapy Given Post-surgery for Advanced Head and Neck Squamous Cell Carcinoma (MK-3475-689)
Scientific title
A Phase III, Randomized, Open-label Study to Evaluate Pembrolizumab as Neoadjuvant Therapy and in Combination With Standard of Care as Adjuvant Therapy for Stage III-IVA Resectable Locoregionally Advanced Head and Neck Squamous Cell Carcinoma (LA HNSCC)
Secondary ID [1] 0 0
MK-3475-689
Secondary ID [2] 0 0
3475-689
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Head and Neck Neoplasms 0 0
Condition category
Condition code
Cancer 0 0 0 0
Non melanoma skin cancer
Cancer 0 0 0 0
Head and neck

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Other interventions - Pembrolizumab 200 mg
Treatment: Other - Radiotherapy 60 Gray/day
Treatment: Other - Radiotherapy 66 Gray/day
Treatment: Other - Radiotherapy 70 Gray/day
Treatment: Drugs - Cisplatin 100 mg/m^2

Experimental: Pembro Neoadjuvant+Pembro SOC Adjuvant - Participants receive 200 mg pembrolizumab by intravenous (IV) infusion administered on Day 1 of a 21-day cycle for 2 cycles as a neoadjuvant prior to surgery. Following surgical resection, high risk participants receive 200 mg pembrolizumab by IV infusion administered on Day 1 every 3 weeks (Q3W) for fifteen 21-day cycles plus standard of care radiotherapy plus cisplatin 100 mg/m^2 by IV infusion on Day 1 Q3W for three 21-day cycles as adjuvant therapy. Following surgical resection, low risk participants receive 200 mg pembrolizumab by IV infusion administered on Day 1 Q3W for fifteen 21-day cycles plus standard of care radiotherapy as adjuvant therapy.

Active Comparator: No Neoadjuvant+SOC Adjuvant - Participants receive no neoadjuvant prior to surgery. Following surgical resection, high risk participants receive standard of care radiotherapy plus cisplatin 100 mg/m^2 by IV infusion on Day 1 Q3W for three 21-day cycles as adjuvant therapy. Following surgical resection, low risk participants receive standard of care radiotherapy as adjuvant therapy.


Other interventions: Pembrolizumab 200 mg
200 mg administered by intravenous (IV) infusion on Day 1 of each 21-day cycle

Treatment: Other: Radiotherapy 60 Gray/day
Low risk participants administered 2 Gray/day in 30 fractions. Administered using intensity modulated radiation therapy.

Treatment: Other: Radiotherapy 66 Gray/day
High risk participants administered 2 Gray/day in 33 fractions. Administered using intensity modulated radiation therapy.

Treatment: Other: Radiotherapy 70 Gray/day
Participants with gross residual disease administered 2 Gray/day in 35 fractions. Administered using intensity modulated radiation therapy.

Treatment: Drugs: Cisplatin 100 mg/m^2
100 mg/m^2 administered by IV infusion on Day 1 of each 21-day cycle
Intervention code [1] 0 0
Other interventions
Intervention code [2] 0 0
Treatment: Other
Intervention code [3] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Event-free Survival (EFS)
Timepoint [1] 0 0
Up to ~80 months
Secondary outcome [1] 0 0
Major Pathological Response (mPR)
Timepoint [1] 0 0
Up to ~64 months
Secondary outcome [2] 0 0
Overall Survival (OS)
Timepoint [2] 0 0
Up to ~92 months
Secondary outcome [3] 0 0
Pathological Complete Response (pCR)
Timepoint [3] 0 0
Up to ~64 months
Secondary outcome [4] 0 0
Change From Baseline in Global Health Status/Quality of Life Scale (GHS/QoL)
Timepoint [4] 0 0
Prior to the first dose of study therapy (Baseline) and at the time of last follow-up (up to ~92 months)
Secondary outcome [5] 0 0
Change From Baseline in Global Health Status/Physical Functioning Scales
Timepoint [5] 0 0
Prior to the first dose of study therapy (Baseline) and at the time of last follow-up (up to ~92 months)
Secondary outcome [6] 0 0
Change from Baseline in Swallowing, Speech, and Pain Symptoms
Timepoint [6] 0 0
Prior to the first dose of study therapy (Baseline) and at the time of last follow-up (up to ~92 months)
Secondary outcome [7] 0 0
Percentage of Participants Experiencing An Adverse Event (AEs)
Timepoint [7] 0 0
From time of first dose of study treatment until the end of follow-up (up to ~92 months)
Secondary outcome [8] 0 0
Percentage of Participants Discontinuing Study Drug Due to AEs
Timepoint [8] 0 0
From time of first dose of study treatment until the end of treatment (up to 12 months)

Eligibility
Key inclusion criteria
- Has histologically confirmed new diagnosis of resectable, non-metastatic, squamous
cell carcinoma that is either: Stage III Human Papillomavirus (HPV) positive
oropharyngeal primary that is tumor size (T) 4, lymph node involvement (N) 0-2, no
distant metastases (M0); Stage III or IVA oropharyngeal HPV negative; or Stage III or
IVA larynx/hypopharynx/oral cavity primaries.

- Is eligible for primary surgery based on investigator decision and per local practice

- Female and male participants of reproductive potential must agree to use adequate
contraception throughout the study period and for up to 180 days after the last dose
of study therapy.

- Male participants must refrain from donating sperm throughout the study period and for
up to 180 days after the last dose of study therapy

- Female participant that is not pregnant or breastfeeding

- Has evaluable tumor burden (measurable and/or non-measurable tumor lesions) assessed
by computed tomography (CT) scan or magnetic resonance imaging (MRI), based on RECIST
version 1.1

- Has provided newly obtained core or excisional biopsy of a tumor lesion not previously
irradiated

- Has results from testing of HPV status for oropharyngeal cancer defined as p16

- Has Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 performed
within 10 days of randomization
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
- Has Stage T4B and/or N3 LA HNSCC and/or distant metastases

- Has cancer outside of the oropharynx, larynx, and hypopharynx or oral cavity. such as
nasopharyngeal, sinus, other para-nasal, or other unknown primary head and neck cancer
(HNC)

- Female participant who has a positive urine pregnancy test within 72 hours prior to
study start or within 24 hours prior to the start of radiotherapy with or without
cisplatin.

- Has received prior therapy with an anti-programmed cell death receptor 1(PD-1),
anti-programmed cell death receptor ligand 1(PD-L1), or anti-programmed cell death
receptor ligand 2 (PD-L2) agent or with an agent directed to another co-inhibitory
T-cell receptor

- Has received prior radiotherapy treatment or systemic anti-cancer therapy including
investigational agents for the HNC under study prior to study start

- Has received a live vaccine within 30 days prior to randomization

- Is currently participating in or has participated in a study of an investigational
agent or has used an investigational device within 4 weeks prior to randomization

- Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy (in
dosing exceeding 10 mg daily of prednisone equivalent) or any other form of
immunosuppressive therapy within 7 days prior to randomization

- Has a known additional malignancy that is progressing or has required active treatment
within the past 3 years with the exception of basal cell carcinoma of the skin,
squamous cell carcinoma of the skin, or carcinoma in situ (e.g. in situ cervical
cancer or breast carcinoma) that have undergone potentially curative therapy

- Has radiographically detectable (even if asymptomatic and/or previously treated)
central nervous system metastases and/or carcinomatous meningitis

- Has Grade =2 audiometric hearing loss

- Has Grade =2 neuropathy

- Has Grade 3-4 bleeding due to the underlying malignancy

- Has received major surgery or has not recovered adequately from the toxicity and/or
complications from the intervention prior to study start

- Has had previous allogeneic tissue/solid organ transplant

- Has severe hypersensitivity (=Grade 3) to pembrolizumab and/or any of its excipients,
radiotherapy, cisplatin or their analogs

- Has an active autoimmune disease that has required systemic treatment in past 2 years

- Has a history of (non-infectious) pneumonitis that required steroids or has current
pneumonitis

- Has an active infection requiring systemic therapy

- Has a known history of human immunodeficiency virus (HIV) infection

- Has a known history of or is positive for Hepatitis B (defined as hepatitis B surface
antigen [HBsAg] reactive) or known active Hepatitis C (defined as Hepatitis C virus
[HCV] ribonucleic acid is detected).

- Has a history or current evidence of any condition, therapy, or laboratory abnormality
that might confound the results of the study, interfere with the participant's
participation for the full duration of the study, or is not in the best interest of
the participant to participate, in the opinion of the investigator

- Has a known psychiatric or substance abuse disorder that would interfere with the
participant's ability to cooperate with the requirements of the study

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 3
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
17/12/2018
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
10/09/2026
Actual
Sample size
Target
714
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,QLD
Recruitment hospital [1] 0 0
The Crown Princess Mary Cancer Centre - Westmead Hospital ( Site 0051) - Westmead
Recruitment hospital [2] 0 0
Royal Brisbane and Women s Hospital ( Site 0050) - Herston
Recruitment postcode(s) [1] 0 0
2145 - Westmead
Recruitment postcode(s) [2] 0 0
4029 - Herston
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
Colorado
Country [3] 0 0
United States of America
State/province [3] 0 0
District of Columbia
Country [4] 0 0
United States of America
State/province [4] 0 0
Florida
Country [5] 0 0
United States of America
State/province [5] 0 0
Idaho
Country [6] 0 0
United States of America
State/province [6] 0 0
Illinois
Country [7] 0 0
United States of America
State/province [7] 0 0
Kansas
Country [8] 0 0
United States of America
State/province [8] 0 0
Kentucky
Country [9] 0 0
United States of America
State/province [9] 0 0
Louisiana
Country [10] 0 0
United States of America
State/province [10] 0 0
Maryland
Country [11] 0 0
United States of America
State/province [11] 0 0
Massachusetts
Country [12] 0 0
United States of America
State/province [12] 0 0
Michigan
Country [13] 0 0
United States of America
State/province [13] 0 0
Minnesota
Country [14] 0 0
United States of America
State/province [14] 0 0
Missouri
Country [15] 0 0
United States of America
State/province [15] 0 0
Montana
Country [16] 0 0
United States of America
State/province [16] 0 0
New Jersey
Country [17] 0 0
United States of America
State/province [17] 0 0
New Mexico
Country [18] 0 0
United States of America
State/province [18] 0 0
New York
Country [19] 0 0
United States of America
State/province [19] 0 0
North Carolina
Country [20] 0 0
United States of America
State/province [20] 0 0
North Dakota
Country [21] 0 0
United States of America
State/province [21] 0 0
Ohio
Country [22] 0 0
United States of America
State/province [22] 0 0
Oregon
Country [23] 0 0
United States of America
State/province [23] 0 0
Pennsylvania
Country [24] 0 0
United States of America
State/province [24] 0 0
South Dakota
Country [25] 0 0
United States of America
State/province [25] 0 0
Tennessee
Country [26] 0 0
United States of America
State/province [26] 0 0
Texas
Country [27] 0 0
United States of America
State/province [27] 0 0
Utah
Country [28] 0 0
United States of America
State/province [28] 0 0
Vermont
Country [29] 0 0
United States of America
State/province [29] 0 0
Virginia
Country [30] 0 0
United States of America
State/province [30] 0 0
Washington
Country [31] 0 0
Argentina
State/province [31] 0 0
Buenos Aires
Country [32] 0 0
Argentina
State/province [32] 0 0
Caba
Country [33] 0 0
Argentina
State/province [33] 0 0
Santa Fe
Country [34] 0 0
Argentina
State/province [34] 0 0
San Juan
Country [35] 0 0
Austria
State/province [35] 0 0
Oberosterreich
Country [36] 0 0
Austria
State/province [36] 0 0
Steiermark
Country [37] 0 0
Austria
State/province [37] 0 0
Salzburg
Country [38] 0 0
Austria
State/province [38] 0 0
Wien
Country [39] 0 0
Belgium
State/province [39] 0 0
Hainaut
Country [40] 0 0
Belgium
State/province [40] 0 0
Oost-Vlaanderen
Country [41] 0 0
Brazil
State/province [41] 0 0
Bahia
Country [42] 0 0
Brazil
State/province [42] 0 0
Ceara
Country [43] 0 0
Brazil
State/province [43] 0 0
Minas Gerais
Country [44] 0 0
Brazil
State/province [44] 0 0
Rio Grande Do Norte
Country [45] 0 0
Brazil
State/province [45] 0 0
Rio Grande Do Sul
Country [46] 0 0
Brazil
State/province [46] 0 0
Sao Paulo
Country [47] 0 0
Brazil
State/province [47] 0 0
Rio de Janeiro
Country [48] 0 0
Canada
State/province [48] 0 0
Alberta
Country [49] 0 0
Canada
State/province [49] 0 0
Ontario
Country [50] 0 0
Canada
State/province [50] 0 0
Quebec
Country [51] 0 0
Chile
State/province [51] 0 0
Region M. De Santiago
Country [52] 0 0
Colombia
State/province [52] 0 0
Atlantico
Country [53] 0 0
Colombia
State/province [53] 0 0
Distrito Capital De Bogota
Country [54] 0 0
Colombia
State/province [54] 0 0
Risaralda
Country [55] 0 0
Colombia
State/province [55] 0 0
Valle Del Cauca
Country [56] 0 0
France
State/province [56] 0 0
Alpes-Maritimes
Country [57] 0 0
France
State/province [57] 0 0
Bouches-du-Rhone
Country [58] 0 0
France
State/province [58] 0 0
Haute-Garonne
Country [59] 0 0
France
State/province [59] 0 0
Val-de-Marne
Country [60] 0 0
France
State/province [60] 0 0
Vaucluse
Country [61] 0 0
France
State/province [61] 0 0
Paris
Country [62] 0 0
Germany
State/province [62] 0 0
Baden-Wurttemberg
Country [63] 0 0
Germany
State/province [63] 0 0
Bayern
Country [64] 0 0
Germany
State/province [64] 0 0
Hessen
Country [65] 0 0
Germany
State/province [65] 0 0
Nordrhein-Westfalen
Country [66] 0 0
Germany
State/province [66] 0 0
Schleswig-Holstein
Country [67] 0 0
Germany
State/province [67] 0 0
Thuringen
Country [68] 0 0
Germany
State/province [68] 0 0
Berlin
Country [69] 0 0
Germany
State/province [69] 0 0
Hamburg
Country [70] 0 0
Hungary
State/province [70] 0 0
Baranya
Country [71] 0 0
Hungary
State/province [71] 0 0
Jasz-Nagykun-Szolnok
Country [72] 0 0
Hungary
State/province [72] 0 0
Budapest
Country [73] 0 0
Ireland
State/province [73] 0 0
Dublin
Country [74] 0 0
Israel
State/province [74] 0 0
Haifa
Country [75] 0 0
Israel
State/province [75] 0 0
Jerusalem
Country [76] 0 0
Israel
State/province [76] 0 0
Petah Tikva
Country [77] 0 0
Israel
State/province [77] 0 0
Ramat Gan
Country [78] 0 0
Israel
State/province [78] 0 0
Tel Aviv
Country [79] 0 0
Japan
State/province [79] 0 0
Aichi
Country [80] 0 0
Japan
State/province [80] 0 0
Chiba
Country [81] 0 0
Japan
State/province [81] 0 0
Hyogo
Country [82] 0 0
Japan
State/province [82] 0 0
Kagawa
Country [83] 0 0
Japan
State/province [83] 0 0
Kanagawa
Country [84] 0 0
Japan
State/province [84] 0 0
Fukuoka
Country [85] 0 0
Japan
State/province [85] 0 0
Hiroshima
Country [86] 0 0
Japan
State/province [86] 0 0
Tokyo
Country [87] 0 0
Korea, Republic of
State/province [87] 0 0
Jeonranamdo
Country [88] 0 0
Korea, Republic of
State/province [88] 0 0
Kyonggi-do
Country [89] 0 0
Korea, Republic of
State/province [89] 0 0
Seoul
Country [90] 0 0
Poland
State/province [90] 0 0
Lodzkie
Country [91] 0 0
Poland
State/province [91] 0 0
Malopolskie
Country [92] 0 0
Poland
State/province [92] 0 0
Mazowieckie
Country [93] 0 0
Poland
State/province [93] 0 0
Pomorskie
Country [94] 0 0
Poland
State/province [94] 0 0
Slaskie
Country [95] 0 0
Portugal
State/province [95] 0 0
Braga
Country [96] 0 0
Portugal
State/province [96] 0 0
Lisboa
Country [97] 0 0
Portugal
State/province [97] 0 0
Porto
Country [98] 0 0
Russian Federation
State/province [98] 0 0
Moskva
Country [99] 0 0
Russian Federation
State/province [99] 0 0
Tatarstan, Respublika
Country [100] 0 0
Russian Federation
State/province [100] 0 0
Yaroslavskaya Oblast
Country [101] 0 0
Spain
State/province [101] 0 0
Barcelona
Country [102] 0 0
Spain
State/province [102] 0 0
La Coruna
Country [103] 0 0
Spain
State/province [103] 0 0
Madrid
Country [104] 0 0
Spain
State/province [104] 0 0
Sevilla
Country [105] 0 0
Switzerland
State/province [105] 0 0
Aargau
Country [106] 0 0
Switzerland
State/province [106] 0 0
Ticino
Country [107] 0 0
Switzerland
State/province [107] 0 0
Geneve
Country [108] 0 0
Taiwan
State/province [108] 0 0
Kaohsiung
Country [109] 0 0
Taiwan
State/province [109] 0 0
Taichung
Country [110] 0 0
Taiwan
State/province [110] 0 0
Tainan
Country [111] 0 0
Taiwan
State/province [111] 0 0
Taipei
Country [112] 0 0
Ukraine
State/province [112] 0 0
Dnipropetrovska Oblast
Country [113] 0 0
Ukraine
State/province [113] 0 0
Kirovohradska Oblast
Country [114] 0 0
Ukraine
State/province [114] 0 0
Kyivska Oblast
Country [115] 0 0
Ukraine
State/province [115] 0 0
Kyiv
Country [116] 0 0
United Kingdom
State/province [116] 0 0
Cambridgeshire
Country [117] 0 0
United Kingdom
State/province [117] 0 0
Kingston Upon Hull
Country [118] 0 0
United Kingdom
State/province [118] 0 0
London, City Of
Country [119] 0 0
United Kingdom
State/province [119] 0 0
Sheffield

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

Ethics approval
Ethics application status

Summary
Brief summary
This is a randomized, active-controlled, open-label study of pembrolizumab (Pembro) given
prior to surgery and pembrolizumab in combination with standard of care radiotherapy (with or
without cisplatin), as post-surgical therapy in treatment naïve participants with newly
diagnosed Stage III/IVA, resectable, locoregionally advanced, head and neck squamous cell
carcinoma (LA-HNSCC). Efficacy outcomes will be stratified by programmed cell death ligand 1
(PD-L1) combined positive score (CPS) status. The primary hypothesis is that pembrolizumab
given before surgery and after surgery in combination with radiotherapy (with or without
cisplatin) improves event-free survival compared to radiotherapy (with or without cisplatin)
given after surgery alone.
Trial website
https://clinicaltrials.gov/ct2/show/NCT03765918
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Medical Director
Address 0 0
Merck Sharp & Dohme LLC
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