Trial Outcomes & Findings for A Study in Non Small Cell Lung Cancer (NCT NCT01139775)
NCT ID: NCT01139775
Last Updated: 2018-05-18
Results Overview
Progression-free survival (PFS) time is defined as the time from the date of randomization to the first date of documented objective progressive disease (PD) or death from any cause. For participants who were not known to have had objective PD as of the data inclusion cut-off date for a particular analysis, PFS was censored at the date of the last objective progression-free disease assessments. For participants who took any subsequent systemic anticancer therapy prior to progression, PFS was censored at the date of the last objective progression-free disease assessment prior to the start date of any subsequent systemic anticancer therapy. PFS time was summarized using Kaplan-Meier estimates.
Recruitment status
COMPLETED
Study phase
PHASE1/PHASE2
Target enrollment
76 participants
Primary outcome timeframe
Randomization up to first date of PD or death from any cause (up to 6 months after the last participant entered treatment)
Results posted on
2018-05-18
Participant Flow
Participant milestones
| Measure |
Phase 1: Pemetrexed + Cisplatin + LY2603618
Cycles 1-2 (21-day cycle):
Day 1: pemetrexed 500 milligrams per square meter (mg/m\^2) + cisplatin 75 mg/m\^2
Day 2: LY2603618 130 to 275 milligrams (mg)
After 2 cycles, participants may have continued on study drug until disease progression, unacceptable toxicity, or other withdrawal criterion was met.
Pemetrexed, cisplatin, and LY2603618 were administered intravenously (IV) over 10 minutes, 1 hour, and 1 hour, respectively.
|
Phase 2: Pemetrexed + Cisplatin + LY2603618
Cycles 1-4 (21-day cycle):
Before 25 Oct 2012:
Day 1: pemetrexed 500 mg/m\^2 + cisplatin 75 mg/m\^2
Day 2: LY2603618 dose determined from phase 1 (275 mg)
After 25 Oct 2012:
Day 1: pemetrexed 500 mg/m\^2 + cisplatin 75 mg/m\^2
After 4 cycles, participants may have continued on maintenance therapy until disease progression, unacceptable toxicity, or other withdrawal criterion was met.
Maintenance therapy (every 21 days):
Before 25 Oct 2012:
Day 1: pemetrexed 500 mg/m\^2
Day 2: LY2603618 dose determined from phase 1 (275 mg)
After 25 Oct 2012:
Day 1: pemetrexed 500 mg/m\^2
If, as of 25 Oct 2012, the participant was in maintenance therapy and randomized to the experimental arm, the participant was eligible to continue with pemetrexed/LY2603618 therapy if the investigator deemed it was in the participant's best interest and the participant consented.
Pemetrexed, cisplatin, and LY2603618 were administered IV over 10 minutes, 1 hour, and 1 hour, respectively.
|
Phase 2: Pemetrexed + Cisplatin
Cycles 1-4 (21-day cycle):
Day 1: pemetrexed 500 mg/m\^2 + cisplatin 75 mg/m\^2
After 4 cycles, participants may have continued on maintenance therapy until disease progression, unacceptable toxicity, or other withdrawal criterion was met.
Maintenance therapy (every 21 days):
Day 1: pemetrexed 500 mg/m\^2
Pemetrexed was administered IV over 10 minutes and cisplatin was administered IV over 1 hour.
|
|---|---|---|---|
|
Overall Study
STARTED
|
14
|
39
|
23
|
|
Overall Study
Received at Least 1 Dose of Study Drug
|
14
|
39
|
22
|
|
Overall Study
COMPLETED
|
13
|
26
|
17
|
|
Overall Study
NOT COMPLETED
|
1
|
13
|
6
|
Reasons for withdrawal
| Measure |
Phase 1: Pemetrexed + Cisplatin + LY2603618
Cycles 1-2 (21-day cycle):
Day 1: pemetrexed 500 milligrams per square meter (mg/m\^2) + cisplatin 75 mg/m\^2
Day 2: LY2603618 130 to 275 milligrams (mg)
After 2 cycles, participants may have continued on study drug until disease progression, unacceptable toxicity, or other withdrawal criterion was met.
Pemetrexed, cisplatin, and LY2603618 were administered intravenously (IV) over 10 minutes, 1 hour, and 1 hour, respectively.
|
Phase 2: Pemetrexed + Cisplatin + LY2603618
Cycles 1-4 (21-day cycle):
Before 25 Oct 2012:
Day 1: pemetrexed 500 mg/m\^2 + cisplatin 75 mg/m\^2
Day 2: LY2603618 dose determined from phase 1 (275 mg)
After 25 Oct 2012:
Day 1: pemetrexed 500 mg/m\^2 + cisplatin 75 mg/m\^2
After 4 cycles, participants may have continued on maintenance therapy until disease progression, unacceptable toxicity, or other withdrawal criterion was met.
Maintenance therapy (every 21 days):
Before 25 Oct 2012:
Day 1: pemetrexed 500 mg/m\^2
Day 2: LY2603618 dose determined from phase 1 (275 mg)
After 25 Oct 2012:
Day 1: pemetrexed 500 mg/m\^2
If, as of 25 Oct 2012, the participant was in maintenance therapy and randomized to the experimental arm, the participant was eligible to continue with pemetrexed/LY2603618 therapy if the investigator deemed it was in the participant's best interest and the participant consented.
Pemetrexed, cisplatin, and LY2603618 were administered IV over 10 minutes, 1 hour, and 1 hour, respectively.
|
Phase 2: Pemetrexed + Cisplatin
Cycles 1-4 (21-day cycle):
Day 1: pemetrexed 500 mg/m\^2 + cisplatin 75 mg/m\^2
After 4 cycles, participants may have continued on maintenance therapy until disease progression, unacceptable toxicity, or other withdrawal criterion was met.
Maintenance therapy (every 21 days):
Day 1: pemetrexed 500 mg/m\^2
Pemetrexed was administered IV over 10 minutes and cisplatin was administered IV over 1 hour.
|
|---|---|---|---|
|
Overall Study
Adverse Event
|
0
|
6
|
2
|
|
Overall Study
Protocol Violation
|
0
|
5
|
0
|
|
Overall Study
Withdrawal by Subject
|
1
|
0
|
2
|
|
Overall Study
Physician Decision
|
0
|
2
|
2
|
Baseline Characteristics
A Study in Non Small Cell Lung Cancer
Baseline characteristics by cohort
| Measure |
Phase 1: Pemetrexed + Cisplatin + LY2603618
n=14 Participants
Cycles 1-2 (21-day cycle):
Day 1: pemetrexed 500 mg/m\^2 + cisplatin 75 mg/m\^2
Day 2: LY2603618 130 to 275 mg
After 2 cycles, participants may have continued on study drug until disease progression, unacceptable toxicity, or other withdrawal criterion was met.
Pemetrexed, cisplatin, and LY2603618 were administered IV over 10 minutes, 1 hour, and 1 hour, respectively.
|
Phase 2: Pemetrexed + Cisplatin + LY2603618
n=39 Participants
Cycles 1-4 (21-day cycle):
Before 25 Oct 2012:
Day 1: pemetrexed 500 mg/m\^2 + cisplatin 75 mg/m\^2
Day 2: LY2603618 dose determined from phase 1 (275 mg)
After 25 Oct 2012:
Day 1: pemetrexed 500 mg/m\^2 + cisplatin 75 mg/m\^2
After 4 cycles, participants may have continued on maintenance therapy until disease progression, unacceptable toxicity, or other withdrawal criterion was met.
Maintenance therapy (every 21 days):
Before 25 Oct 2012:
Day 1: pemetrexed 500 mg/m\^2
Day 2: LY2603618 dose determined from phase 1 (275 mg)
After 25 Oct 2012:
Day 1: pemetrexed 500 mg/m\^2
If, as of 25 Oct 2012, the participant was in maintenance therapy and randomized to the experimental arm, the participant was eligible to continue with pemetrexed/LY2603618 therapy if the investigator deemed it was in the participant's best interest and the participant consented.
Pemetrexed, cisplatin, and LY2603618 were administered IV over 10 minutes, 1 hour, and 1 hour, respectively.
|
Phase 2: Pemetrexed + Cisplatin
n=23 Participants
Cycles 1-4 (21-day cycle):
Day 1: pemetrexed 500 mg/m\^2 + cisplatin 75 mg/m\^2
After 4 cycles, participants may have continued on maintenance therapy until disease progression, unacceptable toxicity, or other withdrawal criterion was met.
Maintenance therapy (every 21 days):
Day 1: pemetrexed 500 mg/m\^2
Pemetrexed was administered IV over 10 minutes, and cisplatin was administered IV over 1 hour.
|
Total
n=76 Participants
Total of all reporting groups
|
|---|---|---|---|---|
|
Sex: Female, Male
Male
|
7 Participants
n=5 Participants
|
24 Participants
n=7 Participants
|
15 Participants
n=5 Participants
|
46 Participants
n=4 Participants
|
|
Race/Ethnicity, Customized
White
|
14 Participants
n=5 Participants
|
39 Participants
n=7 Participants
|
23 Participants
n=5 Participants
|
76 Participants
n=4 Participants
|
|
Region of Enrollment
Spain
|
7 Participants
n=5 Participants
|
24 Participants
n=7 Participants
|
12 Participants
n=5 Participants
|
43 Participants
n=4 Participants
|
|
Region of Enrollment
Germany
|
7 Participants
n=5 Participants
|
15 Participants
n=7 Participants
|
11 Participants
n=5 Participants
|
33 Participants
n=4 Participants
|
|
Age, Continuous
|
57.9 years
STANDARD_DEVIATION 11.4 • n=5 Participants
|
57.9 years
STANDARD_DEVIATION 10.1 • n=7 Participants
|
56.4 years
STANDARD_DEVIATION 9.8 • n=5 Participants
|
57.4 years
STANDARD_DEVIATION 10.1 • n=4 Participants
|
|
Sex: Female, Male
Female
|
7 Participants
n=5 Participants
|
15 Participants
n=7 Participants
|
8 Participants
n=5 Participants
|
30 Participants
n=4 Participants
|
|
Initial Pathological Diagnosis
Adenocarcinoma, Bronchiolalveolar
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
1 Participants
n=4 Participants
|
|
Initial Pathological Diagnosis
Adenocarcinoma, Colon
|
1 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
1 Participants
n=4 Participants
|
|
Initial Pathological Diagnosis
Adenocarcinoma, Lung
|
8 Participants
n=5 Participants
|
38 Participants
n=7 Participants
|
19 Participants
n=5 Participants
|
65 Participants
n=4 Participants
|
|
Initial Pathological Diagnosis
Adenocarcinoma, Moderately Diff., Lung
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
1 Participants
n=4 Participants
|
|
Initial Pathological Diagnosis
Carcinoma, Ampulla of Vater
|
1 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
1 Participants
n=4 Participants
|
|
Initial Pathological Diagnosis
Carcinoma, Breast
|
1 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
1 Participants
n=4 Participants
|
|
Initial Pathological Diagnosis
Carcinoma, Large Cell, Lung
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
1 Participants
n=4 Participants
|
|
Initial Pathological Diagnosis
Carcinoma, Lung
|
0 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
1 Participants
n=4 Participants
|
|
Initial Pathological Diagnosis
Carcinoma, Non-small Cell, Poorly Diff, Lung
|
1 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
1 Participants
n=4 Participants
|
|
Initial Pathological Diagnosis
Carcinoma, Pancreas
|
1 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
1 Participants
n=4 Participants
|
|
Initial Pathological Diagnosis
Mesothelioma, Malignum
|
1 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
1 Participants
n=4 Participants
|
|
Initial Pathological Diagnosis
Pleuritis Carcinomatosa
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
1 Participants
n=4 Participants
|
|
Eastern Cooperative Oncology Group (ECOG) Performance Status
ECOG Status 0
|
11 Participants
n=5 Participants
|
9 Participants
n=7 Participants
|
7 Participants
n=5 Participants
|
27 Participants
n=4 Participants
|
|
Eastern Cooperative Oncology Group (ECOG) Performance Status
ECOG Status 1
|
3 Participants
n=5 Participants
|
30 Participants
n=7 Participants
|
15 Participants
n=5 Participants
|
48 Participants
n=4 Participants
|
|
Eastern Cooperative Oncology Group (ECOG) Performance Status
Missing
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
1 Participants
n=4 Participants
|
PRIMARY outcome
Timeframe: Randomization up to first date of PD or death from any cause (up to 6 months after the last participant entered treatment)Population: All randomized Phase 2 participants.
Progression-free survival (PFS) time is defined as the time from the date of randomization to the first date of documented objective progressive disease (PD) or death from any cause. For participants who were not known to have had objective PD as of the data inclusion cut-off date for a particular analysis, PFS was censored at the date of the last objective progression-free disease assessments. For participants who took any subsequent systemic anticancer therapy prior to progression, PFS was censored at the date of the last objective progression-free disease assessment prior to the start date of any subsequent systemic anticancer therapy. PFS time was summarized using Kaplan-Meier estimates.
Outcome measures
| Measure |
Phase 2: Pemetrexed + Cisplatin + LY2603618
n=39 Participants
Cycles 1-4 (21-day cycle):
Before 25 Oct 2012:
Day 1: pemetrexed 500 mg/m\^2 + cisplatin 75 mg/m\^2
Day 2: LY2603618 dose determined from phase 1 (275 mg)
After 25 Oct 2012:
Day 1: pemetrexed 500 mg/m\^2 + cisplatin 75 mg/m\^2
After 4 cycles, participants may have continued on maintenance therapy until disease progression, unacceptable toxicity, or other withdrawal criterion was met.
Maintenance therapy (every 21 days):
Before 25 Oct 2012:
Day 1: pemetrexed 500 mg/m\^2
Day 2: LY2603618 dose determined from phase 1 (275 mg)
After 25 Oct 2012:
Day 1: pemetrexed 500 mg/m\^2
If, as of 25 Oct 2012, the participant was in maintenance therapy and randomized to the experimental arm, the participant was eligible to continue with pemetrexed/LY2603618 therapy if the investigator deemed it was in the participant's best interest and the participant consented.
Pemetrexed, cisplatin, and LY2603618 were administered IV over 10 minutes, 1 hour, and 1 hour, respectively.
|
Phase 2: Pemetrexed + Cisplatin
n=23 Participants
Cycles 1-4 (21-day cycle):
Day 1: pemetrexed 500 mg/m\^2 + cisplatin 75 mg/m\^2
After 4 cycles, participants may have continued on maintenance therapy until disease progression, unacceptable toxicity, or other withdrawal criterion was met.
Maintenance therapy (every 21 days):
Day 1: pemetrexed 500 mg/m\^2
Pemetrexed was administered IV over 10 minutes, and cisplatin was administered IV over 1 hour.
|
Phase 2: Pemetrexed + Cisplatin
Cycles 1-4 (21-day cycle):
Day 1: pemetrexed 500 mg/m\^2 + cisplatin 75 mg/m\^2
After 4 cycles, participants may have continued on maintenance therapy until disease progression, unacceptable toxicity, or other withdrawal criterion was met.
Maintenance therapy (every 21 days):
Day 1: pemetrexed 500 mg/m\^2
Pemetrexed was administered IV over 10 minutes, and cisplatin was administered IV over 1 hour.
|
|---|---|---|---|
|
Phase 2: Progression-Free Survival Time
|
4.7 months
Interval 4.2 to 7.1
|
1.5 months
Interval 1.3 to 2.9
|
—
|
PRIMARY outcome
Timeframe: Time of first dose to last dosePopulation: Phase 1 participants who received at least 1 dose of any of the study drugs.
The recommended Phase 2 dose for LY2603618 when administered approximately 24 hours after pemetrexed and cisplatin was based on the maximum tolerated dose (MTD) and achievement of predefined LY2603618 plasma systemic exposures targets (area under the LY2603618 plasma concentration versus time curve from time zero to infinity \[AUC(0-∞)\] \>21,000 nanogram\*hour/milliliter \[ng\*h/mL\] and maximum LY2603618 plasma concentration \[Cmax\] \>2000 nanograms/milliliter \[ng/mL\]).
Outcome measures
| Measure |
Phase 2: Pemetrexed + Cisplatin + LY2603618
n=14 Participants
Cycles 1-4 (21-day cycle):
Before 25 Oct 2012:
Day 1: pemetrexed 500 mg/m\^2 + cisplatin 75 mg/m\^2
Day 2: LY2603618 dose determined from phase 1 (275 mg)
After 25 Oct 2012:
Day 1: pemetrexed 500 mg/m\^2 + cisplatin 75 mg/m\^2
After 4 cycles, participants may have continued on maintenance therapy until disease progression, unacceptable toxicity, or other withdrawal criterion was met.
Maintenance therapy (every 21 days):
Before 25 Oct 2012:
Day 1: pemetrexed 500 mg/m\^2
Day 2: LY2603618 dose determined from phase 1 (275 mg)
After 25 Oct 2012:
Day 1: pemetrexed 500 mg/m\^2
If, as of 25 Oct 2012, the participant was in maintenance therapy and randomized to the experimental arm, the participant was eligible to continue with pemetrexed/LY2603618 therapy if the investigator deemed it was in the participant's best interest and the participant consented.
Pemetrexed, cisplatin, and LY2603618 were administered IV over 10 minutes, 1 hour, and 1 hour, respectively.
|
Phase 2: Pemetrexed + Cisplatin
Cycles 1-4 (21-day cycle):
Day 1: pemetrexed 500 mg/m\^2 + cisplatin 75 mg/m\^2
After 4 cycles, participants may have continued on maintenance therapy until disease progression, unacceptable toxicity, or other withdrawal criterion was met.
Maintenance therapy (every 21 days):
Day 1: pemetrexed 500 mg/m\^2
Pemetrexed was administered IV over 10 minutes, and cisplatin was administered IV over 1 hour.
|
Phase 2: Pemetrexed + Cisplatin
Cycles 1-4 (21-day cycle):
Day 1: pemetrexed 500 mg/m\^2 + cisplatin 75 mg/m\^2
After 4 cycles, participants may have continued on maintenance therapy until disease progression, unacceptable toxicity, or other withdrawal criterion was met.
Maintenance therapy (every 21 days):
Day 1: pemetrexed 500 mg/m\^2
Pemetrexed was administered IV over 10 minutes, and cisplatin was administered IV over 1 hour.
|
|---|---|---|---|
|
Phase 1: Recommended Phase 2 Dose of LY2603618
|
275 mg
|
—
|
—
|
SECONDARY outcome
Timeframe: Randomization to the date of death from any cause through the time of study discontinuation (approximately 12 months after last participant was randomized)Population: All randomized Phase 2 participants.
Overall survival (OS) time is defined as the time from the date of randomization to the date of death from any cause. For participants not known to have died as of the data cut-off date, OS time was censored at the last contact date the participant was known to be alive prior to the data cut-off date. OS was summarized using Kaplan-Meier estimates.
Outcome measures
| Measure |
Phase 2: Pemetrexed + Cisplatin + LY2603618
n=39 Participants
Cycles 1-4 (21-day cycle):
Before 25 Oct 2012:
Day 1: pemetrexed 500 mg/m\^2 + cisplatin 75 mg/m\^2
Day 2: LY2603618 dose determined from phase 1 (275 mg)
After 25 Oct 2012:
Day 1: pemetrexed 500 mg/m\^2 + cisplatin 75 mg/m\^2
After 4 cycles, participants may have continued on maintenance therapy until disease progression, unacceptable toxicity, or other withdrawal criterion was met.
Maintenance therapy (every 21 days):
Before 25 Oct 2012:
Day 1: pemetrexed 500 mg/m\^2
Day 2: LY2603618 dose determined from phase 1 (275 mg)
After 25 Oct 2012:
Day 1: pemetrexed 500 mg/m\^2
If, as of 25 Oct 2012, the participant was in maintenance therapy and randomized to the experimental arm, the participant was eligible to continue with pemetrexed/LY2603618 therapy if the investigator deemed it was in the participant's best interest and the participant consented.
Pemetrexed, cisplatin, and LY2603618 were administered IV over 10 minutes, 1 hour, and 1 hour, respectively.
|
Phase 2: Pemetrexed + Cisplatin
n=23 Participants
Cycles 1-4 (21-day cycle):
Day 1: pemetrexed 500 mg/m\^2 + cisplatin 75 mg/m\^2
After 4 cycles, participants may have continued on maintenance therapy until disease progression, unacceptable toxicity, or other withdrawal criterion was met.
Maintenance therapy (every 21 days):
Day 1: pemetrexed 500 mg/m\^2
Pemetrexed was administered IV over 10 minutes, and cisplatin was administered IV over 1 hour.
|
Phase 2: Pemetrexed + Cisplatin
Cycles 1-4 (21-day cycle):
Day 1: pemetrexed 500 mg/m\^2 + cisplatin 75 mg/m\^2
After 4 cycles, participants may have continued on maintenance therapy until disease progression, unacceptable toxicity, or other withdrawal criterion was met.
Maintenance therapy (every 21 days):
Day 1: pemetrexed 500 mg/m\^2
Pemetrexed was administered IV over 10 minutes, and cisplatin was administered IV over 1 hour.
|
|---|---|---|---|
|
Phase 2: Overall Survival
|
12.9 months
Interval 9.3 to
The upper bound of the 90% confidence interval was not calculable.
|
6.6 months
Interval 4.2 to 19.4
|
—
|
SECONDARY outcome
Timeframe: Randomization until date of disease progression (up to 6 months after the last participant was randomized)Population: All randomized Phase 2 participants.
Overall response rate is the best response of CR or PR as classified by the investigators according to the Response Evaluation Criteria in Solid Tumors (RECIST, v1.1) guidelines. CR is defined as the disappearance of all target and non-target lesions, normalization of tumor marker level of non-target lesions, and any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 millimeter (mm). 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 non-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 |
Phase 2: Pemetrexed + Cisplatin + LY2603618
n=39 Participants
Cycles 1-4 (21-day cycle):
Before 25 Oct 2012:
Day 1: pemetrexed 500 mg/m\^2 + cisplatin 75 mg/m\^2
Day 2: LY2603618 dose determined from phase 1 (275 mg)
After 25 Oct 2012:
Day 1: pemetrexed 500 mg/m\^2 + cisplatin 75 mg/m\^2
After 4 cycles, participants may have continued on maintenance therapy until disease progression, unacceptable toxicity, or other withdrawal criterion was met.
Maintenance therapy (every 21 days):
Before 25 Oct 2012:
Day 1: pemetrexed 500 mg/m\^2
Day 2: LY2603618 dose determined from phase 1 (275 mg)
After 25 Oct 2012:
Day 1: pemetrexed 500 mg/m\^2
If, as of 25 Oct 2012, the participant was in maintenance therapy and randomized to the experimental arm, the participant was eligible to continue with pemetrexed/LY2603618 therapy if the investigator deemed it was in the participant's best interest and the participant consented.
Pemetrexed, cisplatin, and LY2603618 were administered IV over 10 minutes, 1 hour, and 1 hour, respectively.
|
Phase 2: Pemetrexed + Cisplatin
n=23 Participants
Cycles 1-4 (21-day cycle):
Day 1: pemetrexed 500 mg/m\^2 + cisplatin 75 mg/m\^2
After 4 cycles, participants may have continued on maintenance therapy until disease progression, unacceptable toxicity, or other withdrawal criterion was met.
Maintenance therapy (every 21 days):
Day 1: pemetrexed 500 mg/m\^2
Pemetrexed was administered IV over 10 minutes, and cisplatin was administered IV over 1 hour.
|
Phase 2: Pemetrexed + Cisplatin
Cycles 1-4 (21-day cycle):
Day 1: pemetrexed 500 mg/m\^2 + cisplatin 75 mg/m\^2
After 4 cycles, participants may have continued on maintenance therapy until disease progression, unacceptable toxicity, or other withdrawal criterion was met.
Maintenance therapy (every 21 days):
Day 1: pemetrexed 500 mg/m\^2
Pemetrexed was administered IV over 10 minutes, and cisplatin was administered IV over 1 hour.
|
|---|---|---|---|
|
Phase 2: Overall Tumor Response Rate: Percentage of Participants Who Achieved a Confirmed Best Response of Completed Response (CR) or Partial Response (PR)
|
43.6 percentage of participants
Interval 28.0 to 60.0
|
21.7 percentage of participants
Interval 7.0 to 44.0
|
—
|
SECONDARY outcome
Timeframe: Baseline, end of Cycle 2Population: Participants with measureable disease (target lesions) at baseline who received at least 1 dose of study drug.
Change in tumor size was based on tumor measurements collected according to RECIST, v1.1 guidelines. Tumor size is the sum of the tumor measurements (longest diameters) of target lesions at each tumor evaluation. Change in tumor size was defined as the change in log tumor size from baseline evaluation to the evaluation at the end of Cycle 2.
Outcome measures
| Measure |
Phase 2: Pemetrexed + Cisplatin + LY2603618
n=39 Participants
Cycles 1-4 (21-day cycle):
Before 25 Oct 2012:
Day 1: pemetrexed 500 mg/m\^2 + cisplatin 75 mg/m\^2
Day 2: LY2603618 dose determined from phase 1 (275 mg)
After 25 Oct 2012:
Day 1: pemetrexed 500 mg/m\^2 + cisplatin 75 mg/m\^2
After 4 cycles, participants may have continued on maintenance therapy until disease progression, unacceptable toxicity, or other withdrawal criterion was met.
Maintenance therapy (every 21 days):
Before 25 Oct 2012:
Day 1: pemetrexed 500 mg/m\^2
Day 2: LY2603618 dose determined from phase 1 (275 mg)
After 25 Oct 2012:
Day 1: pemetrexed 500 mg/m\^2
If, as of 25 Oct 2012, the participant was in maintenance therapy and randomized to the experimental arm, the participant was eligible to continue with pemetrexed/LY2603618 therapy if the investigator deemed it was in the participant's best interest and the participant consented.
Pemetrexed, cisplatin, and LY2603618 were administered IV over 10 minutes, 1 hour, and 1 hour, respectively.
|
Phase 2: Pemetrexed + Cisplatin
n=22 Participants
Cycles 1-4 (21-day cycle):
Day 1: pemetrexed 500 mg/m\^2 + cisplatin 75 mg/m\^2
After 4 cycles, participants may have continued on maintenance therapy until disease progression, unacceptable toxicity, or other withdrawal criterion was met.
Maintenance therapy (every 21 days):
Day 1: pemetrexed 500 mg/m\^2
Pemetrexed was administered IV over 10 minutes, and cisplatin was administered IV over 1 hour.
|
Phase 2: Pemetrexed + Cisplatin
Cycles 1-4 (21-day cycle):
Day 1: pemetrexed 500 mg/m\^2 + cisplatin 75 mg/m\^2
After 4 cycles, participants may have continued on maintenance therapy until disease progression, unacceptable toxicity, or other withdrawal criterion was met.
Maintenance therapy (every 21 days):
Day 1: pemetrexed 500 mg/m\^2
Pemetrexed was administered IV over 10 minutes, and cisplatin was administered IV over 1 hour.
|
|---|---|---|---|
|
Phase 2: Change in Tumor Size
|
-0.30 centimeters
Standard Deviation 0.541
|
-0.14 centimeters
Standard Deviation 0.277
|
—
|
SECONDARY outcome
Timeframe: Cycle 1/Day 2 - immediately prior to end of LY2603618 infusion, and 1, 3, 6, 24, 48, 72, and 144 hours postdose; Cycle 2/Day 2 - predose, immediately prior to end of LY2603618 infusion, and 1, 3, 6, 24, 48, 72, and 144 hours postdosePopulation: Phase 1 participants who received at least 1 dose of LY2603618 and had samples collected for pharmacokinetic analysis.
Cmax is reported for each LY2603618 dose level on Cycle 1 /Day 2 and Cycle 2 /Day 2. The number of pharmacokinetic observations (n) used in the analysis is presented for each dose level and time point.
Outcome measures
| Measure |
Phase 2: Pemetrexed + Cisplatin + LY2603618
n=13 Participants
Cycles 1-4 (21-day cycle):
Before 25 Oct 2012:
Day 1: pemetrexed 500 mg/m\^2 + cisplatin 75 mg/m\^2
Day 2: LY2603618 dose determined from phase 1 (275 mg)
After 25 Oct 2012:
Day 1: pemetrexed 500 mg/m\^2 + cisplatin 75 mg/m\^2
After 4 cycles, participants may have continued on maintenance therapy until disease progression, unacceptable toxicity, or other withdrawal criterion was met.
Maintenance therapy (every 21 days):
Before 25 Oct 2012:
Day 1: pemetrexed 500 mg/m\^2
Day 2: LY2603618 dose determined from phase 1 (275 mg)
After 25 Oct 2012:
Day 1: pemetrexed 500 mg/m\^2
If, as of 25 Oct 2012, the participant was in maintenance therapy and randomized to the experimental arm, the participant was eligible to continue with pemetrexed/LY2603618 therapy if the investigator deemed it was in the participant's best interest and the participant consented.
Pemetrexed, cisplatin, and LY2603618 were administered IV over 10 minutes, 1 hour, and 1 hour, respectively.
|
Phase 2: Pemetrexed + Cisplatin
Cycles 1-4 (21-day cycle):
Day 1: pemetrexed 500 mg/m\^2 + cisplatin 75 mg/m\^2
After 4 cycles, participants may have continued on maintenance therapy until disease progression, unacceptable toxicity, or other withdrawal criterion was met.
Maintenance therapy (every 21 days):
Day 1: pemetrexed 500 mg/m\^2
Pemetrexed was administered IV over 10 minutes, and cisplatin was administered IV over 1 hour.
|
Phase 2: Pemetrexed + Cisplatin
Cycles 1-4 (21-day cycle):
Day 1: pemetrexed 500 mg/m\^2 + cisplatin 75 mg/m\^2
After 4 cycles, participants may have continued on maintenance therapy until disease progression, unacceptable toxicity, or other withdrawal criterion was met.
Maintenance therapy (every 21 days):
Day 1: pemetrexed 500 mg/m\^2
Pemetrexed was administered IV over 10 minutes, and cisplatin was administered IV over 1 hour.
|
|---|---|---|---|
|
Phase 1: Pharmacokinetic: Maximum Plasma Concentration (Cmax) (LY2603618)
130 mg, Cycle 1/Day 2
|
1810 ng/mL
Geometric Coefficient of Variation 14
|
—
|
—
|
|
Phase 1: Pharmacokinetic: Maximum Plasma Concentration (Cmax) (LY2603618)
130 mg, Cycle 2/Day 2
|
1730 ng/mL
Geometric Coefficient of Variation 43
|
—
|
—
|
|
Phase 1: Pharmacokinetic: Maximum Plasma Concentration (Cmax) (LY2603618)
185 mg, Cycle 1/Day 2
|
2200 ng/mL
Geometric Coefficient of Variation 33
|
—
|
—
|
|
Phase 1: Pharmacokinetic: Maximum Plasma Concentration (Cmax) (LY2603618)
185 mg, Cycle 2/Day 2
|
2190 ng/mL
Geometric Coefficient of Variation 58
|
—
|
—
|
|
Phase 1: Pharmacokinetic: Maximum Plasma Concentration (Cmax) (LY2603618)
240 mg, Cycle 1/Day 2
|
3470 ng/mL
Geometric Coefficient of Variation 27
|
—
|
—
|
|
Phase 1: Pharmacokinetic: Maximum Plasma Concentration (Cmax) (LY2603618)
240 mg, Cycle 2/Day 2
|
2750 ng/mL
Geometric Coefficient of Variation 63
|
—
|
—
|
|
Phase 1: Pharmacokinetic: Maximum Plasma Concentration (Cmax) (LY2603618)
275 mg, Cycle 1/Day 2
|
4130 ng/mL
Geometric Coefficient of Variation 29
|
—
|
—
|
|
Phase 1: Pharmacokinetic: Maximum Plasma Concentration (Cmax) (LY2603618)
275 mg, Cycle 2/Day 2
|
3620 ng/mL
Geometric Coefficient of Variation 23
|
—
|
—
|
SECONDARY outcome
Timeframe: Pemetrexed: Cycle 1/Day 1 - immediately prior to end of pemetrexed infusion and 1, 2, 6 and 24 hours postdose. Cisplatin: Cycle 1/Day 1 - immediately prior to end of cisplatin infusion and 0.5, 1, 2, 6, 24, 72, 96, and 168 hours postdose.Population: Phase 1 participants who received at least 1 dose of pemetrexed or cisplatin and had samples collected for pharmacokinetic analysis.
Cmax for pemetrexed and total platinum (t-platinum) from cisplatin is reported. The number of pharmacokinetic observations (n) used in the analysis is presented for each drug.
Outcome measures
| Measure |
Phase 2: Pemetrexed + Cisplatin + LY2603618
n=14 Participants
Cycles 1-4 (21-day cycle):
Before 25 Oct 2012:
Day 1: pemetrexed 500 mg/m\^2 + cisplatin 75 mg/m\^2
Day 2: LY2603618 dose determined from phase 1 (275 mg)
After 25 Oct 2012:
Day 1: pemetrexed 500 mg/m\^2 + cisplatin 75 mg/m\^2
After 4 cycles, participants may have continued on maintenance therapy until disease progression, unacceptable toxicity, or other withdrawal criterion was met.
Maintenance therapy (every 21 days):
Before 25 Oct 2012:
Day 1: pemetrexed 500 mg/m\^2
Day 2: LY2603618 dose determined from phase 1 (275 mg)
After 25 Oct 2012:
Day 1: pemetrexed 500 mg/m\^2
If, as of 25 Oct 2012, the participant was in maintenance therapy and randomized to the experimental arm, the participant was eligible to continue with pemetrexed/LY2603618 therapy if the investigator deemed it was in the participant's best interest and the participant consented.
Pemetrexed, cisplatin, and LY2603618 were administered IV over 10 minutes, 1 hour, and 1 hour, respectively.
|
Phase 2: Pemetrexed + Cisplatin
Cycles 1-4 (21-day cycle):
Day 1: pemetrexed 500 mg/m\^2 + cisplatin 75 mg/m\^2
After 4 cycles, participants may have continued on maintenance therapy until disease progression, unacceptable toxicity, or other withdrawal criterion was met.
Maintenance therapy (every 21 days):
Day 1: pemetrexed 500 mg/m\^2
Pemetrexed was administered IV over 10 minutes, and cisplatin was administered IV over 1 hour.
|
Phase 2: Pemetrexed + Cisplatin
Cycles 1-4 (21-day cycle):
Day 1: pemetrexed 500 mg/m\^2 + cisplatin 75 mg/m\^2
After 4 cycles, participants may have continued on maintenance therapy until disease progression, unacceptable toxicity, or other withdrawal criterion was met.
Maintenance therapy (every 21 days):
Day 1: pemetrexed 500 mg/m\^2
Pemetrexed was administered IV over 10 minutes, and cisplatin was administered IV over 1 hour.
|
|---|---|---|---|
|
Phase 1: Pharmacokinetic: Cmax (Pemetrexed and Cisplatin)
Pemetrexed
|
88300 ng/mL
Geometric Coefficient of Variation 28
|
—
|
—
|
|
Phase 1: Pharmacokinetic: Cmax (Pemetrexed and Cisplatin)
T-platinum from cisplatin
|
3710 ng/mL
Geometric Coefficient of Variation 43
|
—
|
—
|
SECONDARY outcome
Timeframe: Cycle 1/Day 2 - immediately prior to end of LY2603618 infusion and 1, 3, 6, 24, 48, 72, and 144 hours postdose; Cycle 2/Day 2 - predose, immediately prior to end of LY2603618 infusion, and 1, 3, 6, 24, 48, 72, and 144 hours postdosePopulation: Phase 1 participants who received at least 1 dose of LY2603618 and had samples collected for pharmacokinetic analysis.
AUC from time zero to 24 hours (AUC\[0-24\]), AUC from time zero to the last time point with a measurable concentration (AUC\[0-tlast\]), and AUC from time zero to infinity (AUC\[0-∞\]) values are reported for each LY2603618 dose level on Cycle 1 /Day 2 and Cycle 2 /Day 2. The number of pharmacokinetic observations (n) used in the analysis is presented for each dose level and time point.
Outcome measures
| Measure |
Phase 2: Pemetrexed + Cisplatin + LY2603618
n=13 Participants
Cycles 1-4 (21-day cycle):
Before 25 Oct 2012:
Day 1: pemetrexed 500 mg/m\^2 + cisplatin 75 mg/m\^2
Day 2: LY2603618 dose determined from phase 1 (275 mg)
After 25 Oct 2012:
Day 1: pemetrexed 500 mg/m\^2 + cisplatin 75 mg/m\^2
After 4 cycles, participants may have continued on maintenance therapy until disease progression, unacceptable toxicity, or other withdrawal criterion was met.
Maintenance therapy (every 21 days):
Before 25 Oct 2012:
Day 1: pemetrexed 500 mg/m\^2
Day 2: LY2603618 dose determined from phase 1 (275 mg)
After 25 Oct 2012:
Day 1: pemetrexed 500 mg/m\^2
If, as of 25 Oct 2012, the participant was in maintenance therapy and randomized to the experimental arm, the participant was eligible to continue with pemetrexed/LY2603618 therapy if the investigator deemed it was in the participant's best interest and the participant consented.
Pemetrexed, cisplatin, and LY2603618 were administered IV over 10 minutes, 1 hour, and 1 hour, respectively.
|
Phase 2: Pemetrexed + Cisplatin
Cycles 1-4 (21-day cycle):
Day 1: pemetrexed 500 mg/m\^2 + cisplatin 75 mg/m\^2
After 4 cycles, participants may have continued on maintenance therapy until disease progression, unacceptable toxicity, or other withdrawal criterion was met.
Maintenance therapy (every 21 days):
Day 1: pemetrexed 500 mg/m\^2
Pemetrexed was administered IV over 10 minutes, and cisplatin was administered IV over 1 hour.
|
Phase 2: Pemetrexed + Cisplatin
Cycles 1-4 (21-day cycle):
Day 1: pemetrexed 500 mg/m\^2 + cisplatin 75 mg/m\^2
After 4 cycles, participants may have continued on maintenance therapy until disease progression, unacceptable toxicity, or other withdrawal criterion was met.
Maintenance therapy (every 21 days):
Day 1: pemetrexed 500 mg/m\^2
Pemetrexed was administered IV over 10 minutes, and cisplatin was administered IV over 1 hour.
|
|---|---|---|---|
|
Phase 1: Pharmacokinetic: Area Under the Plasma Concentration Versus Time Curve (AUC) (LY2603618)
240 mg, Cycle 2/Day 2, AUC(0-24)
|
22100 ng*h/mL
Geometric Coefficient of Variation 31
|
—
|
—
|
|
Phase 1: Pharmacokinetic: Area Under the Plasma Concentration Versus Time Curve (AUC) (LY2603618)
130 mg, Cycle 2/Day 2, AUC(0-24)
|
9780 ng*h/mL
Geometric Coefficient of Variation 43
|
—
|
—
|
|
Phase 1: Pharmacokinetic: Area Under the Plasma Concentration Versus Time Curve (AUC) (LY2603618)
130 mg, Cycle 1/Day 2, AUC(0-tlast)
|
10200 ng*h/mL
Geometric Coefficient of Variation 26
|
—
|
—
|
|
Phase 1: Pharmacokinetic: Area Under the Plasma Concentration Versus Time Curve (AUC) (LY2603618)
130 mg, Cycle 2/Day 2, AUC(0-tlast)
|
11300 ng*h/mL
Geometric Coefficient of Variation 44
|
—
|
—
|
|
Phase 1: Pharmacokinetic: Area Under the Plasma Concentration Versus Time Curve (AUC) (LY2603618)
130 mg, Cycle 1/Day 2, AUC(0-∞)
|
10200 ng*h/mL
Geometric Coefficient of Variation 26
|
—
|
—
|
|
Phase 1: Pharmacokinetic: Area Under the Plasma Concentration Versus Time Curve (AUC) (LY2603618)
130 mg, Cycle 2/Day 2, AUC(0-∞)
|
11300 ng*h/mL
Geometric Coefficient of Variation 45
|
—
|
—
|
|
Phase 1: Pharmacokinetic: Area Under the Plasma Concentration Versus Time Curve (AUC) (LY2603618)
185 mg, Cycle 1/Day 2, AUC(0-24)
|
13800 ng*h/mL
Geometric Coefficient of Variation 119
|
—
|
—
|
|
Phase 1: Pharmacokinetic: Area Under the Plasma Concentration Versus Time Curve (AUC) (LY2603618)
185 mg, Cycle 2/Day 2, AUC(0-24)
|
12500 ng*h/mL
Geometric Coefficient of Variation 170
|
—
|
—
|
|
Phase 1: Pharmacokinetic: Area Under the Plasma Concentration Versus Time Curve (AUC) (LY2603618)
185 mg, Cycle 1/Day 2, AUC(0-tlast)
|
18300 ng*h/mL
Geometric Coefficient of Variation 192
|
—
|
—
|
|
Phase 1: Pharmacokinetic: Area Under the Plasma Concentration Versus Time Curve (AUC) (LY2603618)
185 mg, Cycle 2/Day 2, AUC(0-tlast)
|
14800 ng*h/mL
Geometric Coefficient of Variation 217
|
—
|
—
|
|
Phase 1: Pharmacokinetic: Area Under the Plasma Concentration Versus Time Curve (AUC) (LY2603618)
185 mg, Cycle 1/Day 2, AUC(0-∞)
|
18400 ng*h/mL
Geometric Coefficient of Variation 193
|
—
|
—
|
|
Phase 1: Pharmacokinetic: Area Under the Plasma Concentration Versus Time Curve (AUC) (LY2603618)
185 mg, Cycle 2/Day 2, AUC(0-∞)
|
15700 ng*h/mL
Geometric Coefficient of Variation 253
|
—
|
—
|
|
Phase 1: Pharmacokinetic: Area Under the Plasma Concentration Versus Time Curve (AUC) (LY2603618)
240 mg, Cycle 1/Day 2, AUC(0-24)
|
26200 ng*h/mL
Geometric Coefficient of Variation 19
|
—
|
—
|
|
Phase 1: Pharmacokinetic: Area Under the Plasma Concentration Versus Time Curve (AUC) (LY2603618)
240 mg, Cycle 1/Day 2, AUC(0-tlast)
|
32200 ng*h/mL
Geometric Coefficient of Variation 21
|
—
|
—
|
|
Phase 1: Pharmacokinetic: Area Under the Plasma Concentration Versus Time Curve (AUC) (LY2603618)
240 mg, Cycle 2/Day 2, AUC(0-tlast)
|
27300 ng*h/mL
Geometric Coefficient of Variation 31
|
—
|
—
|
|
Phase 1: Pharmacokinetic: Area Under the Plasma Concentration Versus Time Curve (AUC) (LY2603618)
240 mg, Cycle 1/Day 2, AUC(0-∞)
|
32300 ng*h/mL
Geometric Coefficient of Variation 21
|
—
|
—
|
|
Phase 1: Pharmacokinetic: Area Under the Plasma Concentration Versus Time Curve (AUC) (LY2603618)
240 mg, Cycle 2/Day 2, AUC(0-∞)
|
27500 ng*h/mL
Geometric Coefficient of Variation 31
|
—
|
—
|
|
Phase 1: Pharmacokinetic: Area Under the Plasma Concentration Versus Time Curve (AUC) (LY2603618)
275 mg, Cycle 1/Day 2, AUC(0-24)
|
28900 ng*h/mL
Geometric Coefficient of Variation 24
|
—
|
—
|
|
Phase 1: Pharmacokinetic: Area Under the Plasma Concentration Versus Time Curve (AUC) (LY2603618)
275 mg, Cycle 2/Day 2, AUC(0-24)
|
23500 ng*h/mL
Geometric Coefficient of Variation 31
|
—
|
—
|
|
Phase 1: Pharmacokinetic: Area Under the Plasma Concentration Versus Time Curve (AUC) (LY2603618)
275 mg, Cycle 1/Day 2, AUC(0-tlast)
|
38100 ng*h/mL
Geometric Coefficient of Variation 36
|
—
|
—
|
|
Phase 1: Pharmacokinetic: Area Under the Plasma Concentration Versus Time Curve (AUC) (LY2603618)
275 mg, Cycle 2/Day 2, AUC(0-tlast)
|
30800 ng*h/mL
Geometric Coefficient of Variation 44
|
—
|
—
|
|
Phase 1: Pharmacokinetic: Area Under the Plasma Concentration Versus Time Curve (AUC) (LY2603618)
275 mg, Cycle 1/Day 2, AUC(0-∞)
|
38300 ng*h/mL
Geometric Coefficient of Variation 37
|
—
|
—
|
|
Phase 1: Pharmacokinetic: Area Under the Plasma Concentration Versus Time Curve (AUC) (LY2603618)
275 mg, Cycle 2/Day 2, AUC(0-∞)
|
30900 ng*h/mL
Geometric Coefficient of Variation 44
|
—
|
—
|
|
Phase 1: Pharmacokinetic: Area Under the Plasma Concentration Versus Time Curve (AUC) (LY2603618)
130 mg, Cycle 1/Day 2, AUC(0-24)
|
8700 ng*h/mL
Geometric Coefficient of Variation 30
|
—
|
—
|
SECONDARY outcome
Timeframe: Pemetrexed: Cycle 1/Day 1 - immediately prior to end of pemetrexed infusion and 1, 2, 6 and 24 hours postdose. Cisplatin: Cycle 1/Day 1 - immediately prior to end of cisplatin infusion and 0.5, 1, 2, 6, 24, 72, 96, and 168 hours postdose.Population: Phase 1 participants who received at least 1 dose of pemetrexed or cisplatin and had samples collected for pharmacokinetic analysis.
AUC(0-tlast) and AUC(0-∞) values are reported for pemetrexed and t-platinum from cisplatin. The number of pharmacokinetic observations (n) used in the analysis is presented for each drug.
Outcome measures
| Measure |
Phase 2: Pemetrexed + Cisplatin + LY2603618
n=14 Participants
Cycles 1-4 (21-day cycle):
Before 25 Oct 2012:
Day 1: pemetrexed 500 mg/m\^2 + cisplatin 75 mg/m\^2
Day 2: LY2603618 dose determined from phase 1 (275 mg)
After 25 Oct 2012:
Day 1: pemetrexed 500 mg/m\^2 + cisplatin 75 mg/m\^2
After 4 cycles, participants may have continued on maintenance therapy until disease progression, unacceptable toxicity, or other withdrawal criterion was met.
Maintenance therapy (every 21 days):
Before 25 Oct 2012:
Day 1: pemetrexed 500 mg/m\^2
Day 2: LY2603618 dose determined from phase 1 (275 mg)
After 25 Oct 2012:
Day 1: pemetrexed 500 mg/m\^2
If, as of 25 Oct 2012, the participant was in maintenance therapy and randomized to the experimental arm, the participant was eligible to continue with pemetrexed/LY2603618 therapy if the investigator deemed it was in the participant's best interest and the participant consented.
Pemetrexed, cisplatin, and LY2603618 were administered IV over 10 minutes, 1 hour, and 1 hour, respectively.
|
Phase 2: Pemetrexed + Cisplatin
Cycles 1-4 (21-day cycle):
Day 1: pemetrexed 500 mg/m\^2 + cisplatin 75 mg/m\^2
After 4 cycles, participants may have continued on maintenance therapy until disease progression, unacceptable toxicity, or other withdrawal criterion was met.
Maintenance therapy (every 21 days):
Day 1: pemetrexed 500 mg/m\^2
Pemetrexed was administered IV over 10 minutes, and cisplatin was administered IV over 1 hour.
|
Phase 2: Pemetrexed + Cisplatin
Cycles 1-4 (21-day cycle):
Day 1: pemetrexed 500 mg/m\^2 + cisplatin 75 mg/m\^2
After 4 cycles, participants may have continued on maintenance therapy until disease progression, unacceptable toxicity, or other withdrawal criterion was met.
Maintenance therapy (every 21 days):
Day 1: pemetrexed 500 mg/m\^2
Pemetrexed was administered IV over 10 minutes, and cisplatin was administered IV over 1 hour.
|
|---|---|---|---|
|
Phase 1: Pharmacokinetic: AUC (Pemetrexed and Cisplatin)
Pemetrexed, AUC(0-tlast)
|
159000 ng*h/mL
Geometric Coefficient of Variation 35
|
—
|
—
|
|
Phase 1: Pharmacokinetic: AUC (Pemetrexed and Cisplatin)
Pemetrexed, AUC (0-∞)
|
160000 ng*h/mL
Geometric Coefficient of Variation 35
|
—
|
—
|
|
Phase 1: Pharmacokinetic: AUC (Pemetrexed and Cisplatin)
T-platinum from cisplatin, AUC (0-tlast)
|
163000 ng*h/mL
Geometric Coefficient of Variation 26
|
—
|
—
|
|
Phase 1: Pharmacokinetic: AUC (Pemetrexed and Cisplatin)
T-platinum from cisplatin, AUC (0-∞)
|
269000 ng*h/mL
Geometric Coefficient of Variation 26
|
—
|
—
|
SECONDARY outcome
Timeframe: Cycle 1/Day 2 - predose, immediately prior to the end of the LY2603618 infusion, and 2-6, 24-48, and 72-96 hours postdosePopulation: Phase 2 participants who received at least 1 dose of LY2603618 and had samples collected for pharmacokinetic analysis.
Outcome measures
| Measure |
Phase 2: Pemetrexed + Cisplatin + LY2603618
n=33 Participants
Cycles 1-4 (21-day cycle):
Before 25 Oct 2012:
Day 1: pemetrexed 500 mg/m\^2 + cisplatin 75 mg/m\^2
Day 2: LY2603618 dose determined from phase 1 (275 mg)
After 25 Oct 2012:
Day 1: pemetrexed 500 mg/m\^2 + cisplatin 75 mg/m\^2
After 4 cycles, participants may have continued on maintenance therapy until disease progression, unacceptable toxicity, or other withdrawal criterion was met.
Maintenance therapy (every 21 days):
Before 25 Oct 2012:
Day 1: pemetrexed 500 mg/m\^2
Day 2: LY2603618 dose determined from phase 1 (275 mg)
After 25 Oct 2012:
Day 1: pemetrexed 500 mg/m\^2
If, as of 25 Oct 2012, the participant was in maintenance therapy and randomized to the experimental arm, the participant was eligible to continue with pemetrexed/LY2603618 therapy if the investigator deemed it was in the participant's best interest and the participant consented.
Pemetrexed, cisplatin, and LY2603618 were administered IV over 10 minutes, 1 hour, and 1 hour, respectively.
|
Phase 2: Pemetrexed + Cisplatin
Cycles 1-4 (21-day cycle):
Day 1: pemetrexed 500 mg/m\^2 + cisplatin 75 mg/m\^2
After 4 cycles, participants may have continued on maintenance therapy until disease progression, unacceptable toxicity, or other withdrawal criterion was met.
Maintenance therapy (every 21 days):
Day 1: pemetrexed 500 mg/m\^2
Pemetrexed was administered IV over 10 minutes, and cisplatin was administered IV over 1 hour.
|
Phase 2: Pemetrexed + Cisplatin
Cycles 1-4 (21-day cycle):
Day 1: pemetrexed 500 mg/m\^2 + cisplatin 75 mg/m\^2
After 4 cycles, participants may have continued on maintenance therapy until disease progression, unacceptable toxicity, or other withdrawal criterion was met.
Maintenance therapy (every 21 days):
Day 1: pemetrexed 500 mg/m\^2
Pemetrexed was administered IV over 10 minutes, and cisplatin was administered IV over 1 hour.
|
|---|---|---|---|
|
Phase 2: Pharmacokinetic: Cmax (LY2603618)
|
4130 ng/mL
Geometric Coefficient of Variation 66
|
—
|
—
|
SECONDARY outcome
Timeframe: Cycle 1/Day 2 - predose, immediately prior to the end of the LY2603618 infusion, and 2-6, 24-48, and 72-96 hours postdosePopulation: Phase 2 participants who received at least 1 dose of LY2603618 and had samples collected for pharmacokinetic analysis.
AUC (0-24), AUC(0-tlast), and AUC(0-∞) values are reported for LY2603618. The number of pharmacokinetic observations (n) used in the analysis is presented.
Outcome measures
| Measure |
Phase 2: Pemetrexed + Cisplatin + LY2603618
n=33 Participants
Cycles 1-4 (21-day cycle):
Before 25 Oct 2012:
Day 1: pemetrexed 500 mg/m\^2 + cisplatin 75 mg/m\^2
Day 2: LY2603618 dose determined from phase 1 (275 mg)
After 25 Oct 2012:
Day 1: pemetrexed 500 mg/m\^2 + cisplatin 75 mg/m\^2
After 4 cycles, participants may have continued on maintenance therapy until disease progression, unacceptable toxicity, or other withdrawal criterion was met.
Maintenance therapy (every 21 days):
Before 25 Oct 2012:
Day 1: pemetrexed 500 mg/m\^2
Day 2: LY2603618 dose determined from phase 1 (275 mg)
After 25 Oct 2012:
Day 1: pemetrexed 500 mg/m\^2
If, as of 25 Oct 2012, the participant was in maintenance therapy and randomized to the experimental arm, the participant was eligible to continue with pemetrexed/LY2603618 therapy if the investigator deemed it was in the participant's best interest and the participant consented.
Pemetrexed, cisplatin, and LY2603618 were administered IV over 10 minutes, 1 hour, and 1 hour, respectively.
|
Phase 2: Pemetrexed + Cisplatin
Cycles 1-4 (21-day cycle):
Day 1: pemetrexed 500 mg/m\^2 + cisplatin 75 mg/m\^2
After 4 cycles, participants may have continued on maintenance therapy until disease progression, unacceptable toxicity, or other withdrawal criterion was met.
Maintenance therapy (every 21 days):
Day 1: pemetrexed 500 mg/m\^2
Pemetrexed was administered IV over 10 minutes, and cisplatin was administered IV over 1 hour.
|
Phase 2: Pemetrexed + Cisplatin
Cycles 1-4 (21-day cycle):
Day 1: pemetrexed 500 mg/m\^2 + cisplatin 75 mg/m\^2
After 4 cycles, participants may have continued on maintenance therapy until disease progression, unacceptable toxicity, or other withdrawal criterion was met.
Maintenance therapy (every 21 days):
Day 1: pemetrexed 500 mg/m\^2
Pemetrexed was administered IV over 10 minutes, and cisplatin was administered IV over 1 hour.
|
|---|---|---|---|
|
Phase 2: Pharmacokinetic: AUC (LY2603618)
AUC (0-24)
|
31400 ng*h/mL
Geometric Coefficient of Variation 49
|
—
|
—
|
|
Phase 2: Pharmacokinetic: AUC (LY2603618)
AUC (0-tlast)
|
39300 ng*h/mL
Geometric Coefficient of Variation 58
|
—
|
—
|
|
Phase 2: Pharmacokinetic: AUC (LY2603618)
AUC (0-∞)
|
41100 ng*h/mL
Geometric Coefficient of Variation 59
|
—
|
—
|
SECONDARY outcome
Timeframe: Randomization to the end of study (approximately 12 months after the last participant entered treatment)Population: All enrolled Phase 2 participants who had the baseline LCSS assessment and at least 1 post-baseline assessment.
Health-related quality of life and participant symptoms were assessed using the LCSS (patient scale). However, improper implementation of questionnaires at the site level reduced the sponsor's ability to accurately evaluate the impacted data. Therefore, the LCSS data should be interpreted with caution. The 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. 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. The total LCSS score was calculated as the mean of 9 questions from the LCSS.
Outcome measures
| Measure |
Phase 2: Pemetrexed + Cisplatin + LY2603618
n=36 Participants
Cycles 1-4 (21-day cycle):
Before 25 Oct 2012:
Day 1: pemetrexed 500 mg/m\^2 + cisplatin 75 mg/m\^2
Day 2: LY2603618 dose determined from phase 1 (275 mg)
After 25 Oct 2012:
Day 1: pemetrexed 500 mg/m\^2 + cisplatin 75 mg/m\^2
After 4 cycles, participants may have continued on maintenance therapy until disease progression, unacceptable toxicity, or other withdrawal criterion was met.
Maintenance therapy (every 21 days):
Before 25 Oct 2012:
Day 1: pemetrexed 500 mg/m\^2
Day 2: LY2603618 dose determined from phase 1 (275 mg)
After 25 Oct 2012:
Day 1: pemetrexed 500 mg/m\^2
If, as of 25 Oct 2012, the participant was in maintenance therapy and randomized to the experimental arm, the participant was eligible to continue with pemetrexed/LY2603618 therapy if the investigator deemed it was in the participant's best interest and the participant consented.
Pemetrexed, cisplatin, and LY2603618 were administered IV over 10 minutes, 1 hour, and 1 hour, respectively.
|
Phase 2: Pemetrexed + Cisplatin
n=22 Participants
Cycles 1-4 (21-day cycle):
Day 1: pemetrexed 500 mg/m\^2 + cisplatin 75 mg/m\^2
After 4 cycles, participants may have continued on maintenance therapy until disease progression, unacceptable toxicity, or other withdrawal criterion was met.
Maintenance therapy (every 21 days):
Day 1: pemetrexed 500 mg/m\^2
Pemetrexed was administered IV over 10 minutes, and cisplatin was administered IV over 1 hour.
|
Phase 2: Pemetrexed + Cisplatin
Cycles 1-4 (21-day cycle):
Day 1: pemetrexed 500 mg/m\^2 + cisplatin 75 mg/m\^2
After 4 cycles, participants may have continued on maintenance therapy until disease progression, unacceptable toxicity, or other withdrawal criterion was met.
Maintenance therapy (every 21 days):
Day 1: pemetrexed 500 mg/m\^2
Pemetrexed was administered IV over 10 minutes, and cisplatin was administered IV over 1 hour.
|
|---|---|---|---|
|
Phase 2: Change From Baseline to Long-term Follow up in Lung Cancer Symptom Scale (LCSS)
Total LCSS
|
-10.7 units on a scale
Standard Deviation 14.1
|
-11.7 units on a scale
Standard Deviation 15.1
|
—
|
|
Phase 2: Change From Baseline to Long-term Follow up in Lung Cancer Symptom Scale (LCSS)
ASBI
|
-11.6 units on a scale
Standard Deviation 13.9
|
-12.6 units on a scale
Standard Deviation 15.4
|
—
|
SECONDARY outcome
Timeframe: Baseline through end of Phase 1Population: All randomized Phase 1 participants.
Overall response rate is presented. Overall response rate is defined as the percentage of participants with a best response of CR or PR as classified by the investigators according to RECIST, v1.1 criteria. CR is defined as the disappearance of all target and non-target lesions, normalization of tumor marker level of non-target lesions, and any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm. 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 non-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 |
Phase 2: Pemetrexed + Cisplatin + LY2603618
n=14 Participants
Cycles 1-4 (21-day cycle):
Before 25 Oct 2012:
Day 1: pemetrexed 500 mg/m\^2 + cisplatin 75 mg/m\^2
Day 2: LY2603618 dose determined from phase 1 (275 mg)
After 25 Oct 2012:
Day 1: pemetrexed 500 mg/m\^2 + cisplatin 75 mg/m\^2
After 4 cycles, participants may have continued on maintenance therapy until disease progression, unacceptable toxicity, or other withdrawal criterion was met.
Maintenance therapy (every 21 days):
Before 25 Oct 2012:
Day 1: pemetrexed 500 mg/m\^2
Day 2: LY2603618 dose determined from phase 1 (275 mg)
After 25 Oct 2012:
Day 1: pemetrexed 500 mg/m\^2
If, as of 25 Oct 2012, the participant was in maintenance therapy and randomized to the experimental arm, the participant was eligible to continue with pemetrexed/LY2603618 therapy if the investigator deemed it was in the participant's best interest and the participant consented.
Pemetrexed, cisplatin, and LY2603618 were administered IV over 10 minutes, 1 hour, and 1 hour, respectively.
|
Phase 2: Pemetrexed + Cisplatin
Cycles 1-4 (21-day cycle):
Day 1: pemetrexed 500 mg/m\^2 + cisplatin 75 mg/m\^2
After 4 cycles, participants may have continued on maintenance therapy until disease progression, unacceptable toxicity, or other withdrawal criterion was met.
Maintenance therapy (every 21 days):
Day 1: pemetrexed 500 mg/m\^2
Pemetrexed was administered IV over 10 minutes, and cisplatin was administered IV over 1 hour.
|
Phase 2: Pemetrexed + Cisplatin
Cycles 1-4 (21-day cycle):
Day 1: pemetrexed 500 mg/m\^2 + cisplatin 75 mg/m\^2
After 4 cycles, participants may have continued on maintenance therapy until disease progression, unacceptable toxicity, or other withdrawal criterion was met.
Maintenance therapy (every 21 days):
Day 1: pemetrexed 500 mg/m\^2
Pemetrexed was administered IV over 10 minutes, and cisplatin was administered IV over 1 hour.
|
|---|---|---|---|
|
Phase 1: Document Any Antitumor Activity Per Radiological Scans and/or Tumor Markers
130 mg
|
0 percentage of participants
Interval 0.0 to 0.0
|
—
|
—
|
|
Phase 1: Document Any Antitumor Activity Per Radiological Scans and/or Tumor Markers
185 mg
|
66.7 percentage of participants
Interval 9.0 to 99.0
|
—
|
—
|
|
Phase 1: Document Any Antitumor Activity Per Radiological Scans and/or Tumor Markers
240 mg
|
25.0 percentage of participants
Interval 1.0 to 81.0
|
—
|
—
|
|
Phase 1: Document Any Antitumor Activity Per Radiological Scans and/or Tumor Markers
275 mg
|
0 percentage of participants
Interval 0.0 to 0.0
|
—
|
—
|
SECONDARY outcome
Timeframe: Cycle 5Population: Zero participants analyzed. Treatment with LY2603618 was discontinued after 25 October 2012, data was not collected for analysis of the Phase 2: Proportion of Participants Receiving Maintenance Therapy.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Randomization until date of disease progression or death (up to 6 months after the last participant was randomized)Population: All randomized Phase 2 participants.
Clinical benefit rate is the best response CR, PR, or SD as classified by the investigators according to the RECIST, v1.1 guidelines. CR is defined as the disappearance of all target and non-target lesions, normalization of tumor marker level of non-target lesions, and any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm. 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 non-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 |
Phase 2: Pemetrexed + Cisplatin + LY2603618
n=39 Participants
Cycles 1-4 (21-day cycle):
Before 25 Oct 2012:
Day 1: pemetrexed 500 mg/m\^2 + cisplatin 75 mg/m\^2
Day 2: LY2603618 dose determined from phase 1 (275 mg)
After 25 Oct 2012:
Day 1: pemetrexed 500 mg/m\^2 + cisplatin 75 mg/m\^2
After 4 cycles, participants may have continued on maintenance therapy until disease progression, unacceptable toxicity, or other withdrawal criterion was met.
Maintenance therapy (every 21 days):
Before 25 Oct 2012:
Day 1: pemetrexed 500 mg/m\^2
Day 2: LY2603618 dose determined from phase 1 (275 mg)
After 25 Oct 2012:
Day 1: pemetrexed 500 mg/m\^2
If, as of 25 Oct 2012, the participant was in maintenance therapy and randomized to the experimental arm, the participant was eligible to continue with pemetrexed/LY2603618 therapy if the investigator deemed it was in the participant's best interest and the participant consented.
Pemetrexed, cisplatin, and LY2603618 were administered IV over 10 minutes, 1 hour, and 1 hour, respectively.
|
Phase 2: Pemetrexed + Cisplatin
n=23 Participants
Cycles 1-4 (21-day cycle):
Day 1: pemetrexed 500 mg/m\^2 + cisplatin 75 mg/m\^2
After 4 cycles, participants may have continued on maintenance therapy until disease progression, unacceptable toxicity, or other withdrawal criterion was met.
Maintenance therapy (every 21 days):
Day 1: pemetrexed 500 mg/m\^2
Pemetrexed was administered IV over 10 minutes, and cisplatin was administered IV over 1 hour.
|
Phase 2: Pemetrexed + Cisplatin
Cycles 1-4 (21-day cycle):
Day 1: pemetrexed 500 mg/m\^2 + cisplatin 75 mg/m\^2
After 4 cycles, participants may have continued on maintenance therapy until disease progression, unacceptable toxicity, or other withdrawal criterion was met.
Maintenance therapy (every 21 days):
Day 1: pemetrexed 500 mg/m\^2
Pemetrexed was administered IV over 10 minutes, and cisplatin was administered IV over 1 hour.
|
|---|---|---|---|
|
Phase 2: Clinical Benefit Rate: Percentage of Participant Who Achieved a Response of Stable Disease (SD), Partial Response (PR), or Complete Response (CR)
|
69.2 percentage of participants
Interval 52.0 to 83.0
|
47.8 percentage of participants
Interval 27.0 to 69.0
|
—
|
OTHER_PRE_SPECIFIED outcome
Timeframe: Randomization through 12 months after the last participant was randomizedPopulation: All enrolled participants.
Deaths that occurred during the study are presented. A summary of serious and other non-serious adverse events regardless of causality is located in the Reported Adverse Events module.
Outcome measures
| Measure |
Phase 2: Pemetrexed + Cisplatin + LY2603618
n=14 Participants
Cycles 1-4 (21-day cycle):
Before 25 Oct 2012:
Day 1: pemetrexed 500 mg/m\^2 + cisplatin 75 mg/m\^2
Day 2: LY2603618 dose determined from phase 1 (275 mg)
After 25 Oct 2012:
Day 1: pemetrexed 500 mg/m\^2 + cisplatin 75 mg/m\^2
After 4 cycles, participants may have continued on maintenance therapy until disease progression, unacceptable toxicity, or other withdrawal criterion was met.
Maintenance therapy (every 21 days):
Before 25 Oct 2012:
Day 1: pemetrexed 500 mg/m\^2
Day 2: LY2603618 dose determined from phase 1 (275 mg)
After 25 Oct 2012:
Day 1: pemetrexed 500 mg/m\^2
If, as of 25 Oct 2012, the participant was in maintenance therapy and randomized to the experimental arm, the participant was eligible to continue with pemetrexed/LY2603618 therapy if the investigator deemed it was in the participant's best interest and the participant consented.
Pemetrexed, cisplatin, and LY2603618 were administered IV over 10 minutes, 1 hour, and 1 hour, respectively.
|
Phase 2: Pemetrexed + Cisplatin
n=39 Participants
Cycles 1-4 (21-day cycle):
Day 1: pemetrexed 500 mg/m\^2 + cisplatin 75 mg/m\^2
After 4 cycles, participants may have continued on maintenance therapy until disease progression, unacceptable toxicity, or other withdrawal criterion was met.
Maintenance therapy (every 21 days):
Day 1: pemetrexed 500 mg/m\^2
Pemetrexed was administered IV over 10 minutes, and cisplatin was administered IV over 1 hour.
|
Phase 2: Pemetrexed + Cisplatin
n=23 Participants
Cycles 1-4 (21-day cycle):
Day 1: pemetrexed 500 mg/m\^2 + cisplatin 75 mg/m\^2
After 4 cycles, participants may have continued on maintenance therapy until disease progression, unacceptable toxicity, or other withdrawal criterion was met.
Maintenance therapy (every 21 days):
Day 1: pemetrexed 500 mg/m\^2
Pemetrexed was administered IV over 10 minutes, and cisplatin was administered IV over 1 hour.
|
|---|---|---|---|
|
Deaths
Deaths during follow-up period
|
0 Participants
|
17 Participants
|
14 Participants
|
|
Deaths
Total deaths
|
0 Participants
|
21 Participants
|
15 Participants
|
|
Deaths
Deaths while on treatment
|
0 Participants
|
3 Participants
|
1 Participants
|
|
Deaths
Death within 30 days of last dose of study drug
|
0 Participants
|
1 Participants
|
0 Participants
|
Adverse Events
Phase 1: Pemetrexed + Cisplatin + LY2603618
Serious events: 1 serious events
Other events: 14 other events
Deaths: 0 deaths
Phase 2: Pemetrexed + Cisplatin + LY2603618
Serious events: 16 serious events
Other events: 37 other events
Deaths: 0 deaths
Phase 2: Pemetrexed + Cisplatin
Serious events: 6 serious events
Other events: 22 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Phase 1: Pemetrexed + Cisplatin + LY2603618
n=14 participants at risk
Cycles 1-2 (21-day cycle):
Day 1: pemetrexed 500 mg/m\^2 + cisplatin 75 mg/m\^2
Day 2: LY2603618 130 to 275 mg
After 2 cycles, participants may have continued on study drug until disease progression, unacceptable toxicity, or other withdrawal criterion was met.
Pemetrexed, cisplatin, and LY2603618 were administered IV over 10 minutes, 1 hour, and 1 hour, respectively.
|
Phase 2: Pemetrexed + Cisplatin + LY2603618
n=39 participants at risk
Cycles 1-4 (21-day cycle):
Before 25 Oct 2012:
Day 1: pemetrexed 500 mg/m\^2 + cisplatin 75 mg/m\^2
Day 2: LY2603618 dose determined from phase 1 (275 mg)
After 25 Oct 2012:
Day 1: pemetrexed 500 mg/m\^2 + cisplatin 75 mg/m\^2
After 4 cycles, participants may have continued on maintenance therapy until disease progression, unacceptable toxicity, or other withdrawal criterion was met.
Maintenance therapy (every 21 days):
Before 25 Oct 2012:
Day 1: pemetrexed 500 mg/m\^2
Day 2: LY2603618 dose determined from phase 1 (275 mg)
After 25 Oct 2012:
Day 1: pemetrexed 500 mg/m\^2
If, as of 25 Oct 2012, the participant was in maintenance therapy and randomized to the experimental arm, the participant was eligible to continue with pemetrexed/LY2603618 therapy if the investigator deemed it was in the participant's best interest and the participant consented.
Pemetrexed, cisplatin, and LY2603618 were administered IV over 10 minutes, 1 hour, and 1 hour, respectively.
|
Phase 2: Pemetrexed + Cisplatin
n=22 participants at risk
Cycles 1-4 (21-day cycle):
Day 1: pemetrexed 500 mg/m\^2 + cisplatin 75 mg/m\^2
After 4 cycles, participants may have continued on maintenance therapy until disease progression, unacceptable toxicity, or other withdrawal criterion was met.
Maintenance therapy (every 21 days):
Day 1: pemetrexed 500 mg/m\^2
Pemetrexed was administered IV over 10 minutes, and cisplatin was administered IV over 1 hour.
|
|---|---|---|---|
|
Blood and lymphatic system disorders
Anaemia
|
7.1%
1/14 • Number of events 1
|
0.00%
0/39
|
0.00%
0/22
|
|
Blood and lymphatic system disorders
Neutropenia
|
0.00%
0/14
|
2.6%
1/39 • Number of events 1
|
0.00%
0/22
|
|
Cardiac disorders
Angina pectoris
|
0.00%
0/14
|
2.6%
1/39 • Number of events 1
|
0.00%
0/22
|
|
Cardiac disorders
Atrial fibrillation
|
0.00%
0/14
|
2.6%
1/39 • Number of events 1
|
0.00%
0/22
|
|
Gastrointestinal disorders
Ileus
|
0.00%
0/14
|
0.00%
0/39
|
4.5%
1/22 • Number of events 1
|
|
Gastrointestinal disorders
Nausea
|
0.00%
0/14
|
2.6%
1/39 • Number of events 1
|
4.5%
1/22 • Number of events 1
|
|
Gastrointestinal disorders
Vomiting
|
0.00%
0/14
|
0.00%
0/39
|
4.5%
1/22 • Number of events 1
|
|
General disorders
Death
|
0.00%
0/14
|
2.6%
1/39 • Number of events 1
|
0.00%
0/22
|
|
General disorders
Pyrexia
|
0.00%
0/14
|
0.00%
0/39
|
4.5%
1/22 • Number of events 1
|
|
Infections and infestations
Infection
|
0.00%
0/14
|
2.6%
1/39 • Number of events 2
|
4.5%
1/22 • Number of events 1
|
|
Infections and infestations
Pneumonia
|
0.00%
0/14
|
2.6%
1/39 • Number of events 1
|
0.00%
0/22
|
|
Infections and infestations
Urinary tract infection bacterial
|
0.00%
0/14
|
2.6%
1/39 • Number of events 1
|
0.00%
0/22
|
|
Injury, poisoning and procedural complications
Femur fracture
|
0.00%
0/14
|
2.6%
1/39 • Number of events 1
|
0.00%
0/22
|
|
Injury, poisoning and procedural complications
Tibia fracture
|
0.00%
0/14
|
2.6%
1/39 • Number of events 1
|
0.00%
0/22
|
|
Investigations
Blood creatinine increased
|
0.00%
0/14
|
2.6%
1/39 • Number of events 1
|
0.00%
0/22
|
|
Investigations
Blood urea increased
|
0.00%
0/14
|
2.6%
1/39 • Number of events 1
|
0.00%
0/22
|
|
Metabolism and nutrition disorders
Hyperglycaemia
|
0.00%
0/14
|
2.6%
1/39 • Number of events 1
|
0.00%
0/22
|
|
Metabolism and nutrition disorders
Hypokalaemia
|
0.00%
0/14
|
2.6%
1/39 • Number of events 1
|
0.00%
0/22
|
|
Metabolism and nutrition disorders
Ketoacidosis
|
0.00%
0/14
|
2.6%
1/39 • Number of events 1
|
0.00%
0/22
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal chest pain
|
0.00%
0/14
|
0.00%
0/39
|
4.5%
1/22 • Number of events 1
|
|
Musculoskeletal and connective tissue disorders
Spinal pain
|
0.00%
0/14
|
2.6%
1/39 • Number of events 1
|
0.00%
0/22
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Metastases to bone
|
0.00%
0/14
|
2.6%
1/39 • Number of events 1
|
0.00%
0/22
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Metastatic pain
|
0.00%
0/14
|
0.00%
0/39
|
4.5%
1/22 • Number of events 1
|
|
Nervous system disorders
Cerebrovascular accident
|
0.00%
0/14
|
2.6%
1/39 • Number of events 1
|
0.00%
0/22
|
|
Nervous system disorders
Convulsion
|
0.00%
0/14
|
0.00%
0/39
|
4.5%
1/22 • Number of events 1
|
|
Nervous system disorders
Ischaemic stroke
|
0.00%
0/14
|
2.6%
1/39 • Number of events 1
|
0.00%
0/22
|
|
Nervous system disorders
Syncope
|
0.00%
0/14
|
0.00%
0/39
|
4.5%
1/22 • Number of events 1
|
|
Psychiatric disorders
Confusional state
|
0.00%
0/14
|
2.6%
1/39 • Number of events 1
|
0.00%
0/22
|
|
Respiratory, thoracic and mediastinal disorders
Acute respiratory distress syndrome
|
0.00%
0/14
|
0.00%
0/39
|
4.5%
1/22 • Number of events 1
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary embolism
|
7.1%
1/14 • Number of events 1
|
12.8%
5/39 • Number of events 5
|
0.00%
0/22
|
|
Respiratory, thoracic and mediastinal disorders
Respiratory failure
|
0.00%
0/14
|
2.6%
1/39 • Number of events 1
|
0.00%
0/22
|
Other adverse events
| Measure |
Phase 1: Pemetrexed + Cisplatin + LY2603618
n=14 participants at risk
Cycles 1-2 (21-day cycle):
Day 1: pemetrexed 500 mg/m\^2 + cisplatin 75 mg/m\^2
Day 2: LY2603618 130 to 275 mg
After 2 cycles, participants may have continued on study drug until disease progression, unacceptable toxicity, or other withdrawal criterion was met.
Pemetrexed, cisplatin, and LY2603618 were administered IV over 10 minutes, 1 hour, and 1 hour, respectively.
|
Phase 2: Pemetrexed + Cisplatin + LY2603618
n=39 participants at risk
Cycles 1-4 (21-day cycle):
Before 25 Oct 2012:
Day 1: pemetrexed 500 mg/m\^2 + cisplatin 75 mg/m\^2
Day 2: LY2603618 dose determined from phase 1 (275 mg)
After 25 Oct 2012:
Day 1: pemetrexed 500 mg/m\^2 + cisplatin 75 mg/m\^2
After 4 cycles, participants may have continued on maintenance therapy until disease progression, unacceptable toxicity, or other withdrawal criterion was met.
Maintenance therapy (every 21 days):
Before 25 Oct 2012:
Day 1: pemetrexed 500 mg/m\^2
Day 2: LY2603618 dose determined from phase 1 (275 mg)
After 25 Oct 2012:
Day 1: pemetrexed 500 mg/m\^2
If, as of 25 Oct 2012, the participant was in maintenance therapy and randomized to the experimental arm, the participant was eligible to continue with pemetrexed/LY2603618 therapy if the investigator deemed it was in the participant's best interest and the participant consented.
Pemetrexed, cisplatin, and LY2603618 were administered IV over 10 minutes, 1 hour, and 1 hour, respectively.
|
Phase 2: Pemetrexed + Cisplatin
n=22 participants at risk
Cycles 1-4 (21-day cycle):
Day 1: pemetrexed 500 mg/m\^2 + cisplatin 75 mg/m\^2
After 4 cycles, participants may have continued on maintenance therapy until disease progression, unacceptable toxicity, or other withdrawal criterion was met.
Maintenance therapy (every 21 days):
Day 1: pemetrexed 500 mg/m\^2
Pemetrexed was administered IV over 10 minutes, and cisplatin was administered IV over 1 hour.
|
|---|---|---|---|
|
Blood and lymphatic system disorders
Anaemia
|
21.4%
3/14 • Number of events 16
|
17.9%
7/39 • Number of events 16
|
13.6%
3/22 • Number of events 6
|
|
Blood and lymphatic system disorders
Leukocytosis
|
0.00%
0/14
|
0.00%
0/39
|
9.1%
2/22 • Number of events 2
|
|
Blood and lymphatic system disorders
Leukopenia
|
7.1%
1/14 • Number of events 2
|
12.8%
5/39 • Number of events 11
|
0.00%
0/22
|
|
Blood and lymphatic system disorders
Lymphopenia
|
7.1%
1/14 • Number of events 1
|
0.00%
0/39
|
0.00%
0/22
|
|
Blood and lymphatic system disorders
Neutropenia
|
42.9%
6/14 • Number of events 13
|
20.5%
8/39 • Number of events 11
|
18.2%
4/22 • Number of events 7
|
|
Blood and lymphatic system disorders
Thrombocytopenia
|
14.3%
2/14 • Number of events 10
|
2.6%
1/39 • Number of events 1
|
4.5%
1/22 • Number of events 1
|
|
Blood and lymphatic system disorders
Thrombocytosis
|
7.1%
1/14 • Number of events 1
|
0.00%
0/39
|
0.00%
0/22
|
|
Ear and labyrinth disorders
Ototoxicity
|
0.00%
0/14
|
20.5%
8/39 • Number of events 22
|
4.5%
1/22 • Number of events 2
|
|
Ear and labyrinth disorders
Tinnitus
|
14.3%
2/14 • Number of events 4
|
12.8%
5/39 • Number of events 7
|
9.1%
2/22 • Number of events 2
|
|
Ear and labyrinth disorders
Vertigo
|
21.4%
3/14 • Number of events 4
|
5.1%
2/39 • Number of events 3
|
4.5%
1/22 • Number of events 1
|
|
Eye disorders
Conjunctivitis
|
7.1%
1/14 • Number of events 9
|
5.1%
2/39 • Number of events 3
|
13.6%
3/22 • Number of events 4
|
|
Eye disorders
Eye oedema
|
0.00%
0/14
|
7.7%
3/39 • Number of events 4
|
4.5%
1/22 • Number of events 1
|
|
Eye disorders
Eyelid oedema
|
7.1%
1/14 • Number of events 1
|
0.00%
0/39
|
0.00%
0/22
|
|
Eye disorders
Lacrimation increased
|
7.1%
1/14 • Number of events 1
|
5.1%
2/39 • Number of events 2
|
4.5%
1/22 • Number of events 1
|
|
Eye disorders
Papilloedema
|
7.1%
1/14 • Number of events 1
|
0.00%
0/39
|
0.00%
0/22
|
|
Gastrointestinal disorders
Abdominal pain
|
0.00%
0/14
|
5.1%
2/39 • Number of events 2
|
9.1%
2/22 • Number of events 2
|
|
Gastrointestinal disorders
Abdominal pain upper
|
21.4%
3/14 • Number of events 3
|
2.6%
1/39 • Number of events 1
|
9.1%
2/22 • Number of events 2
|
|
Gastrointestinal disorders
Constipation
|
14.3%
2/14 • Number of events 4
|
46.2%
18/39 • Number of events 30
|
36.4%
8/22 • Number of events 13
|
|
Gastrointestinal disorders
Diarrhoea
|
21.4%
3/14 • Number of events 5
|
28.2%
11/39 • Number of events 17
|
18.2%
4/22 • Number of events 6
|
|
Gastrointestinal disorders
Dry mouth
|
14.3%
2/14 • Number of events 2
|
2.6%
1/39 • Number of events 1
|
0.00%
0/22
|
|
Gastrointestinal disorders
Dyspepsia
|
14.3%
2/14 • Number of events 2
|
5.1%
2/39 • Number of events 2
|
0.00%
0/22
|
|
Gastrointestinal disorders
Dysphagia
|
7.1%
1/14 • Number of events 1
|
2.6%
1/39 • Number of events 1
|
4.5%
1/22 • Number of events 1
|
|
Gastrointestinal disorders
Flatulence
|
14.3%
2/14 • Number of events 2
|
0.00%
0/39
|
0.00%
0/22
|
|
Gastrointestinal disorders
Gastritis
|
7.1%
1/14 • Number of events 1
|
2.6%
1/39 • Number of events 1
|
0.00%
0/22
|
|
Gastrointestinal disorders
Gastrooesophageal reflux disease
|
14.3%
2/14 • Number of events 2
|
2.6%
1/39 • Number of events 1
|
4.5%
1/22 • Number of events 1
|
|
Gastrointestinal disorders
Nausea
|
85.7%
12/14 • Number of events 44
|
76.9%
30/39 • Number of events 106
|
68.2%
15/22 • Number of events 27
|
|
Gastrointestinal disorders
Toothache
|
7.1%
1/14 • Number of events 1
|
0.00%
0/39
|
0.00%
0/22
|
|
Gastrointestinal disorders
Vomiting
|
50.0%
7/14 • Number of events 13
|
46.2%
18/39 • Number of events 42
|
27.3%
6/22 • Number of events 9
|
|
General disorders
Asthenia
|
14.3%
2/14 • Number of events 2
|
43.6%
17/39 • Number of events 82
|
22.7%
5/22 • Number of events 12
|
|
General disorders
Catheter site pain
|
7.1%
1/14 • Number of events 1
|
0.00%
0/39
|
0.00%
0/22
|
|
General disorders
Catheter site related reaction
|
7.1%
1/14 • Number of events 1
|
0.00%
0/39
|
0.00%
0/22
|
|
General disorders
Catheter site swelling
|
7.1%
1/14 • Number of events 1
|
0.00%
0/39
|
0.00%
0/22
|
|
General disorders
Chest discomfort
|
7.1%
1/14 • Number of events 1
|
0.00%
0/39
|
4.5%
1/22 • Number of events 2
|
|
General disorders
Chest pain
|
0.00%
0/14
|
10.3%
4/39 • Number of events 4
|
9.1%
2/22 • Number of events 3
|
|
General disorders
Chills
|
7.1%
1/14 • Number of events 2
|
2.6%
1/39 • Number of events 2
|
13.6%
3/22 • Number of events 4
|
|
General disorders
Fatigue
|
92.9%
13/14 • Number of events 35
|
35.9%
14/39 • Number of events 23
|
63.6%
14/22 • Number of events 21
|
|
General disorders
Infusion site extravasation
|
0.00%
0/14
|
5.1%
2/39 • Number of events 2
|
0.00%
0/22
|
|
General disorders
Infusion site pain
|
0.00%
0/14
|
5.1%
2/39 • Number of events 2
|
0.00%
0/22
|
|
General disorders
Mucosal inflammation
|
14.3%
2/14 • Number of events 2
|
25.6%
10/39 • Number of events 22
|
18.2%
4/22 • Number of events 7
|
|
General disorders
Oedema
|
21.4%
3/14 • Number of events 3
|
10.3%
4/39 • Number of events 7
|
4.5%
1/22 • Number of events 1
|
|
General disorders
Oedema peripheral
|
21.4%
3/14 • Number of events 3
|
15.4%
6/39 • Number of events 10
|
13.6%
3/22 • Number of events 3
|
|
General disorders
Pyrexia
|
42.9%
6/14 • Number of events 8
|
25.6%
10/39 • Number of events 19
|
40.9%
9/22 • Number of events 10
|
|
Immune system disorders
Hypersensitivity
|
7.1%
1/14 • Number of events 3
|
7.7%
3/39 • Number of events 3
|
0.00%
0/22
|
|
Infections and infestations
Bronchitis
|
0.00%
0/14
|
5.1%
2/39 • Number of events 2
|
9.1%
2/22 • Number of events 2
|
|
Infections and infestations
Candida infection
|
0.00%
0/14
|
5.1%
2/39 • Number of events 2
|
0.00%
0/22
|
|
Infections and infestations
Eye infection
|
7.1%
1/14 • Number of events 1
|
0.00%
0/39
|
0.00%
0/22
|
|
Infections and infestations
Gingivitis
|
7.1%
1/14 • Number of events 2
|
0.00%
0/39
|
4.5%
1/22 • Number of events 1
|
|
Infections and infestations
Herpes simplex
|
7.1%
1/14 • Number of events 1
|
0.00%
0/39
|
0.00%
0/22
|
|
Infections and infestations
Laryngitis
|
7.1%
1/14 • Number of events 1
|
2.6%
1/39 • Number of events 2
|
0.00%
0/22
|
|
Infections and infestations
Nasopharyngitis
|
7.1%
1/14 • Number of events 1
|
12.8%
5/39 • Number of events 5
|
9.1%
2/22 • Number of events 2
|
|
Infections and infestations
Paronychia
|
0.00%
0/14
|
5.1%
2/39 • Number of events 2
|
0.00%
0/22
|
|
Infections and infestations
Pneumonia
|
7.1%
1/14 • Number of events 1
|
0.00%
0/39
|
0.00%
0/22
|
|
Infections and infestations
Respiratory tract infection
|
0.00%
0/14
|
5.1%
2/39 • Number of events 2
|
4.5%
1/22 • Number of events 1
|
|
Infections and infestations
Rhinitis
|
14.3%
2/14 • Number of events 2
|
0.00%
0/39
|
4.5%
1/22 • Number of events 1
|
|
Infections and infestations
Upper respiratory tract infection
|
21.4%
3/14 • Number of events 3
|
2.6%
1/39 • Number of events 1
|
4.5%
1/22 • Number of events 1
|
|
Infections and infestations
Urinary tract infection
|
0.00%
0/14
|
5.1%
2/39 • Number of events 2
|
4.5%
1/22 • Number of events 1
|
|
Injury, poisoning and procedural complications
Contrast media reaction
|
7.1%
1/14 • Number of events 2
|
0.00%
0/39
|
0.00%
0/22
|
|
Injury, poisoning and procedural complications
Infusion related reaction
|
14.3%
2/14 • Number of events 5
|
0.00%
0/39
|
0.00%
0/22
|
|
Investigations
Alanine aminotransferase increased
|
7.1%
1/14 • Number of events 1
|
7.7%
3/39 • Number of events 4
|
0.00%
0/22
|
|
Investigations
Aspartate aminotransferase increased
|
0.00%
0/14
|
7.7%
3/39 • Number of events 4
|
0.00%
0/22
|
|
Investigations
Blood creatinine increased
|
7.1%
1/14 • Number of events 3
|
7.7%
3/39 • Number of events 5
|
4.5%
1/22 • Number of events 1
|
|
Investigations
Blood urea increased
|
0.00%
0/14
|
10.3%
4/39 • Number of events 4
|
0.00%
0/22
|
|
Investigations
C-reactive protein increased
|
0.00%
0/14
|
7.7%
3/39 • Number of events 3
|
4.5%
1/22 • Number of events 1
|
|
Investigations
Neutrophil count decreased
|
14.3%
2/14 • Number of events 6
|
7.7%
3/39 • Number of events 4
|
9.1%
2/22 • Number of events 5
|
|
Investigations
Platelet count decreased
|
7.1%
1/14 • Number of events 3
|
5.1%
2/39 • Number of events 8
|
0.00%
0/22
|
|
Investigations
Weight decreased
|
0.00%
0/14
|
7.7%
3/39 • Number of events 4
|
9.1%
2/22 • Number of events 3
|
|
Investigations
White blood cell count decreased
|
7.1%
1/14 • Number of events 4
|
2.6%
1/39 • Number of events 4
|
0.00%
0/22
|
|
Metabolism and nutrition disorders
Decreased appetite
|
14.3%
2/14 • Number of events 3
|
35.9%
14/39 • Number of events 45
|
54.5%
12/22 • Number of events 19
|
|
Metabolism and nutrition disorders
Dehydration
|
7.1%
1/14 • Number of events 1
|
0.00%
0/39
|
4.5%
1/22 • Number of events 1
|
|
Metabolism and nutrition disorders
Dyslipidaemia
|
7.1%
1/14 • Number of events 1
|
0.00%
0/39
|
0.00%
0/22
|
|
Metabolism and nutrition disorders
Hyperglycaemia
|
14.3%
2/14 • Number of events 3
|
2.6%
1/39 • Number of events 1
|
9.1%
2/22 • Number of events 4
|
|
Metabolism and nutrition disorders
Hypocalcaemia
|
0.00%
0/14
|
5.1%
2/39 • Number of events 2
|
0.00%
0/22
|
|
Metabolism and nutrition disorders
Hypokalaemia
|
7.1%
1/14 • Number of events 2
|
7.7%
3/39 • Number of events 3
|
4.5%
1/22 • Number of events 1
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
7.1%
1/14 • Number of events 1
|
5.1%
2/39 • Number of events 3
|
9.1%
2/22 • Number of events 2
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
7.1%
1/14 • Number of events 1
|
7.7%
3/39 • Number of events 3
|
9.1%
2/22 • Number of events 2
|
|
Musculoskeletal and connective tissue disorders
Bone pain
|
7.1%
1/14 • Number of events 1
|
7.7%
3/39 • Number of events 3
|
9.1%
2/22 • Number of events 2
|
|
Musculoskeletal and connective tissue disorders
Muscle spasms
|
7.1%
1/14 • Number of events 1
|
0.00%
0/39
|
0.00%
0/22
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal chest pain
|
7.1%
1/14 • Number of events 1
|
12.8%
5/39 • Number of events 6
|
4.5%
1/22 • Number of events 1
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal pain
|
21.4%
3/14 • Number of events 3
|
17.9%
7/39 • Number of events 11
|
18.2%
4/22 • Number of events 6
|
|
Musculoskeletal and connective tissue disorders
Osteoarthritis
|
7.1%
1/14 • Number of events 1
|
0.00%
0/39
|
0.00%
0/22
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
14.3%
2/14 • Number of events 3
|
7.7%
3/39 • Number of events 4
|
4.5%
1/22 • Number of events 1
|
|
Musculoskeletal and connective tissue disorders
Spinal pain
|
0.00%
0/14
|
5.1%
2/39 • Number of events 4
|
0.00%
0/22
|
|
Nervous system disorders
Dizziness
|
7.1%
1/14 • Number of events 1
|
15.4%
6/39 • Number of events 12
|
4.5%
1/22 • Number of events 1
|
|
Nervous system disorders
Dysaesthesia
|
7.1%
1/14 • Number of events 2
|
0.00%
0/39
|
0.00%
0/22
|
|
Nervous system disorders
Dysgeusia
|
7.1%
1/14 • Number of events 2
|
5.1%
2/39 • Number of events 2
|
4.5%
1/22 • Number of events 1
|
|
Nervous system disorders
Headache
|
21.4%
3/14 • Number of events 5
|
20.5%
8/39 • Number of events 17
|
9.1%
2/22 • Number of events 2
|
|
Nervous system disorders
Hypoaesthesia
|
0.00%
0/14
|
2.6%
1/39 • Number of events 1
|
9.1%
2/22 • Number of events 3
|
|
Nervous system disorders
Neurotoxicity
|
0.00%
0/14
|
17.9%
7/39 • Number of events 9
|
0.00%
0/22
|
|
Nervous system disorders
Paraesthesia
|
21.4%
3/14 • Number of events 5
|
10.3%
4/39 • Number of events 4
|
4.5%
1/22 • Number of events 1
|
|
Nervous system disorders
Paresis
|
7.1%
1/14 • Number of events 1
|
2.6%
1/39 • Number of events 1
|
0.00%
0/22
|
|
Nervous system disorders
Presyncope
|
7.1%
1/14 • Number of events 2
|
2.6%
1/39 • Number of events 1
|
4.5%
1/22 • Number of events 1
|
|
Nervous system disorders
Somnolence
|
7.1%
1/14 • Number of events 1
|
2.6%
1/39 • Number of events 1
|
0.00%
0/22
|
|
Nervous system disorders
Tremor
|
0.00%
0/14
|
5.1%
2/39 • Number of events 4
|
0.00%
0/22
|
|
Psychiatric disorders
Anxiety
|
0.00%
0/14
|
7.7%
3/39 • Number of events 3
|
9.1%
2/22 • Number of events 2
|
|
Psychiatric disorders
Depression
|
7.1%
1/14 • Number of events 2
|
2.6%
1/39 • Number of events 1
|
4.5%
1/22 • Number of events 1
|
|
Psychiatric disorders
Insomnia
|
35.7%
5/14 • Number of events 6
|
10.3%
4/39 • Number of events 5
|
13.6%
3/22 • Number of events 4
|
|
Renal and urinary disorders
Nephrolithiasis
|
7.1%
1/14 • Number of events 1
|
0.00%
0/39
|
0.00%
0/22
|
|
Reproductive system and breast disorders
Menstruation irregular
|
0.00%
0/7
|
6.7%
1/15 • Number of events 1
|
0.00%
0/8
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
21.4%
3/14 • Number of events 4
|
20.5%
8/39 • Number of events 19
|
13.6%
3/22 • Number of events 3
|
|
Respiratory, thoracic and mediastinal disorders
Dysphonia
|
0.00%
0/14
|
10.3%
4/39 • Number of events 4
|
18.2%
4/22 • Number of events 4
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
0.00%
0/14
|
30.8%
12/39 • Number of events 16
|
31.8%
7/22 • Number of events 9
|
|
Respiratory, thoracic and mediastinal disorders
Epistaxis
|
7.1%
1/14 • Number of events 2
|
12.8%
5/39 • Number of events 5
|
0.00%
0/22
|
|
Respiratory, thoracic and mediastinal disorders
Hiccups
|
14.3%
2/14 • Number of events 5
|
2.6%
1/39 • Number of events 1
|
9.1%
2/22 • Number of events 3
|
|
Respiratory, thoracic and mediastinal disorders
Nasal congestion
|
7.1%
1/14 • Number of events 1
|
0.00%
0/39
|
0.00%
0/22
|
|
Respiratory, thoracic and mediastinal disorders
Oropharyngeal pain
|
14.3%
2/14 • Number of events 2
|
0.00%
0/39
|
4.5%
1/22 • Number of events 1
|
|
Respiratory, thoracic and mediastinal disorders
Pleural effusion
|
0.00%
0/14
|
5.1%
2/39 • Number of events 2
|
0.00%
0/22
|
|
Respiratory, thoracic and mediastinal disorders
Productive cough
|
0.00%
0/14
|
0.00%
0/39
|
18.2%
4/22 • Number of events 4
|
|
Respiratory, thoracic and mediastinal disorders
Rhinitis allergic
|
7.1%
1/14 • Number of events 1
|
2.6%
1/39 • Number of events 1
|
0.00%
0/22
|
|
Respiratory, thoracic and mediastinal disorders
Sneezing
|
7.1%
1/14 • Number of events 1
|
0.00%
0/39
|
0.00%
0/22
|
|
Skin and subcutaneous tissue disorders
Alopecia
|
28.6%
4/14 • Number of events 4
|
12.8%
5/39 • Number of events 5
|
0.00%
0/22
|
|
Skin and subcutaneous tissue disorders
Angioedema
|
7.1%
1/14 • Number of events 1
|
0.00%
0/39
|
0.00%
0/22
|
|
Skin and subcutaneous tissue disorders
Dermatitis acneiform
|
7.1%
1/14 • Number of events 1
|
0.00%
0/39
|
0.00%
0/22
|
|
Skin and subcutaneous tissue disorders
Dry skin
|
14.3%
2/14 • Number of events 2
|
7.7%
3/39 • Number of events 3
|
4.5%
1/22 • Number of events 2
|
|
Skin and subcutaneous tissue disorders
Eczema
|
0.00%
0/14
|
5.1%
2/39 • Number of events 2
|
13.6%
3/22 • Number of events 3
|
|
Skin and subcutaneous tissue disorders
Erythema
|
7.1%
1/14 • Number of events 1
|
5.1%
2/39 • Number of events 2
|
4.5%
1/22 • Number of events 1
|
|
Skin and subcutaneous tissue disorders
Erythema multiforme
|
7.1%
1/14 • Number of events 1
|
0.00%
0/39
|
4.5%
1/22 • Number of events 1
|
|
Skin and subcutaneous tissue disorders
Hyperhidrosis
|
14.3%
2/14 • Number of events 2
|
5.1%
2/39 • Number of events 2
|
4.5%
1/22 • Number of events 1
|
|
Skin and subcutaneous tissue disorders
Nail disorder
|
0.00%
0/14
|
5.1%
2/39 • Number of events 2
|
0.00%
0/22
|
|
Skin and subcutaneous tissue disorders
Night sweats
|
7.1%
1/14 • Number of events 1
|
0.00%
0/39
|
4.5%
1/22 • Number of events 1
|
|
Skin and subcutaneous tissue disorders
Pruritus
|
14.3%
2/14 • Number of events 3
|
2.6%
1/39 • Number of events 1
|
18.2%
4/22 • Number of events 4
|
|
Skin and subcutaneous tissue disorders
Rash
|
14.3%
2/14 • Number of events 3
|
10.3%
4/39 • Number of events 4
|
9.1%
2/22 • Number of events 2
|
|
Skin and subcutaneous tissue disorders
Skin discolouration
|
7.1%
1/14 • Number of events 2
|
0.00%
0/39
|
0.00%
0/22
|
|
Skin and subcutaneous tissue disorders
Skin disorder
|
0.00%
0/14
|
5.1%
2/39 • Number of events 2
|
0.00%
0/22
|
|
Skin and subcutaneous tissue disorders
Skin lesion
|
0.00%
0/14
|
5.1%
2/39 • Number of events 2
|
0.00%
0/22
|
|
Surgical and medical procedures
Catheterisation venous
|
7.1%
1/14 • Number of events 1
|
0.00%
0/39
|
0.00%
0/22
|
|
Vascular disorders
Circulatory collapse
|
7.1%
1/14 • Number of events 2
|
0.00%
0/39
|
0.00%
0/22
|
|
Vascular disorders
Haematoma
|
14.3%
2/14 • Number of events 2
|
10.3%
4/39 • Number of events 4
|
0.00%
0/22
|
|
Vascular disorders
Hypertension
|
21.4%
3/14 • Number of events 7
|
7.7%
3/39 • Number of events 4
|
4.5%
1/22 • Number of events 1
|
|
Vascular disorders
Hypertensive crisis
|
7.1%
1/14 • Number of events 1
|
5.1%
2/39 • Number of events 2
|
0.00%
0/22
|
|
Vascular disorders
Hypotension
|
14.3%
2/14 • Number of events 2
|
2.6%
1/39 • Number of events 1
|
4.5%
1/22 • Number of events 1
|
|
Vascular disorders
Phlebitis
|
0.00%
0/14
|
5.1%
2/39 • Number of events 2
|
4.5%
1/22 • Number of events 1
|
Additional Information
Chief Medical Officer
Eli Lilly and Company
Phone: 800-545-5979
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place
Restriction type: GT60