Durvalumab (MEDI4736 ) plus tremelimumab in resectable, locally advanced squamous cell carcinoma of the oral cavity: a window of opportunity study

Overview

Sponsor-declared trial summary

Key facts

Sponsor

UZ Leuven

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

12 Oct 2018 → 25 Mar 2026

Decision date (initial)

2024-12-05

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

SCINTOMICS · ASTRAZENECA

External identifiers

EU CT number

2024-511511-25-00

EudraCT number

2017-000577-36

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy

The primary objective is to evaluate the biological response in the tumor upon treatment with durvalumab, and in parallel, with combination of durvalumab and tremelimumab.

Secondary objectives 1

1. 1) PD-L1 testing before and after single dose of durvalumab and/or tremelimumab 2) MRI imaging comparison before and after a single dose of durvalumab and/or tremelimumab 3) The feasibility to use a 68 Ga-ligand CXCR4 immunotracer PET-MR to measure immune response in the tumor (optional) 4) Safety analysis of addition of durvalumab with or without tremelimumab to standard of care treatment 5) LRC, TTF and OS after treatment, combining durvalumab (arm 1) or durvalumab + tremelimumab (arm 2) with SOC treatment (radiotherapy with or without chemotherapy) 6) Immune landscape profiling of tumour and tumour environment.

Conditions and MedDRA coding

Resectable, locally advanced squamous cell carcinoma of the oral cavity.

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 1

1. ● Age ≥18 years at the time of screening ● Newly diagnosed disease ● Written informed consent obtained from the patient/legal representative prior to performing any protocol-related procedures, including screening evaluations. ● Histologically or cytologically confirmed resectable locally advanced stage IV SCC of the oral cavity. Staging will be performed according to 7th Edition of the AJCC/UICC Staging System. ● No prior systemic therapy for SCCHN disease is allowed. ● No prior radiation therapy in the head and neck is allowed ● No active second malignancy during the last five years except non-melanomatous skin cancer or carcinoma in situ ● Able and willing to give valid written consent to provide newly acquired tumor tissue for the purpose of the analyses defined in the protocol. ● Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 at enrollment ● Body weight > 30 kg ● Patients must have no prior exposure to immune-mediated therapy, including anti-CTLA-4,including tremelimumab anti-PD-1, anti–PD-L1including durvalumab, or anti–programmed cell death ligand 2 antibodies, excluding therapeutic anticancer vaccines. ● Adequate organ and marrow function: o Adequate bone marrow function demonstrated by neutrophils count ≥ 1,500/mm3, platelet count ≥ 100,000/mm3, Haemoglobin ≥ 9.0 g/dL − Adequate hepatic function: 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; bilirubin ≤ 1.5 times upper limit of normal (ULN). This will not apply to patients with confirmed Gilbert’s syndrome (persistent or recurrent hyperbilirubinemia [predominantly unconjugated bilirubin] in the absence of evidence of hemolysis or hepatic pathology), who will be allowed in consultation with their physician. o Adequate renal function as demonstrated by serum creatinine ≤ 1.5 mg/dL (< 133 μmol/L) or calculated creatinine clearance ≥ 50 ml/min as determined by CKD-EPI [62] – o Prothrombin time (PT) or international normalized ratio (INR) < or = 1.2 times (ULN) o Partial thromboplastin time (PTT) < or = 1.2 times ULN ● Adequate cardiac function assessed by 12-lead ECG ● Women of childbearing potential (WOCBP) must be using an adequate method of contraception to avoid pregnancy throughout the study and 6 months beyond stop of treatment in such a manner that the risk of pregnancy is minimized. In general, the decision for appropriate methods to prevent pregnancy should be determined by discussions between the investigator and the study subject. WOCBP include any female who has experienced menarche and who has not undergone successful surgical sterilization (hysterectomy, bilateral tubal ligation, or bilateral oophorectomy) or is not postmenopausal. Females should not be pregnant or breast feeding. Males should not father a baby while on this study and 6 months beyond because the drugs in this study can affect an unborn baby. ● No participation in another interventional drug or device clinical trial up to 4 weeks after administration of the IP (day 202) ● Absence of any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule; those conditions should be discussed with the patient before registration in the trial ● Before patient registration, written informed consent must be given according to ICH/GCP, and national/local regulations

Exclusion criteria 1

1. ● Histologically or cytologically confirmed head and neck cancer of any other primary anatomic location in the head and neck not specified in the inclusion criteria including patients with SCCHN of unknown primary or non-squamous histologies ● Receipt of: o any radiotherapy or hormonal therapy for cancer treatment within 30 days prior to first dose of study treatment. o any investigational anticancer therapy within 28 days or 5 half-lives, whichever is longer, prior to the first dose of study treatment. ● Current or prior use of immunosuppressive medication within 14 days before the first dose of their assigned IP. The following are exceptions to this criterion unless otherwise indicated: o Intranasal, inhaled, topical steroids, or local steroid injections (eg, intra-articular injection) o Systemic corticosteroids at physiologic doses not to exceed 10 mg/day of prednisone or its equivalent o Steroids as pre-medication for hypersensitivity reactions (eg, CT scan pre-medication) and/or as anti-emetics for the SoC arm ● History of allogeneic organ transplantation ● Active or prior documented autoimmune or inflammatory disorders (including inflammatory bowel disease [eg, Crohn’s disease] with the exception of a prior episode that has resolved; systemic lupus erythematosus; Wegener syndrome [granulomatosis with polyangiitis]; myasthenia gravis; Graves’ disease; rheumatoid arthritis) within the past 3 years prior to the start of treatment. ● 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, or psychiatric illness or social situations that would limit compliance with study requirements or substantially increase the risk of incurring AEs from IP ● Active second malignancy during the last five years except for the following: non melanomatous skin cancer that has been surgically cured, non-invasive malignancies, such as carcinoma in situ. Other in situ carcinomas that have been adequately treated may be permitted. ● Mean QT interval corrected for heart rate ≥470 ms ● 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). ● Receipt of live, attenuated vaccine within 30 days prior to the first dose of IP. Note: Patients, if enrolled, should not receive live vaccine during the study and up to 30 days after the last dose of IP. ● Female patients of childbearing potential who are pregnant or breast-feeding or who are not willing to employ a highly effective method of birth control from screening to 90 days after the last dose of IP therapy and non-sterilized male patients who are sexually active with a female partner of childbearing potential who are not willing to employ male condom plus spermicide from screening to 90 days after the last dose of IP therapy ● Known allergy or hypersensitivity to IP or any IP excipient ● Any condition that, in the opinion of the Investigator, would interfere with evaluation of the IP or interpretation of patient safety or study results ● 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 ● 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. ● Distant metastasis

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. CD8 infiltration in the tumor

Secondary endpoints 1

1. Evaluation by 86Ga-CXCR-4 PET/MR; survival; safety.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 2

Auxiliary 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

UZ Leuven

Sponsor organisation

UZ Leuven

Address

Herestraat 49

City

Leuven

Postcode

3000

Country

Belgium

Scientific contact point

Organisation

UZ Leuven

Contact name

Prof. Dr. Paul Clement

Public contact point

Organisation

UZ Leuven

Contact name

Prof. Dr. Paul Clement

Third parties 1

Locations

1 EU/EEA country · 1 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 7 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

1 submissions — initial application plus substantial / non-substantial modifications