Small Cell Lung Cancer
Conditions
Brief summary
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
Detailed description
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.
Interventions
DRUGTopotecan
IV
Sponsors
Ipsen
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Masking description
Open Label
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Part 1: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (SAEs) | The TEAEs were reported from the time of first study treatment administration (Day 1) up to 30 days after the date of last study treatment administration, approximately 680 days | An adverse event (AE) was any untoward medical occurrence in a participant following or during exposure to a study treatment, whether or not causally related to the study treatment. An undesirable medical condition could be symptoms, signs or abnormal results of an investigation. An SAE was any AE that: resulted in death; was life-threatening; required hospitalization or prolongation of existing hospitalization; resulted in persistent or significant disability or incapacity; resulted in congenital anomaly or birth defect; or was medically important. A TEAE was any AE that occurred or worsened on or after the day of first dose of study treatment and within 30 days after discontinuation of study treatment. |
| Part 1: Number of Participants With Dose-Limiting Toxicities (DLT) | From the start of the first study treatment administration (Day 1) up to 14 days after the second dose of study treatment administration, a maximum of 42 days | A TEAE was considered as DLT if it occurred during the safety evaluation period (i.e. first 28 days of treatment or 14 days after the second dose of study treatment if there was a treatment delay due to non-DLT related reasons) and were deemed related to the study treatment by the investigator. The determination of whether an Adverse Event was considered a Dose Limiting Toxicity was made by the Safety Review Committee (SRC) comprising the Part 1 Investigators and the Medical Monitor(s) of the Sponsor. |
| Part 2: Overall Survival (OS) | From date of randomization (within 7 days before start of study treatment) until death. Assessed up to Part 2 primary analysis DCO date of 08 February 2022 (approximately 900 days) | The OS was defined as the time from randomization date to the date of death from any cause. In the absence of confirmation of death, survival time was censored at the last date the participant was known to be alive. The OS was calculated using Kaplan-Meier technique. Following end of treatment participant and/or family was contacted by telephone every month to assess vital status. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Part 2: PFS | RECIST assessments performed at Baseline (within 28 days before start of study treatment), every 6 weeks post first dose and treatment pause, 30 days after discontinuation of study treatment, then every month thereafter, approximately maximum of 900 days | The PFS was defined as time from randomization to first documented objective PD using RECIST 1.1 (or response assessment in neuro-oncology brain metastases \[RANO-BM\] criteria for central nervous system \[CNS\] lesions) as assessed by blinded independent central review (BICR) or death due to any cause, whichever occurred first. Per RECIST 1.1, progression is defined as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions. The PFS was calculated using Kaplan-Meier technique. Per protocol, participants had CT-scans and brain MRI every 6 weeks to measure tumor lesion size. This was continued throughout treatment until PD or commencement of new anti-neoplastic therapy. |
| Part 2: ORR | RECIST assessments performed at Baseline (within 28 days before start of study treatment), every 6 weeks post first dose and treatment pause, 30 days after discontinuation of study treatment, then every month thereafter, approximately maximum of 900 days | The ORR was defined as percentage of participants with a BOR characterized as either a CR or PR, recorded from randomization until documented PD or death relative to the total number of participants. ORR analysis was based on BOR assessed by BICR using RECIST v1.1. Per RECIST v1.1, CR is disappearance of all target lesions; PR is \>=30% decrease in the sum of the longest diameter of target lesions; and overall response = CR + PR. Per protocol, participants had CT-scans and brain MRI every 6 weeks to measure tumor lesion size. This was continued throughout treatment until PD or commencement of new anti-neoplastic therapy. |
| Part 2: Median Duration of Response (DoR) | RECIST assessments performed at Baseline (within 28 days before start of study treatment), every 6 weeks post first dose and treatment pause, 30 days after discontinuation of study treatment, then every month thereafter, approximately maximum of 900 days | The DoR was defined as time from the first documented objective response (CR or PR, whichever was earlier) to the date of first documented PD or death due to any cause. The DoR analysis was based on BOR assessed by BICR using RECIST v1.1. Per RECIST v1.1, CR is disappearance of all target lesions and PR is \>=30% decrease in the sum of the longest diameter of target lesions. The DoR was calculated using Kaplan-Meier technique. Per protocol, participants had CT-scans and brain MRI every 6 weeks to measure tumor lesion size. This was continued throughout treatment until PD or commencement of new anti-neoplastic therapy. |
| Part 1: Objective Response Rate (ORR) | RECIST assessments performed at Baseline (within 28 days before start of study treatment), every 6 weeks post first dose and treatment pause, 30 days after discontinuation of study treatment, then every month thereafter, approximately maximum of 1177 days | The ORR was defined as the percentage of participants with a best overall response (BOR) characterized as either a complete response (CR) or partial response (PR) recorded from date of first dose of study treatment until documented PD or death. ORR analysis was based on BOR using RECIST v1.1 per investigator assessment. Per RECIST v1.1, CR is disappearance of all target lesions; PR is \>=30% decrease in the sum of the longest diameter of target lesions; and overall response = CR + PR. Per protocol, participants had computed tomography (CT)-scans and brain magnetic resonance imaging (MRI) every 6 weeks to measure tumor lesion size. This was continued throughout treatment until PD or commencement of new anti-neoplastic therapy. |
| Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire - Core 30 (EORTC QLQ-C30)/Lung Cancer Supplement (LC13) Dyspnea Scale at Week 12 | Baseline (Day 1) and Week 12 | The EORTC QLQ-LC13 is a lung cancer specific module used in conjunction with EORTC QLQ-C30 and covers typical symptoms of lung cancer (cough, pain, dyspnea, sore mouth, peripheral neuropathy, hair loss). Scores range from 0-100 and a high score represents a high level of symptomatology/problems/worse QoL. Baseline was defined as the last non-missing measurement taken prior to reference start date. Change from baseline in dyspnea scale was calculated regardless of premature study treatment discontinuation. Participants completed these questionnaires on an electronic tablet every 6 weeks during treatment and it was continued until PD or commencement of new anti-neoplastic therapy. |
| Change From Baseline in EORTC QLQ-LC13 Cough Scale at Week 12 | Baseline (Day 1) and Week 12 | The EORTC QLQ-LC13 is a lung cancer specific module used in conjunction with EORTC QLQ-C30 and covers typical symptoms of lung cancer (cough, pain, dyspnea, sore mouth, peripheral neuropathy, hair loss). Score ranges from 0-100 scale and a high score represents a high level of symptomatology/problems/worse QoL. Baseline was defined as the last non-missing measurement taken prior to reference start date. Change from baseline in cough scale was calculated regardless of premature study treatment discontinuation. Participants completed these questionnaires on an electronic tablet every 6 weeks during treatment and it was continued until PD or commencement of new anti-neoplastic therapy. |
| Part 2: Median Time to Objective Response (OR) | RECIST assessments performed at Baseline (within 28 days before start of study treatment), every 6 weeks post first dose and treatment pause, 30 days after discontinuation of study treatment, then every month thereafter, approximately maximum of 900 days | Time to OR as per RECIST v1.1 criteria according to BICR was defined as time from the date of randomization to the date of first documented objective tumor response (CR or PR, whichever was first). Per RECIST v1.1, CR is disappearance of all target lesions; PR is \>=30% decrease in the sum of the longest diameter of target lesion. Participants with a new anti-cancer therapy prior to OR were censored at the last tumor assessment prior to new anti-cancer therapy. Per protocol, participants had CT-scans and brain MRI every 6 weeks to measure tumor lesion size. This was continued throughout treatment until PD or commencement of new anti-neoplastic therapy. |
| Part 1: Progression-Free Survival (PFS) | RECIST assessments performed at Baseline (within 28 days before start of study treatment), every 6 weeks post first dose and treatment pause, 30 days after discontinuation of study treatment, then every month thereafter, approximately maximum of 1177 days | The PFS was defined as time from first dose of study treatment to the first documented objective PD using RECIST v1.1 or death due to any cause, whichever occurs first. Per RECIST 1.1, progression is defined as at least 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions. The PFS was calculated using Kaplan-Meier technique. Per protocol, participants had CT-scans and brain MRI every 6 weeks to measure tumor lesion size. This was continued throughout treatment until PD or commencement of new anti-neoplastic therapy. |
| Part 1: OS | From Baseline (Day 1) until death. Assessed up to Part 1 DCO date of 11 August 2021 (approximately 1177 days) | The OS was defined as the time from first dose of study treatment to the date of death from any cause. In the absence of confirmation of death, survival time was censored at the last date the participant was known to be alive. The OS was calculated using Kaplan-Meier technique. Following end of treatment participant and/or family was contacted by telephone every month to assess vital status. |
Countries
Australia, Belgium, Brazil, China, France, Germany, Hungary, Italy, Poland, Romania, Russia, Serbia, South Korea, Spain, Taiwan, Turkey (Türkiye), Ukraine, United States
Participant flow
Recruitment details
This Phase III, 2-part (Part 1: \[open-label, single-arm dose evaluation period\] and Part 2 \[randomized, open-label period\]) study was conducted in participants with small cell lung cancer (SCLC) who progressed on or after platinum-based first-line therapy at 11 sites for Part 1 and 116 sites for Part 2 in the USA, Europe, Asia, Australia, Turkey and Brazil. First participant was enrolled on 25 April 2018 and primary analysis data cut-off (DCO) date was 08 February 2022 for Part 2.
Pre-assignment details
Each part consisted of screening stage (up to 28 days), treatment/active follow-up stage, and a long-term monthly follow-up stage. A total of 30 participants in Part 1 received study treatment and 461 participants in Part 2 were randomized to receive study treatment in this study.
Participants by arm
| Arm | Count |
|---|---|
| Part 1: Irinotecan Liposome Injection 85 mg/m^2 Participants received irinotecan liposome injection 85 mg/m\^2 i.v. over 90 minutes every 2 weeks in a 6-week cycle until PD, death, unacceptable study treatment-related toxicity or withdrawal of consent. | 5 |
| Part 1: Irinotecan Liposome Injection 70 mg/m^2 Participants received irinotecan liposome injection 70 mg/m\^2 i.v. over 90 minutes every 2 weeks in a 6-week cycle until PD, death, unacceptable study treatment-related toxicity or withdrawal of consent. | 25 |
| Part 2: Irinotecan Liposome Injection 70 mg/m^2 Eligible participants received irinotecan liposome injection 70 mg/m\^2 i.v. over 90 minutes, every 2 weeks in a 6-week cycle until PD, death, unacceptable study treatment-related toxicity or withdrawal of consent. | 229 |
| Part 2: Topotecan 1.5 mg/m^2 Eligible participants received topotecan 1.5 mg/m\^2 i.v. over 30 minutes daily for 5 consecutive days, every 3 weeks in a 6-week cycle until PD, death, unacceptable study treatment-related toxicity or withdrawal of consent. | 232 |
| Total | 491 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Part 1: Dose Evaluation (Up to Week 172) | Withdrawal by Subject | 0 | 1 | 0 | 0 |
| Part 2: Randomized Study (Upto Week 197) | Investigator decision | 0 | 0 | 2 | 2 |
| Part 2: Randomized Study (Upto Week 197) | Lost to Follow-up | 0 | 0 | 3 | 4 |
| Part 2: Randomized Study (Upto Week 197) | Other | 0 | 0 | 3 | 0 |
| Part 2: Randomized Study (Upto Week 197) | Protocol Violation | 0 | 0 | 1 | 0 |
| Part 2: Randomized Study (Upto Week 197) | Screen failure | 0 | 0 | 0 | 1 |
| Part 2: Randomized Study (Upto Week 197) | Withdrawal by Subject | 0 | 0 | 18 | 14 |
Baseline characteristics
| Characteristic | Part 1: Irinotecan Liposome Injection 85 mg/m^2 | Part 1: Irinotecan Liposome Injection 70 mg/m^2 | Part 2: Irinotecan Liposome Injection 70 mg/m^2 | Part 2: Topotecan 1.5 mg/m^2 | Total |
|---|---|---|---|---|---|
| Age, Customized <65 years | 4 Participants | 18 Participants | 128 Participants | 151 Participants | 301 Participants |
| Age, Customized >=65 years | 1 Participants | 7 Participants | 101 Participants | 81 Participants | 190 Participants |
| Race/Ethnicity, Customized American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 1 Participants |
| Race/Ethnicity, Customized Asian | 0 Participants | 0 Participants | 37 Participants | 36 Participants | 73 Participants |
| Race/Ethnicity, Customized Black or African American | 0 Participants | 0 Participants | 4 Participants | 4 Participants | 8 Participants |
| Race/Ethnicity, Customized Hispanic or Latino | 0 Participants | 2 Participants | 6 Participants | 9 Participants | 17 Participants |
| Race/Ethnicity, Customized Not Hispanic or Latino | 5 Participants | 20 Participants | 214 Participants | 218 Participants | 457 Participants |
| Race/Ethnicity, Customized Not Reported | 0 Participants | 0 Participants | 4 Participants | 9 Participants | 13 Participants |
| Race/Ethnicity, Customized Not Reported/Unknown | 0 Participants | 3 Participants | 9 Participants | 5 Participants | 17 Participants |
| Race/Ethnicity, Customized White | 5 Participants | 25 Participants | 184 Participants | 182 Participants | 396 Participants |
| Sex: Female, Male Female | 2 Participants | 16 Participants | 79 Participants | 69 Participants | 166 Participants |
| Sex: Female, Male Male | 3 Participants | 9 Participants | 150 Participants | 163 Participants | 325 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 5 / 5 | 23 / 25 | 201 / 226 | 205 / 223 |
| other Total, other adverse events | 5 / 5 | 25 / 25 | 212 / 226 | 220 / 223 |
| serious Total, serious adverse events | 4 / 5 | 9 / 25 | 106 / 226 | 88 / 223 |
Outcome results
Primary
Part 1: Number of Participants With Dose-Limiting Toxicities (DLT)
A TEAE was considered as DLT if it occurred during the safety evaluation period (i.e. first 28 days of treatment or 14 days after the second dose of study treatment if there was a treatment delay due to non-DLT related reasons) and were deemed related to the study treatment by the investigator. The determination of whether an Adverse Event was considered a Dose Limiting Toxicity was made by the Safety Review Committee (SRC) comprising the Part 1 Investigators and the Medical Monitor(s) of the Sponsor.
Time frame: From the start of the first study treatment administration (Day 1) up to 14 days after the second dose of study treatment administration, a maximum of 42 days
Population: Part 1: Safety population included all enrolled participants who were treated with at least 1 dose of irinotecan liposome injection.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part 1: Irinotecan Liposome Injection 85 mg/m^2 | Part 1: Number of Participants With Dose-Limiting Toxicities (DLT) | 4 Participants |
| Part 1: Irinotecan Liposome Injection 70 mg/m^2 | Part 1: Number of Participants With Dose-Limiting Toxicities (DLT) | 2 Participants |
Primary
Part 1: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (SAEs)
An adverse event (AE) was any untoward medical occurrence in a participant following or during exposure to a study treatment, whether or not causally related to the study treatment. An undesirable medical condition could be symptoms, signs or abnormal results of an investigation. An SAE was any AE that: resulted in death; was life-threatening; required hospitalization or prolongation of existing hospitalization; resulted in persistent or significant disability or incapacity; resulted in congenital anomaly or birth defect; or was medically important. A TEAE was any AE that occurred or worsened on or after the day of first dose of study treatment and within 30 days after discontinuation of study treatment.
Time frame: The TEAEs were reported from the time of first study treatment administration (Day 1) up to 30 days after the date of last study treatment administration, approximately 680 days
Population: Part 1: Safety population included all enrolled participants who were treated with at least 1 dose of irinotecan liposome injection.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part 1: Irinotecan Liposome Injection 85 mg/m^2 | Part 1: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (SAEs) | Any TEAE | 5 Participants |
| Part 1: Irinotecan Liposome Injection 85 mg/m^2 | Part 1: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (SAEs) | Serious TEAEs | 4 Participants |
| Part 1: Irinotecan Liposome Injection 70 mg/m^2 | Part 1: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (SAEs) | Any TEAE | 25 Participants |
| Part 1: Irinotecan Liposome Injection 70 mg/m^2 | Part 1: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (SAEs) | Serious TEAEs | 9 Participants |
Primary
Part 2: Overall Survival (OS)
The OS was defined as the time from randomization date to the date of death from any cause. In the absence of confirmation of death, survival time was censored at the last date the participant was known to be alive. The OS was calculated using Kaplan-Meier technique. Following end of treatment participant and/or family was contacted by telephone every month to assess vital status.
Time frame: From date of randomization (within 7 days before start of study treatment) until death. Assessed up to Part 2 primary analysis DCO date of 08 February 2022 (approximately 900 days)
Population: Part 2: The ITT population included all randomized participants.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Part 1: Irinotecan Liposome Injection 85 mg/m^2 | Part 2: Overall Survival (OS) | 7.92 months |
| Part 1: Irinotecan Liposome Injection 70 mg/m^2 | Part 2: Overall Survival (OS) | 8.31 months |
p-value: 0.309495% CI: [0.9, 1.37]Stratified log-rank test
Secondary
Change From Baseline in EORTC QLQ-LC13 Cough Scale at Week 12
The EORTC QLQ-LC13 is a lung cancer specific module used in conjunction with EORTC QLQ-C30 and covers typical symptoms of lung cancer (cough, pain, dyspnea, sore mouth, peripheral neuropathy, hair loss). Score ranges from 0-100 scale and a high score represents a high level of symptomatology/problems/worse QoL. Baseline was defined as the last non-missing measurement taken prior to reference start date. Change from baseline in cough scale was calculated regardless of premature study treatment discontinuation. Participants completed these questionnaires on an electronic tablet every 6 weeks during treatment and it was continued until PD or commencement of new anti-neoplastic therapy.
Time frame: Baseline (Day 1) and Week 12
Population: Part 2: The ITT population included all randomized participants. Only participants analyzed at Week 12 are reported.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part 1: Irinotecan Liposome Injection 85 mg/m^2 | Change From Baseline in EORTC QLQ-LC13 Cough Scale at Week 12 | 1.6 scores on a scale | Standard Deviation 25.77 |
| Part 1: Irinotecan Liposome Injection 70 mg/m^2 | Change From Baseline in EORTC QLQ-LC13 Cough Scale at Week 12 | -1.2 scores on a scale | Standard Deviation 27.31 |
Secondary
Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire - Core 30 (EORTC QLQ-C30)/Lung Cancer Supplement (LC13) Dyspnea Scale at Week 12
The EORTC QLQ-LC13 is a lung cancer specific module used in conjunction with EORTC QLQ-C30 and covers typical symptoms of lung cancer (cough, pain, dyspnea, sore mouth, peripheral neuropathy, hair loss). Scores range from 0-100 and a high score represents a high level of symptomatology/problems/worse QoL. Baseline was defined as the last non-missing measurement taken prior to reference start date. Change from baseline in dyspnea scale was calculated regardless of premature study treatment discontinuation. Participants completed these questionnaires on an electronic tablet every 6 weeks during treatment and it was continued until PD or commencement of new anti-neoplastic therapy.
Time frame: Baseline (Day 1) and Week 12
Population: Part 2: The ITT population included all randomized participants. Only participants analyzed at Week 12 are reported.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part 1: Irinotecan Liposome Injection 85 mg/m^2 | Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire - Core 30 (EORTC QLQ-C30)/Lung Cancer Supplement (LC13) Dyspnea Scale at Week 12 | 4.6 scores on a scale | Standard Deviation 20.74 |
| Part 1: Irinotecan Liposome Injection 70 mg/m^2 | Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire - Core 30 (EORTC QLQ-C30)/Lung Cancer Supplement (LC13) Dyspnea Scale at Week 12 | 1.9 scores on a scale | Standard Deviation 19.17 |
Secondary
Part 1: Objective Response Rate (ORR)
The ORR was defined as the percentage of participants with a best overall response (BOR) characterized as either a complete response (CR) or partial response (PR) recorded from date of first dose of study treatment until documented PD or death. ORR analysis was based on BOR using RECIST v1.1 per investigator assessment. Per RECIST v1.1, CR is disappearance of all target lesions; PR is \>=30% decrease in the sum of the longest diameter of target lesions; and overall response = CR + PR. Per protocol, participants had computed tomography (CT)-scans and brain magnetic resonance imaging (MRI) every 6 weeks to measure tumor lesion size. This was continued throughout treatment until PD or commencement of new anti-neoplastic therapy.
Time frame: RECIST assessments performed at Baseline (within 28 days before start of study treatment), every 6 weeks post first dose and treatment pause, 30 days after discontinuation of study treatment, then every month thereafter, approximately maximum of 1177 days
Population: Part 1: Safety population included all enrolled participants who were treated with at least 1 dose of irinotecan liposome injection.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Part 1: Irinotecan Liposome Injection 85 mg/m^2 | Part 1: Objective Response Rate (ORR) | 40 percentage of participants |
| Part 1: Irinotecan Liposome Injection 70 mg/m^2 | Part 1: Objective Response Rate (ORR) | 44 percentage of participants |
Secondary
Part 1: OS
The OS was defined as the time from first dose of study treatment to the date of death from any cause. In the absence of confirmation of death, survival time was censored at the last date the participant was known to be alive. The OS was calculated using Kaplan-Meier technique. Following end of treatment participant and/or family was contacted by telephone every month to assess vital status.
Time frame: From Baseline (Day 1) until death. Assessed up to Part 1 DCO date of 11 August 2021 (approximately 1177 days)
Population: Part 1: Safety population included all enrolled participants who were treated with at least 1 dose of irinotecan liposome injection.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Part 1: Irinotecan Liposome Injection 85 mg/m^2 | Part 1: OS | 10.84 months |
| Part 1: Irinotecan Liposome Injection 70 mg/m^2 | Part 1: OS | 8.08 months |
Secondary
Part 1: Progression-Free Survival (PFS)
The PFS was defined as time from first dose of study treatment to the first documented objective PD using RECIST v1.1 or death due to any cause, whichever occurs first. Per RECIST 1.1, progression is defined as at least 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions. The PFS was calculated using Kaplan-Meier technique. Per protocol, participants had CT-scans and brain MRI every 6 weeks to measure tumor lesion size. This was continued throughout treatment until PD or commencement of new anti-neoplastic therapy.
Time frame: RECIST assessments performed at Baseline (within 28 days before start of study treatment), every 6 weeks post first dose and treatment pause, 30 days after discontinuation of study treatment, then every month thereafter, approximately maximum of 1177 days
Population: Part 1: Safety population included all enrolled participants who were treated with at least 1 dose of irinotecan liposome injection.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Part 1: Irinotecan Liposome Injection 85 mg/m^2 | Part 1: Progression-Free Survival (PFS) | 4.19 months |
| Part 1: Irinotecan Liposome Injection 70 mg/m^2 | Part 1: Progression-Free Survival (PFS) | 3.98 months |
Secondary
Part 2: Median Duration of Response (DoR)
The DoR was defined as time from the first documented objective response (CR or PR, whichever was earlier) to the date of first documented PD or death due to any cause. The DoR analysis was based on BOR assessed by BICR using RECIST v1.1. Per RECIST v1.1, CR is disappearance of all target lesions and PR is \>=30% decrease in the sum of the longest diameter of target lesions. The DoR was calculated using Kaplan-Meier technique. Per protocol, participants had CT-scans and brain MRI every 6 weeks to measure tumor lesion size. This was continued throughout treatment until PD or commencement of new anti-neoplastic therapy.
Time frame: RECIST assessments performed at Baseline (within 28 days before start of study treatment), every 6 weeks post first dose and treatment pause, 30 days after discontinuation of study treatment, then every month thereafter, approximately maximum of 900 days
Population: Part 2: The ITT population included all randomized participants. Only participants with objective response were analyzed.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Part 1: Irinotecan Liposome Injection 85 mg/m^2 | Part 2: Median Duration of Response (DoR) | 4.14 months |
| Part 1: Irinotecan Liposome Injection 70 mg/m^2 | Part 2: Median Duration of Response (DoR) | 4.17 months |
Secondary
Part 2: Median Time to Objective Response (OR)
Time to OR as per RECIST v1.1 criteria according to BICR was defined as time from the date of randomization to the date of first documented objective tumor response (CR or PR, whichever was first). Per RECIST v1.1, CR is disappearance of all target lesions; PR is \>=30% decrease in the sum of the longest diameter of target lesion. Participants with a new anti-cancer therapy prior to OR were censored at the last tumor assessment prior to new anti-cancer therapy. Per protocol, participants had CT-scans and brain MRI every 6 weeks to measure tumor lesion size. This was continued throughout treatment until PD or commencement of new anti-neoplastic therapy.
Time frame: RECIST assessments performed at Baseline (within 28 days before start of study treatment), every 6 weeks post first dose and treatment pause, 30 days after discontinuation of study treatment, then every month thereafter, approximately maximum of 900 days
Population: Part 2: The ITT population included all randomized participants. Only participants with objective response were analyzed.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Part 1: Irinotecan Liposome Injection 85 mg/m^2 | Part 2: Median Time to Objective Response (OR) | 1.68 months |
| Part 1: Irinotecan Liposome Injection 70 mg/m^2 | Part 2: Median Time to Objective Response (OR) | 12.65 months |
Secondary
Part 2: ORR
The ORR was defined as percentage of participants with a BOR characterized as either a CR or PR, recorded from randomization until documented PD or death relative to the total number of participants. ORR analysis was based on BOR assessed by BICR using RECIST v1.1. Per RECIST v1.1, CR is disappearance of all target lesions; PR is \>=30% decrease in the sum of the longest diameter of target lesions; and overall response = CR + PR. Per protocol, participants had CT-scans and brain MRI every 6 weeks to measure tumor lesion size. This was continued throughout treatment until PD or commencement of new anti-neoplastic therapy.
Time frame: RECIST assessments performed at Baseline (within 28 days before start of study treatment), every 6 weeks post first dose and treatment pause, 30 days after discontinuation of study treatment, then every month thereafter, approximately maximum of 900 days
Population: Part 2: The ITT population included all randomized participants.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Part 1: Irinotecan Liposome Injection 85 mg/m^2 | Part 2: ORR | 44.1 percentage of participants |
| Part 1: Irinotecan Liposome Injection 70 mg/m^2 | Part 2: ORR | 21.6 percentage of participants |
p-value: <0.000195% CI: [13.97, 30.61]Cochran-Mantel-Haenszel
Secondary
Part 2: PFS
The PFS was defined as time from randomization to first documented objective PD using RECIST 1.1 (or response assessment in neuro-oncology brain metastases \[RANO-BM\] criteria for central nervous system \[CNS\] lesions) as assessed by blinded independent central review (BICR) or death due to any cause, whichever occurred first. Per RECIST 1.1, progression is defined as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions. The PFS was calculated using Kaplan-Meier technique. Per protocol, participants had CT-scans and brain MRI every 6 weeks to measure tumor lesion size. This was continued throughout treatment until PD or commencement of new anti-neoplastic therapy.
Time frame: RECIST assessments performed at Baseline (within 28 days before start of study treatment), every 6 weeks post first dose and treatment pause, 30 days after discontinuation of study treatment, then every month thereafter, approximately maximum of 900 days
Population: Part 2: The ITT population included all randomized participants.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Part 1: Irinotecan Liposome Injection 85 mg/m^2 | Part 2: PFS | 4.01 months |
| Part 1: Irinotecan Liposome Injection 70 mg/m^2 | Part 2: PFS | 3.25 months |
p-value: 0.705395% CI: [0.77, 1.2]Stratified log-rank test