Non-Small-Cell Lung Cancer
Conditions
Brief summary
The primary objective is to estimate the time to progressive disease for patients who receive LY573636-sodium (hereafter referred to as LY573636) after two previous treatments for metastatic non-small cell lung cancer. Patients will receive an intravenous infusion of study drug once every 21 days. Computed tomography (CT)-scans will be done before the first dose and then after every other treatment.
Interventions
DRUGLY573636-sodium
A loading dose to target 420 micrograms/milliliter (µg/mL) maximum concentration (Cmax) or 380 µg/mL Cmax followed by a lower chronic dose to maintain Cmax within these target ranges, intravenous, every 21 days until disease progression.
Sponsors
Eli Lilly and Company
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Diagnosis of metastatic non-small-cell lung cancer * At least 18 years of age * Have received 2 previous treatment regimens for metastatic non-small-cell lung cancer
Exclusion criteria
* Serious pre-existing medical conditions * Previous cancer (except skin cancer, excluding melanoma) * Have received 3 or more previous treatment regimens for metastatic non- small-cell lung cancer * Active treatment with Coumadin
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Time to Progression | First dose to measured progressive disease or death from study disease up to 10.35 months | Defined as the time from date of first dose to the first observation of progression of disease (PD) or death from study disease. PD was determined using the Response Evaluation Criteria In Solid Tumors (RECIST) criteria (version 1.0). PD is ≥20% increase in sum of longest diameter of target lesions and/or a new lesion. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Complete Response or Partial Response (Objective Response Rate) | First treatment dose to measured progressive disease or death due to any cause up to 10.35 months | Objective response rate is the percentage of participants with complete response (CR) + partial response (PR), as assessed according to the Response Evaluation Criteria In Solid Tumors (RECIST) guidelines (version 1.0). CR is disappearance of all target and non-target lesions; PR is ≥30% decrease in sum of longest diameter of target lesions. Objective response rate is calculated as a total number of participants with CR or PR divided by the total number of participants treated multiplied by 100. |
| Pharmacokinetics: Maximum Concentration (Cmax) of LY573636 | Predose up to 2 hours postdose in Cycles 1 and 2 (21 days cycle) | — |
| Overall Survival Time | First treatment dose to death due to any cause up to 25.23 months | Defined as the time from date of first dose to the date of death due to any cause. |
| Progression-Free Survival | First treatment dose to measured progressive disease or death from any cause up to 10.35 months | Defined as the time from date of first dose to the first observation of progression of disease (PD) or death due to any cause. PD was determined using the Response Evaluation Criteria In Solid Tumors (RECIST) criteria (version 1.0). PD is ≥20% increase in sum of longest diameter of target lesions and/or a new lesion. |
| Duration of Stable Disease | Time from documented stable disease or better to first date of progressive disease up to 10.35 months | Duration of stable disease (SD) is defined from date of documented SD or better to first date of progression of disease (PD) (assessed every cycle during study therapy, or every 2 months during post-therapy until PD). SD is neither sufficient shrinkage to qualify for partial response (PR) nor sufficient increase to qualify for PD. PR is ≥30% decrease in sum of longest diameter of target lesions. PD is ≥20% increase in sum of longest diameter of target lesions and/or a new lesion. |
| Number of Participants With Adverse Events (Safety) | First treatment dose up to 25.23 months | Data are presented as number of participants who experienced serious adverse events or all other nonserious adverse events during the study. A summary of serious adverse events and other nonserious adverse events is located in the Reported Adverse Event section. |
| Duration of Response | Time of response to progressive disease or death up to 10.35 months | The duration of a complete response (CR) or partial response (PR) was defined as the time from first objective status assessment of CR or PR to the first time of progression of disease or death due to any cause. CR or PR is classified according to the Response Evaluation Criteria In Solid Tumors (RECIST) guidelines (version 1.0). CR is disappearance of all target and non-target lesions; PR is ≥30% decrease in sum of longest diameter of target lesions. |
Countries
Germany, Italy
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| LY573636 Target Cmax 420 µg/mL A loading dose of LY573636 to target 420 micrograms/milliliter (µg/mL) maximum concentration (Cmax) followed by a lower chronic dose to maintain Cmax within this target range, intravenous, every 21 days until disease progression. | 32 |
| LY573636 Target Cmax 380 µg/mL A loading dose of LY573636 to target 380 µg/mL Cmax followed by a lower chronic dose to maintain Cmax within this target range, intravenous, every 21 days until disease progression. | 20 |
| Total | 52 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 10 | 2 |
| Overall Study | Disease Related Death | 1 | 3 |
| Overall Study | Not Disease Related Death | 3 | 4 |
| Overall Study | Physician Decision | 1 | 2 |
| Overall Study | Progressive Disease | 15 | 9 |
| Overall Study | Withdrawal by Subject | 2 | 0 |
Baseline characteristics
| Characteristic | LY573636 Target Cmax 420 µg/mL | LY573636 Target Cmax 380 µg/mL | Total |
|---|---|---|---|
| Age, Continuous | 59.7 years STANDARD_DEVIATION 9.14 | 61.1 years STANDARD_DEVIATION 7.9 | 60.2 years STANDARD_DEVIATION 8.63 |
| Pathological Diagnosis Bronchoalveolar Carcinoma | 1 Participants | 0 Participants | 1 Participants |
| Pathological Diagnosis Lung, Adenocarcinoma | 12 Participants | 12 Participants | 24 Participants |
| Pathological Diagnosis Lung, Large Cell | 2 Participants | 0 Participants | 2 Participants |
| Pathological Diagnosis Lung, Squamous Cell | 11 Participants | 7 Participants | 18 Participants |
| Pathological Diagnosis Poorly Differentiated Non-Small-Cell Lung Cancer | 6 Participants | 1 Participants | 7 Participants |
| Race/Ethnicity, Customized Caucasian | 32 Participants | 20 Participants | 52 Participants |
| Region of Enrollment Germany | 19 Participants | 11 Participants | 30 Participants |
| Region of Enrollment Italy | 13 Participants | 9 Participants | 22 Participants |
| Sex: Female, Male Female | 7 Participants | 6 Participants | 13 Participants |
| Sex: Female, Male Male | 25 Participants | 14 Participants | 39 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 30 / 32 | 17 / 20 |
| serious Total, serious adverse events | 17 / 32 | 9 / 20 |
Outcome results
Primary
Time to Progression
Defined as the time from date of first dose to the first observation of progression of disease (PD) or death from study disease. PD was determined using the Response Evaluation Criteria In Solid Tumors (RECIST) criteria (version 1.0). PD is ≥20% increase in sum of longest diameter of target lesions and/or a new lesion.
Time frame: First dose to measured progressive disease or death from study disease up to 10.35 months
Population: All enrolled participants who received at least 1 dose of study drug.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| LY573636 Target Cmax 420 µg/mL | Time to Progression | 3.12 months |
| LY573636 Target Cmax 380 µg/mL | Time to Progression | 1.64 months |
Secondary
Duration of Response
The duration of a complete response (CR) or partial response (PR) was defined as the time from first objective status assessment of CR or PR to the first time of progression of disease or death due to any cause. CR or PR is classified according to the Response Evaluation Criteria In Solid Tumors (RECIST) guidelines (version 1.0). CR is disappearance of all target and non-target lesions; PR is ≥30% decrease in sum of longest diameter of target lesions.
Time frame: Time of response to progressive disease or death up to 10.35 months
Population: Since there were zero participants with CR or PR, the duration of response could not be analyzed.
Secondary
Duration of Stable Disease
Duration of stable disease (SD) is defined from date of documented SD or better to first date of progression of disease (PD) (assessed every cycle during study therapy, or every 2 months during post-therapy until PD). SD is neither sufficient shrinkage to qualify for partial response (PR) nor sufficient increase to qualify for PD. PR is ≥30% decrease in sum of longest diameter of target lesions. PD is ≥20% increase in sum of longest diameter of target lesions and/or a new lesion.
Time frame: Time from documented stable disease or better to first date of progressive disease up to 10.35 months
Population: All enrolled participants who received at least 1 dose of study drug and had a best overall response of stable disease or better.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| LY573636 Target Cmax 420 µg/mL | Duration of Stable Disease | 4.21 months |
| LY573636 Target Cmax 380 µg/mL | Duration of Stable Disease | 4.93 months |
Secondary
Number of Participants With Adverse Events (Safety)
Data are presented as number of participants who experienced serious adverse events or all other nonserious adverse events during the study. A summary of serious adverse events and other nonserious adverse events is located in the Reported Adverse Event section.
Time frame: First treatment dose up to 25.23 months
Population: All enrolled participants who received at least 1 dose of study drug.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| LY573636 Target Cmax 420 µg/mL | Number of Participants With Adverse Events (Safety) | Serious Adverse Events | 17 Participants |
| LY573636 Target Cmax 420 µg/mL | Number of Participants With Adverse Events (Safety) | Other Nonserious Adverse Events | 30 Participants |
| LY573636 Target Cmax 380 µg/mL | Number of Participants With Adverse Events (Safety) | Serious Adverse Events | 9 Participants |
| LY573636 Target Cmax 380 µg/mL | Number of Participants With Adverse Events (Safety) | Other Nonserious Adverse Events | 17 Participants |
Secondary
Overall Survival Time
Defined as the time from date of first dose to the date of death due to any cause.
Time frame: First treatment dose to death due to any cause up to 25.23 months
Population: All enrolled participants who received at least 1 dose of study drug.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| LY573636 Target Cmax 420 µg/mL | Overall Survival Time | 8.48 months |
| LY573636 Target Cmax 380 µg/mL | Overall Survival Time | 7.97 months |
Secondary
Percentage of Participants With Complete Response or Partial Response (Objective Response Rate)
Objective response rate is the percentage of participants with complete response (CR) + partial response (PR), as assessed according to the Response Evaluation Criteria In Solid Tumors (RECIST) guidelines (version 1.0). CR is disappearance of all target and non-target lesions; PR is ≥30% decrease in sum of longest diameter of target lesions. Objective response rate is calculated as a total number of participants with CR or PR divided by the total number of participants treated multiplied by 100.
Time frame: First treatment dose to measured progressive disease or death due to any cause up to 10.35 months
Population: All enrolled participants who received at least 1 dose of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| LY573636 Target Cmax 420 µg/mL | Percentage of Participants With Complete Response or Partial Response (Objective Response Rate) | 0 percentage of participants |
| LY573636 Target Cmax 380 µg/mL | Percentage of Participants With Complete Response or Partial Response (Objective Response Rate) | 0 percentage of participants |
Secondary
Pharmacokinetics: Maximum Concentration (Cmax) of LY573636
Time frame: Predose up to 2 hours postdose in Cycles 1 and 2 (21 days cycle)
Population: Participants who received study drug and had pharmacokinetic (PK) data at the specified time points.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| LY573636 Target Cmax 420 µg/mL | Pharmacokinetics: Maximum Concentration (Cmax) of LY573636 | Cycle 1 | 379.6 micrograms/milliliter (µg/mL) | Geometric Coefficient of Variation 14.1 |
| LY573636 Target Cmax 420 µg/mL | Pharmacokinetics: Maximum Concentration (Cmax) of LY573636 | Cycle 2 | 293.7 micrograms/milliliter (µg/mL) | Geometric Coefficient of Variation 11 |
| LY573636 Target Cmax 380 µg/mL | Pharmacokinetics: Maximum Concentration (Cmax) of LY573636 | Cycle 1 | 337.6 micrograms/milliliter (µg/mL) | Geometric Coefficient of Variation 15.5 |
| LY573636 Target Cmax 380 µg/mL | Pharmacokinetics: Maximum Concentration (Cmax) of LY573636 | Cycle 2 | 316.1 micrograms/milliliter (µg/mL) | Geometric Coefficient of Variation 14.4 |
Secondary
Progression-Free Survival
Defined as the time from date of first dose to the first observation of progression of disease (PD) or death due to any cause. PD was determined using the Response Evaluation Criteria In Solid Tumors (RECIST) criteria (version 1.0). PD is ≥20% increase in sum of longest diameter of target lesions and/or a new lesion.
Time frame: First treatment dose to measured progressive disease or death from any cause up to 10.35 months
Population: All enrolled participants who received at least 1 dose of study drug.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| LY573636 Target Cmax 420 µg/mL | Progression-Free Survival | 2.69 months |
| LY573636 Target Cmax 380 µg/mL | Progression-Free Survival | 1.43 months |