Small Cell Lung Cancer
Conditions
Brief summary
Part A: This study evaluates an experimental treatment in participants with extensive-disease in small-cell lung cancer. Part B: This study evaluates an experimental treatment in participants with extensive-disease in small-cell lung cancer.
Interventions
DRUGLY2523355
Administered intravenously as a 1-hour infusion
Administered subcutaneously
Sponsors
Eli Lilly and Company
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Have histological or cytological evidence of extensive-disease small-cell lung cancer * Have the presence of measurable disease as defined by the Response Evaluation Criteria in Solid Tumors (RECIST 1.1) * Have received at least 1 prior chemotherapy regimen with agents known to provide clinical benefit for small-cell lung cancer and be, in the opinion of the investigator, an appropriate candidate for experimental therapy * Have discontinued all previous therapies for cancer, including chemotherapy, biologic therapy, hormone therapy, or radiotherapy. Participants must have recovered from the acute effects of therapy (except alopecia and fatigue) before study enrollment * Part A: Have a performance status of 0 to 2 on the Eastern Cooperative Oncology Group scale * Part B: Have a performance status of 0 to 1 on the Eastern Cooperative Oncology Group scale
Exclusion criteria
* Have received treatment within 28 days of the first dose of LY2523355 with a drug that has not received regulatory approval for any indication * Have a mixed histological diagnosis of small-cell lung cancer and non-small-cell lung cancer * Have serious preexisting medical conditions that, in the opinion of the investigator, would preclude participation in this study * Part A: Have symptomatic, untreated, or uncontrolled central nervous system (CNS) metastases. Participants with treated CNS metastases are eligible provided their disease is radiographically stable, asymptomatic, and corticosteroid use has been discontinued for at least 2 weeks prior to the first dose of study drug. Screening of asymptomatic participants without history of CNS metastases is not required * Part B: Have symptomatic, untreated, or uncontrolled CNS metastases or a history of CNS metastases. Participants who have received prophylactic radiation are not excluded. Screening of asymptomatic participants without history of CNS metastases is not required
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Part A: Percentage of Participants Achieving an Overall Response (Overall Response Rate) | Date of enrollment to date of measured progressive disease up to 99.6 weeks | The overall response is complete response (CR) + partial response (PR) as classified by the investigators according to the Response Evaluation Criteria In Solid Tumors (RECIST) guidelines. CR is the disappearance of all target and non-target lesions; PR is a ≥30% decrease in sum of longest diameter of target lesions. The overall response rate is calculated as a total number of participants with CR or PR, then divided by the total number of participants treated, then multiplied by 100. |
| Part B: Percentage of Participants Achieving a Best Response (Clinical Benefit Rate) | Date of enrollment to date of measured progressive disease up to 18.1 weeks | Clinical benefit rate is complete response (CR) + partial response (PR) + stable disease (SD) as classified by the investigator according to the Response Evaluation Criteria In Solid Tumors (RECIST) guidelines. CR is the disappearance of all target and non-target lesions; PR is a ≥30% decrease in sum of longest diameter of target lesions. SD is neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease. Clinical benefit rate is calculated as a total number of participants with CR or PR or SD divided by the total number of participants treated, then multiplied by 100. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Part A: Progression-Free Survival | Date of enrollment to date of measured progressive disease or date of death from any cause up to 99.6 weeks | Progression-free survival (PFS) is defined as the time from the date of enrollment (first treatment dose) to the first observation of progression of disease (PD) or death due to any cause. PD was determined using Response Evaluation Criteria In Solid Tumors (RECIST) criteria. PD is a ≥20% increase in sum of longest diameter of target lesions and/or a new lesion. For participants who had no PD or death or starting new anti-cancer therapy, PFS was censored at their last radiological tumor assessment. |
| Part B: Progression-Free Survival | Date of enrollment to date of measured progressive disease or date of death from any cause up to 18.1 weeks | Progression-free survival (PFS) is defined as the time from the date of enrollment (first treatment dose) to the first observation of progression of disease (PD) or death due to any cause. PD was determined using Response Evaluation Criteria In Solid Tumors (RECIST) criteria. PD is a ≥20% increase in sum of longest diameter of target lesions and/or a new lesion. For participants who had no PD or death or starting new anti-cancer therapy, PFS was censored at their last radiological tumor assessment. |
| Part A: Percentage of Participants Achieving a Best Response (Clinical Benefit Rate) | Date of enrollment to date of measured progressive disease 99.6 weeks | Clinical benefit rate is complete response (CR) + partial response (PR) + stable disease (SD) as classified by the investigator according to the Response Evaluation Criteria In Solid Tumors (RECIST) guidelines. CR is the disappearance of all target and non-target lesions; PR is a ≥30% decrease in sum of longest diameter of target lesions. SD is neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease. Clinical benefit rate is calculated as a total number of participants with CR or PR or SD divided by the total number of participants treated, then multiplied by 100. |
| Part B: Percentage of Participants Achieving an Overall Response (Overall Response Rate) | Date of enrollment to date of measured progressive disease up to 18.1 weeks | The overall response is complete response (CR) + partial response (PR) as classified by the investigators according to the Response Evaluation Criteria In Solid Tumors (RECIST) guidelines. CR is the disappearance of all target and non-target lesions; PR is a ≥30% decrease in sum of longest diameter of target lesions. The overall response rate is calculated as a total number of participants with CR or PR divided by the total number of participants treated, then multiplied by 100. |
| Part A: Pharmacokinetics - Maximum Observed Plasma Concentration (Cmax) of LY2523355 and Its Metabolite (LSN2546307) | Days 1,5 and 9 of Cycle 1 (21-day cycle) | — |
| Part B: Pharmacokinetics - Maximum Observed Plasma Concentration (Cmax) of LY2523355 | Day 3 of Cycle 1 (21-day cycle) | — |
| Part A: Pharmacokinetics - Area Under the Plasma Concentration Versus Time Curve of LY2523355 From Time Zero to Infinity [AUC(0-∞)] | Days 1,5 and 9 of Cycle 1 (21-day cycle) | Due to the very limited pharmacokinetic sampling employed in Part A of the study, the AUC(0-∞) of LY2523355 could not be accurately calculated. |
| Part B: Pharmacokinetics - Area Under the Plasma Concentration Versus Time Curve of LY2523355 From Time Zero to Infinity [AUC(0-∞)] | Day 3 of Cycle 1 (21-day cycle) | — |
| Total Lung Cancer Symptom Scale (LCSS) and Average Symptom Burden Index (ASBI) | Baseline and follow-up up to 104 weeks after the first dose of study drug | LCSS is a 9-item questionnaire. Six questions are symptom-specific measures for lung cancer (appetite, fatigue, cough, dyspnea, hemoptysis and pain), and 3 summation items describe total symptomatic distress, activity status, and overall quality of life. Participant responses were measured using visual analogue scales (VAS) with 100-milliliter (mm) lines. The LCSS total score was defined as the mean of the 9 items of the scale, with scores range from 0 (for best outcome) to 100 (for worst outcome). ASBI was calculated as the mean of six symptom-specific questions from the LCSS, with scores range from 0 (for best outcome) to 100 (for worst outcome). |
Countries
Romania, South Korea, United States
Participant flow
Pre-assignment details
This is a nonrandomized, open-label, 2-part study.
Participants by arm
| Arm | Count |
|---|---|
| Part A - 8 mg/m²/Day 8 milligrams per square meter (mg/m²) of LY2523355 per day based on participant's body surface area, administered intravenously as a 1-hour infusion on Days 1, 5, and 9 of each 21-day cycle. | 38 |
| Part B - 5 mg/m²/Day 5 mg/m² of LY2523355 per day based on participant's body surface area, administered intravenously as a 1-hour infusion on Days 1, 2, and 3 plus granulocyte colony-stimulating factor (G-CSF) support given per local package insert beginning on Day 4 of each 21-day cycle. | 18 |
| Part B - 6 mg/m²/Day 6 mg/m² of LY2523355 per day based on participant's body surface area, administered intravenously as a 1-hour infusion on Days 1, 2, and 3 plus G-CSF support given per local package insert beginning on Day 4 of each 21-day cycle. | 8 |
| Total | 64 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Investigator Decision | 0 | 1 | 0 |
| Overall Study | Withdrawal by Subject | 0 | 1 | 0 |
Baseline characteristics
| Characteristic | Part A - 8 mg/m²/Day | Part B - 5 mg/m²/Day | Part B - 6 mg/m²/Day | Total |
|---|---|---|---|---|
| Age, Continuous | 64.88 years STANDARD_DEVIATION 6.3 | 63.33 years STANDARD_DEVIATION 8.4 | 63.40 years STANDARD_DEVIATION 9.1 | 64.26 years STANDARD_DEVIATION 7.2 |
| Race/Ethnicity, Customized Asian | 12 participants | 5 participants | 4 participants | 21 participants |
| Race/Ethnicity, Customized Black or African American | 1 participants | 0 participants | 1 participants | 2 participants |
| Race/Ethnicity, Customized White | 25 participants | 13 participants | 3 participants | 41 participants |
| Region of Enrollment Romania | 9 Participants | 3 Participants | 0 Participants | 12 Participants |
| Region of Enrollment South Korea | 12 Participants | 5 Participants | 4 Participants | 21 Participants |
| Region of Enrollment United States | 17 Participants | 10 Participants | 4 Participants | 31 Participants |
| Sex: Female, Male Female | 11 Participants | 3 Participants | 2 Participants | 16 Participants |
| Sex: Female, Male Male | 27 Participants | 15 Participants | 6 Participants | 48 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 35 / 38 | 18 / 18 | 7 / 8 |
| serious Total, serious adverse events | 8 / 38 | 8 / 18 | 8 / 8 |
Outcome results
Primary
Part A: Percentage of Participants Achieving an Overall Response (Overall Response Rate)
The overall response is complete response (CR) + partial response (PR) as classified by the investigators according to the Response Evaluation Criteria In Solid Tumors (RECIST) guidelines. CR is the disappearance of all target and non-target lesions; PR is a ≥30% decrease in sum of longest diameter of target lesions. The overall response rate is calculated as a total number of participants with CR or PR, then divided by the total number of participants treated, then multiplied by 100.
Time frame: Date of enrollment to date of measured progressive disease up to 99.6 weeks
Population: All participants who received at least 1 dose of study drug in Part A.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Part A | Part A: Percentage of Participants Achieving an Overall Response (Overall Response Rate) | 2.6 percentage of participants |
Primary
Part B: Percentage of Participants Achieving a Best Response (Clinical Benefit Rate)
Clinical benefit rate is complete response (CR) + partial response (PR) + stable disease (SD) as classified by the investigator according to the Response Evaluation Criteria In Solid Tumors (RECIST) guidelines. CR is the disappearance of all target and non-target lesions; PR is a ≥30% decrease in sum of longest diameter of target lesions. SD is neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease. Clinical benefit rate is calculated as a total number of participants with CR or PR or SD divided by the total number of participants treated, then multiplied by 100.
Time frame: Date of enrollment to date of measured progressive disease up to 18.1 weeks
Population: All participants who received at least 1 dose of study drug in Part B.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Part A | Part B: Percentage of Participants Achieving a Best Response (Clinical Benefit Rate) | 26.9 percentage of participants |
Secondary
Part A: Percentage of Participants Achieving a Best Response (Clinical Benefit Rate)
Clinical benefit rate is complete response (CR) + partial response (PR) + stable disease (SD) as classified by the investigator according to the Response Evaluation Criteria In Solid Tumors (RECIST) guidelines. CR is the disappearance of all target and non-target lesions; PR is a ≥30% decrease in sum of longest diameter of target lesions. SD is neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease. Clinical benefit rate is calculated as a total number of participants with CR or PR or SD divided by the total number of participants treated, then multiplied by 100.
Time frame: Date of enrollment to date of measured progressive disease 99.6 weeks
Population: All participants who received at least 1 dose of study drug in Part A.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Part A | Part A: Percentage of Participants Achieving a Best Response (Clinical Benefit Rate) | 23.7 percentage of participants |
Secondary
Part A: Pharmacokinetics - Area Under the Plasma Concentration Versus Time Curve of LY2523355 From Time Zero to Infinity [AUC(0-∞)]
Due to the very limited pharmacokinetic sampling employed in Part A of the study, the AUC(0-∞) of LY2523355 could not be accurately calculated.
Time frame: Days 1,5 and 9 of Cycle 1 (21-day cycle)
Population: No participants were analyzed due to the very limited pharmacokinetic sampling employed in Part A that did not allow accurate calculation of the AUC(0-∞) on Days 1, 5, and 9 of Cycle 1.
Secondary
Part A: Pharmacokinetics - Maximum Observed Plasma Concentration (Cmax) of LY2523355 and Its Metabolite (LSN2546307)
Time frame: Days 1,5 and 9 of Cycle 1 (21-day cycle)
Population: All participants who received 1 dose of study drug on Days 1, 5, and 9 of Cycle 1 and had Cmax samples collected on Days 1, 5, and 9 of Cycle 1 in Part A.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Part A | Part A: Pharmacokinetics - Maximum Observed Plasma Concentration (Cmax) of LY2523355 and Its Metabolite (LSN2546307) | LY2523355 Day 1 | 146 nanograms/milliliter (ng/mL) | Geometric Coefficient of Variation 69.5 |
| Part A | Part A: Pharmacokinetics - Maximum Observed Plasma Concentration (Cmax) of LY2523355 and Its Metabolite (LSN2546307) | LY2523355 Day 5 | 157 nanograms/milliliter (ng/mL) | Geometric Coefficient of Variation 91.4 |
| Part A | Part A: Pharmacokinetics - Maximum Observed Plasma Concentration (Cmax) of LY2523355 and Its Metabolite (LSN2546307) | LY2523355 Day 9 | 100 nanograms/milliliter (ng/mL) | Geometric Coefficient of Variation 420 |
| Part A | Part A: Pharmacokinetics - Maximum Observed Plasma Concentration (Cmax) of LY2523355 and Its Metabolite (LSN2546307) | Metabolite Day 1 | 7.17 nanograms/milliliter (ng/mL) | Geometric Coefficient of Variation 55.4 |
| Part A | Part A: Pharmacokinetics - Maximum Observed Plasma Concentration (Cmax) of LY2523355 and Its Metabolite (LSN2546307) | Metabolite Day 5 | 6.29 nanograms/milliliter (ng/mL) | Geometric Coefficient of Variation 50.8 |
| Part A | Part A: Pharmacokinetics - Maximum Observed Plasma Concentration (Cmax) of LY2523355 and Its Metabolite (LSN2546307) | Metabolite Day 9 | 6.11 nanograms/milliliter (ng/mL) | Geometric Coefficient of Variation 129 |
Secondary
Part A: Progression-Free Survival
Progression-free survival (PFS) is defined as the time from the date of enrollment (first treatment dose) to the first observation of progression of disease (PD) or death due to any cause. PD was determined using Response Evaluation Criteria In Solid Tumors (RECIST) criteria. PD is a ≥20% increase in sum of longest diameter of target lesions and/or a new lesion. For participants who had no PD or death or starting new anti-cancer therapy, PFS was censored at their last radiological tumor assessment.
Time frame: Date of enrollment to date of measured progressive disease or date of death from any cause up to 99.6 weeks
Population: All participants who received at least 1 dose of study drug in Part A. The numbers of participants censored are 4.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Part A | Part A: Progression-Free Survival | 5.3 weeks |
Secondary
Part B: Percentage of Participants Achieving an Overall Response (Overall Response Rate)
The overall response is complete response (CR) + partial response (PR) as classified by the investigators according to the Response Evaluation Criteria In Solid Tumors (RECIST) guidelines. CR is the disappearance of all target and non-target lesions; PR is a ≥30% decrease in sum of longest diameter of target lesions. The overall response rate is calculated as a total number of participants with CR or PR divided by the total number of participants treated, then multiplied by 100.
Time frame: Date of enrollment to date of measured progressive disease up to 18.1 weeks
Population: All participants who received at least 1 dose of study drug in Part B.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Part A | Part B: Percentage of Participants Achieving an Overall Response (Overall Response Rate) | 0 percentage of participants |
Secondary
Part B: Pharmacokinetics - Area Under the Plasma Concentration Versus Time Curve of LY2523355 From Time Zero to Infinity [AUC(0-∞)]
Time frame: Day 3 of Cycle 1 (21-day cycle)
Population: All participants who received 1 dose of study drug on Days 1, 2, and 3 of Cycle 1 and had pharmacokinetic samples collected on Day 3 of Cycle 1 in Part B that enabled calculation of the AUC(0-∞).
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part A | Part B: Pharmacokinetics - Area Under the Plasma Concentration Versus Time Curve of LY2523355 From Time Zero to Infinity [AUC(0-∞)] | 639 nanograms*hour/milliliter (ng*h/mL) | Geometric Coefficient of Variation 41 |
| Part B - 6 mg/m²/Day | Part B: Pharmacokinetics - Area Under the Plasma Concentration Versus Time Curve of LY2523355 From Time Zero to Infinity [AUC(0-∞)] | 1220 nanograms*hour/milliliter (ng*h/mL) | Geometric Coefficient of Variation 38 |
Secondary
Part B: Pharmacokinetics - Maximum Observed Plasma Concentration (Cmax) of LY2523355
Time frame: Day 3 of Cycle 1 (21-day cycle)
Population: All participants who received 1 dose of study drug on Days 1, 2, and 3 of Cycle 1 and had Cmax samples collected on Day 3 of Cycle 1 in Part B.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part A | Part B: Pharmacokinetics - Maximum Observed Plasma Concentration (Cmax) of LY2523355 | 128 nanograms/milliliter (ng/mL) | Geometric Coefficient of Variation 82 |
| Part B - 6 mg/m²/Day | Part B: Pharmacokinetics - Maximum Observed Plasma Concentration (Cmax) of LY2523355 | 258 nanograms/milliliter (ng/mL) | Geometric Coefficient of Variation 32 |
Secondary
Part B: Progression-Free Survival
Progression-free survival (PFS) is defined as the time from the date of enrollment (first treatment dose) to the first observation of progression of disease (PD) or death due to any cause. PD was determined using Response Evaluation Criteria In Solid Tumors (RECIST) criteria. PD is a ≥20% increase in sum of longest diameter of target lesions and/or a new lesion. For participants who had no PD or death or starting new anti-cancer therapy, PFS was censored at their last radiological tumor assessment.
Time frame: Date of enrollment to date of measured progressive disease or date of death from any cause up to 18.1 weeks
Population: All participants who received at least 1 dose of study drug in Part B. The numbers of participants censored are 4.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Part A | Part B: Progression-Free Survival | 6.1 weeks |
Secondary
Total Lung Cancer Symptom Scale (LCSS) and Average Symptom Burden Index (ASBI)
LCSS is a 9-item questionnaire. Six questions are symptom-specific measures for lung cancer (appetite, fatigue, cough, dyspnea, hemoptysis and pain), and 3 summation items describe total symptomatic distress, activity status, and overall quality of life. Participant responses were measured using visual analogue scales (VAS) with 100-milliliter (mm) lines. The LCSS total score was defined as the mean of the 9 items of the scale, with scores range from 0 (for best outcome) to 100 (for worst outcome). ASBI was calculated as the mean of six symptom-specific questions from the LCSS, with scores range from 0 (for best outcome) to 100 (for worst outcome).
Time frame: Baseline and follow-up up to 104 weeks after the first dose of study drug
Population: All participants who received at least 1 dose of study drug and had total LCSS and ASBI scores at baseline and follow-up in Part B.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part A | Total Lung Cancer Symptom Scale (LCSS) and Average Symptom Burden Index (ASBI) | Total LCSS at Baseline | 28.24 units on a scale | Standard Deviation 15.2 |
| Part A | Total Lung Cancer Symptom Scale (LCSS) and Average Symptom Burden Index (ASBI) | Total LCSS at Follow-up | 42.61 units on a scale | Standard Deviation 14.5 |
| Part A | Total Lung Cancer Symptom Scale (LCSS) and Average Symptom Burden Index (ASBI) | ASBI at Baseline | 26.76 units on a scale | Standard Deviation 14.1 |
| Part A | Total Lung Cancer Symptom Scale (LCSS) and Average Symptom Burden Index (ASBI) | ASBI at Follow-up | 36.41 units on a scale | Standard Deviation 11.1 |