Stage II-IVB Operable HNSCC Oral CavityPhase 2NCT03737968

Window of Opportunity Trial of Durvalumab (MEDI4736) or Durvalumab/Tremelimumab as Neoadjuvant Chemotherapy to Identify Immune Dynamics in Surgically Resectable Head and Neck Cancer Patients.

A Phase 2 study testing Durvalumab and durvalumab + tremelimumab in people with Stage II-IVB Operable HNSCC Oral Cavity and Hypopharynx, run by Yonsei University at 1 site in South Korea.

Unknown status

Status not confirmed. The sponsor has not verified this record for over two years, so it may be out of date.

Official record

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Trial summary

Who is it for?: Ages 20 years and olderHealthy volunteers can take part
Conditions the study is for: Stage II-IVB Operable HNSCC Oral Cavity, Hypopharynx, Oropharynx
What is being tested?: Durvalumab and durvalumab + tremelimumab
Type of treatment: Injection or infusion
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 48 participants
Where: 1 siteSouth Korea
Study dates: 2 Jan 2019to Oct 2023
Phase: Phase 2
Are there results?: None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 20 years and older
All sexes
Healthy volunteers accepted
Adult, Older adult

Who may be able to join

Histologically confirmed surgically resectable HNSCC oral cavity, hypopharynx, oropharynx, and larynx
Measurable disease defined as lesions that can be accurately measured by RECIST 1.1.
Written informed consent and any locally-required authorization obtained from the patient prior to performing any protocol-related procedures, including screening evaluations
Age >18 years at time of study entry or Adult male or female
Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
Body weight >30kg

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Life expectancy of at least 12 weeks
Adequate normal organ and marrow function as defined below:
Haemoglobin ≥9.0 g/dL
Absolute neutrophil count (ANC) > 1500 per mm3
Platelet count >75,000 per mm3
Serum bilirubin ≤1.5 x institutional upper limit of normal (ULN).
AST (SGOT)/ALT (SGPT) ≤2.5 x institutional upper limit of normal unless liver metastases are present, in which case it must be ≤5x ULN
Measured creatinine clearance (CL) >40 mL/min or Calculated creatinine clearance CL>40 mL/min by the Cockcroft-Gault formula (Cockcroft and Gault 1976) or by 24-hour urine collection for determination of creatinine clearance:
Males: Creatinine CL (mL/min) = Weight (kg) x (140 - Age) 72 x serum creatinine (mg/dL) Females: Creatinine CL (mL/min) = Weight (kg) x (140 - Age) x 0.85 72 x serum creatinine (mg/dL)
Evidence of post-menopausal status or negative urinary or serum pregnancy test for female pre-menopausal patients. Women will be considered post-menopausal if they have been amenorrheic for 12 months without an alternative medical cause. The following age-specific requirements apply:
Women <50 years of age would be considered post-menopausal if they have been amenorrheic for 12 months or more following cessation of exogenous hormonal treatments and if they have luteinizing hormone and follicle-stimulating hormone levels in the post-menopausal range for the institution or underwent surgical sterilization (bilateral oophorectomy or hysterectomy).
Women ≥50 years of age would be considered post-menopausal if they have been amenorrheic for 12 months or more following cessation of all exogenous hormonal treatments, had radiation-induced menopause with last menses >1 year ago, had chemotherapy-induced menopause with last menses >1 year ago, or underwent surgical sterilization (bilateral oophorectomy, bilateral salpingectomy or hysterectomy).
Patient is willing and able to comply with the protocol for the duration of the study including undergoing treatment and scheduled visits and examinations including follow up.

Who cannot join

Involvement in the planning and/or conduct of the study Participation in another clinical study with an investigational product during the last Concurrent enrolment in another clinical study, unless it is an observational (non-interventional) clinical study or during the follow-up period of an interventional study Any concurrent chemotherapy, IP, biologic, or hormonal therapy for cancer treatment. Concurrent use of hormonal therapy for non-cancer-related conditions (e.g., hormone replacement therapy) is acceptable.
History of allogenic organ transplantation. Any unresolved toxicity NCI CTCAE Grade ≥2 from previous anticancer therapy with the exception of alopecia, vitiligo, and the laboratory values defined in the inclusion criteria
Patients with Grade ≥2 neuropathy will be evaluated on a case-by-case basis after consultation with the Study Physician.
Patients with irreversible toxicity not reasonably expected to be exacerbated by treatment with durvalumab or tremelimumab may be included only after consultation with the Study Physician.
Major surgical procedure (as defined by the Investigator) within 28 days prior to the first dose of IP. Note: Local surgery of isolated lesions for palliative intent is acceptable.
Active or prior documented autoimmune or inflammatory disorders (including inflammatory bowel disease [e.g., colitis or Crohn's disease], diverticulitis [with the exception of diverticulosis], systemic lupus erythematosus, Sarcoidosis syndrome, or Wegener syndrome [granulomatosis with polyangiitis, Graves' disease, rheumatoid arthritis, hypophysitis, uveitis, etc]). The following are exceptions to this criterion:

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Patients with vitiligo or alopecia
Patients with hypothyroidism (e.g., following Hashimoto syndrome) stable on hormone replacement
Any chronic skin condition that does not require systemic therapy
Patients without active disease in the last 5 years may be included but only after consultation with the study physician
Patients with celiac disease controlled by diet alone Uncontrolled intercurrent illness, including but not limited to, ongoing or active infection, symptomatic congestive heart failure, uncontrolled hypertension, unstable angina pectoris, cardiac arrhythmia, interstitial lung disease, serious chronic gastrointestinal conditions associated with diarrhea, or psychiatric illness/social situations that would limit compliance with study requirement, substantially increase risk of incurring AEs or compromise the ability of the patient to give written informed consent History of another primary malignancy except for
Malignancy treated with curative intent and with no known active disease ≥5 years before the first dose of IP and of low potential risk for recurrence
Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease
Adequately treated carcinoma in situ without evidence of disease History of active primary immunodeficiency Active infection including tuberculosis (clinical evaluation that includes clinical history, physical examination and radiographic findings, and TB testing in line with local practice), hepatitis B (known positive HBV surface antigen (HBsAg) result), hepatitis C, or human immunodeficiency virus (positive HIV 1/2 antibodies). Patients with a past or resolved HBV infection (defined as the presence of hepatitis B core antibody [anti-HBc] and absence of HBsAg) are eligible. Patients positive for hepatitis C (HCV) antibody are eligible only if polymerase chain reaction is negative for HCV RNA.
:Current or prior use of immunosuppressive medication within 14 days before the first dose of durvalumab or tremelimumab. The following are exceptions to this criterion:
Intranasal, inhaled, topical steroids, or local steroid injections (e.g., intra articular injection)
Systemic corticosteroids at physiologic doses not to exceed 10 mg/day of prednisone or its equivalent Receipt of live attenuated vaccine within 30 days prior to the first dose of IP. Note: Patients, if enrolled, should not receive live vaccine whilst receiving IP and up to 30 days after the last dose of IP.
Female patients who are pregnant or breastfeeding or male or female patients of reproductive potential who are not willing to employ effective birth control from screening to 90 days after the last dose of durvalumab monotherapy or 180 days after the last dose of durvalumab + tremelimumab combination therapy.
Known allergy or hypersensitivity to any of the study drugs or any of the study drug excipients.
Prior treatment with an anti-PD-1, anti-PD-L1 (including durvalumab), anti-PD-L2, anti-CD137, or anti-cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) antibody (including tremelimumab).
Female patients who are pregnant or breastfeeding or male or female patients of reproductive potential who are not willing to employ effective birth control from screening to 180 days after the last dose of durvalumab + tremelimumab combination therapy or 90 days after the last dose of durvalumab monotherapy, whichever is the longer time period

Trial locations and contacts

1 site in 1 country.

South Korea1 site

Yonsei University Health System, Severance Hospital
Seoul

Other trials in South Korea

About this study

This is a phase II randomized, open label study of durvalumab with/ without tremelimumab as neoadjuvant therapy and durvalumab maintenance after SoC RTx with/without cisplatin as post-surgical adjuvant therapy in treatment naïve participants with newly diagnosed resectable LA HNSCC. The study will be conducted in conformance with Good Clinical Practices (GCP). Approximately 44 participants will be randomized in a 1:1 ratio to below two Arms

Conditions: Stage II-IVB Operable HNSCC Oral Cavity, Hypopharynx, Oropharynx, Larynx
Being tested: Durvalumab, durvalumab + tremelimumab
Keywords: oral cavity, hypopharynx, oropharynx, larynx, medi4736, tremelimumab
Medical subject headings: Laryngeal Diseases

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

DurvalumabDrug
Patients in the durvalumab (MEDI4736) monotherapy treatment group will receive durvalumab (MEDI4736) (1500mg Q4W) once prior to surgery in this study. After surgical resection, these patients will receive the post op adjuvant treatment including RTx with/without cisplatin based on the pathologic findings and physician's discretion. After completion of adjuvant treatment, durvalumab (MEDI4736) 1500mg Q4W as maintenance treatment for up to a maximum of 12 months
durvalumab + tremelimumabDrug
Patients in the durvalumab (MEDI4736) + tremelimumab combination therapy treatment group will receive durvalumab (MEDI4736) (1500mg Q4W) in combination with tremelimumab (75 mg IV Q4W) once prior to surgery in this study. After surgical resection, these patients will receive the post op adjuvant treatment including RTx with/without cisplatin based on the pathologic findings and physician's discretion. After completion of adjuvant treatment, durvalumab (MEDI4736) 1500mg Q4W as maintenance treatment for up to a maximum of 12 months

Study groups in NCT03737968
Study group	Role	What they receive
Durvalumab monotherapy Arm	Experimental	Patients in the durvalumab (MEDI4736) monotherapy treatment group will receive durvalumab (MEDI4736) (1500mg Q4W) once prior to surgery in this study. After surgical resection, these patients will receive the post op adjuvant treatment including RTx with/without cisplatin based on the pathologic findings and physician's discretion. After completion of adjuvant treatment, durvalumab (MEDI4736) 1500mg Q4W as maintenance treatment for up to a maximum of 12 months until confirmed disease progression unless there is unacceptable toxicity, withdrawal of consent, or another discontinuation criterion is met. The first durvalumab (MEDI4736) monotherapy dose at 1500mg Q4W will be within 8 weeks after the completion of adjuvant therapy. If a patient's weight falls to 30kg or below the patient should receive weight-based dosing equivalent to 20 mg/kg of durvalumab Q4W until the weight improves to >30 kg, at which point the patient should start receiving the fixed dosing of durvalumab 1500mg. Receives: Drug: Durvalumab
Durvalumab + tremelimumab combination therapy Arm	Active comparator	Patients in the durvalumab (MEDI4736) + tremelimumab combination therapy treatment group will receive durvalumab (MEDI4736) (1500mg Q4W) in combination with tremelimumab (75 mg IV Q4W) once prior to surgery in this study. After surgical resection, these patients will receive the post op adjuvant treatment including RTx with/without cisplatin based on the pathologic findings and physician's discretion. After completion of adjuvant treatment, durvalumab (MEDI4736) 1500mg Q4W as maintenance treatment for up to a maximum of 12 months until confirmed disease progression unless there is unacceptable toxicity, withdrawal of consent, or another discontinuation criterion is met. The first durvalumab (MEDI4736) monotherapy dose at 1500mg Q4W will be within 8 weeks after the completion of adjuvant therapy. Receives: Drug: durvalumab + tremelimumab

What is being measured

The primary outcome is the main question the study is designed to answer.

locoregional relapse rate
investigate the locoregional relapse rate (LRR)
Measured: every 3 months, assessed up to 2 years
Distant metastatic rate
Distant metastatic rate
Measured: every 3 months, assessed up to 2 years

Secondary outcomes (3)

distant metastases free survival (DMFS)
Measured: every 3 months, assessed up to 2 years
locoregional control (LRC) time
Measured: every 3 months, assessed up to 2 years
progression-free survival (PFS)
Measured: every 3 months, assessed up to 2 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

2 Jan 2019Oct 2023

First posted13 Nov 2018
Study start2 Jan 2019
Primary completionOct 2023 (estimated)
Study completionOct 2023 (estimated)

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Publications (2)Papers the sponsor has linked to this study.
Other trials for Stage II-IVB Operable HNSCC Oral CavityStudies of the same condition, open and under way.
More trials run by Yonsei UniversityThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 2
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Single group
Masking: None (open label)
Enrolment: 48 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT03737968
Sponsor's protocol ID: 4-2018-0787
Status last verified: Mar 2023
First submitted: 8 Nov 2018
Last updated: 21 Mar 2023
Results posted: No
Data monitoring committee: No
FDA-regulated drug: No
FDA-regulated device: No
Individual data sharing: Undecided

Publications

Cha J, Kim CG, Sim NS, Kim G, Son W, Kim D, Jung Y, Hong HJ, Lee HB, Kim J, Kim J, Yoon SO, Go S, Kim J, Seong E, Baek S, Kim KH, Hong MH, Koh YW, Lee I, Kim HR. 4-1BB+ Tregs and inhibitory progenitor exhausted T cells confer resistance to anti-PD-L1 and anti-CTLA-4 combination therapy. Cell Rep Med. 2025 Oct 21;6(10):102408. doi: 10.1016/j.xcrm.2025.102408. Epub 2025 Oct 3.
PubMed 41045934
Cha J, Kim DH, Kim G, Cho JW, Sung E, Baek S, Hong MH, Kim CG, Sim NS, Hong HJ, Lee JE, Hemberg M, Park S, Yoon SO, Ha SJ, Koh YW, Kim HR, Lee I. Single-cell analysis reveals cellular and molecular factors counteracting HPV-positive oropharyngeal cancer immunotherapy outcomes. J Immunother Cancer. 2024 Jun 10;12(6):e008667. doi: 10.1136/jitc-2023-008667.
PubMed 38857913

Study at a glance

From the registry record, last updated by the sponsor on 21 Mar 2023. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Window of Opportunity Trial of Durvalumab (MEDI4736) or Durvalumab/Tremelimumab as Neoadjuvant Chemotherapy to Identify Immune Dynamics in Surgically Resectable Head and Neck Cancer Patients.
ClinicalTrials.gov ID: NCT03737968
Acronym / sponsor ID: 4-2018-0787
Conditions: Stage II-IVB Operable HNSCC Oral Cavity, Hypopharynx, Oropharynx, Larynx
Keywords: oral cavity, hypopharynx, oropharynx, larynx, medi4736, tremelimumab
Phase: Phase 2
Study type: Interventional
Recruitment status: Unknown status
Enrolment: 48 participants (actual)
Lead sponsor: Yonsei UniversityUniversity, hospital or other
Study start: 2 Jan 2019 (actual)
Primary completion: Oct 2023 (estimated)
Study completion: Oct 2023 (estimated)
First posted: 13 Nov 2018 (actual)
Results: Not posted in the source record

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Single group
Masking: None (open label)
Number of arms: 2

Arm	Type	Receives
Durvalumab monotherapy Arm	Experimental	Drug: DurvalumabPatients in the durvalumab (MEDI4736) monotherapy treatment group will receive durvalumab (MEDI4736) (1500mg Q4W) once prior to surgery in this study. After surgical resection, these patients will receive the post op adjuvant treatment including RTx with/without cisplatin based on the pathologic findings and physician's discretion. After completion of adjuvant treatment, durvalumab (MEDI4736) 1500mg Q4W as maintenance treatment for up to a maximum of 12 months until confirmed disease progression unless there is unacceptable toxicity, withdrawal of consent, or another discontinuation criterion is met. The first durvalumab (MEDI4736) monotherapy dose at 1500mg Q4W will be within 8 weeks after the completion of adjuvant therapy. If a patient's weight falls to 30kg or below the patient should receive weight-based dosing equivalent to 20 mg/kg of durvalumab Q4W until the weight improves to >30 kg, at which point the patient should start receiving the fixed dosing of durvalumab 1500mg.
Durvalumab + tremelimumab combination therapy Arm	Active comparator	Drug: durvalumab + tremelimumabPatients in the durvalumab (MEDI4736) + tremelimumab combination therapy treatment group will receive durvalumab (MEDI4736) (1500mg Q4W) in combination with tremelimumab (75 mg IV Q4W) once prior to surgery in this study. After surgical resection, these patients will receive the post op adjuvant treatment including RTx with/without cisplatin based on the pathologic findings and physician's discretion. After completion of adjuvant treatment, durvalumab (MEDI4736) 1500mg Q4W as maintenance treatment for up to a maximum of 12 months until confirmed disease progression unless there is unacceptable toxicity, withdrawal of consent, or another discontinuation criterion is met. The first durvalumab (MEDI4736) monotherapy dose at 1500mg Q4W will be within 8 weeks after the completion of adjuvant therapy.

Who may qualify

Ages: 20 years and older
Sex: All
Healthy volunteers: Accepted
Age groups: Adult, Older adult

Key inclusion criteria (19 listed)

Histologically confirmed surgically resectable HNSCC oral cavity, hypopharynx, oropharynx, and larynx
Measurable disease defined as lesions that can be accurately measured by RECIST 1.1.
Written informed consent and any locally-required authorization obtained from the patient prior to performing any protocol-related procedures, including screening evaluations
Age >18 years at time of study entry or Adult male or female
Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1

Key exclusion criteria (21 listed)

Involvement in the planning and/or conduct of the study Participation in another clinical study with an investigational product during the last Concurrent enrolment in another clinical study, unless it is an observational (non-interventional) clinical study or during the follow-up period of an interventional study Any concurrent chemotherapy, IP, biologic, or hormonal therapy for cancer treatment. Concurrent use of hormonal therapy for non-cancer-related conditions (e.g., hormone replacement therapy) is acceptable.
History of allogenic organ transplantation. Any unresolved toxicity NCI CTCAE Grade ≥2 from previous anticancer therapy with the exception of alopecia, vitiligo, and the laboratory values defined in the inclusion criteria
Patients with Grade ≥2 neuropathy will be evaluated on a case-by-case basis after consultation with the Study Physician.
Patients with irreversible toxicity not reasonably expected to be exacerbated by treatment with durvalumab or tremelimumab may be included only after consultation with the Study Physician.
Major surgical procedure (as defined by the Investigator) within 28 days prior to the first dose of IP. Note: Local surgery of isolated lesions for palliative intent is acceptable.

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
DurvalumabPatients in the durvalumab (MEDI4736) monotherapy treatment group will receive durvalumab (MEDI4736) (1500mg Q4W) once prior to surgery in this study. After surgical resection, these patients will receive the post op adjuvant treatment including RTx with/without cisplatin based on the pathologic findings and physician's discretion. After completion of adjuvant treatment, durvalumab (MEDI4736) 1500mg Q4W as maintenance treatment for up to a maximum of 12 months	Drug	Durvalumab monotherapy Arm
durvalumab + tremelimumabPatients in the durvalumab (MEDI4736) + tremelimumab combination therapy treatment group will receive durvalumab (MEDI4736) (1500mg Q4W) in combination with tremelimumab (75 mg IV Q4W) once prior to surgery in this study. After surgical resection, these patients will receive the post op adjuvant treatment including RTx with/without cisplatin based on the pathologic findings and physician's discretion. After completion of adjuvant treatment, durvalumab (MEDI4736) 1500mg Q4W as maintenance treatment for up to a maximum of 12 months	Drug	Durvalumab + tremelimumab combination therapy Arm

Primary outcome

locoregional relapse rate
Time frame: every 3 months, assessed up to 2 years
investigate the locoregional relapse rate (LRR)
Distant metastatic rate
Time frame: every 3 months, assessed up to 2 years
Distant metastatic rate

3 secondary outcomes

distant metastases free survival (DMFS)
Time frame: every 3 months, assessed up to 2 years
locoregional control (LRC) time
Time frame: every 3 months, assessed up to 2 years
progression-free survival (PFS)
Time frame: every 3 months, assessed up to 2 years

Results and safety

Results are not available in the source record.

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 21 Mar 2023.
Derived from this study: PubMed 41045934Cha J, Kim CG, Sim NS, Kim G, Son W, Kim D, Jung Y, Hong HJ, Lee HB, Kim J, Kim J, Yoon SO, Go S, Kim J, Seong E, Baek S, Kim KH, Hong MH, Koh YW, Lee I, Kim HR. 4-1BB+ Tregs and inhibitory progenitor exhausted T cells confer resistance to anti-PD-L1 and anti-CTLA-4 combination therapy. Cell Rep Med. 2025 Oct 21;6(10):102408. doi: 10.1016/j.xcrm.2025.102408. Epub 2025 Oct 3.
Derived from this study: PubMed 38857913Cha J, Kim DH, Kim G, Cho JW, Sung E, Baek S, Hong MH, Kim CG, Sim NS, Hong HJ, Lee JE, Hemberg M, Park S, Yoon SO, Ha SJ, Koh YW, Kim HR, Lee I. Single-cell analysis reveals cellular and molecular factors counteracting HPV-positive oropharyngeal cancer immunotherapy outcomes. J Immunother Cancer. 2024 Jun 10;12(6):e008667. doi: 10.1136/jitc-2023-008667.
Individual participant dataSharing planned: Undecided

Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

The record lists no contact. Use the official record to reach the sponsor.

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Durvalumab and durvalumab + tremelimumab in people with Stage II-IVB Operable HNSCC Oral Cavity and Hypopharynx, run by Yonsei University at 1 site in South Korea.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 19 inclusion and 21 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: status not confirmed, as of the sponsor's last update on 21 Mar 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in South Korea. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

locoregional relapse rate (time frame: every 3 months, assessed up to 2 years). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03737968, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 Mar 2023.