The study will be conducted in two parts:
Part 1: Open-label dose-finding study of irinotecan liposome injection. 30 patients were
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
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: To compare overall survival following treatment with irinotecan liposome
injection with overall survival following treatment with intravenous (IV) topotecan.
- 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
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.
- 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
- 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.