Non Small Cell Lung Cancer
Conditions
Brief summary
The primary purpose of this study is to evaluate the efficacy and safety of LY2603618 in combination with pemetrexed and any side effects that might be associated with it along with determining the effects of LY2603618 in combination with pemetrexed in participants with advanced or metastatic Non-small Cell Lung Cancer (NSCLC).
Interventions
DRUGLY2603618
150 milligram per square meter (mg/m\^2) intravenously on Day 2 of each 21 day cycle repeating every 21 days for a minimum of 2 cycles continuing until disease progression
DRUGPemetrexed
500 mg/m\^2 intravenously on Day 1 of each 21 Day cycle repeating every 21 days for a minimum of 2 cycles or 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
* Must agree to have a tumor biopsy at screening * Must have a diagnosis of advanced or metastatic non-squamous non-small cell lung cancer that has progressed after certain prior treatment * Must be available for the duration of the study and willing to follow the study procedures * If participant is a woman that is capable of having children, must have a negative pregnancy test within 7 days of taking first dose of study drug * Must have discontinued radiation therapy at least 4 weeks before entering this study
Exclusion criteria
* Must not have taken an unapproved drug as treatment for any indication within the last 28 days before starting study treatment. * Must not be pregnant or lactating, are considering becoming pregnant, or are considering fathering a child. Males and females with reproductive potential must agree to use medically approved contraceptive precautions during the trial until the participant's physician considers it safe to become pregnant or father a child. * Must not have known positive test in human immunodeficiency virus (HIV), hepatitis B surface antigen (HBSAg), or hepatitis C antibodies (HCAb). * Must not have previously participated in a study involving LY2603618 * Must not have previously taken pemetrexed for cancer * Must not have a known allergy to LY2603618 or pemetrexed * Must not currently have an infection that may affect participant's ability to tolerate the therapy * Must not have a serious medical condition or disorder that would make it unsafe for you to participate in the study such as uncontrolled diabetes or chest pain due to heart disease * If taking certain medications called non-steroidal anti-inflammatory drugs (NSAIDS), such as ibuprofen, must be able to stop taking these medications according to certain guidelines
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Overall Tumor Response - Percentage of Participants Achieving Complete Response (CR) or Partial Response (PR) [Overall Response Rate (ORR)] | Baseline until Progressive Disease or Study Discontinuation (Up to 23 Months) | Overall response rate is the best response of complete response (CR) or partial response (PR) as classified by the investigators according to the Response Evaluation Criteria In Solid Tumors (RECIST v1.1). CR is a disappearance of all target and non-target lesions and normalization of tumor marker level. PR is an at least 30% decrease in the sum of the diameters of target lesions (taking as reference the baseline sum diameter) without progression of not-target lesions or appearance of new lesions. Overall response rate is calculated as a total number of participants with CR or PR divided by the total number of participants with at least 1 measurable lesion, multiplied by 100. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Progression-free Survival (PFS) | Baseline to Progressive Disease or Death Due to Any Cause (Up to 27.1 Months) | Progression-free survival (PFS) time was defined as the time from the date of randomization to the first date of progressive disease (symptomatic or objective) or death due to any cause, whichever occurred first. For participants who were not known to have died or progressed as of the data-inclusion cutoff date, PFS time was censored at the date of the last objective progression-free disease assessment prior to the date of any subsequent systematic anticancer therapy. PFS was summarized using Kaplan-Meier estimates. |
| Duration of Response | First Observation of CR or PR until Progressive Disease or Death Due to Any Cause (Up to 23 Months) | Duration of Response is defined as the time from the first observation of CR or PR to the first observation of progressive disease (PD) or death from any cause. A response is defined as a confirmed objective status of CR or PR. For participants who are not known to have died as of the data inclusion cut-off date and who do not have PD, the duration will be censored at the date of the last objective progression free disease assessment prior to the date of any subsequent anticancer therapy. |
| Change in Symptom Burden Scores of Lung Cancer Symptom Scale (LCSS) | Baseline until End of Study (Up to 27.1 Months) | The LCSS participants scale 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. Scores range from 0 (for best outcome) to 100 (for worst outcome). The Average Symptom Burden Index (ASBI) was calculated as the mean of 6 symptom-specific questions from the LCSS. |
| Percentage of Participants Who Achieved a Best Response of Complete Response (CR), Partial Response (PR), or Stable Disease (SD) (Clinical Benefit Rate) | Baseline until Progressive Disease or Study Discontinuation (Up to 23 Months) | Clinical benefit rate is the best response CR, PR, or stable disease (SD) as classified by the investigators according to the RECIST v1.1. CR is a disappearance of all target and non-target lesions and normalization of tumor marker level. PR is an at least 30% decrease in the sum of the diameters of target lesions (taking as reference the baseline sum diameter) without progression of not-target lesions or appearance of new lesions. SD is neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease, taking as reference the smallest sum diameter since treatment started. Clinical benefit rate is calculated as a total number of participants with CR, PR, or SD divided by the total number of participants with at least 1 measurable lesion, multiplied by 100. |
| PK: Maximum Plasma Concentration (Cmax) of Pemetrexed | Day 1 and Day 2 of Cycle 1 and Cycle 2: Prior to End of Infusion (EOI); EOI + 1-2 hour (hr); EOI + 4-6- hr; EOI + 20-28 hr | — |
| PK: Area Under the Plasma Concentration vs. Time Curve From Time Zero to Infinity [AUC(0-∞)] of LY2603618 | Day 2 and Day 3 of Cycle 1 and Cycle 2: Prior to End of Infusion (EOI); EOI + 1-2 hr; EOI + 4-6 hr; EOI + 20-28 hr; anytime on Day 8 of Cycle 1 and Cycle 2 | — |
| PK: Area Under the Plasma Concentration vs. Time Curve From Time Zero to Infinity [AUC(0-∞)] of Pemetrexed | Day 1 and Day 2 of Cycle 1 and Cycle 2: Prior to End of Infusion (EOI); EOI + 1-2 hour (hr); EOI + 4-6- hr; EOI + 20-28 hr | — |
| Pharmacokinetics (PK): Maximum Plasma Concentration (Cmax) of LY2603618 | Day 2 and Day 3 of Cycle 1 and Cycle 2: Prior to End of Infusion (EOI); EOI + 1-2 hr; EOI + 4-6 hr; EOI + 20-28 hr; anytime on Day 8 of Cycle 1 and Cycle 2 | — |
Countries
Italy, South Korea, Taiwan, United States
Participant flow
Pre-assignment details
Participants that had progressive disease were completers.
Participants by arm
| Arm | Count |
|---|---|
| LY2603618 and Pemetrexed LY2603618: 150 mg/m2 intravenously on Day 2 of each 21 day cycle repeating every 21 days for a minimum of 2 cycles continuing until disease progression
Pemetrexed: 500mg/m2 intravenously on Day 1 of each 21 Day cycle repeating every 21 days for a minimum of 2 cycles or until disease progression | 55 |
| Total | 55 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 7 |
| Overall Study | Death | 1 |
| Overall Study | Physician Decision | 1 |
| Overall Study | Sponsor Decision | 1 |
Baseline characteristics
| Characteristic | LY2603618 and Pemetrexed |
|---|---|
| Age, Continuous | 61.2 years STANDARD_DEVIATION 8.6 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 55 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 21 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 33 Participants |
| Region of Enrollment Italy | 12 participants |
| Region of Enrollment Korea, Republic of | 14 participants |
| Region of Enrollment Taiwan | 5 participants |
| Region of Enrollment United States | 24 participants |
| Sex: Female, Male Female | 21 Participants |
| Sex: Female, Male Male | 34 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 51 / 55 |
| serious Total, serious adverse events | 16 / 55 |
Outcome results
Primary
Overall Tumor Response - Percentage of Participants Achieving Complete Response (CR) or Partial Response (PR) [Overall Response Rate (ORR)]
Overall response rate is the best response of complete response (CR) or partial response (PR) as classified by the investigators according to the Response Evaluation Criteria In Solid Tumors (RECIST v1.1). CR is a disappearance of all target and non-target lesions and normalization of tumor marker level. PR is an at least 30% decrease in the sum of the diameters of target lesions (taking as reference the baseline sum diameter) without progression of not-target lesions or appearance of new lesions. Overall response rate is calculated as a total number of participants with CR or PR divided by the total number of participants with at least 1 measurable lesion, multiplied by 100.
Time frame: Baseline until Progressive Disease or Study Discontinuation (Up to 23 Months)
Population: All randomized participants who received at least 1 dose of drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| LY2603618 and Pemetrexed | Overall Tumor Response - Percentage of Participants Achieving Complete Response (CR) or Partial Response (PR) [Overall Response Rate (ORR)] | 9.1 percentage of participants |
Secondary
Change in Symptom Burden Scores of Lung Cancer Symptom Scale (LCSS)
The LCSS participants scale 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. Scores range from 0 (for best outcome) to 100 (for worst outcome). The Average Symptom Burden Index (ASBI) was calculated as the mean of 6 symptom-specific questions from the LCSS.
Time frame: Baseline until End of Study (Up to 27.1 Months)
Population: The LCSS evaluable population consisted of all enrolled participants who had a baseline LCSS measurement and at least 1 post-baseline measurement. The population was evaluated for changes in the ASBI (improved, stable, worsened), with improvement/worsening based on trends seen in sets of consecutive ASBI assessments with respect to baseline ASBI.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| LY2603618 and Pemetrexed | Change in Symptom Burden Scores of Lung Cancer Symptom Scale (LCSS) | Improved | 12 participants |
| LY2603618 and Pemetrexed | Change in Symptom Burden Scores of Lung Cancer Symptom Scale (LCSS) | Worsened | 6 participants |
| LY2603618 and Pemetrexed | Change in Symptom Burden Scores of Lung Cancer Symptom Scale (LCSS) | Stable | 18 participants |
| LY2603618 and Pemetrexed | Change in Symptom Burden Scores of Lung Cancer Symptom Scale (LCSS) | Unknown | 10 participants |
Secondary
Duration of Response
Duration of Response is defined as the time from the first observation of CR or PR to the first observation of progressive disease (PD) or death from any cause. A response is defined as a confirmed objective status of CR or PR. For participants who are not known to have died as of the data inclusion cut-off date and who do not have PD, the duration will be censored at the date of the last objective progression free disease assessment prior to the date of any subsequent anticancer therapy.
Time frame: First Observation of CR or PR until Progressive Disease or Death Due to Any Cause (Up to 23 Months)
Population: All randomized participants who received at least 1 dose of drug with Best Overall Response of Complete Response or Partial Response.5 participants were censored.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| LY2603618 and Pemetrexed | Duration of Response | 8.7 months |
Secondary
Percentage of Participants Who Achieved a Best Response of Complete Response (CR), Partial Response (PR), or Stable Disease (SD) (Clinical Benefit Rate)
Clinical benefit rate is the best response CR, PR, or stable disease (SD) as classified by the investigators according to the RECIST v1.1. CR is a disappearance of all target and non-target lesions and normalization of tumor marker level. PR is an at least 30% decrease in the sum of the diameters of target lesions (taking as reference the baseline sum diameter) without progression of not-target lesions or appearance of new lesions. SD is neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease, taking as reference the smallest sum diameter since treatment started. Clinical benefit rate is calculated as a total number of participants with CR, PR, or SD divided by the total number of participants with at least 1 measurable lesion, multiplied by 100.
Time frame: Baseline until Progressive Disease or Study Discontinuation (Up to 23 Months)
Population: All randomized participants who received at least 1 dose of drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| LY2603618 and Pemetrexed | Percentage of Participants Who Achieved a Best Response of Complete Response (CR), Partial Response (PR), or Stable Disease (SD) (Clinical Benefit Rate) | 45.5 percentage of participants |
Secondary
Pharmacokinetics (PK): Maximum Plasma Concentration (Cmax) of LY2603618
Time frame: Day 2 and Day 3 of Cycle 1 and Cycle 2: Prior to End of Infusion (EOI); EOI + 1-2 hr; EOI + 4-6 hr; EOI + 20-28 hr; anytime on Day 8 of Cycle 1 and Cycle 2
Population: All randomized participants who received at least 1 dose of drug and evaluable PK data.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| LY2603618 and Pemetrexed | Pharmacokinetics (PK): Maximum Plasma Concentration (Cmax) of LY2603618 | Day 2/Cycle 1 (n=41) | 3430 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 50 |
| LY2603618 and Pemetrexed | Pharmacokinetics (PK): Maximum Plasma Concentration (Cmax) of LY2603618 | Day 2/Cycle 2 (n=48) | 3560 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 40 |
Secondary
PK: Area Under the Plasma Concentration vs. Time Curve From Time Zero to Infinity [AUC(0-∞)] of LY2603618
Time frame: Day 2 and Day 3 of Cycle 1 and Cycle 2: Prior to End of Infusion (EOI); EOI + 1-2 hr; EOI + 4-6 hr; EOI + 20-28 hr; anytime on Day 8 of Cycle 1 and Cycle 2
Population: All randomized participants who received at least 1 dose of drug and had evaluable PK data
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| LY2603618 and Pemetrexed | PK: Area Under the Plasma Concentration vs. Time Curve From Time Zero to Infinity [AUC(0-∞)] of LY2603618 | Day 2/Cycle 1 (n=41) | 38000 nanograms*hour per milliliter (ng*h/mL) | Geometric Coefficient of Variation 85 |
| LY2603618 and Pemetrexed | PK: Area Under the Plasma Concentration vs. Time Curve From Time Zero to Infinity [AUC(0-∞)] of LY2603618 | Day 2/Cycle 2 (n=48) | 41500 nanograms*hour per milliliter (ng*h/mL) | Geometric Coefficient of Variation 88 |
Secondary
PK: Area Under the Plasma Concentration vs. Time Curve From Time Zero to Infinity [AUC(0-∞)] of Pemetrexed
Time frame: Day 1 and Day 2 of Cycle 1 and Cycle 2: Prior to End of Infusion (EOI); EOI + 1-2 hour (hr); EOI + 4-6- hr; EOI + 20-28 hr
Population: All randomized participants who received at least 1 dose of drug and had evaluable PK data.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| LY2603618 and Pemetrexed | PK: Area Under the Plasma Concentration vs. Time Curve From Time Zero to Infinity [AUC(0-∞)] of Pemetrexed | Day 1/Cycle 1(n=40) | 193 microgram*hour per milliliter (µg*hr/mL) | Geometric Coefficient of Variation 31 |
| LY2603618 and Pemetrexed | PK: Area Under the Plasma Concentration vs. Time Curve From Time Zero to Infinity [AUC(0-∞)] of Pemetrexed | Day 1/Cycle 2(n=43) | 202 microgram*hour per milliliter (µg*hr/mL) | Geometric Coefficient of Variation 33 |
Secondary
PK: Maximum Plasma Concentration (Cmax) of Pemetrexed
Time frame: Day 1 and Day 2 of Cycle 1 and Cycle 2: Prior to End of Infusion (EOI); EOI + 1-2 hour (hr); EOI + 4-6- hr; EOI + 20-28 hr
Population: All randomized participants who received at least 1 dose of drug and evaluable PK data.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| LY2603618 and Pemetrexed | PK: Maximum Plasma Concentration (Cmax) of Pemetrexed | Day 1/Cycle 1 (n=40) | 102 microgram per milliliter (μg/mL) | Geometric Coefficient of Variation 50 |
| LY2603618 and Pemetrexed | PK: Maximum Plasma Concentration (Cmax) of Pemetrexed | Day 1/Cycle 2 (n=43) | 96.8 microgram per milliliter (μg/mL) | Geometric Coefficient of Variation 42 |
Secondary
Progression-free Survival (PFS)
Progression-free survival (PFS) time was defined as the time from the date of randomization to the first date of progressive disease (symptomatic or objective) or death due to any cause, whichever occurred first. For participants who were not known to have died or progressed as of the data-inclusion cutoff date, PFS time was censored at the date of the last objective progression-free disease assessment prior to the date of any subsequent systematic anticancer therapy. PFS was summarized using Kaplan-Meier estimates.
Time frame: Baseline to Progressive Disease or Death Due to Any Cause (Up to 27.1 Months)
Population: All randomized participants who received at least 1 dose of drug. 9 participants were censored.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| LY2603618 and Pemetrexed | Progression-free Survival (PFS) | 2.3 months |