Trial Outcomes & Findings for Study of Erlotinib With or Without Investigational Drug (U3-1287) in Subjects With Advanced Non-small Cell Lung Cancer (NCT NCT01211483)

Last Updated: 2021-06-16

Results Overview

Progression-free survival (PFS) was defined as the time from the date of randomization to the earlier of the dates of first objective documentation of radiographic disease progression or death due to any cause (as per Response Evaluation Criteria in Solid Tumors \[RECIST\] Version 1.1).

Recruitment status

COMPLETED

Study phase

PHASE1/PHASE2

Target enrollment

222 participants

Primary outcome timeframe

Time from the randomization date up to the date of first objective documentation of disease progression or death due to any cause (whichever comes first), up to 3 years 2 months

Results posted on

2021-06-16

Participant Flow

A total of 222 participants who met all inclusion criteria and no exclusion criteria were enrolled in this Phase 1b/Phase 2 study at 52 sites in Europe and Israel and 14 sites in the United States.

Of the 222 participants enrolled, 3 were randomized but not dosed. Two participants died before dosing and 1 participant withdrew the consent. Data on the 219 participants are presented in this report.

Participant milestones

Participant milestones
Measure	Phase 1b: U31287 18 mg/kg + Erlotinib Participants who received U3-1287 18 mg/kg intravenously (IV) every three weeks (Q3W) and Erlotinib 150 mg/day orally (PO).	Phase 2: U3-1287 18 mg/kg + Erlotinib Participants who were randomized to receive U3-1287 18 mg/kg intravenously (IV) every three weeks (Q3W) and Erlotinib 150 mg/day orally (PO).	Phase 2: U3-1287 9 mg/kg + Erlotinib Participants who were randomized to receive U3-1287 9 mg/kg IV Q3W and Erlotinib 150 mg/day PO.	Phase 2: Placebo + Erlotinib Participants who were randomized to receive placebo matching U3-1287 IV Q3W and Erlotinib150 mg/day PO.
Phase 1b STARTED	7	0	0	0
Phase 1b COMPLETED	0	0	0	0
Phase 1b NOT COMPLETED	7	0	0	0
Phase 2 STARTED	0	72	72	71
Phase 2 COMPLETED	0	0	0	0
Phase 2 NOT COMPLETED	0	72	72	71

Reasons for withdrawal

Reasons for withdrawal
Measure	Phase 1b: U31287 18 mg/kg + Erlotinib Participants who received U3-1287 18 mg/kg intravenously (IV) every three weeks (Q3W) and Erlotinib 150 mg/day orally (PO).	Phase 2: U3-1287 18 mg/kg + Erlotinib Participants who were randomized to receive U3-1287 18 mg/kg intravenously (IV) every three weeks (Q3W) and Erlotinib 150 mg/day orally (PO).	Phase 2: U3-1287 9 mg/kg + Erlotinib Participants who were randomized to receive U3-1287 9 mg/kg IV Q3W and Erlotinib 150 mg/day PO.	Phase 2: Placebo + Erlotinib Participants who were randomized to receive placebo matching U3-1287 IV Q3W and Erlotinib150 mg/day PO.
Phase 1b Death	6	0	0	0
Phase 1b Withdrawal by Subject	1	0	0	0
Phase 2 Lost to Follow-up	0	1	1	2
Phase 2 Death	0	64	53	53
Phase 2 Withdrawal by Subject	0	1	10	5
Phase 2 Study terminated by Sponsor	0	6	8	11

Baseline Characteristics

Study of Erlotinib With or Without Investigational Drug (U3-1287) in Subjects With Advanced Non-small Cell Lung Cancer

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Phase 1b: U3127 18mg/kg + Erlotinib n=7 Participants Participants who received U3-1287 18 mg/kg intravenously (IV) every three weeks (Q3W) and Erlotinib 150 mg/day orally (PO).	Phase 2: U3-1287 18 mg/kg + Erlotinib n=70 Participants Participants who were randomized to receive U3-1287 18 mg/kg intravenously (IV) every three weeks (Q3W) and Erlotinib 150 mg/day orally (PO).	Phase 2: U3-1287 9 mg/kg + Erlotinib n=71 Participants Participants who were randomized to receive U3-1287 9 mg/kg IV Q3W and Erlotinib 150 mg/day PO.	Phase 2: Placebo + Erlotinib n=71 Participants Participants who were randomized to receive placebo matching U3-1287 IV Q3W and Erlotinib150 mg/day PO.	Total n=219 Participants Total of all reporting groups
Age, Continuous	68 years n=5 Participants	62.0 years n=7 Participants	65.0 years n=5 Participants	60.0 years n=4 Participants	62.5 years n=21 Participants
Age, Customized <60 years	2 Participants n=5 Participants	28 Participants n=7 Participants	24 Participants n=5 Participants	33 Participants n=4 Participants	87 Participants n=21 Participants
Age, Customized ≥60 years	5 Participants n=5 Participants	42 Participants n=7 Participants	47 Participants n=5 Participants	38 Participants n=4 Participants	132 Participants n=21 Participants
Sex: Female, Male Female	3 Participants n=5 Participants	32 Participants n=7 Participants	23 Participants n=5 Participants	28 Participants n=4 Participants	86 Participants n=21 Participants
Sex: Female, Male Male	4 Participants n=5 Participants	38 Participants n=7 Participants	48 Participants n=5 Participants	43 Participants n=4 Participants	133 Participants n=21 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	1 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	1 Participants n=21 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants	1 Participants n=7 Participants	0 Participants n=5 Participants	1 Participants n=4 Participants	2 Participants n=21 Participants
Race (NIH/OMB) White	7 Participants n=5 Participants	68 Participants n=7 Participants	71 Participants n=5 Participants	69 Participants n=4 Participants	215 Participants n=21 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	1 Participants n=4 Participants	1 Participants n=21 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants

PRIMARY outcome

Timeframe: Time from the randomization date up to the date of first objective documentation of disease progression or death due to any cause (whichever comes first), up to 3 years 2 months

Population: Progression-free survival was assessed in the Full Analysis Set in Phase 2 of the study. Efficacy was not assessed in the Phase 1b portion of the study.

Outcome measures

Outcome measures
Measure	Phase 2: U3-1287 18 mg/kg + Erlotinib n=70 Participants Participants who were randomized to receive U3-1287 18 mg/kg intravenously (IV) every three weeks (Q3W) and Erlotinib 150 mg/day orally (PO).	Phase 2: U3-1287 9 mg/kg + Erlotinib n=71 Participants Participants who were randomized to receive U3-1287 9 mg/kg IV Q3W and Erlotinib 150 mg/day PO.	Phase 2: Placebo + Erlotinib n=71 Participants Participants who were randomized to receive placebo matching U3-1287 IV Q3W and Erlotinib150 mg/day PO.	Phase 2: Placebo + Erlotinib Participants who were randomized to receive placebo matching U3-1287 IV Q3W and Erlotinib150 mg/day PO.
Progression-Free Survival Following U3-1287 (AMG 888) in Combination With Erlotinib	1.4 months Interval 1.3 to 2.7	2.5 months Interval 1.5 to 3.0	1.6 months Interval 1.4 to 2.6	—

PRIMARY outcome

Timeframe: Time from the randomization date up to the date of first objective documentation of disease progression or death due to any cause (whichever comes first), up to 3 years 2 months

Population: Progression-free survival was assessed in participants with high heregulin-expressing tumors in the Full Analysis Set in Phase 2 of the study. Efficacy was not assessed in the Phase 1b portion of the study.

Outcome measures

Outcome measures
Measure	Phase 2: U3-1287 18 mg/kg + Erlotinib n=17 Participants Participants who were randomized to receive U3-1287 18 mg/kg intravenously (IV) every three weeks (Q3W) and Erlotinib 150 mg/day orally (PO).	Phase 2: U3-1287 9 mg/kg + Erlotinib n=16 Participants Participants who were randomized to receive U3-1287 9 mg/kg IV Q3W and Erlotinib 150 mg/day PO.	Phase 2: Placebo + Erlotinib n=18 Participants Participants who were randomized to receive placebo matching U3-1287 IV Q3W and Erlotinib150 mg/day PO.	Phase 2: Placebo + Erlotinib Participants who were randomized to receive placebo matching U3-1287 IV Q3W and Erlotinib150 mg/day PO.
Progression-Free Survival in Participants With High Heregulin-Expressing Tumors Following U3-1287 (AMG 888) in Combination With Erlotinib	3.4 months Interval 1.2 to 5.7	3.0 months Interval 1.5 to 5.7	1.4 months Interval 1.2 to 2.3	—

PRIMARY outcome

Timeframe: Time from the randomization date up to the date of first objective documentation of disease progression or death due to any cause (whichever comes first), up to 3 years 2 months

Population: Progression-free survival was assessed in participants with low heregulin-expressing tumors in the Full Analysis Set in Phase 2 of the study. Efficacy was not assessed in the Phase 1b portion of the study.

Outcome measures

Outcome measures
Measure	Phase 2: U3-1287 18 mg/kg + Erlotinib n=19 Participants Participants who were randomized to receive U3-1287 18 mg/kg intravenously (IV) every three weeks (Q3W) and Erlotinib 150 mg/day orally (PO).	Phase 2: U3-1287 9 mg/kg + Erlotinib n=15 Participants Participants who were randomized to receive U3-1287 9 mg/kg IV Q3W and Erlotinib 150 mg/day PO.	Phase 2: Placebo + Erlotinib n=16 Participants Participants who were randomized to receive placebo matching U3-1287 IV Q3W and Erlotinib150 mg/day PO.	Phase 2: Placebo + Erlotinib Participants who were randomized to receive placebo matching U3-1287 IV Q3W and Erlotinib150 mg/day PO.
Progression-Free Survival in Participants With Low Heregulin-Expressing Tumors Following U3-1287 (AMG 888) in Combination With Erlotinib	1.4 months Interval 1.1 to 8.5	2.1 months Interval 1.3 to 3.0	1.4 months Interval 1.3 to 8.1	—

SECONDARY outcome

Timeframe: Time from the randomization date up to the date of death due to any cause, up to 3 years 2 months

Population: Overall survival was assessed in Full Analysis Set in Phase 2 of the study. Efficacy was not assessed in the Phase 1b portion of the study.

Overall Survival (OS) was defined as the time from the randomization date to the date of death.

Outcome measures

Outcome measures
Measure	Phase 2: U3-1287 18 mg/kg + Erlotinib n=70 Participants Participants who were randomized to receive U3-1287 18 mg/kg intravenously (IV) every three weeks (Q3W) and Erlotinib 150 mg/day orally (PO).	Phase 2: U3-1287 9 mg/kg + Erlotinib n=71 Participants Participants who were randomized to receive U3-1287 9 mg/kg IV Q3W and Erlotinib 150 mg/day PO.	Phase 2: Placebo + Erlotinib n=71 Participants Participants who were randomized to receive placebo matching U3-1287 IV Q3W and Erlotinib150 mg/day PO.	Phase 2: Placebo + Erlotinib Participants who were randomized to receive placebo matching U3-1287 IV Q3W and Erlotinib150 mg/day PO.
Overall Survival Following U3-1287 (AMG 888) in Combination With Erlotinib	5.3 months Interval 4.0 to 6.9	6.3 months Interval 4.7 to 9.3	7.2 months Interval 5.4 to 10.6	—

SECONDARY outcome

Timeframe: Time from date of randomization up to date of first documentation of objective response of either CR or PR (whichever comes first), up to 3 years 2 months

Population: Objective response rate was assessed in participants with measurable disease in the Full Analysis Set in Phase 2 of the study. Efficacy was not assessed in the Phase 1b portion of the study.

Objective response was defined as the best response of either complete response (CR) or partial response (PR). As per Response Evaluation Criteria in Solid Tumors Version 1.1, CR was defined as a disappearance of all target lesions and PR was defined as at least a 30% decrease in the sum of diameters of target lesions.

Outcome measures

Outcome measures
Measure	Phase 2: U3-1287 18 mg/kg + Erlotinib n=70 Participants Participants who were randomized to receive U3-1287 18 mg/kg intravenously (IV) every three weeks (Q3W) and Erlotinib 150 mg/day orally (PO).	Phase 2: U3-1287 9 mg/kg + Erlotinib n=70 Participants Participants who were randomized to receive U3-1287 9 mg/kg IV Q3W and Erlotinib 150 mg/day PO.	Phase 2: Placebo + Erlotinib n=71 Participants Participants who were randomized to receive placebo matching U3-1287 IV Q3W and Erlotinib150 mg/day PO.	Phase 2: Placebo + Erlotinib Participants who were randomized to receive placebo matching U3-1287 IV Q3W and Erlotinib150 mg/day PO.
Objective Response Following U3-1287 (AMG 888) in Combination With Erlotinib	6 Participants	9 Participants	4 Participants	—

SECONDARY outcome

Timeframe: Time from date of randomization up to date of first documentation of objective response of either CR or PR (whichever comes first), up to 3 years 2 months

Population: Time to objective response was assessed among participants with objective response of CR or PR in the Full Analysis Set in Phase 2 of the study. Efficacy was not assessed in the Phase 1b portion of the study.

Time to objective response was defined as the time from the date of randomization to the date of the first documentation of objective response (complete response \[CR\] or partial response \[PR\]). As per Response Evaluation Criteria in Solid Tumors Version 1.1, CR was defined as a disappearance of all target lesions and PR was defined as at least a 30% decrease in the sum of diameters of target lesions.

Outcome measures

Outcome measures
Measure	Phase 2: U3-1287 18 mg/kg + Erlotinib n=6 Participants Participants who were randomized to receive U3-1287 18 mg/kg intravenously (IV) every three weeks (Q3W) and Erlotinib 150 mg/day orally (PO).	Phase 2: U3-1287 9 mg/kg + Erlotinib n=9 Participants Participants who were randomized to receive U3-1287 9 mg/kg IV Q3W and Erlotinib 150 mg/day PO.	Phase 2: Placebo + Erlotinib n=4 Participants Participants who were randomized to receive placebo matching U3-1287 IV Q3W and Erlotinib150 mg/day PO.	Phase 2: Placebo + Erlotinib Participants who were randomized to receive placebo matching U3-1287 IV Q3W and Erlotinib150 mg/day PO.
Time to Objective Response Following U3-1287 (AMG 888) in Combination With Erlotinib	6.14 weeks Interval 5.29 to 6.43	6.29 weeks Interval 6.14 to 6.29	12.00 weeks Interval 6.29 to 17.29	—

SECONDARY outcome

Timeframe: For participants whose best response is SD as the time from date of first documentation of stable disease up to the date of first documentation of progressive disease, up to 3 years 2 months

Population: Duration of stable disease (SD) was assessed among participants with best response of SD in the Full Analysis Set in Phase 2 of the study. Efficacy was not assessed in the Phase 1b portion of the study.

Duration of stable disease (SD) was defined for participants whose best response is SD as the time from the date of randomization to the date of the first documentation of progressive disease. SD was defined as neither sufficient shrinkage to qualify for partial response (PR; at least a 30% decrease in the sum of diameters of target lesions) nor sufficient increase to qualify for progressive disease (PD; at least a 20% increase in the sum of diameters of target lesions).

Outcome measures

Outcome measures
Measure	Phase 2: U3-1287 18 mg/kg + Erlotinib n=21 Participants Participants who were randomized to receive U3-1287 18 mg/kg intravenously (IV) every three weeks (Q3W) and Erlotinib 150 mg/day orally (PO).	Phase 2: U3-1287 9 mg/kg + Erlotinib n=27 Participants Participants who were randomized to receive U3-1287 9 mg/kg IV Q3W and Erlotinib 150 mg/day PO.	Phase 2: Placebo + Erlotinib n=24 Participants Participants who were randomized to receive placebo matching U3-1287 IV Q3W and Erlotinib150 mg/day PO.	Phase 2: Placebo + Erlotinib Participants who were randomized to receive placebo matching U3-1287 IV Q3W and Erlotinib150 mg/day PO.
Duration of Stable Disease Following U3-1287 (AMG 888) in Combination With Erlotinib	25.14 weeks Interval 18.14 to 36.14	17.29 weeks Interval 12.86 to 24.71	19.57 weeks Interval 12.29 to 37.14	—

SECONDARY outcome

Timeframe: Time from date of randomization up to the date of first objective documentation of disease progression, up to 3 years 2 months

Population: Time to disease progression was assessed in the Full Analysis Set in Phase 2 of the study. Efficacy was not assessed in the Phase 1b portion of the study.

Time to disease progression was defined as the time from the randomization date to the date of first objective documentation of disease progression. As per Response Evaluation Criteria in Solid Tumors Version 1.1, progressive disease (PD) was defined as at least a 20% increase in the sum of diameters of target lesions.

Outcome measures

Outcome measures
Measure	Phase 2: U3-1287 18 mg/kg + Erlotinib n=70 Participants Participants who were randomized to receive U3-1287 18 mg/kg intravenously (IV) every three weeks (Q3W) and Erlotinib 150 mg/day orally (PO).	Phase 2: U3-1287 9 mg/kg + Erlotinib n=71 Participants Participants who were randomized to receive U3-1287 9 mg/kg IV Q3W and Erlotinib 150 mg/day PO.	Phase 2: Placebo + Erlotinib n=71 Participants Participants who were randomized to receive placebo matching U3-1287 IV Q3W and Erlotinib150 mg/day PO.	Phase 2: Placebo + Erlotinib Participants who were randomized to receive placebo matching U3-1287 IV Q3W and Erlotinib150 mg/day PO.
Time to Disease Progression Following U3-1287 (AMG 888) in Combination With Erlotinib	9.29 weeks Interval 6.14 to 16.14	11.14 weeks Interval 6.71 to 13.0	7.86 weeks Interval 6.29 to 12.14	—

SECONDARY outcome

Timeframe: Cycle 1: predose, end of infusion (EOI), 3 hour (h) postdose; Cycle 2: predose; Cycle 3: predose, EOI, 3 h, 6h, 24 h, 72 h, 168 h, 336 h; Cycle 4, Cycle 5, Cycle 7, and Cycle 9: predose (each cycle is 21 days)

Population: Area under the curve from 0 to tau was assessed in patients with available samples the Pharmacokinetic (PK) Analysis Set. The PK analysis sets for Phase 1b and Phase 2 were combined for the PK analyses.

AUC was calculated from the concentration-time data at Cycle 3 using a noncompartmental analysis (NCA) method.

Outcome measures

Outcome measures
Measure	Phase 2: U3-1287 18 mg/kg + Erlotinib n=13 Participants Participants who were randomized to receive U3-1287 18 mg/kg intravenously (IV) every three weeks (Q3W) and Erlotinib 150 mg/day orally (PO).	Phase 2: U3-1287 9 mg/kg + Erlotinib n=7 Participants Participants who were randomized to receive U3-1287 9 mg/kg IV Q3W and Erlotinib 150 mg/day PO.	Phase 2: Placebo + Erlotinib Participants who were randomized to receive placebo matching U3-1287 IV Q3W and Erlotinib150 mg/day PO.	Phase 2: Placebo + Erlotinib Participants who were randomized to receive placebo matching U3-1287 IV Q3W and Erlotinib150 mg/day PO.
Pharmacokinetic Parameter of Cycle 3 Patritumab Area Under the Concentration-time Curve Over the Dosing Interval 0 to τ (AUC) Following U3-1287 (AMG 888) in Combination With Erlotinib	61316.6 hour*ug/mL Standard Deviation 29364.06	27713.6 hour*ug/mL Standard Deviation 8076.02	—	—

SECONDARY outcome

Population: Concentration at end of infusion and minimum concentration were assessed in patients with available samples in the Pharmacokinetic Analysis Set. The PK analysis sets for Phase 1b and Phase 2 were combined for the PK analyses.

Concentration end of infusion (CEOI) was defined as the concentration within ± 5 minutes of the end of infusion. Cmin was defined as minimum (trough) observed concentration within ± 15% of the prescribed dosing interval. Preinfusion patritumab concentrations observed within 15% of nominal time after the start of the previous infusion (ie, 21 days ± 3.15 days) were considered trough concentrations

Outcome measures

Outcome measures
Measure	Phase 2: U3-1287 18 mg/kg + Erlotinib n=26 Participants Participants who were randomized to receive U3-1287 18 mg/kg intravenously (IV) every three weeks (Q3W) and Erlotinib 150 mg/day orally (PO).	Phase 2: U3-1287 9 mg/kg + Erlotinib n=27 Participants Participants who were randomized to receive U3-1287 9 mg/kg IV Q3W and Erlotinib 150 mg/day PO.	Phase 2: Placebo + Erlotinib Participants who were randomized to receive placebo matching U3-1287 IV Q3W and Erlotinib150 mg/day PO.	Phase 2: Placebo + Erlotinib Participants who were randomized to receive placebo matching U3-1287 IV Q3W and Erlotinib150 mg/day PO.
Pharmacokinetic Parameter of Cycle 3 Patritumab Concentration End of Infusion (CEOI) and Minimum (Trough) Concentration (Cmin) Following U3-1287 (AMG 888) in Combination With Erlotinib Cmin	65.86 ug/mL Standard Deviation 93.64	17.67 ug/mL Standard Deviation 11.48	—	—
Pharmacokinetic Parameter of Cycle 3 Patritumab Concentration End of Infusion (CEOI) and Minimum (Trough) Concentration (Cmin) Following U3-1287 (AMG 888) in Combination With Erlotinib CEOI	473.67 ug/mL Standard Deviation 495.91	183.90 ug/mL Standard Deviation 71.82	—	—

SECONDARY outcome

Timeframe: Cycle 3, Day 1: predose, 1 h, 2 h, 3 h, 6h, 24 h postdose (each cycle is 21 days)

Population: Erlotinib concentrations were assessed in patients with available samples in the Pharmacokinetic Analysis Set. The PK analysis sets for Phase 1b and Phase 2 were combined for the PK analyses.

Outcome measures

Outcome measures
Measure	Phase 2: U3-1287 18 mg/kg + Erlotinib n=6 Participants Participants who were randomized to receive U3-1287 18 mg/kg intravenously (IV) every three weeks (Q3W) and Erlotinib 150 mg/day orally (PO).	Phase 2: U3-1287 9 mg/kg + Erlotinib n=4 Participants Participants who were randomized to receive U3-1287 9 mg/kg IV Q3W and Erlotinib 150 mg/day PO.	Phase 2: Placebo + Erlotinib n=2 Participants Participants who were randomized to receive placebo matching U3-1287 IV Q3W and Erlotinib150 mg/day PO.	Phase 2: Placebo + Erlotinib Participants who were randomized to receive placebo matching U3-1287 IV Q3W and Erlotinib150 mg/day PO.
Erlotinib Concentrations at Cycle 3 Day 1 Following U3-1287 (AMG 888) in Combination With Erlotinib Predose	837.42 ng/mL Standard Deviation 587.65	1547.25 ng/mL Standard Deviation 1273.15	1315.00 ng/mL Standard Deviation 318.20	—
Erlotinib Concentrations at Cycle 3 Day 1 Following U3-1287 (AMG 888) in Combination With Erlotinib 1 h	1115.50 ng/mL Standard Deviation 611.27	1954.00 ng/mL Standard Deviation 1249.95	1754.00 ng/mL Standard Deviation 1083.29	—
Erlotinib Concentrations at Cycle 3 Day 1 Following U3-1287 (AMG 888) in Combination With Erlotinib 2 h	1578.33 ng/mL Standard Deviation 421.83	1832.00 ng/mL Standard Deviation 1269.61	1820.00 ng/mL Standard Deviation 296.99	—
Erlotinib Concentrations at Cycle 3 Day 1 Following U3-1287 (AMG 888) in Combination With Erlotinib 3 h	1573.17 ng/mL Standard Deviation 481.37	2041.25 ng/mL Standard Deviation 1510.75	1855.00 ng/mL Standard Deviation 148.49	—
Erlotinib Concentrations at Cycle 3 Day 1 Following U3-1287 (AMG 888) in Combination With Erlotinib 6 h	1902.00 ng/mL Standard Deviation 618.28	2362.50 ng/mL Standard Deviation 1383.51	1845.00 ng/mL Standard Deviation 91.92	—
Erlotinib Concentrations at Cycle 3 Day 1 Following U3-1287 (AMG 888) in Combination With Erlotinib 24 h	1144.00 ng/mL Standard Deviation 672.69	2300.00 ng/mL Standard Deviation 1797.03	976.00 ng/mL Standard Deviation 147.08	—

SECONDARY outcome

Timeframe: Cycle 1: predose, end of infusion (EOI), 3 hour (h) postdose; Cycle 2: predose; Cycle 3: predose, EOI, 3 h, 6h, 24 h, 72 h, 168 h, 336 h; Cycle 5, Cycle 7, and Cycle 9: predose (each cycle is 21 days)

Trough concentrations (Cmin) was defined as minimum (trough) observed concentration within ± 15% of the prescribed dosing interval. Erlotinib Cmin was predose (or for participants with at least 2 prior doses, within 15% of nominal time after postdose) plasma erlotinib concentration.

Outcome measures

Outcome measures
Measure	Phase 2: U3-1287 18 mg/kg + Erlotinib n=77 Participants Participants who were randomized to receive U3-1287 18 mg/kg intravenously (IV) every three weeks (Q3W) and Erlotinib 150 mg/day orally (PO).	Phase 2: U3-1287 9 mg/kg + Erlotinib n=69 Participants Participants who were randomized to receive U3-1287 9 mg/kg IV Q3W and Erlotinib 150 mg/day PO.	Phase 2: Placebo + Erlotinib n=70 Participants Participants who were randomized to receive placebo matching U3-1287 IV Q3W and Erlotinib150 mg/day PO.	Phase 2: Placebo + Erlotinib Participants who were randomized to receive placebo matching U3-1287 IV Q3W and Erlotinib150 mg/day PO.
Pharmacokinetic Parameter of Erlotinib Trough (Cmin) Concentrations From Participants Receiving 150 mg Erlotinib Following U3-1287 (AMG 888) in Combination With Erlotinib Cycle 1 Day1	0 ng/mL Standard Deviation 0	0 ng/mL Standard Deviation 0	0 ng/mL Standard Deviation 0	—
Pharmacokinetic Parameter of Erlotinib Trough (Cmin) Concentrations From Participants Receiving 150 mg Erlotinib Following U3-1287 (AMG 888) in Combination With Erlotinib Cycle 2 Day 1	943.09 ng/mL Standard Deviation 865.13	1490.18 ng/mL Standard Deviation 1381.34	1263.47 ng/mL Standard Deviation 1328.56	—
Pharmacokinetic Parameter of Erlotinib Trough (Cmin) Concentrations From Participants Receiving 150 mg Erlotinib Following U3-1287 (AMG 888) in Combination With Erlotinib Cycle 3 Day 1	912.42 ng/mL Standard Deviation 785.91	1419.95 ng/mL Standard Deviation 911.77	1084.58 ng/mL Standard Deviation 851.85	—
Pharmacokinetic Parameter of Erlotinib Trough (Cmin) Concentrations From Participants Receiving 150 mg Erlotinib Following U3-1287 (AMG 888) in Combination With Erlotinib Cycle 5 Day 1	394.80 ng/mL Standard Deviation 256.72	1333.45 ng/mL Standard Deviation 1155.66	540.75 ng/mL Standard Deviation 307.70	—
Pharmacokinetic Parameter of Erlotinib Trough (Cmin) Concentrations From Participants Receiving 150 mg Erlotinib Following U3-1287 (AMG 888) in Combination With Erlotinib Cycle 7 Day 1	—	1602.50 ng/mL Standard Deviation 1113.69	627.00 ng/mL Standard Deviation 19.80	—
Pharmacokinetic Parameter of Erlotinib Trough (Cmin) Concentrations From Participants Receiving 150 mg Erlotinib Following U3-1287 (AMG 888) in Combination With Erlotinib Cycle 9 Day 1	161.00 ng/mL Standard Deviation NA Standard deviation could not be calculated on a single patient.	1850.00 ng/mL Standard Deviation NA Standard deviation could not be calculated on a single patient.	646.50 ng/mL Standard Deviation 78.49	—

SECONDARY outcome

Timeframe: From the date of signing the informed consent form up to 53 days after the last dose of patritumab/placebo or up to 30 days after the last dose of erlotinib if patritumab/placebo was discontinued earlier, up to 3 years 2 months

Population: TEAEs Occurring in ≥10% of Participants Following U3-1287 (AMG 888) in Combination with Erlotinib were analyzed in the Safety Analysis Set.

A treatment-emergent adverse event (TEAE) was defined as an adverse event (AE) that: emerged during treatment, having been absent at pretreatment; or reemerged during treatment, having been present at baseline but stopped prior to treatment; or worsened in severity since treatment relative to the pretreatment state, when the AE was continuous.

Outcome measures

Outcome measures
Measure	Phase 2: U3-1287 18 mg/kg + Erlotinib n=7 Participants Participants who were randomized to receive U3-1287 18 mg/kg intravenously (IV) every three weeks (Q3W) and Erlotinib 150 mg/day orally (PO).	Phase 2: U3-1287 9 mg/kg + Erlotinib n=70 Participants Participants who were randomized to receive U3-1287 9 mg/kg IV Q3W and Erlotinib 150 mg/day PO.	Phase 2: Placebo + Erlotinib n=71 Participants Participants who were randomized to receive placebo matching U3-1287 IV Q3W and Erlotinib150 mg/day PO.	Phase 2: Placebo + Erlotinib n=71 Participants Participants who were randomized to receive placebo matching U3-1287 IV Q3W and Erlotinib150 mg/day PO.
Treatment-Emergent Adverse Events Occurring in ≥10% of Participants Following U3-1287 (AMG 888) in Combination With Erlotinib Blood and Lymphatic System Disorders	1 Participants	14 Participants	12 Participants	8 Participants
Treatment-Emergent Adverse Events Occurring in ≥10% of Participants Following U3-1287 (AMG 888) in Combination With Erlotinib Gastrointestinal Disorders	7 Participants	59 Participants	58 Participants	38 Participants
Treatment-Emergent Adverse Events Occurring in ≥10% of Participants Following U3-1287 (AMG 888) in Combination With Erlotinib Diarrhoea	5 Participants	47 Participants	50 Participants	23 Participants
Treatment-Emergent Adverse Events Occurring in ≥10% of Participants Following U3-1287 (AMG 888) in Combination With Erlotinib Gastrooesophageal reflux disease	1 Participants	0 Participants	0 Participants	2 Participants
Treatment-Emergent Adverse Events Occurring in ≥10% of Participants Following U3-1287 (AMG 888) in Combination With Erlotinib Lip dry	1 Participants	1 Participants	0 Participants	0 Participants
Treatment-Emergent Adverse Events Occurring in ≥10% of Participants Following U3-1287 (AMG 888) in Combination With Erlotinib Oral pain	1 Participants	0 Participants	1 Participants	0 Participants
Treatment-Emergent Adverse Events Occurring in ≥10% of Participants Following U3-1287 (AMG 888) in Combination With Erlotinib Vomiting	2 Participants	18 Participants	7 Participants	5 Participants
Treatment-Emergent Adverse Events Occurring in ≥10% of Participants Following U3-1287 (AMG 888) in Combination With Erlotinib Oedema peripheral	2 Participants	9 Participants	9 Participants	4 Participants
Treatment-Emergent Adverse Events Occurring in ≥10% of Participants Following U3-1287 (AMG 888) in Combination With Erlotinib Mucosal inflammation	2 Participants	1 Participants	5 Participants	1 Participants
Treatment-Emergent Adverse Events Occurring in ≥10% of Participants Following U3-1287 (AMG 888) in Combination With Erlotinib Temperature intolerance	1 Participants	0 Participants	0 Participants	0 Participants
Treatment-Emergent Adverse Events Occurring in ≥10% of Participants Following U3-1287 (AMG 888) in Combination With Erlotinib Asthenia	0 Participants	7 Participants	4 Participants	6 Participants
Treatment-Emergent Adverse Events Occurring in ≥10% of Participants Following U3-1287 (AMG 888) in Combination With Erlotinib Decreased appetite	4 Participants	18 Participants	17 Participants	14 Participants
Treatment-Emergent Adverse Events Occurring in ≥10% of Participants Following U3-1287 (AMG 888) in Combination With Erlotinib Hyponatraemia	1 Participants	4 Participants	1 Participants	3 Participants
Treatment-Emergent Adverse Events Occurring in ≥10% of Participants Following U3-1287 (AMG 888) in Combination With Erlotinib Alopecia	1 Participants	2 Participants	2 Participants	2 Participants
Treatment-Emergent Adverse Events Occurring in ≥10% of Participants Following U3-1287 (AMG 888) in Combination With Erlotinib Decubitus ulcer	1 Participants	2 Participants	0 Participants	0 Participants
Treatment-Emergent Adverse Events Occurring in ≥10% of Participants Following U3-1287 (AMG 888) in Combination With Erlotinib Dermatitis acneiform	2 Participants	1 Participants	2 Participants	1 Participants
Treatment-Emergent Adverse Events Occurring in ≥10% of Participants Following U3-1287 (AMG 888) in Combination With Erlotinib Rash generalized	0 Participants	8 Participants	8 Participants	4 Participants
Treatment-Emergent Adverse Events Occurring in ≥10% of Participants Following U3-1287 (AMG 888) in Combination With Erlotinib Nasal congestion	1 Participants	0 Participants	0 Participants	0 Participants
Treatment-Emergent Adverse Events Occurring in ≥10% of Participants Following U3-1287 (AMG 888) in Combination With Erlotinib Infections and Infestations	6 Participants	27 Participants	26 Participants	16 Participants
Treatment-Emergent Adverse Events Occurring in ≥10% of Participants Following U3-1287 (AMG 888) in Combination With Erlotinib Oral candidiasis	1 Participants	3 Participants	6 Participants	0 Participants
Treatment-Emergent Adverse Events Occurring in ≥10% of Participants Following U3-1287 (AMG 888) in Combination With Erlotinib Blood creatinine increased	1 Participants	1 Participants	2 Participants	0 Participants
Treatment-Emergent Adverse Events Occurring in ≥10% of Participants Following U3-1287 (AMG 888) in Combination With Erlotinib Cardiac Disorders	1 Participants	8 Participants	7 Participants	7 Participants
Treatment-Emergent Adverse Events Occurring in ≥10% of Participants Following U3-1287 (AMG 888) in Combination With Erlotinib Ocular hyperaemia	1 Participants	0 Participants	0 Participants	0 Participants
Treatment-Emergent Adverse Events Occurring in ≥10% of Participants Following U3-1287 (AMG 888) in Combination With Erlotinib Vision blurred	1 Participants	0 Participants	2 Participants	0 Participants
Treatment-Emergent Adverse Events Occurring in ≥10% of Participants Following U3-1287 (AMG 888) in Combination With Erlotinib Back pain	2 Participants	6 Participants	3 Participants	4 Participants
Treatment-Emergent Adverse Events Occurring in ≥10% of Participants Following U3-1287 (AMG 888) in Combination With Erlotinib Flank pain	1 Participants	0 Participants	1 Participants	0 Participants
Treatment-Emergent Adverse Events Occurring in ≥10% of Participants Following U3-1287 (AMG 888) in Combination With Erlotinib Muscular weakness	1 Participants	3 Participants	1 Participants	1 Participants
Treatment-Emergent Adverse Events Occurring in ≥10% of Participants Following U3-1287 (AMG 888) in Combination With Erlotinib Musculoskeletal chest pain	1 Participants	3 Participants	4 Participants	3 Participants
Treatment-Emergent Adverse Events Occurring in ≥10% of Participants Following U3-1287 (AMG 888) in Combination With Erlotinib Myalgia	1 Participants	0 Participants	1 Participants	0 Participants
Treatment-Emergent Adverse Events Occurring in ≥10% of Participants Following U3-1287 (AMG 888) in Combination With Erlotinib Contusion	2 Participants	0 Participants	2 Participants	0 Participants
Treatment-Emergent Adverse Events Occurring in ≥10% of Participants Following U3-1287 (AMG 888) in Combination With Erlotinib Fall	2 Participants	1 Participants	2 Participants	1 Participants
Treatment-Emergent Adverse Events Occurring in ≥10% of Participants Following U3-1287 (AMG 888) in Combination With Erlotinib Sunburn	1 Participants	0 Participants	0 Participants	0 Participants
Treatment-Emergent Adverse Events Occurring in ≥10% of Participants Following U3-1287 (AMG 888) in Combination With Erlotinib Neoplasms benign, malignant and unspecified (incl cysts and polyps)	1 Participants	5 Participants	7 Participants	12 Participants
Treatment-Emergent Adverse Events Occurring in ≥10% of Participants Following U3-1287 (AMG 888) in Combination With Erlotinib Tumour associated fever	1 Participants	0 Participants	0 Participants	0 Participants
Treatment-Emergent Adverse Events Occurring in ≥10% of Participants Following U3-1287 (AMG 888) in Combination With Erlotinib Dizziness	1 Participants	0 Participants	1 Participants	0 Participants
Treatment-Emergent Adverse Events Occurring in ≥10% of Participants Following U3-1287 (AMG 888) in Combination With Erlotinib Headache	2 Participants	2 Participants	3 Participants	2 Participants
Treatment-Emergent Adverse Events Occurring in ≥10% of Participants Following U3-1287 (AMG 888) in Combination With Erlotinib Paraesthesia	1 Participants	0 Participants	1 Participants	2 Participants
Treatment-Emergent Adverse Events Occurring in ≥10% of Participants Following U3-1287 (AMG 888) in Combination With Erlotinib Depression	1 Participants	3 Participants	3 Participants	3 Participants
Treatment-Emergent Adverse Events Occurring in ≥10% of Participants Following U3-1287 (AMG 888) in Combination With Erlotinib Glossitis	1 Participants	0 Participants	0 Participants	0 Participants
Treatment-Emergent Adverse Events Occurring in ≥10% of Participants Following U3-1287 (AMG 888) in Combination With Erlotinib Insomnia	1 Participants	2 Participants	4 Participants	1 Participants
Treatment-Emergent Adverse Events Occurring in ≥10% of Participants Following U3-1287 (AMG 888) in Combination With Erlotinib Investigations	2 Participants	21 Participants	24 Participants	16 Participants
Treatment-Emergent Adverse Events Occurring in ≥10% of Participants Following U3-1287 (AMG 888) in Combination With Erlotinib Any TEAE	7 Participants	69 Participants	70 Participants	69 Participants
Treatment-Emergent Adverse Events Occurring in ≥10% of Participants Following U3-1287 (AMG 888) in Combination With Erlotinib Anaemia	1 Participants	7 Participants	6 Participants	5 Participants
Treatment-Emergent Adverse Events Occurring in ≥10% of Participants Following U3-1287 (AMG 888) in Combination With Erlotinib Abdominal distension	1 Participants	0 Participants	0 Participants	1 Participants
Treatment-Emergent Adverse Events Occurring in ≥10% of Participants Following U3-1287 (AMG 888) in Combination With Erlotinib Abdominal pain	1 Participants	9 Participants	9 Participants	3 Participants
Treatment-Emergent Adverse Events Occurring in ≥10% of Participants Following U3-1287 (AMG 888) in Combination With Erlotinib Abdominal pain upper	0 Participants	5 Participants	5 Participants	8 Participants
Treatment-Emergent Adverse Events Occurring in ≥10% of Participants Following U3-1287 (AMG 888) in Combination With Erlotinib Constipation	1 Participants	9 Participants	10 Participants	4 Participants
Treatment-Emergent Adverse Events Occurring in ≥10% of Participants Following U3-1287 (AMG 888) in Combination With Erlotinib Faecal incontinence	1 Participants	0 Participants	0 Participants	0 Participants
Treatment-Emergent Adverse Events Occurring in ≥10% of Participants Following U3-1287 (AMG 888) in Combination With Erlotinib Nausea	3 Participants	26 Participants	17 Participants	14 Participants
Treatment-Emergent Adverse Events Occurring in ≥10% of Participants Following U3-1287 (AMG 888) in Combination With Erlotinib Oral disorder	1 Participants	0 Participants	0 Participants	0 Participants
Treatment-Emergent Adverse Events Occurring in ≥10% of Participants Following U3-1287 (AMG 888) in Combination With Erlotinib Stomatitis	2 Participants	2 Participants	1 Participants	0 Participants
Treatment-Emergent Adverse Events Occurring in ≥10% of Participants Following U3-1287 (AMG 888) in Combination With Erlotinib General Disorders and Administration Site Conditions	5 Participants	44 Participants	45 Participants	34 Participants
Treatment-Emergent Adverse Events Occurring in ≥10% of Participants Following U3-1287 (AMG 888) in Combination With Erlotinib Fatigue	4 Participants	18 Participants	22 Participants	13 Participants
Treatment-Emergent Adverse Events Occurring in ≥10% of Participants Following U3-1287 (AMG 888) in Combination With Erlotinib Gait disturbance	1 Participants	1 Participants	0 Participants	0 Participants
Treatment-Emergent Adverse Events Occurring in ≥10% of Participants Following U3-1287 (AMG 888) in Combination With Erlotinib General physical health deterioration	0 Participants	11 Participants	10 Participants	7 Participants
Treatment-Emergent Adverse Events Occurring in ≥10% of Participants Following U3-1287 (AMG 888) in Combination With Erlotinib Non-cardiac chest pain	1 Participants	0 Participants	0 Participants	1 Participants
Treatment-Emergent Adverse Events Occurring in ≥10% of Participants Following U3-1287 (AMG 888) in Combination With Erlotinib Pain	1 Participants	0 Participants	0 Participants	0 Participants
Treatment-Emergent Adverse Events Occurring in ≥10% of Participants Following U3-1287 (AMG 888) in Combination With Erlotinib Pyrexia	0 Participants	8 Participants	6 Participants	4 Participants
Treatment-Emergent Adverse Events Occurring in ≥10% of Participants Following U3-1287 (AMG 888) in Combination With Erlotinib Metabolism and Nutrition Disorders	5 Participants	30 Participants	34 Participants	20 Participants
Treatment-Emergent Adverse Events Occurring in ≥10% of Participants Following U3-1287 (AMG 888) in Combination With Erlotinib Blood pressure increased	1 Participants	0 Participants	0 Participants	0 Participants
Treatment-Emergent Adverse Events Occurring in ≥10% of Participants Following U3-1287 (AMG 888) in Combination With Erlotinib Blood urea increased	1 Participants	0 Participants	0 Participants	0 Participants
Treatment-Emergent Adverse Events Occurring in ≥10% of Participants Following U3-1287 (AMG 888) in Combination With Erlotinib Weight decreased	1 Participants	10 Participants	16 Participants	8 Participants
Treatment-Emergent Adverse Events Occurring in ≥10% of Participants Following U3-1287 (AMG 888) in Combination With Erlotinib Ventricular arrhythmia	1 Participants	0 Participants	0 Participants	0 Participants
Treatment-Emergent Adverse Events Occurring in ≥10% of Participants Following U3-1287 (AMG 888) in Combination With Erlotinib Hypokalaemia	1 Participants	12 Participants	11 Participants	3 Participants
Treatment-Emergent Adverse Events Occurring in ≥10% of Participants Following U3-1287 (AMG 888) in Combination With Erlotinib Hypomagnesaemia	3 Participants	0 Participants	4 Participants	0 Participants
Treatment-Emergent Adverse Events Occurring in ≥10% of Participants Following U3-1287 (AMG 888) in Combination With Erlotinib Skin and Subcutaneous Tissue Disorders	7 Participants	51 Participants	60 Participants	48 Participants
Treatment-Emergent Adverse Events Occurring in ≥10% of Participants Following U3-1287 (AMG 888) in Combination With Erlotinib Drug eruption	1 Participants	1 Participants	1 Participants	0 Participants
Treatment-Emergent Adverse Events Occurring in ≥10% of Participants Following U3-1287 (AMG 888) in Combination With Erlotinib Dry skin	4 Participants	5 Participants	12 Participants	6 Participants
Treatment-Emergent Adverse Events Occurring in ≥10% of Participants Following U3-1287 (AMG 888) in Combination With Erlotinib Ecchymosis	1 Participants	0 Participants	0 Participants	0 Participants
Treatment-Emergent Adverse Events Occurring in ≥10% of Participants Following U3-1287 (AMG 888) in Combination With Erlotinib Erythema	1 Participants	1 Participants	0 Participants	0 Participants
Treatment-Emergent Adverse Events Occurring in ≥10% of Participants Following U3-1287 (AMG 888) in Combination With Erlotinib Onychoclasis	1 Participants	0 Participants	1 Participants	1 Participants
Treatment-Emergent Adverse Events Occurring in ≥10% of Participants Following U3-1287 (AMG 888) in Combination With Erlotinib Pruritus	2 Participants	1 Participants	2 Participants	2 Participants
Treatment-Emergent Adverse Events Occurring in ≥10% of Participants Following U3-1287 (AMG 888) in Combination With Erlotinib Rash	7 Participants	35 Participants	38 Participants	28 Participants
Treatment-Emergent Adverse Events Occurring in ≥10% of Participants Following U3-1287 (AMG 888) in Combination With Erlotinib Skin exfoliation	2 Participants	1 Participants	0 Participants	1 Participants
Treatment-Emergent Adverse Events Occurring in ≥10% of Participants Following U3-1287 (AMG 888) in Combination With Erlotinib Respiratory, Thoracic, and Mediastinal Disorders	5 Participants	32 Participants	32 Participants	32 Participants
Treatment-Emergent Adverse Events Occurring in ≥10% of Participants Following U3-1287 (AMG 888) in Combination With Erlotinib Cough	2 Participants	5 Participants	11 Participants	11 Participants
Treatment-Emergent Adverse Events Occurring in ≥10% of Participants Following U3-1287 (AMG 888) in Combination With Erlotinib Dyspnoea	0 Participants	12 Participants	17 Participants	12 Participants
Treatment-Emergent Adverse Events Occurring in ≥10% of Participants Following U3-1287 (AMG 888) in Combination With Erlotinib Epistaxis	1 Participants	6 Participants	6 Participants	2 Participants
Treatment-Emergent Adverse Events Occurring in ≥10% of Participants Following U3-1287 (AMG 888) in Combination With Erlotinib Hiccups	1 Participants	0 Participants	0 Participants	1 Participants
Treatment-Emergent Adverse Events Occurring in ≥10% of Participants Following U3-1287 (AMG 888) in Combination With Erlotinib Oropharyngeal pain	1 Participants	0 Participants	1 Participants	3 Participants
Treatment-Emergent Adverse Events Occurring in ≥10% of Participants Following U3-1287 (AMG 888) in Combination With Erlotinib Postnasal drip	1 Participants	0 Participants	0 Participants	0 Participants
Treatment-Emergent Adverse Events Occurring in ≥10% of Participants Following U3-1287 (AMG 888) in Combination With Erlotinib Candidiasis	3 Participants	3 Participants	6 Participants	0 Participants
Treatment-Emergent Adverse Events Occurring in ≥10% of Participants Following U3-1287 (AMG 888) in Combination With Erlotinib Device related infection	1 Participants	1 Participants	0 Participants	0 Participants
Treatment-Emergent Adverse Events Occurring in ≥10% of Participants Following U3-1287 (AMG 888) in Combination With Erlotinib Fungal skin infection	1 Participants	3 Participants	0 Participants	1 Participants
Treatment-Emergent Adverse Events Occurring in ≥10% of Participants Following U3-1287 (AMG 888) in Combination With Erlotinib Paronychia	0 Participants	8 Participants	5 Participants	1 Participants
Treatment-Emergent Adverse Events Occurring in ≥10% of Participants Following U3-1287 (AMG 888) in Combination With Erlotinib Eye disorders	2 Participants	1 Participants	0 Participants	0 Participants
Treatment-Emergent Adverse Events Occurring in ≥10% of Participants Following U3-1287 (AMG 888) in Combination With Erlotinib Dry eye	1 Participants	0 Participants	0 Participants	0 Participants
Treatment-Emergent Adverse Events Occurring in ≥10% of Participants Following U3-1287 (AMG 888) in Combination With Erlotinib Musculoskeletal and connective tissue disorders	4 Participants	3 Participants	1 Participants	0 Participants
Treatment-Emergent Adverse Events Occurring in ≥10% of Participants Following U3-1287 (AMG 888) in Combination With Erlotinib Injury, poisoning and procedural complications	4 Participants	6 Participants	9 Participants	2 Participants
Treatment-Emergent Adverse Events Occurring in ≥10% of Participants Following U3-1287 (AMG 888) in Combination With Erlotinib Thermal burn	1 Participants	0 Participants	0 Participants	0 Participants
Treatment-Emergent Adverse Events Occurring in ≥10% of Participants Following U3-1287 (AMG 888) in Combination With Erlotinib Nervous system disorders	5 Participants	4 Participants	2 Participants	3 Participants
Treatment-Emergent Adverse Events Occurring in ≥10% of Participants Following U3-1287 (AMG 888) in Combination With Erlotinib Ataxia	1 Participants	1 Participants	0 Participants	1 Participants
Treatment-Emergent Adverse Events Occurring in ≥10% of Participants Following U3-1287 (AMG 888) in Combination With Erlotinib Tinea cruris	1 Participants	0 Participants	0 Participants	0 Participants
Treatment-Emergent Adverse Events Occurring in ≥10% of Participants Following U3-1287 (AMG 888) in Combination With Erlotinib Urinary tract infection	1 Participants	5 Participants	4 Participants	2 Participants
Treatment-Emergent Adverse Events Occurring in ≥10% of Participants Following U3-1287 (AMG 888) in Combination With Erlotinib Dysgeusia	2 Participants	1 Participants	2 Participants	1 Participants
Treatment-Emergent Adverse Events Occurring in ≥10% of Participants Following U3-1287 (AMG 888) in Combination With Erlotinib Hyperaesthesia	1 Participants	0 Participants	0 Participants	0 Participants
Treatment-Emergent Adverse Events Occurring in ≥10% of Participants Following U3-1287 (AMG 888) in Combination With Erlotinib Hypoaesthesia	1 Participants	0 Participants	0 Participants	0 Participants
Treatment-Emergent Adverse Events Occurring in ≥10% of Participants Following U3-1287 (AMG 888) in Combination With Erlotinib Peroneal nerve palsy	1 Participants	0 Participants	0 Participants	0 Participants
Treatment-Emergent Adverse Events Occurring in ≥10% of Participants Following U3-1287 (AMG 888) in Combination With Erlotinib Presyncope	1 Participants	0 Participants	0 Participants	0 Participants
Treatment-Emergent Adverse Events Occurring in ≥10% of Participants Following U3-1287 (AMG 888) in Combination With Erlotinib Psychiatric disorders	2 Participants	11 Participants	12 Participants	12 Participants
Treatment-Emergent Adverse Events Occurring in ≥10% of Participants Following U3-1287 (AMG 888) in Combination With Erlotinib Anxiety	1 Participants	0 Participants	1 Participants	4 Participants
Treatment-Emergent Adverse Events Occurring in ≥10% of Participants Following U3-1287 (AMG 888) in Combination With Erlotinib Confusional state	1 Participants	0 Participants	0 Participants	1 Participants
Treatment-Emergent Adverse Events Occurring in ≥10% of Participants Following U3-1287 (AMG 888) in Combination With Erlotinib Libido decreased	1 Participants	0 Participants	0 Participants	0 Participants
Treatment-Emergent Adverse Events Occurring in ≥10% of Participants Following U3-1287 (AMG 888) in Combination With Erlotinib Renal and urinary disorders	4 Participants	7 Participants	2 Participants	2 Participants
Treatment-Emergent Adverse Events Occurring in ≥10% of Participants Following U3-1287 (AMG 888) in Combination With Erlotinib Haematuria	1 Participants	2 Participants	0 Participants	0 Participants
Treatment-Emergent Adverse Events Occurring in ≥10% of Participants Following U3-1287 (AMG 888) in Combination With Erlotinib Incontinence	1 Participants	0 Participants	1 Participants	0 Participants
Treatment-Emergent Adverse Events Occurring in ≥10% of Participants Following U3-1287 (AMG 888) in Combination With Erlotinib Nocturia	1 Participants	0 Participants	0 Participants	1 Participants
Treatment-Emergent Adverse Events Occurring in ≥10% of Participants Following U3-1287 (AMG 888) in Combination With Erlotinib Pollakiuria	1 Participants	0 Participants	1 Participants	0 Participants
Treatment-Emergent Adverse Events Occurring in ≥10% of Participants Following U3-1287 (AMG 888) in Combination With Erlotinib Proteinuria	2 Participants	0 Participants	0 Participants	0 Participants
Treatment-Emergent Adverse Events Occurring in ≥10% of Participants Following U3-1287 (AMG 888) in Combination With Erlotinib Urinary hesitation	1 Participants	0 Participants	0 Participants	0 Participants

Adverse Events

Phase 1b: U31287 18mg/kg + Erlotinib

Serious events: 3 serious events

Other events: 7 other events

Deaths: 6 deaths

Phase 2: U3-1287 18 mg/kg + Erlotinib

Serious events: 35 serious events

Other events: 69 other events

Deaths: 64 deaths

Phase 2: U3-1287 9 mg/kg + Erlotinib

Serious events: 24 serious events

Other events: 70 other events

Deaths: 53 deaths

Phase 2: Placebo + Erlotinib

Serious events: 24 serious events

Other events: 69 other events

Deaths: 53 deaths

Serious adverse events

Other adverse events

Additional Information

Contact for Clinical Trial Information

Daiichi Sankyo

Phone: 908-992-6400

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place