A Randomized, Double-Blind, Placebo-Controlled Phase 3 Study of Rovalpituzumab Tesirine as
Maintenance Therapy Following First-Line Platinum-Based Chemotherapy in Subjects with
Extensive Stage Small Cell Lung Cancer (MERU)

Small cell lung cancer (SCLC) is an important unmet medical need, representing
15-20% of the 220,000 annual new cases of lung cancer. SCLC has been staged
using the Veterans Administration (VA) staging system as limited versus
extensive stage disease. Approximately one-third of newly diagnosed patients
have limited stage disease while the rest has extensive stage.

Standard initial chemotherapy for all patients with a suitable performance
status consists of a platinum salt (carboplatin or cisplatin) in combination
with a second agent (usually etoposide or irinotecan). Response rates to
initial therapy are high, ranging from 60 - 70% (for extensive stage). However,
responses are typically not durable and recurrence rates are high, leading to
median survival of approximately 9 - 11 months.
Extensive stage disease subjects achieving SD or better during first-line
platinum-based therapy have median progression-free survival (PFS) of
approximately 2.1 - 2.3 months and median OS of approximately 6.9 - 8.9 months
from the completion of first-line therapy. Exploration of clinical benefit
maintenance strategies in extensive disease SCLC with the goal of prolonging
PFS and OS after completion of first-line standard therapies is therefore
warranted.

The positive results of a phase 1 trial support the further clinical
development of Rova-T.

The primary objective of the study is to evaluate if rovalpituzumab tesirine
improves progression-free and overall survival in subjects with extensive-stage
SCLC who have ongoing clinical benefit (SD, PR, or CR) following the completion
of 4 cycles of first-line, platinum-based chemotherapy (cisplatin or
carboplatin plus irinotecan or etoposide) compared to placebo.

The secondary objectives of the study are to evaluate rovalpituzumab tesirine
anti-tumor activity by determining objective response rate (ORR), clinical
benefit rate (CBR), duration of response (DOR), and to assess change in patient
reported outcomes (PRO) with EORTC QLCC30/LC13 questionnaires.

This is the first randomized, double-blind, multicenter, Phase 3 study
comparing Rova-T versus placebo as maintenance therapy following first-line
platinum-based therapy in subjects with extensive-stage SCLC.

Upon completion of first-line chemotherapy, eligible subjects must be offered
prophylactic cranial irradiation (PCI), if offering this procedure is not
contradictory to country or institutional guidelines. Subjects receiving PCI
must complete it prior to randomization into the study.

Subjects will be assigned in a 1:1 ratio to receive Rova-T or placebo in
combination with dexamethasone or placebo on day 1 of a 6-week cycle, omitting
every third cycle until disease progression. Survival Follow-up will continue
until the endpoint of death, the subject becomes lost to follow-up or withdraws
consent or termination of the study by AbbVie, whichever occurs first.

Randomization will be stratified by best response to first-line platinum-based
chemotherapy (SD vs. PR/CR), DLL3 expression, history of central nervous system
(CNS) metastases (Yes vs. No), and for subjects with no history of CNS
metastases, PCI vs. no PCI.

Subjects will receive one of the following treatments: 0.3 mg/kg Rova-T or
placebo IV infusion. Subjects will receive their assigned therapy on Day 1 of
each 6-week cycle, omitting every third cycle. Furthermore, subjects will also
receive 8 mg orally (PO) of dexamethasone or placebo twice daily on Day -1, Day
1 (the day of dosing), and Day 2 of each 6-week cycle, also omitting every
third cycle.

Disease progression will be assessed by study-specific CT every 6 weeks. An
echocardiogram will be done before every cycle. Subject will be asked to
monitor their weight via a daily fluid retention questionnaire. Furthermore,
subjects will be advised to protect themselves from sunlight for this might
induce skin reactions.

An end of treatment visit will be conducted when disease progression occurs.
For all subjects who discontinue study treatment for reasons other than disease
progression, the first follow-up visit will occur at 6 weeks (± 1 week) after
the last Disease Response/Assessment, then every 6 weeks (± 1 week) until
disease progression or initiation of new anti-cancer therapy, whichever occurs
first. At disease progression an optional collection of fresh tumor tissue may
be conducted.

After disease progression or if subjects stop treatment and decline further
study radiographic assessments prior to the endpoint of disease progression,
subjects will be followed for subsequent anti-cancer therapies (dates and
responses), as well as survival status. This will occur every 6 weeks (± 1
week) until the endpoint of death, the subject becomes lost to follow-up or
withdraws consent, or termination of the study by AbbVie, whichever occurs
first.

Although response rates to first-line platinum-based chemotherapy in ED SCLC is
high, SCLC nearly invariably recurs, which may be attributed to the relative
resistance of cancer stem cells (CSCs)/ tumor-initiating cells (TICs) to
conventional chemotherapy. By targeting this resistant, residual cell
population, Rova-T has a unique mechanistic rationale for benefit in
post-chemotherapy maintenance setting.

The most frequent treatment-emergent adverse event (TEAE) terms considered
related to Rova-T have included fatigue, pleural effusion and peripheral edema,
while the most frequent, related TEAE groups of Grade 3 or higher have included
thrombocytopenia, serosal effusions, and skin reactions. Safety assessments
will include regular assessments at protocol-specified time points of routine
physical examination, laboratory and imaging tests, echocardiograms, a fluid
retention questionnaire, daily weights, and spot urine protein testing. This
concludes that subjects participating in the study will have a higher burden
because of participation in the trial. This burden consists of extra visits to
the site, an Echocardiogram, additional blood draws besides the standard safety
labs. In addition, the subjects will complete daily fluid retention
questionnaires. Furthermore, every 6 weeks a CT will be performed.