Study of Irinotecan Liposome Injection (ONIVYDE®) in Patients With Small Cell Lung Cancer

The study will be conducted in two parts:

Part 1: Open-label dose finding study of irinotecan liposome injection. Approximately 24-36
patients will be enrolled.

Part 1 Primary Objectives:

- Describe the safety and tolerability of irinotecan liposome injection monotherapy
administered every 2 weeks

- Determine the optimal irinotecan liposome injection monotherapy dose for Part 2 of this
study

Part 2: A randomized, efficacy study of irinotecan liposome injection versus IV topotecan.

Approximately 450 patients will be enrolled in part 2.

Part 2 objectives: Detailed in the Primary & Secondary outcome measure sections.

Inclusion Criteria:

- At least 18 years of age.

- Able to understand and provide an informed consent

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

- Life expectancy >12 weeks

- Histopathologically or cytologically confirmed small cell lung cancer

- Evaluable disease as defined by RECIST Version 1.1 guidelines (patients with non
measurable lesions only are eligible).

- Radiologically confirmed progression on or after first-line platinum based
chemotherapy (carboplatin or cisplatin), immunotherapy, or chemo-radiation including
platinum-based chemotherapy for treatment of limited or extensive stage Small Cell
Lung Cancer (SCLC).

- Recovered from the effects of any prior chemotherapy, surgery, radiotherapy or other
anti-neoplastic therapy (recovered to Grade 1 or better, with the exception of
alopecia).

- Adequate bone marrow reserves

- Adequate hepatic function Adequate renal function

- Electrocardiogram during the Screening period without any clinically significant
findings, per investigator's assessment

Exclusion Criteria

- Any medical or social condition deemed by the Investigator to be likely to interfere
with a patient's ability to sign informed consent, cooperate and participate in the
study, or interfere with the interpretation of the results

- Pregnant or breast feeding;

- Patients with large cell neuroendocrine lung carcinoma.

- Patients who have received prior topoisomerase I inhibitor treatment, retreatment with
e platinum-based regimen, antibody-drug conjugates or molecular targeted agents, more
than one line of immunotherapy, or any other additional regimen of prior cytotoxic
chemotherapy.

- Patients with the symptomatic Central Nervous System (CNS) metastasis and/or who have
developed new or progressive brain metastasis following prophylactic and/or
therapeutic cranial radiation (whole brain stereotactic radiation).

- Patients with carcinomatous meningitis.

- Unable to discontinue the use of strong CYP3A4 or UGT1A1 inhibitors at least 1 week or
strong CYP3A4 inducers at least 2 weeks prior to receiving the first dose of
irinotecan liposome injection.

- Have a previous or concurrent cancer that is distinct in primary (non-pulmonary) site
or SCLC histology

- Investigational therapy administered within 4 weeks, or within a time interval less
than at least 5 half-lives of the investigational agent, whichever is less, prior to
the first scheduled day of dosing in this study.

- Severe cardiovascular and pulmonary diseases

- New York Heart Association Class III or IV congestive heart failure, ventricular
arrhythmias, or uncontrolled blood pressure.

- Active infection

- Known hypersensitivity to any of the components of irinotecan liposome injection,
other liposomal products, or topotecan.

- Clinically significant gastrointestinal disorder including hepatic disorders,
bleeding, inflammation, occlusion, or diarrhea > grade 1.