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Submitted by: Trishia Torero 2016-05-02 00:00:00 Last Updated by: Trishia Torero 2020-10-30 15:31:25


A Phase III Randomized, Open-Label, Multi-Center, Global Study of MEDI4736 Alone or in Combination with Tremelimumab versus Standard of Care in the Treatment of First-line Recurrent or Metastatic Squamous Cell Head and Neck Cancer Patients (KESTREL)

PHRR160503-001220

D419LC00001

2016-CT0333

A Phase III Randomized, Open-Label, Multi-Center, Global Study of MEDI4736 Alone or in Combination with Tremelimumab versus Standard of Care in the Treatment of First-line Recurrent or Metastatic Squamous Cell Head and Neck Cancer Patients (KESTREL)

In this study, the efficacy of MEDI4736 + tremelimumab combination therapy in terms of PFS compared to SoC is being evaluated in SCCHN patients with recurrent or metastatic SCCHN who have received no prior systemic chemotherapy for recurrent or metastatic disease. The contribution of MEDI4736 monotherapy to the efficacy of combination treatment regimen and the efficacy of MEDI4736 monotherapy compared to SoC will also be evaluated in a prospective, randomized fashion.

Regime Classification Priority
2010 - 2016 Health Technology Development Drug Discovery and Development
Start Date Duration in Months Target Completion Date Actual Completion Date
2016-05-02 36 2019-05-02 0000-00-00

Ongoing

Institution Classification Region LTO #
AstraZeneca Pharmaceuticals (Philippines) Inc. Private Business NCR CDRR-NCR-S-17
Institution Classification Region LTO #
AstraZeneca Pharmaceuticals (Philippines) Inc. Private Business NCR CDRR-NCR-S-17
Institution Region
AstraZeneca Pharmaceuticals (Philippines) Inc. NCR
Name E-Mail Institution and Institution Address
Samia T. Necesito samia.necesito@astrazeneca.com 16F, Inoza Tower, 40th Street, Bonifacio Global City,Taguig, Metro Manila
Name E-Mail Institution and Institution Address
Samia T. Necesito samia.necesito@astrazeneca.com 16F, Inoza Tower, 40th Street, Bonifacio Global City,Taguig, Metro Manila
Name Expertise Affiliation
Annielyn Beryl Ong-Cornel, MD Oncology University of Perpetual Help System DALTA - Las Piñas
Gerardo Cornelio, MD Oncology San Juan de Dios Hospital
Jorge Ignacio, MD Oncology Philippine General Hospital
Ma. Noemi Alsay-Uy, MD Oncology Chong Hua Hospital
Rubi K. Li, MD Oncology St. Luke's Medical Center - Quezon City
Project Location Institutional Ethics Review Board
University of Perpetual Help System DALTA - Las Piñas N/A
San Juan de Dios Hospital San Juan de Dios Educational Foundation Inc., Hospital Ethics Review Committee
Philippine General Hospital Philippine General Hospital Ethics Review Board
Chong Hua Hospital Chong Hua Hospital Institutional Review Board
St. Luke's Medical Center - Quezon City St. Luke's Medical Center Institutional Ethics Review Board

Squamous Cell Head and Neck Cancer

To assess the efficacy of MEDI4736 + tremelimumab combination therapy compared to SoC in terms of PFS and OS

To further assess the efficacy of MEDI4736 + tremelimumab combination therapy compared to SoC in terms of PFS, ORR, DoR, APF12, PFS2, OS, and OS24

To assess the efficacy of MEDI4736 monotherapy compared to SoC in terms of PFS, ORR, PFS2, OS, and OS24

To assess the efficacy of MEDI4736 + tremelimumab combination therapy compared to MEDI4736 monotherapy in terms of PFS, ORR, and OS

To assess disease-related symptoms and health-related quality of life in patients treated with MEDI4736 + tremelimumab combination therapy compared to SoC using the European Organisation for Research and Treatment of Cancer (EORTC) 30-item Core Quality of Life Questionnaire (QLQ-C30) version 3 and the 35-item Head and Neck Quality of Life Questionnaire (QLQ-H&N35) module

To assess the PK of MEDI4736 + tremelimumab combination therapy and MEDI4736 monotherapy

To investigate the immunogenicity of MEDI4736 and tremelimumab

 

Completed

  • Austria
  • Belgium
  • Brazil
  • Canada
  • France
  • Germany
  • Greece
  • India
  • Italy
  • Japan
  • Philippines
  • Poland
  • Romania
  • Russia
  • Slovakia
  • South Korea
  • Spain
  • Taiwan
  • Thailand
  • Ukraine
  • United Kingdom
  • United States
  • Vietnam

Clinical Trial

D419LC00001

20151203124312

2016-04-11

0000-00-00

20

2

Unspecified

02 May 2016

For inclusion in the study, patients should fulfill the following criteria:
SoC procedures obtained prior to informed consent for other purposes may be used for screening if the patient/legal representative consents to allow use of these procedures for screening purposes.
Patients must meet all of the following criteria:
1. Age ≥18 years at the time of screening
2. Written informed consent and any locally required authorization (eg, Health Insurance Portability and Accountability Act in the United States, European Union [EU] Data Privacy Directive in the EU) obtained from the patient/legal representative prior to performing any protocol-related procedures, including screening evaluations. (For patients aged 3. Histologically confirmed recurrent or metastatic SCCHN (oral cavity, oropharynx, hypopharynx, or larynx) not amenable to local curative therapy with surgery or radiation therapy.
4. No prior systemic chemotherapy for recurrent or metastatic disease
5. Able and willing to give valid written consent to provide newly acquired tumor tissue (preferred) or archival tissue (6. For patients with OPC only: confirmed HPV status by p16 IHC prior to randomization.
7. Confirmed PD-L1–positive or –negative SCCHN by the Ventana SP263 IHC assay
- On newly acquired tumor tissue (preferred) or archival tissue (- If the patient’s PD-L1 status has already been assessed using the analytically validated Ventana assay as a part of the screening process for another AstraZeneca/MedImmune study, this test result can be used for the determination of eligibility.
- Note: A positive PD-L1 sample is measured using a defined cut-off based on ≥25% of tumor cells with membrane staining of any intensity for PD-L1. A negative PD-L1 sample is determined by 0% to 24% of tumor cells with membrane staining for PD-L1.
8. World Health Organization (WHO)/ECOG performance status of 0 or 1 at enrollment
9. At least 1 lesion, not previously irradiated, that can be accurately measured at baseline as ≥10 mm in the longest diameter (except lymph nodes, which must have a short axis ≥15 mm) with CT or MRI and that is suitable for accurate repeated measurements as per RECIST 1.1 guidelines. Lesions in a previously irradiated field can be used as measurable disease provided that there has been demonstrated progression in the lesion and the lesion measures at least 20 mm.
10. Patients must have no prior exposure to immune-mediated therapy, including anti-CTLA-4, anti-PD-1, anti-PD-L1, or anti-programmed cell death ligand 2 antibodies, excluding therapeutic anticancer vaccines. Exposure to other investigational agents may be permitted after discussion with the Sponsor.
11. Adequate organ and marrow function independent of transfusion for at least 7 days prior to screening and independent of growth factor support for at least 14 days prior to screening, defined as follows:
- Hemoglobin ≥9 g/dL
- Absolute neutrophil count ≥1500/mm3
- Platelet count ≥100000/mm3
- Serum bilirubin ≤1.5 × the 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.
- ALT and AST ≤2.5 × ULN; for patients with hepatic metastases, ALT and AST ≤5 × ULN
- Calculated creatinine clearance >40 mL/min as determined by Cockcroft-Gault (using actual body weight) (creatinine clearance of 60 mL/min is needed if cisplatin is used)
12. 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 folliclestimulating hormone levels in the post-menopausal range for the institution.
- Women 1 year ago, had chemotherapy-induced menopause with >1 year interval since last menses, or underwent surgical sterilization (bilateral oophorectomy or hysterectomy).

Patients should not enter the study if any of the following exclusion criteria are fulfilled:
1. Histologically 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 (eg, nasopharynx or salivary gland)
2. Received any systemic therapy for recurrent or metastatic SCCHN
3. Tumor progression or recurrence within 6 months of last dose of platinum therapy in the primary treatment setting
4. Receipt of any radiotherapy or hormonal therapy for cancer treatment within 30 days prior to first dose of study treatment
5. Receipt of last dose of an approved (marketed) anticancer therapy (chemotherapy, targeted therapy, biologic therapy, mAbs, etc) within 21 days prior to the first dose of study treatment. If sufficient washout time has not occurred due to the schedule or PK properties of an agent, a longer washout period will be required, as agreed upon by AstraZeneca and the Investigator.
6. Receipt of any investigational anticancer therapy within 28 days or 5 half-lives, whichever is longer, prior to the first dose of study treatment.
7. 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.
8. Any unresolved toxicity National Cancer Institute (NCI) Common Terminology Criteria for Adverse Event (CTCAE) Grade ≥2 from previous anticancer therapy with the exception of alopecia, vitiligo, lymphopenia, and the laboratory values defined in the inclusion criterion
- Patients with Grade ≥2 neuropathy will be evaluated on a case-by-case basis and may be included after consultation with the Study Physician.
- Patients with a toxicity not reasonably expected to be exacerbated by treatment with their assigned IP (eg, hearing loss) may be included after consultation with the Study Physician.
9. 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:
- Intranasal, inhaled, topical steroids, or local steroid injections (eg, intra-articular injection)
- Systemic corticosteroids at physiologic doses not to exceed 10 mg/day of prednisone or its equivalent
- Steroids as pre-medication for hypersensitivity reactions (eg, CT scan pre-medication)
10. History of allogeneic organ transplantation
11. Active or prior documented autoimmune or inflammatory disorders (including inflammatory bowel disease [eg, colitis, Crohn’s disease], diverticulitis with the exception of a prior episode that has resolved or diverticulosis, celiac disease, or other serious gastrointestinal chronic conditions associated with diarrhea; systemic lupus erythematosus; Wegener syndrome [granulomatosis with polyangiitis]; myasthenia gravis; Graves’ disease; rheumatoid arthritis, hypophysitis, uveitis, etc) within the past 3 years prior to the start of treatment. The following are exceptions to this criterion:
- Patients with vitiligo or alopecia
- Patients with hypothyroidism (eg, following Hashimoto syndrome) stable on hormone replacement or psoriasis not requiring systemic treatment
12. 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, substantially increase the risk of incurring AEs from IP, or compromise the ability of the patient to give written informed consent
13. History of another primary malignancy within the last 5 years except for the following:
- Non-invasive malignancies, such as cervical carcinoma in situ or nonmelanomatous carcinoma of the skin that has been surgically cured. Other in situ carcinomas that have been adequately treated may be permitted after detailed discussion with the Sponsor.
14. Patients with a history of brain metastases, spinal cord compression, or leptomeningeal carcinomatosis, or involvement of any other anatomic area that, in the opinion of the Investigator, may cause significant symptoms if an inflammatory reaction occurs
15. Mean QT interval corrected for heart rate ≥470 ms calculated from 3 electrocardiograms (ECGs) using Fridericia’s Correction
16. History of active primary immunodeficiency
17. Known history of previous clinical diagnosis of tuberculosis
18. Active infection including hepatitis B, hepatitis C, or human immunodeficiency virus (HIV)
19. 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.
20. 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 MEDI4736 monotherapy or 180 days after the last dose of MEDI4736 + tremelimumab combination 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 MEDI4736 monotherapy or 180 days after the last dose of MEDI4736 + tremelimumab combination therapy. For patients randomized to receive SoC treatment, follow the local prescribing information relating to contraception, the time limit for such precautions, and any additional restrictions for agents in the SoC treatment regimen
21. Known allergy or hypersensitivity to IP or any IP excipient
22. Any condition that, in the opinion of the Investigator, would interfere with evaluation of the IP or interpretation of patient safety or stud results
23. For patients randomized to the SoC arm, any contraindication to a specific SoC agent as specified by the accompanying package insert or Summary of Product Characteristics
24. Patient weight of

Interventional

MEDI4736 + tremelimumab

MEDI4736 monotherapy: (1500 mg) will be administered via IV infusion every 4 weeks (q4w) until PD.
MEDI4736 + tremelimumab combination therapy: Tremelimumab (75 mg) will be administered via IV infusion q4w for a maximum of 4 doses, and MEDI4736 (1500 mg) will be administered via IV infusion q4w until PD.

Date Amendment Classification Reason
2020-10-16 Amendments related to the protocol Informed consent

Randomized

Open Label

Unspecified

Not Applicable

To assess the efficacy of MEDI4736 + tremelimumab combination therapy compared to SoC in terms of PFS and OS

Phase III

Utilization Utilization Info
Publication
Oral Presentation
Drug Literature
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Others
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