A Phase III, Randomized, Double-blind, Placebo-controlled, Multi-center, International Study of Durvalumab or Durvalumab and Tremelimumab as Consolidation Treatment for Patients with Limited Stage Small-Cell Lung Cancer Who Have Not Progressed Following Concurrent Chemoradiation Therapy

- 18 years or older at the time of screening,
- Histologically or cytologically documented limited-stage SCLC (Stage I-III
SCLC [T any, N any, M0] according to the American Joint Committee on Cancer
Staging Manual [AJCC Cancer Staging Manual, 8th Edition] or the International
Association for the Study of Lung Cancer Staging Manual in Thoracic Oncology
[IASLC Staging Manual in Thoracic Oncology 2016]), ie, patients whose disease
can be encompassed within a radical radiation portal. Patients who are Stage I
or II must be medically inoperable
- World Health Organization (WHO)/Eastern Cooperative Oncology Group (ECOG)
performance status (PS) of 0 or 1 at enrollment and randomization
- Received an appropriate first line concurrent chemoradiotherapy regimen as
defined below, unless after consultation with the global study medical team an
alternative is acceptable
* Received 4 cycles of platinum-based chemotherapy concurrent with RT, which
must be completed within 1 to 42 days prior to randomization and the first dose
of IP.
* The chemotherapy regimen must contain platinum and IV etoposide, administered
as per local standard-of-care regimens.
* Received a total dose of radiation of 60 to 66 Gy over 6 weeks for standard
QD radiation schedules or 45 Gy over 3 weeks for hyperfractionated BID
radiation schedules.
* Radiotherapy must have commenced no later than the end of Cycle 2 of
chemotherapy.
* Receipt of 3 cycles of platinum-based chemotherapy concurrent with RT will be
permitted if the patient has achieved disease control and in the opinion of the
Investigator, no additional benefit will be expected with additional cycle of
chemotherapy.,
- Patients must have achieved CR, PR, or SD and not have progressed following
definitive, platinum-based chemotherapy, concurrent with radiotherapy.
- PCI may be delivered at the discretion of investigator and local standard of
care and must be conducted after the end of cCRT and completed between 1 to 42
days to first dose of IP.
- Tumor sample requirements:
* Mandatory availability of tumor sample, which may include a core needle
biopsy, newly cut unstained slides, or fine needle aspirate (FNA) cell block
samples.
* A newly acquired tumor biopsy is optional, provided that a biopsy procedure
is technically feasible and the procedure is not associated with unacceptable
clinical risk.
- Adequate organ and marrow function independent of transfusion, infusion, or
growth factor support for at least 14 days prior to obtaining screening labs,
- Must have a life expectancy of at least 12 weeks, - Body weight >30 kg

- Mixed SCLC and NSCLC histology,
- Extensive-stage SCLC,
- Any history of Grade >=2 pneumonitis,
- History of allogeneic organ transplantation,
- 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,
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,
- Uncontrolled intercurrent illness, including but not limited to, ongoing or
active infection, symptomatic congestive heart failure, uncontrolled
hypertension, unstable angina pectoris, uncontrolled cardiac arrhythmia, active
ILD, serious chronic GI conditions associated with diarrhea, or psychiatric
illness/social situations that would limit compliance with study requirements,
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:
* 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 non-melanoma skin cancer or lentigo maligna without
evidence of disease
* Adequately treated carcinoma in situ without evidence of disease,
- History of leptomeningeal carcinomatosis,
- History of active primary immunodeficiency, - Active infection including
tuberculosis (clinical evaluation that includes clinical history, physical
examination and radiographic findings, and tuberculosis testing in line with
local practice), hepatitis B (known positive HBV surface antigen [HBsAg]
result), hepatitis C (HCV), or human immunodeficiency virus (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 HCV antibody are eligible only if polymerase chain
reaction is negative for HCV RNA.,
- Any unresolved toxicity NCI Common Terminology Criteria for Adverse Events
(CTCAE) Grade >=2 from previous CRT 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 or tremelimumab may be included only after
consultation with the Study Physician.,
- Brain metastases or spinal cord compression. All patients will have an MRI
(preferred) or CT, preferably with IV contrast of the brain, prior to study
entry.,
- 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), - Known
allergy or hypersensitivity to any of the study drugs or any of the study drug
excipients,
- Patients who received sequential CRT for LD-SCLC (no overlap of RT with
chemotherapy), - Patients whose conditions have progressed while on concurrent
CRT,
- Receipt of chemotherapy that exceeds 4 cycles in total. Chemotherapy regimens
other than etoposide and platinum are not permitted.,
- Prior exposure to immune-mediated therapy including, but not limited to,
other anti-CTLA-4, anti-PD-1, anti-PD-L1, and anti-programmed cell death ligand
2 (anti-PD-L2) antibodies, excluding therapeutic anticancer vaccines.,
- Any concurrent chemotherapy, IP, biologic, or hormonal therapy for cancer
treatment. Concurrent use of hormonal therapy for non-cancer-related conditions
(eg, hormone replacement therapy) is acceptable.,
- Receipt of live attenuated vaccine within 30 days prior to the first dose of
IP. Note: Patients, if randomized, should not receive live vaccine while
receiving IP and up to 30 days after the last dose of IP.,
- Major surgical procedure (as defined by the Investigator) within 42 days
prior to the first dose of IP.,
- Current or prior use of immunosuppressive medication within 14 days before
the first dose of durvalumab or tremelimumab. The following are exceptions to
this criterion:
* 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 scan
premedication),
- Female patients who are pregnant or breastfeeding and male or female patients
of reproductive potential who are not willing to employ effective birth control
from screening to 180 days after the last dose of IP.