Durvalumab ± Tremelimumab in Combination With Platinum Based Chemotherapy in Untreated Extensive-Stage Small Cell Lung Cancer (CASPIAN)

Primary objective of this study is to assess the efficacy of durvalumab + tremelimumab + EP
treatment compared with EP and the efficacy of durvalumab + EP treatment compared with EP in
terms of OS.

All patients will be randomized in a 1:1:1 ratio in a stratified manner according to the
planned platinum-based therapy for Cycle 1 (cisplatin or carboplatin) to receive treatment
with durvalumab + tremelimumab + EP (Arm 1), durvalumab + EP (Arm 2), or standard of care- EP
(Arm 3). Arm 1 and Arm 2 patients receive the treatment until confirmed disease progression
while Arm 3 patients receive up to 6 cycles of EP and prophylactic cranial irradiation if
clinically indicated, at the Investigators' discretion.Patients who have discontinued
treatment due to toxicity or symptomatic deterioration, clinical progression, or who have
commenced subsequent anticancer therapy will be followed up until confirmed disease
progression and for survival.

Targeted population are adult patients (aged ≥18 years) with histologically or cytologically
documented extensive disease (American Joint Committee on Cancer Stage (7th edition) IV SCLC
[T any, N any,M1 a/b]), or T3-4 due to multiple lung nodules that are too extensive or have
tumor/nodal volume that is too large to be encompassed in a tolerable radiation plan.
Patients must have WHO/ECOG performance status of 0 or 1.

Tumor assessments will be performed at Screening as baseline with follow-up at Week 6 ±1 week
from the date of randomization, at Week 12 ±1 week from the date of randomization, and then
every 8 weeks ±1 week until confirmed objective disease progression.

An independent data monitoring committee (IDMC) comprised of independent experts will be
convened to confirm the safety and tolerability of the proposed dose and schedule of
durvalumab ± tremelimumab in combination with platinum based chemotherapy at two early stages
of enrolment.

Inclusion criteria:

1. Histologically or cytologically documented extensive disease. Brain metastases; must
be asymptomatic or treated and stable off steroids and anti-convulsants for at least 1
month prior to study treatment.

2. Suitable to receive a platinum-based chemotherapy regimen as 1st line treatment.

3. Life expectancy ≥12 weeks at Day 1.

4. ECOG 0 or 1 at enrolment.

5. No prior exposure to immune-mediated therapy excluding therapeutic anticancer
vaccines.

Exclusion criteria:

1. Any history of radiotherapy to the chest prior to systemic therapy or planned
consolidation chest radiation therapy (except paliative care outside of the chest).

2. Paraneoplastic syndrome of autoimmune nature, requiring systemic treatment or clinical
symptomatology suggesting worsening of PNS

3. Active infection including tuberculosis, HIV, hepatitis B anc C

4. Active or prior documented autoimmune or inflammatory disorders

5. Uncontrolled intercurrent illness, including but not limited to interstitial lung
disease.