Phase 2 Study of Alisertib (MLN8237) in Combination With Paclitaxel Versus Placebo in Combination With Paclitaxel as Second Line Therapy for Small Cell Lung Cancer (SCLC)

The drug tested in this study is called alisertib. Alisertib is being tested to treat people
who have Small Cell Lung Cancer (SCLC). This study determined the safety and efficacy for
alisertib when given twice a day along with paclitaxel.

This open label study enrolled 178 patients. Participants were randomly assigned (by chance,
like flipping a coin) to one of the two treatment groups—which remained undisclosed to the
patient and study doctor during the study (unless there is an urgent medical need) and
participants were stratified at baseline as to whether brain mets were present or not;
whether they were sensitive to prior therapy or were relapsed/refractory to prior therapy;
and by world region:

- Alisertib 40 mg + Paclitaxel 60 mg/m^2

- Paclitaxel 80 mg/m^2 + Placebo (dummy inactive pill) - this is a tablet that looks like
the study drug but has no active ingredient

All participants received treatment until their disease progressed or they experienced
unacceptable alisertib-related toxicity.

This multi-center trial was conducted world-wide. The overall time to participate in this
study was approximately up to 22 months. Participants made multiple visits to the clinic, and
were contacted by telephone every month for 6 months after the end of treatment (EOT) for
follow-up assessment of progression free survival and for overall survival every 2 months
until death, study closure, or 14 months after randomization of the last participant.

Inclusion Criteria

Each participant must meet all the following inclusion criteria to be enrolled in the
study:

1. Male or female participants ≥ 18 years old.

2. Have a pathologically (histology or cytology) confirmed diagnosis of SCLC.

3. Have received and progressed after a platinum-based standard chemotherapy regimen for
first line treatment of SCLC, either limited stage (LS) or extensive stage (ES).

4. Have measurable disease within ≤ 2 weeks before randomization. Clear radiographic
evidence of disease progression after initial therapy should have been documented.

5. Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1 (PS 0-1).

6. Participants with treated brain metastases (surgery, whole or stereotactic brain
radiation) are allowed provided the lesions have been stable for at least 2 weeks and
the participant is off steroids or is on a stable dose of steroids. Participants
should be without neurologic dysfunction that would confound the evaluation of
neurological and/or other AEs.

Exclusion Criteria

Participants meeting any of the following exclusion criteria are not to be randomized to
treatment:

1. Any prior therapy for second-line treatment of SCLC.

2. Participants who relapsed ≥ 180 days after their response to first-line treatment.

3. Prior treatment with an Aurora A specific-targeted or pan-Aurora-targeted agent,
including alisertib, or any other investigational agent.

4. Prior treatment with paclitaxel or any other taxane agent.

5. Known hypersensitivity to Cremophor® EL, paclitaxel, or its components.

6. Any comorbid condition or unresolved toxicity that would preclude administration of
alisertib or weekly paclitaxel.

7. Prior history of ≥ Grade 2 neurotoxicity that is not resolved to ≤ Grade 1.

8. Participants with symptomatic and/or progressive brain metastases or with
carcinomatous meningitis.

9. Treatment with clinically significant enzyme inducers within 14 days prior to the
first dose of alisertib and during study conduct. Major prohibited enzyme inducers
include: phenytoin, carbamazepine, phenobarbital, rifampin, rifabutin, rifapentine,
and St. John's wort.

10. Inability to swallow alisertib or other orally administered medications.

11. Requirement for administration of proton pump inhibitor (PPI), H2 antagonist, or
pancreatic enzymes.

12. Diagnosed with or treated for another malignancy within 2 years before the first dose
of study drug, or previously diagnosed with another malignancy and have any evidence
of residual disease.

13. Other severe acute or chronic medical or psychiatric condition(s) per protocol.

14. History of myocardial infarction, unstable symptomatic ischemic heart disease,
uncontrolled hypertension despite appropriate medical therapy, any ongoing cardiac
arrhythmias of Grade > 2, thromboembolic events (eg, deep vein thrombosis, pulmonary
embolism, or symptomatic cerebrovascular events), or any other cardiac condition (eg,
pericardial effusion or restrictive cardiomyopathy) within 6 months before receiving
the first dose of study drug.

15. Known history of human immunodeficiency virus (HIV) infection, hepatitis B or
hepatitis C.

16. Surgery within 3 weeks (or 2 weeks for a minor surgery) before study enrollment and
not fully recovered to baseline or to a stable clinical status.

17. Participants who are pregnant, lactating, or do not agree to use effective methods of
contraception during the study treatment period through 6 months after the last dose
of study drug per protocol.