Efficacy Study of Pharmacokinetic(PK)/Pharmacodynamic(PD) Relationship of Monotherapy MORAb-004 in Metastatic Melanoma

PFS was defined as the time (in weeks) from the date of randomization to the date of the first sign of disease progression (PD) based on Response Evaluation Criteria in Solid Tumours (RECIST) version 1.1, or date of death, regardless of cause. PD greater than or equal to (\>=) 20 percent (%) increase in the nadir of total tumor burden (TTB) (minimum 5 millimeter \[mm\]). Participants who were alive with no disease progression had their PFS time censored at the date of their last tumor assessment. Participants who received a new anti-cancer therapy before disease progression had their PFS time censored at the date of their last tumor assessment before the new anti-cancer therapy was started. PFS was analyzed using Kaplan Meier method.

Time frame: Week 24

Population: Primary efficacy population included all participants in the safety population who meet all key eligibility criteria (including measurable disease at baseline after at least 1 systemic treatment) analyzed by the dose level to which they were randomized.

OBD is defined as the dose level/exposure level at which three parameters are met: 1) adequate pharmacokinetic (PK) profile with a serum half-life (t1/2) of \>=48 hours, 2) at least minimal demonstration of antitumor efficacy (50% or greater PFS rate at 16 weeks), and 3) change of 25% or greater from baseline value in any of the pharmacodynamic (PD) parameters assessed in the study in 30% of participants at that dose level.

Time frame: Day 1 Cycle 1 (Cycle length = 28 days)

Population: All participants in the safety population who receive at least one dose of MORAb-004 and who had at least one on-treatment PK/PD assessment performed that is sufficient to evaluate the endpoint of interest. Here overall number of participants analyzed are participants who were available for this outcome measure.

OS was defined as the time (in weeks) from the date of randomization to the date of death, regardless of cause. In the absence of death confirmation, or for participants alive at the time of analysis, the survival time was censored at the date of the last study follow-up. OS was calculated using the Kaplan-Meier method. As per planned analysis, efficacy outcomes was planned to be analyzed until cut-off date (02 December 2013).

Time frame: Date of first study treatment (Day 1) to date of death or up to approximately 2 years 7 months

Population: Primary efficacy population included all participants in the safety population who meet all key eligibility criteria (including measurable disease at baseline after at least 1 systemic treatment) analyzed by the dose level to which they were randomized. Participants without documentation of death at the time of analysis were censored at the date last known to be alive.

ORR was defined as the percentage of participants with best overall response (BOR) of complete response (CR) or partial response (PR) that occurred (defined by RECIST version 1.1) using CT/MRI. Per RECIST 1.1, CR= disappearance of all lesions; PR greater than or equal to (\>=) 30percent (%) decrease from baseline in TTB. As per planned analysis, efficacy outcomes was planned to be analyzed until cut-off date (02 December 2013).

Time frame: Date of first study treatment (Day 1) to complete response or partial response, assessed up to approximately 2 years 7 months

Population: ORR population included a subset of participants from the primary efficacy population who had at least 1 on-study radiologic evaluation performed (in addition to their baseline evaluation), analyzed by the dose level received.

PFS was defined as the time (in weeks) from the date of randomization to the date of the first observation of PD (RECIST version 1.1) or date of death, regardless of the cause. PD \>=20% increase in the nadir of TTB (minimum 5 mm). Participants who were alive with no disease progression had their PFS time censored at the date of their last tumor assessment. Participants who received new anti-cancer therapy before disease progression had their PFS time censored at the date of their last tumor assessment before the new anti-cancer therapy was initiated. PFS was based on the Kaplan-Meier method.

Time frame: Week 16 and Week 52

Population: Primary efficacy population included all participants in the safety population who meet all key eligibility criteria (including measurable disease at baseline after at least 1 systemic treatment) analyzed by the dose level to which they were randomized.