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

A randomized, open label phase 3 study of irinotecan liposome injection (ONIVYDE®) versus topotecan in patients with small cell lung cancer who have progressed on or after platinum-based first-line therapy

The study was conducted in two parts:

1. Dose determination of irinotecan liposome injection
2. A randomized, efficacy study of irinotecan liposome injection versus topotecan

The study was conducted in two parts:

Part 1: Open-label dose-finding study of irinotecan liposome injection. 30 patients were planned to 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 intravenous (IV) topotecan.

Approximately 450 patients were planned to be enrolled in part 2.

Part 2 objectives: To compare overall survival following treatment with irinotecan liposome injection with overall survival following treatment with IV topotecan.

Eligibility Criteria:
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), or chemo-radiation including platinum-based chemotherapy for treatment of limited or extensive stage Small Cell Lung Cancer (SCLC). In addition to platinum-based regimen, one line of immunotherapy as monotherapy or in combination, in first or in second line setting is allowed.
* 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, peripheral neuropathy, or ototoxicity).
* Adequate bone marrow reserves
* Adequate hepatic function
* Adequate renal function
* Electrocardiogram during the Screening period without any clinically significant findings, per investigator's assessment
* Patients with certain types of asymptomatic CNS metastases that meet ALL the following criteria are eligible.

  1. Patients with asymptomatic CNS metastases prior to enrollment
  2. Prior radiation for CNS metastatic disease is completed ≥4 weeks prior to enrollment
  3. CNS metastases that are stable or have decreased according to the post radiation follow-up scan that is conducted at least 4 weeks after completion of radiation treatment for CNS lesion.
  4. Patients have discontinued corticosteroids or are on stable low-dose steroids (prednisone or equivalent 10 mg daily or less) for at least 1 week after completion of radiation for CNS lesion prior to enrollment.

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 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 within 3 months 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.