Trial Outcomes & Findings for A Study of Nab-Paclitaxel and Carboplatin Plus Necitumumab (LY3012211) in Participants With Stage IV Squamous NSCLC (NCT NCT02392507)

NCT ID: NCT02392507

Last Updated: 2020-11-19

Results Overview

ORR was the percentage of participants achieving a best overall response of complete response (CR) or partial response (PR) as per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. CR defined as the disappearance of all target and non-target lesions and no appearance of new lesions. PR defined as at least a 30% decrease in the sum of the longest diameters (LD) of target lesions (taking as reference the baseline sum LD), no progression of nontarget lesions, and no appearance of new lesions. Progressive disease (PD) was at least a 20% increase in the sum of the diameters of target lesions, with reference being the smallest sum on study and an absolute increase of at least 5 mm, or unequivocal progression of non-target lesions, or 1 or more new lesions.

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 54 participants
• Primary outcome timeframe: From Date of Randomization to Objective Disease Progression (Up to 18 Months)
• Results posted on: 2020-11-19

Participant Flow

Participants with known best overall response and off study treatment were considered to be completed.

Participant milestones

Measure	Necitumumab + Nab-Paclitaxel + Carboplatin Induction: Necitumumab administered intravenously (IV) at 800 milligram (mg) on day 1 and 8 of each cycle (3 week cycles); nab-paclitaxel administered IV at 100 milligram per square meter (mg/m²) on day 1, 8 and 15 of each cycle; carboplatin administered IV at a concentration of AUC (area under curve) 6 milligram per milliliter over time (mg\*min/mL) on day 1 of each cycle, for a maximum of 4 cycles. Maintenance: Necitumumab administered IV at 800 mg on day 1 and 8 of each cycle; nab-paclitaxel administered IV at 100mg/m² on day 1 and 8 of each cycle (3 week cycles). Participants may continue to receive treatment until discontinuation criteria are met.
Induction Regimen STARTED	54
Induction Regimen Received at Least 1 Dose of Study Drug	54
Induction Regimen COMPLETED	47
Induction Regimen NOT COMPLETED	7
Maintenance Regimen STARTED	34
Maintenance Regimen COMPLETED	32
Maintenance Regimen NOT COMPLETED	2

Reasons for withdrawal

Measure	Necitumumab + Nab-Paclitaxel + Carboplatin Induction: Necitumumab administered intravenously (IV) at 800 milligram (mg) on day 1 and 8 of each cycle (3 week cycles); nab-paclitaxel administered IV at 100 milligram per square meter (mg/m²) on day 1, 8 and 15 of each cycle; carboplatin administered IV at a concentration of AUC (area under curve) 6 milligram per milliliter over time (mg\*min/mL) on day 1 of each cycle, for a maximum of 4 cycles. Maintenance: Necitumumab administered IV at 800 mg on day 1 and 8 of each cycle; nab-paclitaxel administered IV at 100mg/m² on day 1 and 8 of each cycle (3 week cycles). Participants may continue to receive treatment until discontinuation criteria are met.
Induction Regimen Death	3
Induction Regimen On Study Treatment at Study Conclusion	1
Induction Regimen Physician Decision	1
Induction Regimen Withdrawal by Subject	2
Maintenance Regimen Death	1
Maintenance Regimen On Study Treatment at Study Conclusion	1

Baseline Characteristics

A Study of Nab-Paclitaxel and Carboplatin Plus Necitumumab (LY3012211) in Participants With Stage IV Squamous NSCLC

Baseline characteristics by cohort

Measure	Necitumumab + Nab-Paclitaxel + Carboplatin n=54 Participants Induction: Necitumumab administered IV at 800 mg on day 1 and 8 of each cycle (3 week cycles); nab-paclitaxel administered IV at 100 mg/m² on day 1, 8 and 15 of each cycle; carboplatin administered IV at a concentration of AUC 6 mg\*min/mL on day 1 of each cycle, for a maximum of 4 cycles. Maintenance: Necitumumab administered IV at 800 mg on day 1 and 8 of each cycle; nab-paclitaxel administered IV at 100mg/m² on day 1 and 8 of each cycle (3 week cycles). Participants may continue to receive treatment until discontinuation criteria are met.
Age, Continuous	65.96 years STANDARD_DEVIATION 7.48 • n=5 Participants
Sex: Female, Male Female	12 Participants n=5 Participants
Sex: Female, Male Male	42 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	4 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	50 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	0 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	53 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	15 Participants n=5 Participants
Region of Enrollment Germany	4 Participants n=5 Participants
Region of Enrollment Spain	27 Participants n=5 Participants
Region of Enrollment Greece	8 Participants n=5 Participants

PRIMARY outcome

Timeframe: From Date of Randomization to Objective Disease Progression (Up to 18 Months)

Population: All randomized participants who received at least 1 dose of study drug and who had a complete radiographic assessment at baseline and at least 1 complete radiographic assessment post-baseline.

ORR was the percentage of participants achieving a best overall response of complete response (CR) or partial response (PR) as per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. CR defined as the disappearance of all target and non-target lesions and no appearance of new lesions. PR defined as at least a 30% decrease in the sum of the longest diameters (LD) of target lesions (taking as reference the baseline sum LD), no progression of nontarget lesions, and no appearance of new lesions. Progressive disease (PD) was at least a 20% increase in the sum of the diameters of target lesions, with reference being the smallest sum on study and an absolute increase of at least 5 mm, or unequivocal progression of non-target lesions, or 1 or more new lesions.

Outcome measures

Measure	Necitumumab + Nab-Paclitaxel + Carboplatin n=51 Participants Induction: Necitumumab administered IV at 800 mg on day 1 and 8 of each cycle (3 week cycles); nab-paclitaxel administered IV at 100 mg/m² on day 1, 8 and 15 of each cycle; carboplatin administered IV at a concentration of AUC 6 mg\*min/mL on day 1 of each cycle, for a maximum of 4 cycles. Maintenance: Necitumumab administered IV at 800 mg on day 1 and 8 of each cycle; nab-paclitaxel administered IV at 100mg/m² on day 1 and 8 of each cycle (3 week cycles). Participants may continue to receive treatment until discontinuation criteria are met.	Carboplatin Carboplatin administered IV at a concentration of AUC 6 mg\*min/mL on day 1 of each cycle, for a maximum of 4 cycles.	Paclitaxel Nab-paclitaxel administered IV at 100 mg/m² on day 1, 8 and 15 of each cycle.
Percentage of Participants Who Achieve Best Overall Tumor Response of Complete Response or Partial Response (Objective Tumor Response Rate [ORR])	51.0 percentage of participants	—	—

SECONDARY outcome

Timeframe: From Date of Randomization to Measured Progressive Disease or Death Due to Any Cause (Up to 18 Months)

Population: All randomized participants who received at least 1 dose of study drug. Censored participants = 15.

PFS defined as time from date of randomization until first radiographic documentation of measured PD defined by response evaluation criteria in solid tumors (RECIST) v1.1 or death from any cause. PD was at least 20% increase in sum of diameters of target lesions with reference being smallest sum on study and an absolute increase of at least 5 mm,or unequivocal progression of non-target lesions,or 1 or more new lesions.If participant does not have complete baseline disease assessment,PFS time censored at date of randomization,regardless of whether or not objectively determined disease progression or death observed for participant.If participant was not known to have died or have objective progression as of data inclusion cutoff date for analysis,the PFS time censored at last adequate tumor assessment date.The use of new anticancer therapy prior to occurrence of PD resulted in censoring at the date of last radiographic assessment prior to initiation of new therapy.

Outcome measures

Measure	Necitumumab + Nab-Paclitaxel + Carboplatin n=54 Participants Induction: Necitumumab administered IV at 800 mg on day 1 and 8 of each cycle (3 week cycles); nab-paclitaxel administered IV at 100 mg/m² on day 1, 8 and 15 of each cycle; carboplatin administered IV at a concentration of AUC 6 mg\*min/mL on day 1 of each cycle, for a maximum of 4 cycles. Maintenance: Necitumumab administered IV at 800 mg on day 1 and 8 of each cycle; nab-paclitaxel administered IV at 100mg/m² on day 1 and 8 of each cycle (3 week cycles). Participants may continue to receive treatment until discontinuation criteria are met.	Carboplatin Carboplatin administered IV at a concentration of AUC 6 mg\*min/mL on day 1 of each cycle, for a maximum of 4 cycles.	Paclitaxel Nab-paclitaxel administered IV at 100 mg/m² on day 1, 8 and 15 of each cycle.
Progression Free Survival (PFS)	5.59 Months Interval 4.24 to 7.69	—	—

SECONDARY outcome

Timeframe: From Date of Randomization until Death Due to Any Cause (Up to 18 Months)

Population: All randomized participants who received at least 1 dose of study drug. Censored participants = 35.

OS defined as the time from the date of randomization to the date of death due to any cause. Participants who are alive at the time of study completion or are lost to follow-up will be censored at the time they were last known to be alive.

Outcome measures

Measure	Necitumumab + Nab-Paclitaxel + Carboplatin n=54 Participants Induction: Necitumumab administered IV at 800 mg on day 1 and 8 of each cycle (3 week cycles); nab-paclitaxel administered IV at 100 mg/m² on day 1, 8 and 15 of each cycle; carboplatin administered IV at a concentration of AUC 6 mg\*min/mL on day 1 of each cycle, for a maximum of 4 cycles. Maintenance: Necitumumab administered IV at 800 mg on day 1 and 8 of each cycle; nab-paclitaxel administered IV at 100mg/m² on day 1 and 8 of each cycle (3 week cycles). Participants may continue to receive treatment until discontinuation criteria are met.	Carboplatin Carboplatin administered IV at a concentration of AUC 6 mg\*min/mL on day 1 of each cycle, for a maximum of 4 cycles.	Paclitaxel Nab-paclitaxel administered IV at 100 mg/m² on day 1, 8 and 15 of each cycle.
Overall Survival (OS)	15.54 Months Interval 10.18 to The upper limit of the 95% CI was not calculated due to the high censoring rate.	—	—

SECONDARY outcome

Timeframe: From Date of Randomization to Objective Disease Progression or Start of New Anticancer Therapy (Up to 18 Months)

Population: All randomized participants who received at least 1 dose of study drug and who had a complete radiographic assessment at baseline.

Disease Control Rate (DCR) was the percentage of participants with a best overall response of CR, PR, or Stable Disease (SD) as per Response using RECIST v1.1 criteria. CR defined as the disappearance of all target and nontarget lesions and no appearance of new lesions. PR defined as at least a 30% decrease in the sum of the LD of target lesions (taking as reference the baseline sum LD), no progression of non-target lesions, and no appearance of new lesions. SD was neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD for target lesions, no progression of non-target lesions, and no appearance of new lesions. PD was at least a 20% increase in the sum of the diameters of target lesions, with reference being the smallest sum on study and an absolute increase of at least 5 mm, or unequivocal progression of non-target lesions, or 1 or more new lesions.

Outcome measures

Measure	Necitumumab + Nab-Paclitaxel + Carboplatin n=51 Participants Induction: Necitumumab administered IV at 800 mg on day 1 and 8 of each cycle (3 week cycles); nab-paclitaxel administered IV at 100 mg/m² on day 1, 8 and 15 of each cycle; carboplatin administered IV at a concentration of AUC 6 mg\*min/mL on day 1 of each cycle, for a maximum of 4 cycles. Maintenance: Necitumumab administered IV at 800 mg on day 1 and 8 of each cycle; nab-paclitaxel administered IV at 100mg/m² on day 1 and 8 of each cycle (3 week cycles). Participants may continue to receive treatment until discontinuation criteria are met.	Carboplatin Carboplatin administered IV at a concentration of AUC 6 mg\*min/mL on day 1 of each cycle, for a maximum of 4 cycles.	Paclitaxel Nab-paclitaxel administered IV at 100 mg/m² on day 1, 8 and 15 of each cycle.
Percentage of Participants Who Achieve Best Overall Disease Response of Complete Response (CR), Partial Response (PR) or Stable Disease (SD) (Disease Control Rate [DCR])	78.4 percentage of participants	—	—

SECONDARY outcome

Timeframe: Cycle 3 and cycle 4: predose

Population: All randomized participants who received at least 1 dose of study drug and had evaluable PK data.

The Cmin is the minimum observed serum/plasma concentration of Necitumumab, Nab-Paclitaxel, and Carboplatin.

Outcome measures

Measure	Necitumumab + Nab-Paclitaxel + Carboplatin n=37 Participants Induction: Necitumumab administered IV at 800 mg on day 1 and 8 of each cycle (3 week cycles); nab-paclitaxel administered IV at 100 mg/m² on day 1, 8 and 15 of each cycle; carboplatin administered IV at a concentration of AUC 6 mg\*min/mL on day 1 of each cycle, for a maximum of 4 cycles. Maintenance: Necitumumab administered IV at 800 mg on day 1 and 8 of each cycle; nab-paclitaxel administered IV at 100mg/m² on day 1 and 8 of each cycle (3 week cycles). Participants may continue to receive treatment until discontinuation criteria are met.	Carboplatin n=32 Participants Carboplatin administered IV at a concentration of AUC 6 mg\*min/mL on day 1 of each cycle, for a maximum of 4 cycles.	Paclitaxel n=3 Participants Nab-paclitaxel administered IV at 100 mg/m² on day 1, 8 and 15 of each cycle.
Pharmacokinetics (PK): Minimum Concentration (Cmin) of Necitumumab, Nab-Paclitaxel, and Carboplatin Cycle 3	65.2 nanogram per milliliter (ng/mL) Geometric Coefficient of Variation 86.9	0.131 nanogram per milliliter (ng/mL) Geometric Coefficient of Variation 36	33.6 nanogram per milliliter (ng/mL) Geometric Coefficient of Variation 393
Pharmacokinetics (PK): Minimum Concentration (Cmin) of Necitumumab, Nab-Paclitaxel, and Carboplatin Cycle 4	90 nanogram per milliliter (ng/mL) Geometric Coefficient of Variation 74.9	0.209 nanogram per milliliter (ng/mL) Geometric Coefficient of Variation 197	107 nanogram per milliliter (ng/mL) Geometric Coefficient of Variation 313

SECONDARY outcome

Timeframe: Cycle 1, 3 and 4: predose and <15minutes (min) post end-of-infusion

Population: All randomized participants who received at least 1 dose of study drug and had evaluable PK data.

The Cmax is the maximum observed serum/plasma concentration of Necitumumab, Nab-Paclitaxel, and Carboplatin.

Outcome measures

Measure	Necitumumab + Nab-Paclitaxel + Carboplatin n=36 Participants Induction: Necitumumab administered IV at 800 mg on day 1 and 8 of each cycle (3 week cycles); nab-paclitaxel administered IV at 100 mg/m² on day 1, 8 and 15 of each cycle; carboplatin administered IV at a concentration of AUC 6 mg\*min/mL on day 1 of each cycle, for a maximum of 4 cycles. Maintenance: Necitumumab administered IV at 800 mg on day 1 and 8 of each cycle; nab-paclitaxel administered IV at 100mg/m² on day 1 and 8 of each cycle (3 week cycles). Participants may continue to receive treatment until discontinuation criteria are met.	Carboplatin n=32 Participants Carboplatin administered IV at a concentration of AUC 6 mg\*min/mL on day 1 of each cycle, for a maximum of 4 cycles.	Paclitaxel n=37 Participants Nab-paclitaxel administered IV at 100 mg/m² on day 1, 8 and 15 of each cycle.
PK: Maximum Concentration (Cmax) of Necitumumab, Nab-Paclitaxel, and Carboplatin Cycle 4	277 ng/mL Geometric Coefficient of Variation 42.5	10.5 ng/mL Geometric Coefficient of Variation 160	221 ng/mL Geometric Coefficient of Variation 77.6
PK: Maximum Concentration (Cmax) of Necitumumab, Nab-Paclitaxel, and Carboplatin Cycle 1	231 ng/mL Geometric Coefficient of Variation 27.1	16.4 ng/mL Geometric Coefficient of Variation 22	343 ng/mL Geometric Coefficient of Variation 81.2
PK: Maximum Concentration (Cmax) of Necitumumab, Nab-Paclitaxel, and Carboplatin Cycle 3	291 ng/mL Geometric Coefficient of Variation 46.5	16 ng/mL Geometric Coefficient of Variation 26.4	284 ng/mL Geometric Coefficient of Variation 73

SECONDARY outcome

Timeframe: Predose Cycle 1 Through Short Term Follow Up (Up To 18 Months)

Population: All randomized participants who received at least 1 dose of study drug and had evaluable data for antibodies.

A participant was considered to have an anti-drug antibody response if anti-drug antibodies (ADA) were detected at any time point.

Outcome measures

Measure	Necitumumab + Nab-Paclitaxel + Carboplatin n=54 Participants Induction: Necitumumab administered IV at 800 mg on day 1 and 8 of each cycle (3 week cycles); nab-paclitaxel administered IV at 100 mg/m² on day 1, 8 and 15 of each cycle; carboplatin administered IV at a concentration of AUC 6 mg\*min/mL on day 1 of each cycle, for a maximum of 4 cycles. Maintenance: Necitumumab administered IV at 800 mg on day 1 and 8 of each cycle; nab-paclitaxel administered IV at 100mg/m² on day 1 and 8 of each cycle (3 week cycles). Participants may continue to receive treatment until discontinuation criteria are met.	Carboplatin Carboplatin administered IV at a concentration of AUC 6 mg\*min/mL on day 1 of each cycle, for a maximum of 4 cycles.	Paclitaxel Nab-paclitaxel administered IV at 100 mg/m² on day 1, 8 and 15 of each cycle.
Immunogenicity: Number of Participants Developing Anti-drug Antibodies to Necitumumab	3 Participants	—	—

Adverse Events

Necitumumab + Nab-paclitaxel + Carboplatin: Induction Phase

Serious events: 18 serious events

Other events: 54 other events

Deaths: 3 deaths

Necitumumab + Nab-paclitaxel: Maintenance Phase

Serious events: 5 serious events

Other events: 31 other events

Deaths: 1 deaths

Serious adverse events

Measure	Necitumumab + Nab-paclitaxel + Carboplatin: Induction Phase n=54 participants at risk Necitumumab administered IV at 800 mg on day 1 and 8 of each cycle (3 week cycles); nab-paclitaxel administered IV at 100 mg/m² on day 1, 8 and 15 of each cycle; carboplatin administered IV at a concentration of AUC 6 mg\*min/mL on day 1 of each cycle, for a maximum of 4 cycles. Participants may continue to receive treatment until discontinuation criteria are met.	Necitumumab + Nab-paclitaxel: Maintenance Phase n=34 participants at risk Necitumumab administered IV at 800 mg on day 1 and 8 of each cycle; nab-paclitaxel administered IV at 100mg/m² on day 1 and 8 of each cycle (3 week cycles). Participants may continue to receive treatment until discontinuation criteria are met.
Blood and lymphatic system disorders Febrile neutropenia	1.9% 1/54 • Number of events 2 • Baseline Up to 49 Months All randomized participants who received at least 1 dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/34 • Baseline Up to 49 Months All randomized participants who received at least 1 dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.
Blood and lymphatic system disorders Leukopenia	1.9% 1/54 • Number of events 1 • Baseline Up to 49 Months All randomized participants who received at least 1 dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/34 • Baseline Up to 49 Months All randomized participants who received at least 1 dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.
Blood and lymphatic system disorders Neutropenia	1.9% 1/54 • Number of events 1 • Baseline Up to 49 Months All randomized participants who received at least 1 dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/34 • Baseline Up to 49 Months All randomized participants who received at least 1 dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.
Cardiac disorders Atrial fibrillation	1.9% 1/54 • Number of events 1 • Baseline Up to 49 Months All randomized participants who received at least 1 dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/34 • Baseline Up to 49 Months All randomized participants who received at least 1 dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.
Cardiac disorders Myocardial infarction	0.00% 0/54 • Baseline Up to 49 Months All randomized participants who received at least 1 dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	2.9% 1/34 • Number of events 1 • Baseline Up to 49 Months All randomized participants who received at least 1 dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.
Gastrointestinal disorders Diarrhoea	3.7% 2/54 • Number of events 2 • Baseline Up to 49 Months All randomized participants who received at least 1 dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/34 • Baseline Up to 49 Months All randomized participants who received at least 1 dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.
Gastrointestinal disorders Gastric ulcer	1.9% 1/54 • Number of events 1 • Baseline Up to 49 Months All randomized participants who received at least 1 dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/34 • Baseline Up to 49 Months All randomized participants who received at least 1 dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.
Gastrointestinal disorders Gastrointestinal pain	1.9% 1/54 • Number of events 1 • Baseline Up to 49 Months All randomized participants who received at least 1 dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/34 • Baseline Up to 49 Months All randomized participants who received at least 1 dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.
Gastrointestinal disorders Ileus	1.9% 1/54 • Number of events 1 • Baseline Up to 49 Months All randomized participants who received at least 1 dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/34 • Baseline Up to 49 Months All randomized participants who received at least 1 dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.
Gastrointestinal disorders Nausea	3.7% 2/54 • Number of events 2 • Baseline Up to 49 Months All randomized participants who received at least 1 dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/34 • Baseline Up to 49 Months All randomized participants who received at least 1 dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.
Gastrointestinal disorders Small intestinal perforation	1.9% 1/54 • Number of events 1 • Baseline Up to 49 Months All randomized participants who received at least 1 dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/34 • Baseline Up to 49 Months All randomized participants who received at least 1 dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.
Gastrointestinal disorders Vomiting	1.9% 1/54 • Number of events 1 • Baseline Up to 49 Months All randomized participants who received at least 1 dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/34 • Baseline Up to 49 Months All randomized participants who received at least 1 dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.
General disorders Death	0.00% 0/54 • Baseline Up to 49 Months All randomized participants who received at least 1 dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	2.9% 1/34 • Number of events 1 • Baseline Up to 49 Months All randomized participants who received at least 1 dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.
General disorders Fatigue	3.7% 2/54 • Number of events 2 • Baseline Up to 49 Months All randomized participants who received at least 1 dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	2.9% 1/34 • Number of events 1 • Baseline Up to 49 Months All randomized participants who received at least 1 dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.
General disorders Multiple organ dysfunction syndrome	1.9% 1/54 • Number of events 1 • Baseline Up to 49 Months All randomized participants who received at least 1 dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/34 • Baseline Up to 49 Months All randomized participants who received at least 1 dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.
Immune system disorders Hypersensitivity	1.9% 1/54 • Number of events 1 • Baseline Up to 49 Months All randomized participants who received at least 1 dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/34 • Baseline Up to 49 Months All randomized participants who received at least 1 dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.
Infections and infestations Diverticulitis	1.9% 1/54 • Number of events 1 • Baseline Up to 49 Months All randomized participants who received at least 1 dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/34 • Baseline Up to 49 Months All randomized participants who received at least 1 dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.
Infections and infestations Gastroenteritis	1.9% 1/54 • Number of events 1 • Baseline Up to 49 Months All randomized participants who received at least 1 dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/34 • Baseline Up to 49 Months All randomized participants who received at least 1 dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.
Infections and infestations Lung infection	1.9% 1/54 • Number of events 1 • Baseline Up to 49 Months All randomized participants who received at least 1 dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/34 • Baseline Up to 49 Months All randomized participants who received at least 1 dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.
Infections and infestations Pneumonia	0.00% 0/54 • Baseline Up to 49 Months All randomized participants who received at least 1 dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	2.9% 1/34 • Number of events 1 • Baseline Up to 49 Months All randomized participants who received at least 1 dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.
Infections and infestations Pulmonary sepsis	1.9% 1/54 • Number of events 1 • Baseline Up to 49 Months All randomized participants who received at least 1 dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/34 • Baseline Up to 49 Months All randomized participants who received at least 1 dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.
Infections and infestations Respiratory tract infection	3.7% 2/54 • Number of events 2 • Baseline Up to 49 Months All randomized participants who received at least 1 dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/34 • Baseline Up to 49 Months All randomized participants who received at least 1 dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.
Infections and infestations Sepsis	1.9% 1/54 • Number of events 1 • Baseline Up to 49 Months All randomized participants who received at least 1 dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/34 • Baseline Up to 49 Months All randomized participants who received at least 1 dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.
Infections and infestations Urinary tract infection	1.9% 1/54 • Number of events 1 • Baseline Up to 49 Months All randomized participants who received at least 1 dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/34 • Baseline Up to 49 Months All randomized participants who received at least 1 dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.
Injury, poisoning and procedural complications Fall	1.9% 1/54 • Number of events 1 • Baseline Up to 49 Months All randomized participants who received at least 1 dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	2.9% 1/34 • Number of events 1 • Baseline Up to 49 Months All randomized participants who received at least 1 dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.
Injury, poisoning and procedural complications Femur fracture	1.9% 1/54 • Number of events 1 • Baseline Up to 49 Months All randomized participants who received at least 1 dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	2.9% 1/34 • Number of events 1 • Baseline Up to 49 Months All randomized participants who received at least 1 dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.
Injury, poisoning and procedural complications Hip fracture	1.9% 1/54 • Number of events 1 • Baseline Up to 49 Months All randomized participants who received at least 1 dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/34 • Baseline Up to 49 Months All randomized participants who received at least 1 dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.
Investigations Neutrophil count decreased	3.7% 2/54 • Number of events 2 • Baseline Up to 49 Months All randomized participants who received at least 1 dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/34 • Baseline Up to 49 Months All randomized participants who received at least 1 dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.
Metabolism and nutrition disorders Dehydration	1.9% 1/54 • Number of events 1 • Baseline Up to 49 Months All randomized participants who received at least 1 dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/34 • Baseline Up to 49 Months All randomized participants who received at least 1 dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.
Metabolism and nutrition disorders Hyperglycaemia	1.9% 1/54 • Number of events 1 • Baseline Up to 49 Months All randomized participants who received at least 1 dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/34 • Baseline Up to 49 Months All randomized participants who received at least 1 dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.
Metabolism and nutrition disorders Hypomagnesaemia	1.9% 1/54 • Number of events 1 • Baseline Up to 49 Months All randomized participants who received at least 1 dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/34 • Baseline Up to 49 Months All randomized participants who received at least 1 dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.
Musculoskeletal and connective tissue disorders Pathological fracture	1.9% 1/54 • Number of events 1 • Baseline Up to 49 Months All randomized participants who received at least 1 dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/34 • Baseline Up to 49 Months All randomized participants who received at least 1 dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.
Nervous system disorders Cerebrovascular accident	1.9% 1/54 • Number of events 1 • Baseline Up to 49 Months All randomized participants who received at least 1 dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/34 • Baseline Up to 49 Months All randomized participants who received at least 1 dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.
Psychiatric disorders Delirium	1.9% 1/54 • Number of events 1 • Baseline Up to 49 Months All randomized participants who received at least 1 dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/34 • Baseline Up to 49 Months All randomized participants who received at least 1 dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.
Renal and urinary disorders Urinary retention	0.00% 0/54 • Baseline Up to 49 Months All randomized participants who received at least 1 dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	2.9% 1/34 • Number of events 2 • Baseline Up to 49 Months All randomized participants who received at least 1 dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.
Respiratory, thoracic and mediastinal disorders Chronic obstructive pulmonary disease	1.9% 1/54 • Number of events 1 • Baseline Up to 49 Months All randomized participants who received at least 1 dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/34 • Baseline Up to 49 Months All randomized participants who received at least 1 dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.
Respiratory, thoracic and mediastinal disorders Interstitial lung disease	1.9% 1/54 • Number of events 1 • Baseline Up to 49 Months All randomized participants who received at least 1 dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/34 • Baseline Up to 49 Months All randomized participants who received at least 1 dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.
Respiratory, thoracic and mediastinal disorders Pneumothorax	1.9% 1/54 • Number of events 1 • Baseline Up to 49 Months All randomized participants who received at least 1 dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/34 • Baseline Up to 49 Months All randomized participants who received at least 1 dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.
Skin and subcutaneous tissue disorders Rash maculo-papular	1.9% 1/54 • Number of events 1 • Baseline Up to 49 Months All randomized participants who received at least 1 dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/34 • Baseline Up to 49 Months All randomized participants who received at least 1 dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.
Vascular disorders Peripheral ischaemia	1.9% 1/54 • Number of events 1 • Baseline Up to 49 Months All randomized participants who received at least 1 dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/34 • Baseline Up to 49 Months All randomized participants who received at least 1 dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.

Other adverse events

Measure	Necitumumab + Nab-paclitaxel + Carboplatin: Induction Phase n=54 participants at risk Necitumumab administered IV at 800 mg on day 1 and 8 of each cycle (3 week cycles); nab-paclitaxel administered IV at 100 mg/m² on day 1, 8 and 15 of each cycle; carboplatin administered IV at a concentration of AUC 6 mg\*min/mL on day 1 of each cycle, for a maximum of 4 cycles. Participants may continue to receive treatment until discontinuation criteria are met.	Necitumumab + Nab-paclitaxel: Maintenance Phase n=34 participants at risk Necitumumab administered IV at 800 mg on day 1 and 8 of each cycle; nab-paclitaxel administered IV at 100mg/m² on day 1 and 8 of each cycle (3 week cycles). Participants may continue to receive treatment until discontinuation criteria are met.
Investigations Neutrophil count decreased	59.3% 32/54 • Number of events 85 • Baseline Up to 49 Months All randomized participants who received at least 1 dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	2.9% 1/34 • Number of events 1 • Baseline Up to 49 Months All randomized participants who received at least 1 dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.
Investigations Platelet count decreased	31.5% 17/54 • Number of events 38 • Baseline Up to 49 Months All randomized participants who received at least 1 dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	5.9% 2/34 • Number of events 2 • Baseline Up to 49 Months All randomized participants who received at least 1 dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.
Blood and lymphatic system disorders Anaemia	63.0% 34/54 • Number of events 101 • Baseline Up to 49 Months All randomized participants who received at least 1 dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	44.1% 15/34 • Number of events 27 • Baseline Up to 49 Months All randomized participants who received at least 1 dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.
Blood and lymphatic system disorders Leukopenia	7.4% 4/54 • Number of events 4 • Baseline Up to 49 Months All randomized participants who received at least 1 dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/34 • Baseline Up to 49 Months All randomized participants who received at least 1 dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.
Blood and lymphatic system disorders Neutropenia	5.6% 3/54 • Number of events 6 • Baseline Up to 49 Months All randomized participants who received at least 1 dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/34 • Baseline Up to 49 Months All randomized participants who received at least 1 dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.
Gastrointestinal disorders Constipation	33.3% 18/54 • Number of events 24 • Baseline Up to 49 Months All randomized participants who received at least 1 dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	5.9% 2/34 • Number of events 2 • Baseline Up to 49 Months All randomized participants who received at least 1 dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.
Gastrointestinal disorders Diarrhoea	35.2% 19/54 • Number of events 36 • Baseline Up to 49 Months All randomized participants who received at least 1 dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	11.8% 4/34 • Number of events 6 • Baseline Up to 49 Months All randomized participants who received at least 1 dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.
Gastrointestinal disorders Nausea	29.6% 16/54 • Number of events 25 • Baseline Up to 49 Months All randomized participants who received at least 1 dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	5.9% 2/34 • Number of events 3 • Baseline Up to 49 Months All randomized participants who received at least 1 dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.
Gastrointestinal disorders Stomatitis	13.0% 7/54 • Number of events 11 • Baseline Up to 49 Months All randomized participants who received at least 1 dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	5.9% 2/34 • Number of events 2 • Baseline Up to 49 Months All randomized participants who received at least 1 dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.
Gastrointestinal disorders Vomiting	18.5% 10/54 • Number of events 14 • Baseline Up to 49 Months All randomized participants who received at least 1 dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	8.8% 3/34 • Number of events 3 • Baseline Up to 49 Months All randomized participants who received at least 1 dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.
General disorders Asthenia	14.8% 8/54 • Number of events 14 • Baseline Up to 49 Months All randomized participants who received at least 1 dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	5.9% 2/34 • Number of events 2 • Baseline Up to 49 Months All randomized participants who received at least 1 dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.
General disorders Fatigue	59.3% 32/54 • Number of events 77 • Baseline Up to 49 Months All randomized participants who received at least 1 dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	17.6% 6/34 • Number of events 10 • Baseline Up to 49 Months All randomized participants who received at least 1 dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.
General disorders Mucosal inflammation	5.6% 3/54 • Number of events 8 • Baseline Up to 49 Months All randomized participants who received at least 1 dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/34 • Baseline Up to 49 Months All randomized participants who received at least 1 dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.
General disorders Oedema peripheral	11.1% 6/54 • Number of events 6 • Baseline Up to 49 Months All randomized participants who received at least 1 dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	5.9% 2/34 • Number of events 2 • Baseline Up to 49 Months All randomized participants who received at least 1 dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.
General disorders Pyrexia	7.4% 4/54 • Number of events 4 • Baseline Up to 49 Months All randomized participants who received at least 1 dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	8.8% 3/34 • Number of events 3 • Baseline Up to 49 Months All randomized participants who received at least 1 dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.
Infections and infestations Conjunctivitis	5.6% 3/54 • Number of events 4 • Baseline Up to 49 Months All randomized participants who received at least 1 dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	2.9% 1/34 • Number of events 3 • Baseline Up to 49 Months All randomized participants who received at least 1 dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.
Infections and infestations Paronychia	3.7% 2/54 • Number of events 2 • Baseline Up to 49 Months All randomized participants who received at least 1 dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	14.7% 5/34 • Number of events 9 • Baseline Up to 49 Months All randomized participants who received at least 1 dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.
Infections and infestations Respiratory tract infection	16.7% 9/54 • Number of events 12 • Baseline Up to 49 Months All randomized participants who received at least 1 dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	17.6% 6/34 • Number of events 8 • Baseline Up to 49 Months All randomized participants who received at least 1 dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.
Infections and infestations Urinary tract infection	5.6% 3/54 • Number of events 3 • Baseline Up to 49 Months All randomized participants who received at least 1 dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	5.9% 2/34 • Number of events 2 • Baseline Up to 49 Months All randomized participants who received at least 1 dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.
Infections and infestations Vaginal infection	8.3% 1/12 • Number of events 1 • Baseline Up to 49 Months All randomized participants who received at least 1 dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/6 • Baseline Up to 49 Months All randomized participants who received at least 1 dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.
Injury, poisoning and procedural complications Fall	5.6% 3/54 • Number of events 3 • Baseline Up to 49 Months All randomized participants who received at least 1 dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/34 • Baseline Up to 49 Months All randomized participants who received at least 1 dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.
Investigations Alanine aminotransferase increased	7.4% 4/54 • Number of events 4 • Baseline Up to 49 Months All randomized participants who received at least 1 dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	2.9% 1/34 • Number of events 1 • Baseline Up to 49 Months All randomized participants who received at least 1 dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.
Investigations Aspartate aminotransferase increased	7.4% 4/54 • Number of events 6 • Baseline Up to 49 Months All randomized participants who received at least 1 dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	5.9% 2/34 • Number of events 2 • Baseline Up to 49 Months All randomized participants who received at least 1 dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.
Investigations Blood cholesterol increased	1.9% 1/54 • Number of events 1 • Baseline Up to 49 Months All randomized participants who received at least 1 dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	5.9% 2/34 • Number of events 2 • Baseline Up to 49 Months All randomized participants who received at least 1 dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.
Investigations Blood creatinine increased	11.1% 6/54 • Number of events 8 • Baseline Up to 49 Months All randomized participants who received at least 1 dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	5.9% 2/34 • Number of events 3 • Baseline Up to 49 Months All randomized participants who received at least 1 dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.
Investigations Lymphocyte count decreased	11.1% 6/54 • Number of events 22 • Baseline Up to 49 Months All randomized participants who received at least 1 dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	17.6% 6/34 • Number of events 11 • Baseline Up to 49 Months All randomized participants who received at least 1 dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.
Investigations Weight decreased	9.3% 5/54 • Number of events 5 • Baseline Up to 49 Months All randomized participants who received at least 1 dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/34 • Baseline Up to 49 Months All randomized participants who received at least 1 dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.
Investigations White blood cell count decreased	22.2% 12/54 • Number of events 46 • Baseline Up to 49 Months All randomized participants who received at least 1 dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	2.9% 1/34 • Number of events 1 • Baseline Up to 49 Months All randomized participants who received at least 1 dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.
Metabolism and nutrition disorders Decreased appetite	24.1% 13/54 • Number of events 22 • Baseline Up to 49 Months All randomized participants who received at least 1 dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	2.9% 1/34 • Number of events 1 • Baseline Up to 49 Months All randomized participants who received at least 1 dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.
Metabolism and nutrition disorders Hypoalbuminaemia	13.0% 7/54 • Number of events 21 • Baseline Up to 49 Months All randomized participants who received at least 1 dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	2.9% 1/34 • Number of events 1 • Baseline Up to 49 Months All randomized participants who received at least 1 dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.
Metabolism and nutrition disorders Hypocalcaemia	18.5% 10/54 • Number of events 16 • Baseline Up to 49 Months All randomized participants who received at least 1 dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	2.9% 1/34 • Number of events 3 • Baseline Up to 49 Months All randomized participants who received at least 1 dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.
Metabolism and nutrition disorders Hypoglycaemia	1.9% 1/54 • Number of events 1 • Baseline Up to 49 Months All randomized participants who received at least 1 dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	5.9% 2/34 • Number of events 2 • Baseline Up to 49 Months All randomized participants who received at least 1 dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.
Metabolism and nutrition disorders Hypokalaemia	18.5% 10/54 • Number of events 14 • Baseline Up to 49 Months All randomized participants who received at least 1 dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/34 • Baseline Up to 49 Months All randomized participants who received at least 1 dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.
Metabolism and nutrition disorders Hypomagnesaemia	48.1% 26/54 • Number of events 60 • Baseline Up to 49 Months All randomized participants who received at least 1 dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	20.6% 7/34 • Number of events 25 • Baseline Up to 49 Months All randomized participants who received at least 1 dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.
Metabolism and nutrition disorders Hyponatraemia	9.3% 5/54 • Number of events 9 • Baseline Up to 49 Months All randomized participants who received at least 1 dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/34 • Baseline Up to 49 Months All randomized participants who received at least 1 dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.
Metabolism and nutrition disorders Hypophosphataemia	22.2% 12/54 • Number of events 27 • Baseline Up to 49 Months All randomized participants who received at least 1 dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	5.9% 2/34 • Number of events 5 • Baseline Up to 49 Months All randomized participants who received at least 1 dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.
Musculoskeletal and connective tissue disorders Arthralgia	9.3% 5/54 • Number of events 5 • Baseline Up to 49 Months All randomized participants who received at least 1 dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	2.9% 1/34 • Number of events 1 • Baseline Up to 49 Months All randomized participants who received at least 1 dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.
Musculoskeletal and connective tissue disorders Back pain	9.3% 5/54 • Number of events 6 • Baseline Up to 49 Months All randomized participants who received at least 1 dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	5.9% 2/34 • Number of events 3 • Baseline Up to 49 Months All randomized participants who received at least 1 dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.
Musculoskeletal and connective tissue disorders Muscular weakness	5.6% 3/54 • Number of events 3 • Baseline Up to 49 Months All randomized participants who received at least 1 dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/34 • Baseline Up to 49 Months All randomized participants who received at least 1 dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.
Musculoskeletal and connective tissue disorders Musculoskeletal chest pain	5.6% 3/54 • Number of events 3 • Baseline Up to 49 Months All randomized participants who received at least 1 dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/34 • Baseline Up to 49 Months All randomized participants who received at least 1 dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.
Musculoskeletal and connective tissue disorders Myalgia	9.3% 5/54 • Number of events 5 • Baseline Up to 49 Months All randomized participants who received at least 1 dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/34 • Baseline Up to 49 Months All randomized participants who received at least 1 dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.
Musculoskeletal and connective tissue disorders Pain in extremity	5.6% 3/54 • Number of events 4 • Baseline Up to 49 Months All randomized participants who received at least 1 dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	2.9% 1/34 • Number of events 1 • Baseline Up to 49 Months All randomized participants who received at least 1 dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.
Nervous system disorders Dizziness	3.7% 2/54 • Number of events 2 • Baseline Up to 49 Months All randomized participants who received at least 1 dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	5.9% 2/34 • Number of events 2 • Baseline Up to 49 Months All randomized participants who received at least 1 dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.
Nervous system disorders Dysgeusia	9.3% 5/54 • Number of events 6 • Baseline Up to 49 Months All randomized participants who received at least 1 dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	2.9% 1/34 • Number of events 1 • Baseline Up to 49 Months All randomized participants who received at least 1 dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.
Nervous system disorders Paraesthesia	1.9% 1/54 • Number of events 1 • Baseline Up to 49 Months All randomized participants who received at least 1 dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	11.8% 4/34 • Number of events 6 • Baseline Up to 49 Months All randomized participants who received at least 1 dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.
Nervous system disorders Peripheral motor neuropathy	7.4% 4/54 • Number of events 6 • Baseline Up to 49 Months All randomized participants who received at least 1 dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	5.9% 2/34 • Number of events 7 • Baseline Up to 49 Months All randomized participants who received at least 1 dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.
Nervous system disorders Peripheral sensory neuropathy	13.0% 7/54 • Number of events 9 • Baseline Up to 49 Months All randomized participants who received at least 1 dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	26.5% 9/34 • Number of events 17 • Baseline Up to 49 Months All randomized participants who received at least 1 dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.
Psychiatric disorders Depression	7.4% 4/54 • Number of events 4 • Baseline Up to 49 Months All randomized participants who received at least 1 dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/34 • Baseline Up to 49 Months All randomized participants who received at least 1 dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.
Psychiatric disorders Insomnia	9.3% 5/54 • Number of events 5 • Baseline Up to 49 Months All randomized participants who received at least 1 dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/34 • Baseline Up to 49 Months All randomized participants who received at least 1 dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.
Respiratory, thoracic and mediastinal disorders Cough	7.4% 4/54 • Number of events 4 • Baseline Up to 49 Months All randomized participants who received at least 1 dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	20.6% 7/34 • Number of events 7 • Baseline Up to 49 Months All randomized participants who received at least 1 dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.
Respiratory, thoracic and mediastinal disorders Dysphonia	3.7% 2/54 • Number of events 2 • Baseline Up to 49 Months All randomized participants who received at least 1 dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	5.9% 2/34 • Number of events 2 • Baseline Up to 49 Months All randomized participants who received at least 1 dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.
Respiratory, thoracic and mediastinal disorders Dyspnoea	22.2% 12/54 • Number of events 14 • Baseline Up to 49 Months All randomized participants who received at least 1 dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	8.8% 3/34 • Number of events 4 • Baseline Up to 49 Months All randomized participants who received at least 1 dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.
Respiratory, thoracic and mediastinal disorders Epistaxis	20.4% 11/54 • Number of events 16 • Baseline Up to 49 Months All randomized participants who received at least 1 dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	2.9% 1/34 • Number of events 5 • Baseline Up to 49 Months All randomized participants who received at least 1 dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.
Respiratory, thoracic and mediastinal disorders Haemoptysis	3.7% 2/54 • Number of events 2 • Baseline Up to 49 Months All randomized participants who received at least 1 dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	5.9% 2/34 • Number of events 2 • Baseline Up to 49 Months All randomized participants who received at least 1 dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.
Respiratory, thoracic and mediastinal disorders Nasal congestion	11.1% 6/54 • Number of events 6 • Baseline Up to 49 Months All randomized participants who received at least 1 dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/34 • Baseline Up to 49 Months All randomized participants who received at least 1 dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	5.6% 3/54 • Number of events 3 • Baseline Up to 49 Months All randomized participants who received at least 1 dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/34 • Baseline Up to 49 Months All randomized participants who received at least 1 dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.
Respiratory, thoracic and mediastinal disorders Productive cough	5.6% 3/54 • Number of events 4 • Baseline Up to 49 Months All randomized participants who received at least 1 dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/34 • Baseline Up to 49 Months All randomized participants who received at least 1 dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.
Skin and subcutaneous tissue disorders Alopecia	14.8% 8/54 • Number of events 8 • Baseline Up to 49 Months All randomized participants who received at least 1 dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/34 • Baseline Up to 49 Months All randomized participants who received at least 1 dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.
Skin and subcutaneous tissue disorders Dermatitis acneiform	29.6% 16/54 • Number of events 32 • Baseline Up to 49 Months All randomized participants who received at least 1 dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	11.8% 4/34 • Number of events 5 • Baseline Up to 49 Months All randomized participants who received at least 1 dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.
Skin and subcutaneous tissue disorders Dry skin	14.8% 8/54 • Number of events 11 • Baseline Up to 49 Months All randomized participants who received at least 1 dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	14.7% 5/34 • Number of events 5 • Baseline Up to 49 Months All randomized participants who received at least 1 dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.
Skin and subcutaneous tissue disorders Nail discolouration	0.00% 0/54 • Baseline Up to 49 Months All randomized participants who received at least 1 dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	5.9% 2/34 • Number of events 4 • Baseline Up to 49 Months All randomized participants who received at least 1 dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.
Skin and subcutaneous tissue disorders Pruritus	7.4% 4/54 • Number of events 5 • Baseline Up to 49 Months All randomized participants who received at least 1 dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/34 • Baseline Up to 49 Months All randomized participants who received at least 1 dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.
Skin and subcutaneous tissue disorders Rash	37.0% 20/54 • Number of events 59 • Baseline Up to 49 Months All randomized participants who received at least 1 dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	17.6% 6/34 • Number of events 9 • Baseline Up to 49 Months All randomized participants who received at least 1 dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.
Skin and subcutaneous tissue disorders Skin fissures	9.3% 5/54 • Number of events 7 • Baseline Up to 49 Months All randomized participants who received at least 1 dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	2.9% 1/34 • Number of events 1 • Baseline Up to 49 Months All randomized participants who received at least 1 dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.

Additional Information

Chief Medical Officer

Eli Lilly and Company

Phone: 800-545-5979

Email: clinicaltrials.gov@lilly.com

Results disclosure agreements

• Principal investigator is a sponsor employee The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days from the time submitted to the sponsor for review. The sponsor cannot require changes to the communication and cannot extend the embargo.
• Publication restrictions are in place

Restriction type: OTHER