An exploratory study of durvalumab (MEDI4736) uptake during concurrent chemoradiotherapy in stage III NSCLC patients using 89Zr-labeled durvalumab PET

* Have a histologically or cytologically confirmed diagnosis of thoracic
disease stage III NSCLC and planned to receive concurrent chemotherapy and
radiotherapy on the thorax.
* Patients with oligometastatic stage IV comprising a thoracic stage III and up
to 2 distant metastases amenable for radical local consolidative therapy are
also eligible.
* 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 obtained from the subject prior to performing any
protocol-related procedures, including screening evaluations.
* Age > 18 years at time of study entry.
* Have a World Health Organisation (WHO) performance status of 0 or 1.
* Life expectancy of > 3 months.
* Have measurable disease based on RECIST 1.1.
* Must consent to allow use of PD-L1 measurements obtained from tumor
biopsies.
* Adequate organ and bone marrow function, as deemed acceptable by the treating
physician in the context of cCRT.
* Females of childbearing potential must use reliable methods of contraception
from the time of screening until 3 months after discontinuing study treatment.
Acceptable methods of contraception include total sexual abstinence, tubal
ligation, hormonal contraceptives that are not prone to drug-drug interactions,
copper-banded intra-uterine devices and vasectomised partner. All methods of
contraception must be used in combination with the use of a condom by their
male sexual partners for intercourse.
* Subject is willing and able to comply with the protocol for the duration of
the study including undergoing treatment and scheduled visits and examinations
including follow up.

* Concurrent enrolment in another clinical study, unless it is an observational
(non-interventional) clinical study, or during the follow-up period of an
interventional study.
* Participation in another clinical study with an investigational product
during the last 4 weeks.
* Receipt of the last dose of anticancer therapy (chemotherapy, immunotherapy,
endocrine therapy, targeted therapy, biologic therapy, tumor embolization,
monoclonal antibodies) * 30 days prior to the first dose of study drug If
sufficient wash-out time has not occurred due to the schedule or PK properties
of an agent, a longer wash-out period will be required, as agreed by
AstraZeneca/MedImmune and the investigator.
* Any unresolved toxicity NCI CTCAE Grade *2 from previous anticancer therapy
with the exception of alopecia, vitiligo, and the laboratory values defined in
the inclusion criteria.
* Patients with Grade *2 neuropathy will be evaluated on a case-by-case basis
after consultation with the Study Physician.
* Patients with irreversible toxicity not reasonably expected to be exacerbated
by treatment with durvalumab may be included only after consultation with the
Study Physician.
* Major surgical procedure (as defined by the Investigator) within 28 days
prior to the first dose of IP. Note: Limited surgical excision of isolated
lesions for palliative or diagnostic reasons is acceptable.
* History of allogenic organ transplantation.
* Active or prior documented autoimmune or inflammatory disorders (including
inflammatory bowel disease [e.g., colitis or Crohn's disease], diverticulitis
[with the exception of diverticulosis], systemic lupus erythematosus,
Sarcoidosis syndrome, or Wegener syndrome [granulomatosis with polyangiitis,
Graves' disease, rheumatoid arthritis, hypophysitis, uveitis, etc]). The
following are exceptions to this criterion:
a. Patients with vitiligo or alopecia
b. Patients with hypothyroidism (e.g., following Hashimoto syndrome) stable on
hormone replacement
c. Any chronic skin condition that does not require systemic therapy
d. Patients without active disease in the last year may be included but only
after consultation with the study physician
e. Patients with celiac disease controlled by diet alone.
* Active infection as judged to be unacceptable by the treating physician in
the context of cCRT.
* History of active primary immunodeficiency.
* Current or prior use of immunosuppressive medication within 14 days before
the first dose of durvalumab. The following are exceptions to this criterion:
a. Intranasal, inhaled, topical steroids, or local steroid injections (e.g.,
intra articular injection)
b. Systemic corticosteroids at physiologic doses not to exceed 10 mg/day of
prednisone or its equivalent
c. Steroids as premedication for hypersensitivity reactions (e.g., CT scan
premedication).
* Uncontrolled intercurrent illness, including but not limited to, ongoing or
active infection, symptomatic congestive heart failure, uncontrolled
hypertension, unstable angina pectoris, cardiac arrhythmia, interstitial lung
disease, serious chronic gastrointestinal conditions associated with diarrhea,
or psychiatric illness/social situations that would limit compliance with study
requirement, substantially increase risk of incurring AEs or compromise the
ability of the patient to give written informed consent.
* History of another primary malignancy except for
a. Malignancy treated with curative intent and with no known active disease *2
years before the first dose of IP and of low potential risk for recurrence
b. Adequately treated non-melanoma skin cancer or lentigo maligna without
evidence of disease
c. Adequately treated carcinoma in situ without evidence of disease.
* History of leptomeningeal carcinomatosis.
* Patients with suspected brain metastases at screening should have an MRI
(preferred) or CT each with IV contrast of the brain prior to study entry.
Patients with more than 2 brain metastases will be excluded. Patients with 1 or
2 brain metastases that are not amenable for stereotactic radiotherapy will be
excluded.
* Receipt of live attenuated vaccine within 30 days prior to the first dose of
IP. Note: Patients, if enrolled, should not receive live vaccine whilst
receiving IP and up to 30 days after the last dose of IP.
* Female patients who are pregnant or breastfeeding or male or female patients
of reproductive potential who are not willing to employ effective birth control
from screening to 90 days after the last dose of durvalumab monotherapy.
* Known allergy or hypersensitivity to any of the study drugs or any of the
study drug excipients.
* Prior randomisation or treatment in a previous durvalumab clinical study
regardless of treatment arm assignment.
* Any prior anti PD-1, PD-L1 and CTLA-4 therapy.