During the Phase I part of the study, participants receive dalotuzumab intravenously (IV) at 5 mg/kg weekly plus open-label erlotinib at 150 mg daily for 4 weeks. After 4 weeks of therapy, participants in Phase I who do not have disease progression and are satisfactorily tolerating study drug can continue to receive study drug.

During the Phase I part of the study, participants receive dalotuzumab intravenously (IV) at 10 mg/kg weekly plus open-label erlotinib at 150 mg daily for 4 weeks. After 4 weeks of therapy, participants in Phase I who do not have disease progression and are satisfactorily tolerating study drug can continue to receive study drug.

During the Phase II part of the study, participants are randomized to receive dalotuzumab intravenously (IV) at 10 mg/kg weekly plus open-label erlotinib at 150 mg daily until disease progression or occurrence of unacceptable toxic effects.

During the Phase II part of the study, participants are randomized to receive open-label erlotinib at 150 mg daily until disease progression or occurrence of unacceptable toxic effects.

Dalotuzumab 20 mg/mL in sterile solution. Intravenous (IV) infusion over 60 minutes at 5 mg/kg, administered weekly at dosage according to treatment group.

A DLT was an AE related (definitely, probably, or possibly) to study therapy and occurring within first 4 weeks of therapy.

Hematologic DLTs included Grade (Gr)4 neutropenia lasting for ≥7 days, Gr 3/Gr 4 neutropenia with fever >38.5 °C and/or infection requiring antibiotic or anti-fungal treatment, and Gr 4 thrombocytopenia (25.0 x 10^9/L).

Non-hematologic DLT defined as any ≥Gr 3 nonhematologic toxicity, except Gr 3 reversible rash; Gr 3 nausea, vomiting, diarrhea, dehydration, or hyperglycemia occurring in setting of inadequate compliance with supportive care; alopecia; anorexia; asthenia; inadequately-treated hypersensitivity reactions; Gr 3 elevated transaminases (≤1 week duration); or infusion reactions to dalotuzumab.

Any drug-related AEs that led to dose modification of dalotuzumab/erlotinib or any unresolved drug-related toxicity that caused a ≥3 week delay of next scheduled dose of study drug, regardless of Common Terminology Criteria grade, were DLTs.

PFS was defined as the time from randomization until either the emergence of radiographic evidence of disease progression or death due to any cause, whichever occurs first. Disease progression was classified as a radiographic assessment of progressive disease (PD) according to Response Evaluation Criteria in Solid Tumors (RECIST) using computed tomography (CT) or magnetic resonance imaging (MRI). As pre-specified by the protocol, final analysis of PFS was to take place after approximately 49 PFS events or deaths had occurred in the Phase II part of the trial. A non-parametric Kaplan-Meier method was used to estimate the median PFS time for each treatment group. Participants who discontinued from the study for reasons other than progression of disease were treated as right-censored observations at the time of the last response evaluation. Participants who withdrew from the study due to PD were considered to have a disease progression between the last visit and the time of withdrawal.

OS was defined as the time from randomization to death in months due to any cause. Participants without documented death at the time of the final analysis were censored at the date of the last follow-up. The nonparametric Kaplan-Meier method was used to estimate the survival time distribution and the median survival of each treatment group.

During the Phase I part of the study, participants received dalotuzumab IV at 5 mg/kg weekly plus open-label erlotinib at 150 mg daily for 4 weeks. After 4 weeks of therapy, participants in Phase I who did not have disease progression and were satisfactorily tolerating study drug could continue to receive study drug.

A DLT was an AE related (definitely, probably, or possibly) to study therapy and occurring within first 4 weeks of therapy.

Hematologic DLTs included Grade (Gr)4 neutropenia lasting for ≥7 days, Gr 3/Gr 4 neutropenia with fever >38.5 °C and/or infection requiring antibiotic or anti-fungal treatment, and Gr 4 thrombocytopenia (25.0 x 10^9/L).

Non-hematologic DLT defined as any ≥Gr 3 nonhematologic toxicity, except Gr 3 reversible rash; Gr 3 nausea, vomiting, diarrhea, dehydration, or hyperglycemia occurring in setting of inadequate compliance with supportive care; alopecia; anorexia; asthenia; inadequately-treated hypersensitivity reactions; Gr 3 elevated transaminases (≤1 week duration); or infusion reactions to dalotuzumab.

Any drug-related AEs that led to dose modification of dalotuzumab/erlotinib or any unresolved drug-related toxicity that caused a ≥3 week delay of next scheduled dose of study drug, regardless of Common Terminology Criteria grade, were DLTs.

Participants in the Phase I part of the study who received at least one dose of dalotuzumab in combination with erlotinib during the first 4 weeks of treatment and were evaluable for DLT assessment. Participants in the Phase II part of the study were not evaluated for DLTs.

During the Phase I part of the study, participants received dalotuzumab IV at 5 mg/kg weekly plus open-label erlotinib at 150 mg daily for 4 weeks. After 4 weeks of therapy, participants in Phase I who did not have disease progression and were satisfactorily tolerating study drug could continue to receive study drug.