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

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).

Time frame: 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.

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). Heregulin (HRG) high is defined as delta cycle threshold value \< 3.9.

Time frame: 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.

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). Heregulin (HRG) low is defined as a delta cycle threshold value ≥ 3.9.

Time frame: 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.

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).

Time frame: 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.

Time frame: 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.

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.

Time frame: 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.

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

Time frame: 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.

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

Time frame: 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.

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

Time frame: 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: 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.

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.

Time frame: 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)

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.

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.

Time frame: 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 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.

Time frame: 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.

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.

Time frame: 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.