A Study Evaluating Dalotuzumab (MK-0646) in Combination With Erlotinib for Participants With Non-Small Cell Lung Cancer (MK-0646-007)

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.

Time frame: Duration of time required to collect approximately 49 deaths or PFS events (assessed up to ~20 months total on this study from randomization to cut-off date)

Population: All randomized participants in Phase II who received ≥1 dose of study treatment, had a baseline radiological (CT or MRI) disease assessment, and had ≥1 post-baseline radiological (CT or MRI) disease assessment subsequent to ≥1 dose of study treatment for reason other than discontinuation for AE. Phase I participants were not assessed for PFS.

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.

Time frame: Up to 4 weeks after initiation of treatment

Population: 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.

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.

Time frame: Duration of time required to collect approximately 49 deaths or PFS events (assessed up to ~20 months total on this study from randomization to cut-off date)

Population: Intent to Treat (IIT) Population; all randomized participants in Phase II included regardless of compliance to planned treatment. Phase I participants were not assessed for OS.

ORR was defined as the percentage of participants in the Phase II analysis population having complete response (CR) or partial response (PR) during the course of the study. RECIST criteria were used to quantify response rate. For evaluation of target lesions, CR was defined as disappearance of all target lesions and PR was defined as at least a 30% decrease in the sum of the longest diameter (LD) of target lesions, taking as reference the baseline sum of the LD. For evaluation of non-target lesions, CR was defined as disappearance of all non-target lesions and normalization of tumor marker level. Confirmation of response required a second assessment performed 4 weeks or more after the initial assessment. If the confirmation assessment contradicted the initial assessment, it was considered that a response had not been observed. If the confirmation assessment of a participant was not available, that participant was not considered as a responder in the response rate analyses.

Time frame: Duration of time required to collect approximately 49 deaths or PFS events (assessed up to ~20 months total on this study from randomization to cut-off date)

Population: All randomized participants in Phase II who received ≥1 dose of study treatment, had a baseline radiological (CT or MRI) disease assessment, and had ≥1 post-baseline radiological (CT or MRI) disease assessment subsequent to ≥1 dose of study treatment for reason other than discontinuation for AE. Phase I participants were not assessed for ORR.