Clinical Trials List
Protocol NumberD9075C00001
NCT Number(ClinicalTrials.gov Identfier)NCT05211895
Active
2022-02-01 - 2029-12-31
Phase III
Recruiting9
ICD-10C33
Malignant neoplasm of trachea
ICD-10Z51.12
Encounter for antineoplastic immunotherapy
ICD-9162.0
Malignant neoplasm of trachea
A Phase III, Randomised, Double-blind, Placebo-controlled, Multicentre, International Study of NCT05211895
-
Trial Applicant
-
Sponsor
AstraZeneca
-
Trial scale
Multi-Regional Multi-Center
-
Update
2026/02/01
Investigators and Locations
Co-Principal Investigator
- Heng-Sheng Chao 未分科
- Chia-I Shen 無
- Hsu-ching Huang 無
- 蕭慈慧 無
- Yung-Hung Luo 無
- YEN-HAN TSENG 無
- 趙恒勝 無
- Chi-Lu Chiang 無
- Yi-Wei Chen 無
The Actual Total Number of Participants Enrolled
0 Recruiting
The Actual Total Number of Participants Enrolled
0 Recruiting
Co-Principal Investigator
- KUO-HSUAN HSU 無
- 李柏昕 無
- YEN-HSIANG HUANG 無
- 黃靖文 無
- JENG-SEN TSENG 無
The Actual Total Number of Participants Enrolled
0 Recruiting
Co-Principal Investigator
- Yu-Min Yeh 無
- Seu-Chun Yang 無
- Yi-Ting Yen 無
- Wu-Chou Su 無
- Jui-Hung Tsai 無
- Chian-Wei Chen 無
- Shang-Yin Wu 無
- Po-Lan Su 無
- 林逢嘉 無
- Chun-Hui Lee 無
- 蔡政軒 無
- Chin-Wei Kuo 無
The Actual Total Number of Participants Enrolled
0 Recruiting
The Actual Total Number of Participants Enrolled
0 Recruiting
Co-Principal Investigator
- FENG-MING HSU 無
- 楊文綺 無
- 錢穎群 無
- 廖唯昱 無
- 吳尚俊 無
- James Chih-Hsin Yang 無
- 廖斌志 無
- 陳苓諭 無
- 陳冠宇 無
- 蔡子修 無
- Chia-Chi Lin 無
- 徐偉勛 無
- 黃俊凱 無
- CHAO-CHI HO CHAO-CHI HO 無
- 楊景堯 無
- Jih-Hsiang Lee 無
- 藍耿學 無
- Chong-Jen Yu 無
- 許嘉林 無
- YEN-TING LIN 無
The Actual Total Number of Participants Enrolled
0 Recruiting
The Actual Total Number of Participants Enrolled
0 Recruiting
Co-Principal Investigator
- Chien-Ying Liu 無
- Chih-Hsi Kuo 無
- 枋岳甫 無
- Wen-Cheng Chang 無
- 黃宗楨 無
- Chih-Hung Chen 無
- Ping-Chih Hsu 無
- 邱立忠 無
- Jia-Shiuan Ju 無
- 林信吟 無
- 柯皓文 無
- Chih-Liang Wang 無
- Shih-Hong Li 無
- 吳教恩 無
- 白冰清 無
- Chih-Hung Chen 未分科
- 林定佑 無
- 張境夫 無
- Chun-Chieh Wang 無
The Actual Total Number of Participants Enrolled
0 Recruiting
Co-Principal Investigator
- Yu-Chao Lin 無
- 陳鴻仁 無
- Chih-Yen Tu 無
- Chia-Hsiang Li 無
The Actual Total Number of Participants Enrolled
0 Recruiting
Condition/Disease
Non-Small Cell Lung Cancer
Objectives
This is a Phase III, randomised, double-blind, placebo-controlled,
multicentre, international study assessing the efficacy and safety of durvalumab (MEDI4736)
and domvanalimab (AB154) compared with durvalumab plus placebo in adults with locally
advanced (Stage III), unresectable NSCLC whose disease has not progressed following
definitive platinum-based cCRT.
Test Drug
Durvalumab
Domvanalimab
Domvanalimab
Active Ingredient
Durvalumab (MEDI4736)
AB154
AB154
Dosage Form
Injection
Injection
Injection
Dosage
50 mg/ml
60 mg/ml
60 mg/ml
Endpoints
To demonstrate superiority of durvalumab plus domvanalimab relative to durvalumab plus placebo in participants with locally advanced, unresectable NSCLC who have not progressed on prior platinum-based cCRT, with:
PD-L1 TC ≥ 50%
assessment by PFS as assessed by BICR
PD-L1 TC ≥ 50%
assessment by PFS as assessed by BICR
Inclution Criteria
In order to expedite tissue analysis, Part I screening procedures may begin before cCRT has
been completed. Participants are eligible to be included in the study only if all of the following
criteria apply:
Part I Screening
Age
1 Participant must be ≥ 18 years at the time of screening. For participants aged 18-19 years
and enrolled in Japan, a written informed consent should be obtained from the participant
and their legally acceptable representative (until the Civil Code is amended for Japan for
the legal age of adulthood to be ≥ 18 years on April 1st, 2022).
Type of Participant and Disease Characteristics
2 Participants must have histologically or cytologically documented NSCLC and have been
treated with concurrent CRT for locally advanced (Stage III), unresectable disease
(according to Version 8 of the International Staging Manual for the Study of Lung Cancer Staging Manual in Thoracic Oncology [Goldstraw et al 2016]). Initial staging procedures
performed prior to initiation of any component of definitive treatment should include:
Positron Emission Tomography – Computed Tomography (PET-CT) scan. Full body
scan preferred, but scan from at least the base of skull to mid-thigh permissible. The
scan must be performed up to 42 days prior to the first dose of concurrent
chemoradiotherapy, or induction chemotherapy cycles if utilised.
Brain imaging with MRI or high-quality CT with IV contrast is encouraged during
initial staging.
Except for cT4 disease, biopsy strongly preferred to prove nodal status N2 or N3 via
endobronchial ultrasound, mediastinoscopy, or thoracoscopy.
3 Tumour sample requirements as follows: Provision of a tumour tissue sample (obtained
≤ 3 months prior to screening Part 1 is preferred; ≤ 6 months old is acceptable if no
sample of ≤ 3 months is available). An FFPE block sufficient for sectioning 20 slides
(5 micron thickness) is preferred. If FFPE blocks cannot be submitted, then a set of
newly-cut, unstained slides to enable the necessary testing may be provided.
4 Tumour PD-L1 status ≥ 1% as determined using the Ventana SP263 PD-L1 IHC assay by
a central laboratory. PD-L1 status must be known to enable randomisation. Participants
with unknown PD-L1 status are not eligible for the study.
5 Documented EGFR and ALK wild-type status. If a local laboratory performs the test, a
well-validated, locally-approved test must be used. If local EGFR and ALK results are not
available at the time of screening, the assays will be performed in the central laboratory.
Participants with sensitizing EGFR mutations (eg, exon 19 deletion or exon 21 L858R,
exon 21 L861Q, exon 18 G719X, or exon 20 insertion or S768I mutation) or ALK
rearrangements are excluded from the study.
6 Tumours harbouring mutations in any of the following genes, if known, as determined by
existing local test results: ROS1, RET, MET, BRAF, NTRK1, NTRK2, and ERBB2 are
excluded.
Informed Consent
7 Capable of giving signed informed consent for tumour sample collection that includes
compliance with the requirements and restrictions listed in the pre-screening informed
consent form (Part I screening ICF) as described in Appendix A, which includes
compliance with the requirements and restrictions listed in the ICF and this protocol.
Provision of signed and dated written Part I screening ICF prior to any mandatory study
specific procedures and analyses.
Part II Screening
Participants may enter Part II screening even if the results of the Part I screening procedures
are still pending.
Participants are eligible to be randomised to the study only if all of the following Part II
inclusion criteria and none of the exclusion criteria apply:
8 Participants must have not progressed following definitive, platinum-based, concurrent
chemoradiation therapy. Screening imaging should include brain imaging (MRI is the
preferred modality however high-quality CT with IV contrast is acceptable).
9 Participants must have received at least 2 cycles of platinum--based chemotherapy
concurrent with radiation therapy, which must be completed within 1 to 28 days prior to
the first dose of study intervention in the study (1 cycle is defined as 21 or 28 days). For
participants who are recovering from toxicities associated with prior treatment, the first
dose of study intervention may be delayed by up to 28 days from the end of
chemoradiation therapy. Sites are strongly encouraged to complete screening within the
first 14 days of the 28-day screening period.
10 The platinum-based chemotherapy regimen must have contained cisplatin or carboplatin
and one of the following agents: etoposide, vinblastine, vinorelbine, a taxane (paclitaxel
or docetaxel), or pemetrexed, according to the local standard of care regimens.
Gemcitabine is not permitted.
11 The last dose of chemotherapy must be administered prior to, or concurrently with, the
final dose of radiation. Consolidation chemotherapy after radiation is not permitted but
administration of 1-2 induction cycles of chemotherapy prior to cCRT is acceptable.
Where possible, chemotherapy regimens should be given according to National
Comprehensive Cancer Network (NCCN) Guidelines or European Society for Medical
Oncology (ESMO) Guidelines.
12 A total dose of radiation of 60 Gy ± 10% (54 Gy to 66 Gy) as part of the chemoradiation
therapy is required to be randomised. Radiation therapy should be administered by
intensity modulated RT (preferred) or a 3D-conforming technique. Sites are also
encouraged to adhere to the following organ dosimetric specifications:
Mean lung dose must be < 20 Gy and/or V20 must be < 35%
Mean oesophagus dose must be < 34 Gy
Heart V45 < 35% or V30 < 50%
13 World Health Organization (WHO) Performance Status of 0 or 1 at randomisation.
14 Adequate organ and marrow function as defined below:
Absolute neutrophil count > 1.5 × 109/L (1500 per mm3)
Platelet count > 100 × 109/L (100,000 per mm3)
Haemoglobin ≥ 9.0 g/dL (5.59 mmol/L)
CrCL > 40 mL/min by the Cockcroft-Gault formula (Cockcroft and Gault 1976)
using actual body weight.
Serum bilirubin ≤ 1.5 × ULN. This will not apply to participants with confirmed
Gilbert’s syndrome (ie, persistent or recurrent hyperbilirubinemia that is
predominantly unconjugated in the absence of evidence of haemolysis or hepatic
pathology) who will be allowed in consultation with their physician. In the presence
of documented Gilbert’s syndrome, serum bilirubin < 3 × ULN is accepted.
AST and ALT ≤ 2.5 × ULN.
15 Minimum life expectancy of 12 weeks at randomisation
Weight
16 Body weight > 30 kg at enrolment and randomisation
Sex
17 Male or female.
ReproductionContraceptive use by men or women should be consistent with local regulations
regarding the methods of contraception for those participating in clinical studies.
18 Negative pregnancy test (serum) for WOCBP:
19 Female participants must be 1 year post-menopausal, surgically sterile, or using 1 highly
effective form of birth control (a highly effective method of contraception is defined as
one that can achieve a failure rate of less than 1% per year when used consistently and
correctly). WOCBP must agree to use one highly effective method of birth control. They
should have been stable on their chosen method of birth control for a minimum of
3 months before entering the study to 115 days after the last dose (see Appendix G for a
complete list of highly effective birth control methods). Non-sterilised male partners of a
WOCBP must use a male condom and spermicide (condom alone in countries where
spermicides are not approved) throughout this period.
20 Male participants who intend to be sexually active with a WOCBP must be surgically
sterile or using an acceptable method of contraception (see Appendix G) from the time of
screening throughout the total duration of the study, and for drugs that are potentially
genotoxic the drug washout period (115 days after the last dose of study intervention) to
prevent pregnancy in a partner. Male participants must not donate or bank sperm during
this same time period.
Informed Consent
21 Capable of giving signed informed consent as described in Appendix A, which includes
compliance with the requirements and restrictions listed in the IFC and this protocol.
22 For Optional Genomic initiative participation only: Provision of signed and dated written
Optional Genetic Research Information informed consent prior to collection of sample for
optional genetic research that supports Genomic Initiative. If a participant declines to
participate in the genetics research, there will be no penalty or loss of benefit to the
participant. A participant who declines genetics research participation will not be
excluded from any other aspect of the main study.
been completed. Participants are eligible to be included in the study only if all of the following
criteria apply:
Part I Screening
Age
1 Participant must be ≥ 18 years at the time of screening. For participants aged 18-19 years
and enrolled in Japan, a written informed consent should be obtained from the participant
and their legally acceptable representative (until the Civil Code is amended for Japan for
the legal age of adulthood to be ≥ 18 years on April 1st, 2022).
Type of Participant and Disease Characteristics
2 Participants must have histologically or cytologically documented NSCLC and have been
treated with concurrent CRT for locally advanced (Stage III), unresectable disease
(according to Version 8 of the International Staging Manual for the Study of Lung Cancer Staging Manual in Thoracic Oncology [Goldstraw et al 2016]). Initial staging procedures
performed prior to initiation of any component of definitive treatment should include:
Positron Emission Tomography – Computed Tomography (PET-CT) scan. Full body
scan preferred, but scan from at least the base of skull to mid-thigh permissible. The
scan must be performed up to 42 days prior to the first dose of concurrent
chemoradiotherapy, or induction chemotherapy cycles if utilised.
Brain imaging with MRI or high-quality CT with IV contrast is encouraged during
initial staging.
Except for cT4 disease, biopsy strongly preferred to prove nodal status N2 or N3 via
endobronchial ultrasound, mediastinoscopy, or thoracoscopy.
3 Tumour sample requirements as follows: Provision of a tumour tissue sample (obtained
≤ 3 months prior to screening Part 1 is preferred; ≤ 6 months old is acceptable if no
sample of ≤ 3 months is available). An FFPE block sufficient for sectioning 20 slides
(5 micron thickness) is preferred. If FFPE blocks cannot be submitted, then a set of
newly-cut, unstained slides to enable the necessary testing may be provided.
4 Tumour PD-L1 status ≥ 1% as determined using the Ventana SP263 PD-L1 IHC assay by
a central laboratory. PD-L1 status must be known to enable randomisation. Participants
with unknown PD-L1 status are not eligible for the study.
5 Documented EGFR and ALK wild-type status. If a local laboratory performs the test, a
well-validated, locally-approved test must be used. If local EGFR and ALK results are not
available at the time of screening, the assays will be performed in the central laboratory.
Participants with sensitizing EGFR mutations (eg, exon 19 deletion or exon 21 L858R,
exon 21 L861Q, exon 18 G719X, or exon 20 insertion or S768I mutation) or ALK
rearrangements are excluded from the study.
6 Tumours harbouring mutations in any of the following genes, if known, as determined by
existing local test results: ROS1, RET, MET, BRAF, NTRK1, NTRK2, and ERBB2 are
excluded.
Informed Consent
7 Capable of giving signed informed consent for tumour sample collection that includes
compliance with the requirements and restrictions listed in the pre-screening informed
consent form (Part I screening ICF) as described in Appendix A, which includes
compliance with the requirements and restrictions listed in the ICF and this protocol.
Provision of signed and dated written Part I screening ICF prior to any mandatory study
specific procedures and analyses.
Part II Screening
Participants may enter Part II screening even if the results of the Part I screening procedures
are still pending.
Participants are eligible to be randomised to the study only if all of the following Part II
inclusion criteria and none of the exclusion criteria apply:
8 Participants must have not progressed following definitive, platinum-based, concurrent
chemoradiation therapy. Screening imaging should include brain imaging (MRI is the
preferred modality however high-quality CT with IV contrast is acceptable).
9 Participants must have received at least 2 cycles of platinum--based chemotherapy
concurrent with radiation therapy, which must be completed within 1 to 28 days prior to
the first dose of study intervention in the study (1 cycle is defined as 21 or 28 days). For
participants who are recovering from toxicities associated with prior treatment, the first
dose of study intervention may be delayed by up to 28 days from the end of
chemoradiation therapy. Sites are strongly encouraged to complete screening within the
first 14 days of the 28-day screening period.
10 The platinum-based chemotherapy regimen must have contained cisplatin or carboplatin
and one of the following agents: etoposide, vinblastine, vinorelbine, a taxane (paclitaxel
or docetaxel), or pemetrexed, according to the local standard of care regimens.
Gemcitabine is not permitted.
11 The last dose of chemotherapy must be administered prior to, or concurrently with, the
final dose of radiation. Consolidation chemotherapy after radiation is not permitted but
administration of 1-2 induction cycles of chemotherapy prior to cCRT is acceptable.
Where possible, chemotherapy regimens should be given according to National
Comprehensive Cancer Network (NCCN) Guidelines or European Society for Medical
Oncology (ESMO) Guidelines.
12 A total dose of radiation of 60 Gy ± 10% (54 Gy to 66 Gy) as part of the chemoradiation
therapy is required to be randomised. Radiation therapy should be administered by
intensity modulated RT (preferred) or a 3D-conforming technique. Sites are also
encouraged to adhere to the following organ dosimetric specifications:
Mean lung dose must be < 20 Gy and/or V20 must be < 35%
Mean oesophagus dose must be < 34 Gy
Heart V45 < 35% or V30 < 50%
13 World Health Organization (WHO) Performance Status of 0 or 1 at randomisation.
14 Adequate organ and marrow function as defined below:
Absolute neutrophil count > 1.5 × 109/L (1500 per mm3)
Platelet count > 100 × 109/L (100,000 per mm3)
Haemoglobin ≥ 9.0 g/dL (5.59 mmol/L)
CrCL > 40 mL/min by the Cockcroft-Gault formula (Cockcroft and Gault 1976)
using actual body weight.
Serum bilirubin ≤ 1.5 × ULN. This will not apply to participants with confirmed
Gilbert’s syndrome (ie, persistent or recurrent hyperbilirubinemia that is
predominantly unconjugated in the absence of evidence of haemolysis or hepatic
pathology) who will be allowed in consultation with their physician. In the presence
of documented Gilbert’s syndrome, serum bilirubin < 3 × ULN is accepted.
AST and ALT ≤ 2.5 × ULN.
15 Minimum life expectancy of 12 weeks at randomisation
Weight
16 Body weight > 30 kg at enrolment and randomisation
Sex
17 Male or female.
ReproductionContraceptive use by men or women should be consistent with local regulations
regarding the methods of contraception for those participating in clinical studies.
18 Negative pregnancy test (serum) for WOCBP:
19 Female participants must be 1 year post-menopausal, surgically sterile, or using 1 highly
effective form of birth control (a highly effective method of contraception is defined as
one that can achieve a failure rate of less than 1% per year when used consistently and
correctly). WOCBP must agree to use one highly effective method of birth control. They
should have been stable on their chosen method of birth control for a minimum of
3 months before entering the study to 115 days after the last dose (see Appendix G for a
complete list of highly effective birth control methods). Non-sterilised male partners of a
WOCBP must use a male condom and spermicide (condom alone in countries where
spermicides are not approved) throughout this period.
20 Male participants who intend to be sexually active with a WOCBP must be surgically
sterile or using an acceptable method of contraception (see Appendix G) from the time of
screening throughout the total duration of the study, and for drugs that are potentially
genotoxic the drug washout period (115 days after the last dose of study intervention) to
prevent pregnancy in a partner. Male participants must not donate or bank sperm during
this same time period.
Informed Consent
21 Capable of giving signed informed consent as described in Appendix A, which includes
compliance with the requirements and restrictions listed in the IFC and this protocol.
22 For Optional Genomic initiative participation only: Provision of signed and dated written
Optional Genetic Research Information informed consent prior to collection of sample for
optional genetic research that supports Genomic Initiative. If a participant declines to
participate in the genetics research, there will be no penalty or loss of benefit to the
participant. A participant who declines genetics research participation will not be
excluded from any other aspect of the main study.
Exclusion Criteria
Participants are excluded from the study if any of the following criteria apply:
Medical conditions
1 As judged by the investigator, any evidence of diseases (such as severe or uncontrolled
systemic diseases, including uncontrolled hypertension, active bleeding diseases, active
infection, active ILD/pneumonitis, serious chronic gastrointestinal conditions associated
with diarrhoea, psychiatric illness/social situations); or a history of allogeneic organ
transplant, which, in the investigator’s opinion, makes it undesirable for the participant to
participate in the study, or that would jeopardize compliance with the protocol
2 History of another primary malignancy, except for malignancy treated with curative intent
with no known active disease ≥ 5 years before the first dose of study intervention and of
low potential risk for recurrence, basal cell carcinoma of the skin, squamous cell
carcinoma of the skin or lentigo maligna that has undergone potentially curative therapy
or adequately treated carcinoma in situ or Ta tumours without evidence of disease
3 Prior allogeneic bone marrow transplantation or stem cell/solid organ transplantation
4 Active or prior documented autoimmune or inflammatory disorders (including
inflammatory bowel disease [eg, colitis or Crohn’s disease], diverticulitis [with the
exception of diverticulosis], systemic lupus erythematosus, sarcoidosis syndrome, or
Wegener syndrome [granulomatosis with polyangiitis, rheumatoid arthritis, hypophysitis,
uveitis, etc.]), autoimmune pneumonitis and autoimmune myocarditis. The following are
exceptions to this criterion:
Participants with vitiligo or alopecia
Participants with hypothyroidism (eg, following Hashimoto syndrome) stable on
hormone replacement
Any chronic skin condition that does not require systemic therapy
Participants without active disease in the last 5 years at randomisation may be
included but only after consultation with the study physician
Participants with celiac disease controlled by diet alone
5 Severe infection within 4 weeks prior to initiation of study treatment
6 History of idiopathic pulmonary fibrosis, organizing pneumonia, drug-induced
pneumonitis, or idiopathic pneumonitis, or evidence of active pneumonitis, ILD, pleural
effusion, or pulmonary fibrosis diagnosed in the past 6 months prior to randomisation.
7 History of leptomeningeal carcinomatosis
8 History of primary immunodeficiency
9 Active hepatitis infection, positive HCV antibody, HBV surface antigen (HbsAg) or HBV
core antibody (anti-HBc) at screening. Participants with a past or resolved HBV infection
(defined as the presence of anti-HBc and absence of HbsAg) are eligible. Participants
positive for HCV antibody are eligible only if polymerase chain reaction is negative for
HCV RNA
10 Positive test for HIV (positive HIV 1/2 antibodies) or known to have active tuberculosis
infection (clinical evaluation that may include clinical history, physical examination, and
radiographic findings, or tuberculosis testing in line with local practice)
11 Active EBV infection, or known or suspected chronic active EBV infection at screening
12 Mixed small cell and NSCLC cancer histology
13 Participants who receive sequential (not inclusive of induction) chemoradiation therapy
for locally advanced, unresectable NSCLC
14 Participants with locally advanced, unresectable NSCLC who have progressed during
definitive platinum--based cCRT
15 Participants who have had disease considered for surgical treatment as part of their care
plan, such as Pancoast or superior sulcus tumours
16 Participants with T4 lesions that invade major vascular structures such as pulmonary
artery or cardiac tissues are ineligible.
17 Investigator judgement of 1 or more of the following:
Mean resting corrected QT interval > 470 ms, obtained from triplicate ECGs
performed at screening
History of QT prolongation associated with other medications that required
discontinuation of that medication, or any current concomitant medication known to
prolong the QT interval and cause TdP
Congenital long QT syndrome, family history of long QT syndrome, or unexplained
sudden cardiac death < 40 years of age in first-degree relatives
18 History of symptomatic congestive heart failure; unstable angina pectoris; uncontrolled
cardiac arrhythmia (multifocal premature ventricular contractions, bigeminy, trigeminy,
ventricular tachycardia), which is symptomatic or requires treatment (CTCAE Grade 3);
symptomatic or uncontrolled atrial fibrillation despite treatment; or asymptomatic
sustained ventricular tachycardia. Participants with atrial fibrillation controlled by
medication or arrhythmias controlled by pacemakers may be permitted upon discussion
with the clinical study lead.
19 Subjects with a history of myocardial infarction, transient ischemic attack, pulmonary
embolism, or stroke diagnosed in the past 6 months, or venous thrombosis diagnosed in
the past 3 months
Prior/concomitant therapy
20 Known allergy or hypersensitivity to any of the study interventions.
21 Receipt of prior or current cancer treatment for NSCLC, including but not limited to,
radiation therapy, investigational agents, chemotherapy, and mAbs. Prior surgical
resection of metachronus NSCLC (ie, Stage I or II) is permitted.
22 Prior exposure to immune-mediated therapy including, but not limited to, anti-TIGIT,
anti–CTLA-4, anti-PD-1, anti-PD-L1, anti-PD-L2 antibodies, excluding therapeutic
anticancer vaccines. Live attenuated vaccines within 30 days prior to the first dose of the
study intervention are not permitted.
23 Participants who are expected to require any other form of antineoplastic therapy while
participating in the trial are excluded.
24 Current or prior use of immunosuppressive medication within 14 days before the first
dose of durvalumab plus domvanalimab. The following are exceptions to this criterion:
Intranasal, inhaled, topical steroids or local steroid injections (eg, intraarticular
injection).
Systemic corticosteroids at physiologic doses not to exceed 10 mg/day of prednisone
or its equivalent.
Steroids as premedication for hypersensitivity reactions or as an antiemetic (eg, CT
scan premedication).
25 Major surgical procedure (as defined by the investigator) within 4 weeks prior to the first
dose of study intervention. Prior surgical resection of metachronous NSCLC (i.e., Stage I
or II) is permitted.
26 Any unresolved toxicity CTCAE > Grade 2 from the prior chemoradiation therapy
(excluding alopecia). Participants with irreversible toxicity that is not reasonably expected
to be exacerbated by study drug may be included (eg, hearing loss) after consultation with
the Clinical Study Lead. Participants with peripheral neuropathy after consultation with
the Clinical Study Lead.
27 Participants with CTCAE ≥ Grade 2 pneumonitis from prior chemoradiation therapy
28 Any prior Grade ≥ 3 immune-related adverse event (irAE) while receiving any previous
immunotherapy agent, or any unresolved irAE > Grade 1.
29 Any concurrent anticancer treatment. Concurrent use of hormonal therapy for
noncancer-related conditions (eg, hormone replacement therapy) is allowed.
Prior/Concurrent Clinical Study Experience
30 Previous treatment in the present study
31 Concurrent participation in another clinical study, unless it is an observational
(non-interventional) clinical study, or the follow-up period of an interventional study
32 Participation in another clinical study with a study intervention during the last 3 months
prior to randomisation or concurrent enrolment in another clinical study, unless it is an
observational, noninterventional clinical study during the follow-up period of an
interventional study
33 Prior randomisation or treatment in a previous durvalumab or domvanalimab clinical
study regardless of treatment arm assignment
34 Receipt of any immunotherapy, or investigational drug within 4 weeks prior to the first
dose of study drug; and in the case of monoclonal antibodies 6 weeks prior to the first
dose of study drug
Other
35 Participants with a known sensitivity to durvalumab or domvanalimab, any anti-TIGIT, or
any excipients of the products
36 Judgement by the investigator that the participant is unsuitable to participate in the study
and the participant is unlikely to comply with study procedures, restrictions, and
requirements
37 Female participants who are pregnant or breastfeeding, or male or female participants of
reproductive potential who are not willing to employ effective birth control from
screening to 115 days after the last dose of study treatment.
Medical conditions
1 As judged by the investigator, any evidence of diseases (such as severe or uncontrolled
systemic diseases, including uncontrolled hypertension, active bleeding diseases, active
infection, active ILD/pneumonitis, serious chronic gastrointestinal conditions associated
with diarrhoea, psychiatric illness/social situations); or a history of allogeneic organ
transplant, which, in the investigator’s opinion, makes it undesirable for the participant to
participate in the study, or that would jeopardize compliance with the protocol
2 History of another primary malignancy, except for malignancy treated with curative intent
with no known active disease ≥ 5 years before the first dose of study intervention and of
low potential risk for recurrence, basal cell carcinoma of the skin, squamous cell
carcinoma of the skin or lentigo maligna that has undergone potentially curative therapy
or adequately treated carcinoma in situ or Ta tumours without evidence of disease
3 Prior allogeneic bone marrow transplantation or stem cell/solid organ transplantation
4 Active or prior documented autoimmune or inflammatory disorders (including
inflammatory bowel disease [eg, colitis or Crohn’s disease], diverticulitis [with the
exception of diverticulosis], systemic lupus erythematosus, sarcoidosis syndrome, or
Wegener syndrome [granulomatosis with polyangiitis, rheumatoid arthritis, hypophysitis,
uveitis, etc.]), autoimmune pneumonitis and autoimmune myocarditis. The following are
exceptions to this criterion:
Participants with vitiligo or alopecia
Participants with hypothyroidism (eg, following Hashimoto syndrome) stable on
hormone replacement
Any chronic skin condition that does not require systemic therapy
Participants without active disease in the last 5 years at randomisation may be
included but only after consultation with the study physician
Participants with celiac disease controlled by diet alone
5 Severe infection within 4 weeks prior to initiation of study treatment
6 History of idiopathic pulmonary fibrosis, organizing pneumonia, drug-induced
pneumonitis, or idiopathic pneumonitis, or evidence of active pneumonitis, ILD, pleural
effusion, or pulmonary fibrosis diagnosed in the past 6 months prior to randomisation.
7 History of leptomeningeal carcinomatosis
8 History of primary immunodeficiency
9 Active hepatitis infection, positive HCV antibody, HBV surface antigen (HbsAg) or HBV
core antibody (anti-HBc) at screening. Participants with a past or resolved HBV infection
(defined as the presence of anti-HBc and absence of HbsAg) are eligible. Participants
positive for HCV antibody are eligible only if polymerase chain reaction is negative for
HCV RNA
10 Positive test for HIV (positive HIV 1/2 antibodies) or known to have active tuberculosis
infection (clinical evaluation that may include clinical history, physical examination, and
radiographic findings, or tuberculosis testing in line with local practice)
11 Active EBV infection, or known or suspected chronic active EBV infection at screening
12 Mixed small cell and NSCLC cancer histology
13 Participants who receive sequential (not inclusive of induction) chemoradiation therapy
for locally advanced, unresectable NSCLC
14 Participants with locally advanced, unresectable NSCLC who have progressed during
definitive platinum--based cCRT
15 Participants who have had disease considered for surgical treatment as part of their care
plan, such as Pancoast or superior sulcus tumours
16 Participants with T4 lesions that invade major vascular structures such as pulmonary
artery or cardiac tissues are ineligible.
17 Investigator judgement of 1 or more of the following:
Mean resting corrected QT interval > 470 ms, obtained from triplicate ECGs
performed at screening
History of QT prolongation associated with other medications that required
discontinuation of that medication, or any current concomitant medication known to
prolong the QT interval and cause TdP
Congenital long QT syndrome, family history of long QT syndrome, or unexplained
sudden cardiac death < 40 years of age in first-degree relatives
18 History of symptomatic congestive heart failure; unstable angina pectoris; uncontrolled
cardiac arrhythmia (multifocal premature ventricular contractions, bigeminy, trigeminy,
ventricular tachycardia), which is symptomatic or requires treatment (CTCAE Grade 3);
symptomatic or uncontrolled atrial fibrillation despite treatment; or asymptomatic
sustained ventricular tachycardia. Participants with atrial fibrillation controlled by
medication or arrhythmias controlled by pacemakers may be permitted upon discussion
with the clinical study lead.
19 Subjects with a history of myocardial infarction, transient ischemic attack, pulmonary
embolism, or stroke diagnosed in the past 6 months, or venous thrombosis diagnosed in
the past 3 months
Prior/concomitant therapy
20 Known allergy or hypersensitivity to any of the study interventions.
21 Receipt of prior or current cancer treatment for NSCLC, including but not limited to,
radiation therapy, investigational agents, chemotherapy, and mAbs. Prior surgical
resection of metachronus NSCLC (ie, Stage I or II) is permitted.
22 Prior exposure to immune-mediated therapy including, but not limited to, anti-TIGIT,
anti–CTLA-4, anti-PD-1, anti-PD-L1, anti-PD-L2 antibodies, excluding therapeutic
anticancer vaccines. Live attenuated vaccines within 30 days prior to the first dose of the
study intervention are not permitted.
23 Participants who are expected to require any other form of antineoplastic therapy while
participating in the trial are excluded.
24 Current or prior use of immunosuppressive medication within 14 days before the first
dose of durvalumab plus domvanalimab. The following are exceptions to this criterion:
Intranasal, inhaled, topical steroids or local steroid injections (eg, intraarticular
injection).
Systemic corticosteroids at physiologic doses not to exceed 10 mg/day of prednisone
or its equivalent.
Steroids as premedication for hypersensitivity reactions or as an antiemetic (eg, CT
scan premedication).
25 Major surgical procedure (as defined by the investigator) within 4 weeks prior to the first
dose of study intervention. Prior surgical resection of metachronous NSCLC (i.e., Stage I
or II) is permitted.
26 Any unresolved toxicity CTCAE > Grade 2 from the prior chemoradiation therapy
(excluding alopecia). Participants with irreversible toxicity that is not reasonably expected
to be exacerbated by study drug may be included (eg, hearing loss) after consultation with
the Clinical Study Lead. Participants with peripheral neuropathy after consultation with
the Clinical Study Lead.
27 Participants with CTCAE ≥ Grade 2 pneumonitis from prior chemoradiation therapy
28 Any prior Grade ≥ 3 immune-related adverse event (irAE) while receiving any previous
immunotherapy agent, or any unresolved irAE > Grade 1.
29 Any concurrent anticancer treatment. Concurrent use of hormonal therapy for
noncancer-related conditions (eg, hormone replacement therapy) is allowed.
Prior/Concurrent Clinical Study Experience
30 Previous treatment in the present study
31 Concurrent participation in another clinical study, unless it is an observational
(non-interventional) clinical study, or the follow-up period of an interventional study
32 Participation in another clinical study with a study intervention during the last 3 months
prior to randomisation or concurrent enrolment in another clinical study, unless it is an
observational, noninterventional clinical study during the follow-up period of an
interventional study
33 Prior randomisation or treatment in a previous durvalumab or domvanalimab clinical
study regardless of treatment arm assignment
34 Receipt of any immunotherapy, or investigational drug within 4 weeks prior to the first
dose of study drug; and in the case of monoclonal antibodies 6 weeks prior to the first
dose of study drug
Other
35 Participants with a known sensitivity to durvalumab or domvanalimab, any anti-TIGIT, or
any excipients of the products
36 Judgement by the investigator that the participant is unsuitable to participate in the study
and the participant is unlikely to comply with study procedures, restrictions, and
requirements
37 Female participants who are pregnant or breastfeeding, or male or female participants of
reproductive potential who are not willing to employ effective birth control from
screening to 115 days after the last dose of study treatment.
The Estimated Number of Participants
-
Taiwan
40 participants
-
Global
860 participants
