Trial Outcomes & Findings for A Study of Advanced or Metastatic Non-small Cell Lung Cancer (NCT NCT00988858)
NCT ID: NCT00988858
Last Updated: 2019-09-17
Results Overview
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.
COMPLETED
PHASE2
55 participants
Baseline until Progressive Disease or Study Discontinuation (Up to 23 Months)
2019-09-17
Participant Flow
Participants that had progressive disease were completers.
Participant milestones
| Measure |
LY2603618 and Pemetrexed
LY2603618: 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 or until disease progression
Pemetrexed: 500mg/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
|
|---|---|
|
Overall Study
STARTED
|
55
|
|
Overall Study
COMPLETED
|
45
|
|
Overall Study
NOT COMPLETED
|
10
|
Reasons for withdrawal
| Measure |
LY2603618 and Pemetrexed
LY2603618: 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 or until disease progression
Pemetrexed: 500mg/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
|
|---|---|
|
Overall Study
Adverse Event
|
7
|
|
Overall Study
Death
|
1
|
|
Overall Study
Physician Decision
|
1
|
|
Overall Study
Sponsor Decision
|
1
|
Baseline Characteristics
A Study of Advanced or Metastatic Non-small Cell Lung Cancer
Baseline characteristics by cohort
| Measure |
LY2603618 and Pemetrexed
n=55 Participants
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
|
|---|---|
|
Age, Continuous
|
61.2 years
STANDARD_DEVIATION 8.6 • n=5 Participants
|
|
Sex: Female, Male
Female
|
21 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
34 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
0 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
55 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
21 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Black or African American
|
1 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
33 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
|
Region of Enrollment
United States
|
24 participants
n=5 Participants
|
|
Region of Enrollment
Taiwan
|
5 participants
n=5 Participants
|
|
Region of Enrollment
Korea, Republic of
|
14 participants
n=5 Participants
|
|
Region of Enrollment
Italy
|
12 participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Baseline until Progressive Disease or Study Discontinuation (Up to 23 Months)Population: All randomized participants who received at least 1 dose of drug.
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.
Outcome measures
| Measure |
LY2603618 and Pemetrexed
n=55 Participants
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
|
|---|---|
|
Overall Tumor Response - Percentage of Participants Achieving Complete Response (CR) or Partial Response (PR) [Overall Response Rate (ORR)]
|
9.1 percentage of participants
Interval 3.7 to 18.2
|
SECONDARY outcome
Timeframe: Baseline until Progressive Disease or Study Discontinuation (Up to 23 Months)Population: All randomized participants who received at least 1 dose of drug.
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.
Outcome measures
| Measure |
LY2603618 and Pemetrexed
n=55 Participants
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
|
|---|---|
|
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
Interval 33.9 to 57.4
|
SECONDARY outcome
Timeframe: 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.
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.
Outcome measures
| Measure |
LY2603618 and Pemetrexed
n=55 Participants
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
|
|---|---|
|
Progression-free Survival (PFS)
|
2.3 months
Interval 1.4 to 3.3
|
SECONDARY outcome
Timeframe: 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.
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.
Outcome measures
| Measure |
LY2603618 and Pemetrexed
n=55 Participants
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
|
|---|---|
|
Duration of Response
|
8.7 months
Interval 7.0 to
Upper limit is not estimable based on sample size.
|
SECONDARY outcome
Timeframe: 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.
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.
Outcome measures
| Measure |
LY2603618 and Pemetrexed
n=46 Participants
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
|
|---|---|
|
Change in Symptom Burden Scores of Lung Cancer Symptom Scale (LCSS)
Improved
|
12 participants
|
|
Change in Symptom Burden Scores of Lung Cancer Symptom Scale (LCSS)
Worsened
|
6 participants
|
|
Change in Symptom Burden Scores of Lung Cancer Symptom Scale (LCSS)
Stable
|
18 participants
|
|
Change in Symptom Burden Scores of Lung Cancer Symptom Scale (LCSS)
Unknown
|
10 participants
|
SECONDARY outcome
Timeframe: 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 2Population: All randomized participants who received at least 1 dose of drug and evaluable PK data.
Outcome measures
| Measure |
LY2603618 and Pemetrexed
n=48 Participants
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
|
|---|---|
|
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
|
|
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 outcome
Timeframe: 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 hrPopulation: All randomized participants who received at least 1 dose of drug and evaluable PK data.
Outcome measures
| Measure |
LY2603618 and Pemetrexed
n=43 Participants
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
|
|---|---|
|
PK: Maximum Plasma Concentration (Cmax) of Pemetrexed
Day 1/Cycle 1 (n=40)
|
102 microgram per milliliter (μg/mL)
Geometric Coefficient of Variation 50
|
|
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 outcome
Timeframe: 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 2Population: All randomized participants who received at least 1 dose of drug and had evaluable PK data
Outcome measures
| Measure |
LY2603618 and Pemetrexed
n=48 Participants
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
|
|---|---|
|
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
|
|
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 outcome
Timeframe: 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 hrPopulation: All randomized participants who received at least 1 dose of drug and had evaluable PK data.
Outcome measures
| Measure |
LY2603618 and Pemetrexed
n=43 Participants
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
|
|---|---|
|
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
|
|
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
|
Adverse Events
LY2603618 and Pemetrexed
Serious adverse events
| Measure |
LY2603618 and Pemetrexed
n=55 participants at risk
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
|
|---|---|
|
Blood and lymphatic system disorders
Febrile neutropenia
|
1.8%
1/55 • Number of events 1
|
|
Blood and lymphatic system disorders
Neutropenia
|
1.8%
1/55 • Number of events 1
|
|
Blood and lymphatic system disorders
Thrombocytopenia
|
3.6%
2/55 • Number of events 2
|
|
Gastrointestinal disorders
Diarrhoea
|
1.8%
1/55 • Number of events 1
|
|
Gastrointestinal disorders
Gastritis
|
1.8%
1/55 • Number of events 1
|
|
General disorders
Asthenia
|
1.8%
1/55 • Number of events 1
|
|
Infections and infestations
Pneumonia
|
1.8%
1/55 • Number of events 1
|
|
Infections and infestations
Pseudomembranous colitis
|
1.8%
1/55 • Number of events 1
|
|
Infections and infestations
Sepsis
|
1.8%
1/55 • Number of events 1
|
|
Injury, poisoning and procedural complications
Road traffic accident
|
1.8%
1/55 • Number of events 1
|
|
Injury, poisoning and procedural complications
Spinal compression fracture
|
1.8%
1/55 • Number of events 1
|
|
Injury, poisoning and procedural complications
Tibia fracture
|
1.8%
1/55 • Number of events 1
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Pericardial effusion malignant
|
1.8%
1/55 • Number of events 1
|
|
Nervous system disorders
Convulsion
|
1.8%
1/55 • Number of events 1
|
|
Psychiatric disorders
Confusional state
|
1.8%
1/55 • Number of events 1
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
1.8%
1/55 • Number of events 1
|
|
Respiratory, thoracic and mediastinal disorders
Haemoptysis
|
1.8%
1/55 • Number of events 1
|
|
Respiratory, thoracic and mediastinal disorders
Pleural effusion
|
1.8%
1/55 • Number of events 2
|
|
Respiratory, thoracic and mediastinal disorders
Pneumothorax
|
3.6%
2/55 • Number of events 2
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary embolism
|
1.8%
1/55 • Number of events 1
|
|
Skin and subcutaneous tissue disorders
Dermatitis
|
1.8%
1/55 • Number of events 1
|
Other adverse events
| Measure |
LY2603618 and Pemetrexed
n=55 participants at risk
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
|
|---|---|
|
Blood and lymphatic system disorders
Anaemia
|
18.2%
10/55 • Number of events 12
|
|
Blood and lymphatic system disorders
Leukopenia
|
14.5%
8/55 • Number of events 13
|
|
Blood and lymphatic system disorders
Neutropenia
|
27.3%
15/55 • Number of events 35
|
|
Blood and lymphatic system disorders
Thrombocytopenia
|
7.3%
4/55 • Number of events 6
|
|
Gastrointestinal disorders
Abdominal pain
|
10.9%
6/55 • Number of events 6
|
|
Gastrointestinal disorders
Constipation
|
20.0%
11/55 • Number of events 15
|
|
Gastrointestinal disorders
Diarrhoea
|
12.7%
7/55 • Number of events 7
|
|
Gastrointestinal disorders
Dyspepsia
|
5.5%
3/55 • Number of events 3
|
|
Gastrointestinal disorders
Nausea
|
32.7%
18/55 • Number of events 28
|
|
Gastrointestinal disorders
Stomatitis
|
9.1%
5/55 • Number of events 5
|
|
Gastrointestinal disorders
Vomiting
|
21.8%
12/55 • Number of events 12
|
|
General disorders
Face oedema
|
7.3%
4/55 • Number of events 4
|
|
General disorders
Fatigue
|
36.4%
20/55 • Number of events 27
|
|
General disorders
Pyrexia
|
9.1%
5/55 • Number of events 5
|
|
Infections and infestations
Herpes zoster
|
5.5%
3/55 • Number of events 3
|
|
Investigations
Alanine aminotransferase increased
|
12.7%
7/55 • Number of events 7
|
|
Investigations
Aspartate aminotransferase increased
|
10.9%
6/55 • Number of events 6
|
|
Metabolism and nutrition disorders
Decreased appetite
|
16.4%
9/55 • Number of events 9
|
|
Metabolism and nutrition disorders
Dehydration
|
5.5%
3/55 • Number of events 3
|
|
Metabolism and nutrition disorders
Hypokalaemia
|
7.3%
4/55 • Number of events 4
|
|
Metabolism and nutrition disorders
Hyponatraemia
|
5.5%
3/55 • Number of events 4
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
9.1%
5/55 • Number of events 6
|
|
Musculoskeletal and connective tissue disorders
Myalgia
|
5.5%
3/55 • Number of events 3
|
|
Nervous system disorders
Dizziness
|
9.1%
5/55 • Number of events 5
|
|
Nervous system disorders
Headache
|
7.3%
4/55 • Number of events 5
|
|
Nervous system disorders
Peripheral sensory neuropathy
|
7.3%
4/55 • Number of events 6
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
12.7%
7/55 • Number of events 8
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
12.7%
7/55 • Number of events 7
|
|
Respiratory, thoracic and mediastinal disorders
Haemoptysis
|
5.5%
3/55 • Number of events 3
|
|
Respiratory, thoracic and mediastinal disorders
Nasal congestion
|
5.5%
3/55 • Number of events 3
|
|
Skin and subcutaneous tissue disorders
Rash
|
7.3%
4/55 • Number of events 4
|
|
Vascular disorders
Flushing
|
5.5%
3/55 • Number of events 3
|
Additional Information
Chief Medical Officer
Eli Lilly and Company
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place
Restriction type: GT60