Clinical Trials List
Protocol NumberD933BC00001
NCT Number(ClinicalTrials.gov Identfier)NCT03509012
Active
2018-12-01 - 2019-11-07
Phase I
Not yet recruiting1
Recruiting3
ICD-9162.9
Malignant neoplasm of bronchus and lung, unspecified
A Phase I Multicenter Study of Immunotherapy in Combination With Chemoradiation in Patients With Advanced Solid Tumors (CLOVER)
-
Trial Applicant
-
Sponsor
AZ
-
Trial scale
Multi-Regional Multi-Center
-
Update
2026/02/01
Investigators and Locations
Co-Principal Investigator
- 林進清 Division of Radiation Therapy
- 李權 Division of Radiation Therapy
- JENG-SEN TSENG Division of Thoracic Medicine
- 陳建志 Division of Radiation Therapy
- YEN-HSIANG HUANG Division of Thoracic Medicine
- 林敬薇 Division of Radiation Therapy
- KUO-HSUAN HSU Division of Thoracic Medicine
- YI-CHUN LIU Division of Radiation Therapy
The Actual Total Number of Participants Enrolled
0 Not yet recruiting
Co-Principal Investigator
- Chi-Lu Chiang Division of Thoracic Medicine
- Heng-Sheng Chao Division of Thoracic Medicine
- 蕭慈慧 Division of Thoracic Medicine
- 趙恒勝 Division of Thoracic Medicine
- Chao-Hua Chiu Division of Thoracic Medicine
- Yi-Wei Chen Division of Hematology & Oncology
The Actual Total Number of Participants Enrolled
1 Recruiting
Audit
None
Co-Principal Investigator
- Chih-Hung Chen Division of Hematology & Oncology
- 枋岳甫 Division of Infectious Disease
- Chan-Keng Yang Division of Hematology & Oncology
- Cheng-Ta Yang Division of Hematology & Oncology
- 柯皓文 Division of Hematology & Oncology
- 黃振洋 Division of Hematology & Oncology
- Chien-Ying Liu Division of Hematology & Oncology
- Ping-Chih Hsu Division of Hematology & Oncology
- 謝任富 Division of Radiology
- Wen-Cheng Chang Division of Hematology & Oncology
- Chih-Hsi Kuo Division of Hematology & Oncology
- Shih-Hong Li Division of Hematology & Oncology
- 吳教恩 Division of Hematology & Oncology
The Actual Total Number of Participants Enrolled
0 Recruiting
Co-Principal Investigator
Audit
None
Co-Principal Investigator
- James Chih-Hsin Yang Division of Hematology & Oncology
- Chong-Jen Yu Division of General Internal Medicine
- 蔡子修 Division of General Internal Medicine
- 楊文綺 未分科
- Jih-Hsiang Lee Division of Hematology & Oncology
- CHAO-CHI HO CHAO-CHI HO Division of General Internal Medicine
- 楊景堯 Division of Hematology & Oncology
- FENG-MING HSU Division of Radiation Therapy
- 徐偉勛 Division of General Internal Medicine
- 廖唯昱 未分科
- 陳苓諭 Division of Hematology & Oncology
- 廖斌志 Division of Hematology & Oncology
- JIN-YUAN SHIH Division of General Internal Medicine
- 許嘉林 Division of General Internal Medicine
The Actual Total Number of Participants Enrolled
0 Recruiting
Audit
None
Condition/Disease
Carcinoma, Squamous Cell of Head and Neck Carcinoma, Non-Small-Cell Lung Small Cell Lung Carcinoma
Objectives
Primary objective:
To assess the safety and tolerability profile of
durvalumab ± tremelimumab in combination with
chemoradiation.
Secondary objective:
To assess the efficacy/antitumor activity of
durvalumab ± tremelimumab in combination with
chemoradiation
Test Drug
Durvalumab (MEDI4736) / Tremelimumab
Active Ingredient
Humanized anti-CTLA-4 mAb
Humanized anti-PD-1 mAb
Humanized anti-PD-1 mAb
Dosage Form
Dosage
500mg
20 mg/mL
20 mg/mL
Endpoints
Primary Outcome Measures :
Number of subjects with Dose Limiting Toxicities (DLTs) [ Time Frame: From first dose of durvalumab until 28 days after completion of radiation therapy ]
Number of subjects with Adverse Events (AEs) [ Time Frame: From first dose of durvalumab up to 90 days after the last dose of study treatment ]
Secondary Outcome Measures :
Progression-free survival (PFS) [ Time Frame: From first dose until the date of objective disease progression or death, in the absence of progression at 12, 18 and 24 months, up to 4 years. ]
Overall Survival (OS) [ Time Frame: From first dose until death due to any cause through study completion, up to 4 years ]
Objective response rate (ORR) [ Time Frame: From first dose until disease progression, or the last evaluable assessment in the absence of progression, assessed up to 4 years. ]
Number (%) of patients with an overall response of complete response (CR) or partial response (PR).
Best objective response (BoR) [ Time Frame: From first dose until disease progression, or the last evaluable assessment in the absence of progression, assessed up to 4 years. ]
The best response based on the overall visit responses from each RECIST 1.1 assessment or the last evaluable assessment in the absence of RECIST 1.1 progression.
Duration of response (DoR) [ Time Frame: From first dose until disease progression, or death, in the absence of progression, assessed up to 4 years. ]
Time from the date of first documented response until the first date of documented progression or death in the absence of disease progression.
Disease control rate (DCR) [ Time Frame: From first dose until disease progression, at 18 weeks and 48 weeks. ]
Disease-free survival (DFS) [ Time Frame: From first dose until disease progression or death, in the absence of progression at 12, 18 and 24 months, assessed up to 4 years. ]
Number of subjects with Dose Limiting Toxicities (DLTs) [ Time Frame: From first dose of durvalumab until 28 days after completion of radiation therapy ]
Number of subjects with Adverse Events (AEs) [ Time Frame: From first dose of durvalumab up to 90 days after the last dose of study treatment ]
Secondary Outcome Measures :
Progression-free survival (PFS) [ Time Frame: From first dose until the date of objective disease progression or death, in the absence of progression at 12, 18 and 24 months, up to 4 years. ]
Overall Survival (OS) [ Time Frame: From first dose until death due to any cause through study completion, up to 4 years ]
Objective response rate (ORR) [ Time Frame: From first dose until disease progression, or the last evaluable assessment in the absence of progression, assessed up to 4 years. ]
Number (%) of patients with an overall response of complete response (CR) or partial response (PR).
Best objective response (BoR) [ Time Frame: From first dose until disease progression, or the last evaluable assessment in the absence of progression, assessed up to 4 years. ]
The best response based on the overall visit responses from each RECIST 1.1 assessment or the last evaluable assessment in the absence of RECIST 1.1 progression.
Duration of response (DoR) [ Time Frame: From first dose until disease progression, or death, in the absence of progression, assessed up to 4 years. ]
Time from the date of first documented response until the first date of documented progression or death in the absence of disease progression.
Disease control rate (DCR) [ Time Frame: From first dose until disease progression, at 18 weeks and 48 weeks. ]
Disease-free survival (DFS) [ Time Frame: From first dose until disease progression or death, in the absence of progression at 12, 18 and 24 months, assessed up to 4 years. ]
Inclution Criteria
Inclusion criteria
For inclusion in the study patients should fulfill the following criteria:
1. Age ≥18 years at the time of screening
2. Capable of giving signed informed consent, which includes compliance with the
requirements and restrictions listed in the informed consent form (ICF) and in this
protocol. Written informed consent and any locally required authorization (eg,
Health Insurance Portability and Accountability Act in the US and European Union
[EU] Data Privacy Directive in the EU) should be obtained from the patient/legal
representative prior to performing any protocol-related procedures, including
screening evaluations. (For patients aged <20 years and enrolling in Japan, a written
informed consent should be obtained from the patient and his or her legally
acceptable representative.)
3. Meet the advanced solid tumor-specific criteria for their tumor type (detailed
below). (Additional tumor types may be added via subsequent protocol
amendments. See specific eligibility criteria for each tumor type below.)
4. Able and willing to give valid written consent to provide tumor tissue at screening
and further tumor tissue while on study as defined in the clinical protocol
5. World Health Organization (WHO)/ECOG performance status of 0 or 1
6. Body weight >30 kg at enrollment and treatment assignment
7. At least 1 lesion, not previously irradiated, that qualifies as a RECIST 1.1 target
lesion (TL) at baseline (within 28 days prior to start of study treatment)
8. No prior exposure to immune-mediated therapy, including but not limited to other
anti-CTLA-4, anti-PD-1, anti-PD-L1, anti-PD-L2 antibodies, or therapeutic
anticancer vaccines
9. 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
(1.5× 109
/L)
Platelet count ≥100000/mm3
(100× 109
/L)
Serum bilirubin ≤1.5× the 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
Measured creatinine clearance (CL) >40 mL/min or calculated CL >40 mL/min
as determined by Cockcroft-Gault (using actual body weight)
Males:
Creatinine CL = Weight (kg) × (140 - Age)
(mL/min) 72× serum creatinine (mg/dL)
Females:
Creatinine CL = Weight (kg) × (140 - Age) × 0.85
(mL/min) 72× serum creatinine (mg/dL)
10. 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).
11. Life expectancy of ≥12 weeks at treatment assignment
12. Mandatory 18F-fluoro-deoxyglucose positron emission tomography (FDG-PET)/
computed tomography (CT) scan and brain magnetic resonance imaging (MRI;
preferred) or high-quality brain CT with intravenous (IV) contrast at the time of
staging
13. Genetics research study (optional)
For inclusion in the optional (DNA) genetics research study, patients must fulfil the
following criteria:
Provide informed consent for the genetic sampling and analyses
If a patient declines to participate in the genetics research, there will be no penalty
or loss of benefit to the patient. A patient who declines genetics research
participation will not be excluded from any other aspect of the main study.
HNSCC cohort
14. Patients with histologically or cytologically confirmed locally advanced HNSCC (in
accordance with the American Joint Committee on Cancer Stage [7th edition; AJCC
Cancer Staging Manual Version 7]) who are eligible for definitive chemoradiation
treatment and not considered for primary surgery based on Investigator decision or
patient refusal. Patients with oral cavity cancer are excluded from participation if
resection of the primary tumor is considered technically feasible by an oral or head
and neck cancer surgical subspecialist. Patients whose primary tumor is technically
resectable but who refuse surgery due to morbidity (eg, total glossectomy) are also
eligible.
15. Patients with the following sub-types of HNSCC are eligible for this study:
Unresectable oral cavity Stage IVa and IVb
Larynx: Stage IVa and IVb
Hypopharynx: T3-4N0, T2-4N1-3 (Stage III, IVa, and IVb)
HPV-negative oropharynx: T3-4N0 or T2-4N1-3 (Stage III, IVa, and IVb)
HPV-positive oropharynx: ≥10 pack/year history smoking status and N2b/N2c
OR T4 or N3 irrespective of smoking history (Stages III, IVa, and IVb)
16. For patients with oropharyngeal HNSCC only: known HPV status. HPV status will
be determined by p16 immunohistochemistry (IHC; where p16+ is defined as ≥70%
diffuse nuclear and cytoplasmic staining in tumor cells) and/or HPV DNA
(polymerase chain reaction, in situ hybridization) per local standards.
17. Calculated creatinine clearance ≥60 mL/min as determined by Cockcroft-Gault
(using actual body weight)
NSCLC cohort
18. Histologically or cytologically documented NSCLC who present with locally
advanced, unresectable (Stage III) disease (according to version 8 of the
International Association for the Study of Lung Cancer Staging Manual in Thoracic
Oncology [IASLC Staging Manual in Thoracic Oncology]).
19. Except for overt cT4 disease, nodal status N2 or N3 should be proven by biopsy, via
endobronchial ultrasound, mediastinoscopy, or thoracoscopy. Absent biopsy, nodal
status should be confirmed with whole body FDG-PET/CT.
20. Pulmonary function
Forced expiratory volume in 1s>1L or 40% predictive value
Transfer coefficient of the lung for carbon monoxide (KCO) >30% predicted
Pulmonary function testing results for up to 8 weeks prior to registration are
permitted.
SCLC cohort
21. Patients must have histologically or cytologically documented limited-stage SCLC
(American Joint Committee on Cancer Stage [8th edition; AJCC Cancer Staging
Manual Version 8] I-III SCLC [T any, N any, M0]), that is, patients whose disease
can be encompassed within a radical radiation portal.
22. Pulmonary function
Forced expiratory volume in 1s>1L or 40% predictive value
Transfer coefficient of the lung for carbon monoxide (KCO) >40% predicted
Pulmonary function testing results for up to 8 weeks prior to registration are
permitted
For inclusion in the study patients should fulfill the following criteria:
1. Age ≥18 years at the time of screening
2. Capable of giving signed informed consent, which includes compliance with the
requirements and restrictions listed in the informed consent form (ICF) and in this
protocol. Written informed consent and any locally required authorization (eg,
Health Insurance Portability and Accountability Act in the US and European Union
[EU] Data Privacy Directive in the EU) should be obtained from the patient/legal
representative prior to performing any protocol-related procedures, including
screening evaluations. (For patients aged <20 years and enrolling in Japan, a written
informed consent should be obtained from the patient and his or her legally
acceptable representative.)
3. Meet the advanced solid tumor-specific criteria for their tumor type (detailed
below). (Additional tumor types may be added via subsequent protocol
amendments. See specific eligibility criteria for each tumor type below.)
4. Able and willing to give valid written consent to provide tumor tissue at screening
and further tumor tissue while on study as defined in the clinical protocol
5. World Health Organization (WHO)/ECOG performance status of 0 or 1
6. Body weight >30 kg at enrollment and treatment assignment
7. At least 1 lesion, not previously irradiated, that qualifies as a RECIST 1.1 target
lesion (TL) at baseline (within 28 days prior to start of study treatment)
8. No prior exposure to immune-mediated therapy, including but not limited to other
anti-CTLA-4, anti-PD-1, anti-PD-L1, anti-PD-L2 antibodies, or therapeutic
anticancer vaccines
9. 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
(1.5× 109
/L)
Platelet count ≥100000/mm3
(100× 109
/L)
Serum bilirubin ≤1.5× the 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
Measured creatinine clearance (CL) >40 mL/min or calculated CL >40 mL/min
as determined by Cockcroft-Gault (using actual body weight)
Males:
Creatinine CL = Weight (kg) × (140 - Age)
(mL/min) 72× serum creatinine (mg/dL)
Females:
Creatinine CL = Weight (kg) × (140 - Age) × 0.85
(mL/min) 72× serum creatinine (mg/dL)
10. 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).
11. Life expectancy of ≥12 weeks at treatment assignment
12. Mandatory 18F-fluoro-deoxyglucose positron emission tomography (FDG-PET)/
computed tomography (CT) scan and brain magnetic resonance imaging (MRI;
preferred) or high-quality brain CT with intravenous (IV) contrast at the time of
staging
13. Genetics research study (optional)
For inclusion in the optional (DNA) genetics research study, patients must fulfil the
following criteria:
Provide informed consent for the genetic sampling and analyses
If a patient declines to participate in the genetics research, there will be no penalty
or loss of benefit to the patient. A patient who declines genetics research
participation will not be excluded from any other aspect of the main study.
HNSCC cohort
14. Patients with histologically or cytologically confirmed locally advanced HNSCC (in
accordance with the American Joint Committee on Cancer Stage [7th edition; AJCC
Cancer Staging Manual Version 7]) who are eligible for definitive chemoradiation
treatment and not considered for primary surgery based on Investigator decision or
patient refusal. Patients with oral cavity cancer are excluded from participation if
resection of the primary tumor is considered technically feasible by an oral or head
and neck cancer surgical subspecialist. Patients whose primary tumor is technically
resectable but who refuse surgery due to morbidity (eg, total glossectomy) are also
eligible.
15. Patients with the following sub-types of HNSCC are eligible for this study:
Unresectable oral cavity Stage IVa and IVb
Larynx: Stage IVa and IVb
Hypopharynx: T3-4N0, T2-4N1-3 (Stage III, IVa, and IVb)
HPV-negative oropharynx: T3-4N0 or T2-4N1-3 (Stage III, IVa, and IVb)
HPV-positive oropharynx: ≥10 pack/year history smoking status and N2b/N2c
OR T4 or N3 irrespective of smoking history (Stages III, IVa, and IVb)
16. For patients with oropharyngeal HNSCC only: known HPV status. HPV status will
be determined by p16 immunohistochemistry (IHC; where p16+ is defined as ≥70%
diffuse nuclear and cytoplasmic staining in tumor cells) and/or HPV DNA
(polymerase chain reaction, in situ hybridization) per local standards.
17. Calculated creatinine clearance ≥60 mL/min as determined by Cockcroft-Gault
(using actual body weight)
NSCLC cohort
18. Histologically or cytologically documented NSCLC who present with locally
advanced, unresectable (Stage III) disease (according to version 8 of the
International Association for the Study of Lung Cancer Staging Manual in Thoracic
Oncology [IASLC Staging Manual in Thoracic Oncology]).
19. Except for overt cT4 disease, nodal status N2 or N3 should be proven by biopsy, via
endobronchial ultrasound, mediastinoscopy, or thoracoscopy. Absent biopsy, nodal
status should be confirmed with whole body FDG-PET/CT.
20. Pulmonary function
Forced expiratory volume in 1s>1L or 40% predictive value
Transfer coefficient of the lung for carbon monoxide (KCO) >30% predicted
Pulmonary function testing results for up to 8 weeks prior to registration are
permitted.
SCLC cohort
21. Patients must have histologically or cytologically documented limited-stage SCLC
(American Joint Committee on Cancer Stage [8th edition; AJCC Cancer Staging
Manual Version 8] I-III SCLC [T any, N any, M0]), that is, patients whose disease
can be encompassed within a radical radiation portal.
22. Pulmonary function
Forced expiratory volume in 1s>1L or 40% predictive value
Transfer coefficient of the lung for carbon monoxide (KCO) >40% predicted
Pulmonary function testing results for up to 8 weeks prior to registration are
permitted
Exclusion Criteria
Exclusion criteria
Patients should not enter the study if any of the following exclusion criteria are fulfilled:
1. Concurrent enrollment in another interventional clinical study, unless it is an
observational (noninterventional) clinical study or during the follow-up period of an
interventional study
2. Patients with simultaneous primary malignancies or bilateral tumors. Bilateral
tonsil cancers and T1-2, N0, or M0 differentiated thyroid carcinoma (surgically
resected or management deferred) are exempted.
3. Current or prior use of immunosuppressive medication within 14 days before the
first dose of their assigned investigational product (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 premedication for hypersensitivity reactions (eg, CT premedication)
and/or as anti-emetics
4. History of allogeneic organ transplantation
5. Active or prior documented autoimmune or inflammatory disorders (including
inflammatory bowel disease [eg, colitis, Crohn’s disease], diverticulitis [with the
exception of diverticulosis], systemic lupus erythematosus, Sarcoidosis syndrome or
Wegener syndrome [granulomatosis with polyangitis, Graves’ disease, rheumatoid
arthritis, hypophysitis, uveitis, etc]). The following are exceptions to this criterion:
Patients with vitiligo or alopecia
Patients with hypothyroidism (eg, 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
6. Uncontrolled intercurrent illness, including, but not limited to ongoing or active
infection, symptomatic congestive heart failure, uncontrolled hypertension, unstable
angina pectoris, cardiac arrhythmia, ILD, serious chronic GI conditions associated
with diarrhea, 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
7. 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 nonmelanoma skin cancer or lentigo maligna without
evidence of disease
Adequately treated carcinoma in situ without evidence of disease
8. History of leptomeningeal carcinomatosis
9. Brain metastases or spinal cord compression. Patients with suspected brain
metastases at screening should have an MRI (preferred) or CT scan, each preferably
with IV contrast, of the brain prior to study entry. Brain metastases will not be
recorded as RECIST Target Lesions at baseline.
10. History of active primary immunodeficiency
11. Active infection including tuberculosis (TB; clinical evaluation that includes
clinical history, physical examination and radiographic findings, and TB testing in
line with local practice), hepatitis B (known positive hepatitis B virus [HBV]
surface antigen [HBsAg] result), hepatitis C, or human immunodeficiency virus
(HIV; positive HIV 1/2 antibodies). Patients with a past or resolved HBV infection
(defined as the presence of hepatitis B core antibody and absence of HBsAg) are
eligible. Patients positive for hepatitis C virus (HCV) antibody are eligible only if
polymerase chain reaction is negative for HCV ribonucleic acid (RNA).
12. Has a paraneoplastic syndrome (PNS) of autoimmune nature, requiring systemic
treatment (systemic steroids or immunosuppressive agents) or has a clinical
symptomatology, suggesting worsening of PNS
13. Any contraindications to protocol-specified chemotherapies
14. 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.
15. Female patients of childbearing potential who are pregnant or breastfeeding or who
are not willing to employ a highly effective method of birth control from screening
to 90 days after the last dose of durvalumab or 180 days after the last dose of
durvalumab + tremelimumab and nonsterilized 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
durvalumab or 180 days after the last dose of durvalumab + tremelimumab
16. Known allergy or hypersensitivity to IP or any IP excipient
17. Any condition that, in the opinion of the Investigator, would interfere with
evaluation of the IP or interpretation of patient safety or study results
18. Judgment by the Investigator that the patient is unsuitable to participate in the study,
and the patient is unlikely to comply with study procedures, restrictions, and
requirements.
19. Involvement in the planning and/or conduct of the study (applies to both
AstraZeneca/MedImmune staff and/or staff at the study site)
20. Previous IP assignment in the present study
21. Participation in another clinical study with an IP during the 4 weeks prior to
treatment assignment
22. Major surgical procedure (as defined by the Investigator) within 28 days prior to the
first dose of IP
23. Prior randomization or treatment in a previous durvalumab and/or tremelimumab
clinical study regardless of treatment arm assignment
24. Genetics research study (optional)
Exclusion criteria for participation in the optional (DNA) genetics research
component of the study are as follows:
Previous allogeneic bone marrow transplant
Non-leukocyte-depleted whole blood transfusion in 120 days of genetic sample
collection
25. Patients with active ILD/pneumonitis or with a history of ILD/pneumonitis
requiring steroids
26. Mean QT interval corrected for heart rate using Fridericia's formula (QTcF)
≥470 ms calculated from 3 ECGs (within 15 minutes at 5 minutes apart)
HNSCC cohort
27. 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 (nasopharyngeal, paranasal sinuses, nasal cavity tumors, salivary gland, lip,
etc) including patients with HNSCC of unknown primary
28. Definitive clinical or radiological evidence of distant (beyond cervical lymph node
and neck tissue) metastatic disease (Stage IVc)
29. Gross total excision of both primary and nodal disease; this includes tonsillectomy,
local excision of primary site, and nodal excision that removes all clinically and
radiologically evident disease. Patients with at least 1 lesion that qualifies as a
RECIST 1.1 TL remaining either in the neck or primary site remain eligible.
30. Receipt of prior or current treatment for HNSCC. This includes but is not limited to
radiation therapy, investigational agents, chemotherapy, and mAbs.
31. CTCAE Grade ≥2 hearing loss and/or CTCAE Grade ≥1 neuropathy
NSCLC cohort
32. Mixed SCLC and NSCLC histology
33. Receipt of prior or current cancer treatment, including but not limited to, radiation
therapy, investigational agents, chemotherapy, and mAbs. Prior surgical resection
only (ie, Stage I or II) is permitted.
34. If more than 35% of the total (left and right) volume of the lung (excluding the
GTV) will receive a radiation dose of 20 Gy or more (V20) and the mean lung dose
exceeds 20 Gy (RBE)
35. If more than 25% of the heart volume receives a radiation dose of 50 Gy or more
(V50)
SCLC cohort
36. Mixed SCLC and NSCLC histology
37. Extensive-stage SCLC
38. If more than 35% of the total (left and right) volume of the lung (excluding the
GTV) will receive a radiation dose of 20 Gy or more (V20) and the mean lung dose
exceeds 20 Gy (RBE)
39. If more than 25% of the heart volume receives a radiation dose of 50 Gy or more
(V50)
Patients should not enter the study if any of the following exclusion criteria are fulfilled:
1. Concurrent enrollment in another interventional clinical study, unless it is an
observational (noninterventional) clinical study or during the follow-up period of an
interventional study
2. Patients with simultaneous primary malignancies or bilateral tumors. Bilateral
tonsil cancers and T1-2, N0, or M0 differentiated thyroid carcinoma (surgically
resected or management deferred) are exempted.
3. Current or prior use of immunosuppressive medication within 14 days before the
first dose of their assigned investigational product (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 premedication for hypersensitivity reactions (eg, CT premedication)
and/or as anti-emetics
4. History of allogeneic organ transplantation
5. Active or prior documented autoimmune or inflammatory disorders (including
inflammatory bowel disease [eg, colitis, Crohn’s disease], diverticulitis [with the
exception of diverticulosis], systemic lupus erythematosus, Sarcoidosis syndrome or
Wegener syndrome [granulomatosis with polyangitis, Graves’ disease, rheumatoid
arthritis, hypophysitis, uveitis, etc]). The following are exceptions to this criterion:
Patients with vitiligo or alopecia
Patients with hypothyroidism (eg, 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
6. Uncontrolled intercurrent illness, including, but not limited to ongoing or active
infection, symptomatic congestive heart failure, uncontrolled hypertension, unstable
angina pectoris, cardiac arrhythmia, ILD, serious chronic GI conditions associated
with diarrhea, 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
7. 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 nonmelanoma skin cancer or lentigo maligna without
evidence of disease
Adequately treated carcinoma in situ without evidence of disease
8. History of leptomeningeal carcinomatosis
9. Brain metastases or spinal cord compression. Patients with suspected brain
metastases at screening should have an MRI (preferred) or CT scan, each preferably
with IV contrast, of the brain prior to study entry. Brain metastases will not be
recorded as RECIST Target Lesions at baseline.
10. History of active primary immunodeficiency
11. Active infection including tuberculosis (TB; clinical evaluation that includes
clinical history, physical examination and radiographic findings, and TB testing in
line with local practice), hepatitis B (known positive hepatitis B virus [HBV]
surface antigen [HBsAg] result), hepatitis C, or human immunodeficiency virus
(HIV; positive HIV 1/2 antibodies). Patients with a past or resolved HBV infection
(defined as the presence of hepatitis B core antibody and absence of HBsAg) are
eligible. Patients positive for hepatitis C virus (HCV) antibody are eligible only if
polymerase chain reaction is negative for HCV ribonucleic acid (RNA).
12. Has a paraneoplastic syndrome (PNS) of autoimmune nature, requiring systemic
treatment (systemic steroids or immunosuppressive agents) or has a clinical
symptomatology, suggesting worsening of PNS
13. Any contraindications to protocol-specified chemotherapies
14. 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.
15. Female patients of childbearing potential who are pregnant or breastfeeding or who
are not willing to employ a highly effective method of birth control from screening
to 90 days after the last dose of durvalumab or 180 days after the last dose of
durvalumab + tremelimumab and nonsterilized 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
durvalumab or 180 days after the last dose of durvalumab + tremelimumab
16. Known allergy or hypersensitivity to IP or any IP excipient
17. Any condition that, in the opinion of the Investigator, would interfere with
evaluation of the IP or interpretation of patient safety or study results
18. Judgment by the Investigator that the patient is unsuitable to participate in the study,
and the patient is unlikely to comply with study procedures, restrictions, and
requirements.
19. Involvement in the planning and/or conduct of the study (applies to both
AstraZeneca/MedImmune staff and/or staff at the study site)
20. Previous IP assignment in the present study
21. Participation in another clinical study with an IP during the 4 weeks prior to
treatment assignment
22. Major surgical procedure (as defined by the Investigator) within 28 days prior to the
first dose of IP
23. Prior randomization or treatment in a previous durvalumab and/or tremelimumab
clinical study regardless of treatment arm assignment
24. Genetics research study (optional)
Exclusion criteria for participation in the optional (DNA) genetics research
component of the study are as follows:
Previous allogeneic bone marrow transplant
Non-leukocyte-depleted whole blood transfusion in 120 days of genetic sample
collection
25. Patients with active ILD/pneumonitis or with a history of ILD/pneumonitis
requiring steroids
26. Mean QT interval corrected for heart rate using Fridericia's formula (QTcF)
≥470 ms calculated from 3 ECGs (within 15 minutes at 5 minutes apart)
HNSCC cohort
27. 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 (nasopharyngeal, paranasal sinuses, nasal cavity tumors, salivary gland, lip,
etc) including patients with HNSCC of unknown primary
28. Definitive clinical or radiological evidence of distant (beyond cervical lymph node
and neck tissue) metastatic disease (Stage IVc)
29. Gross total excision of both primary and nodal disease; this includes tonsillectomy,
local excision of primary site, and nodal excision that removes all clinically and
radiologically evident disease. Patients with at least 1 lesion that qualifies as a
RECIST 1.1 TL remaining either in the neck or primary site remain eligible.
30. Receipt of prior or current treatment for HNSCC. This includes but is not limited to
radiation therapy, investigational agents, chemotherapy, and mAbs.
31. CTCAE Grade ≥2 hearing loss and/or CTCAE Grade ≥1 neuropathy
NSCLC cohort
32. Mixed SCLC and NSCLC histology
33. Receipt of prior or current cancer treatment, including but not limited to, radiation
therapy, investigational agents, chemotherapy, and mAbs. Prior surgical resection
only (ie, Stage I or II) is permitted.
34. If more than 35% of the total (left and right) volume of the lung (excluding the
GTV) will receive a radiation dose of 20 Gy or more (V20) and the mean lung dose
exceeds 20 Gy (RBE)
35. If more than 25% of the heart volume receives a radiation dose of 50 Gy or more
(V50)
SCLC cohort
36. Mixed SCLC and NSCLC histology
37. Extensive-stage SCLC
38. If more than 35% of the total (left and right) volume of the lung (excluding the
GTV) will receive a radiation dose of 20 Gy or more (V20) and the mean lung dose
exceeds 20 Gy (RBE)
39. If more than 25% of the heart volume receives a radiation dose of 50 Gy or more
(V50)
The Estimated Number of Participants
-
Taiwan
92 participants
-
Global
300 participants
