It was planned to examine methylthioadenosine phosphorylase (MTAP) gene deletion, folate receptor alpha (FRα) and folylpoly-gamma-glutamate synthetase (FPGS) expression, and to correlate the results with the clinical data to determine the association between these factors and clinical outcome to treatment. However, due to the small number of participants with partial response (n=1), the planned statistical analyses that would correlate responders/non responders with pharmacogenomics data are no longer valid and the analyses were not conducted.

Pharmacology toxicity was defined as serious and non-serious adverse events. Summaries of these adverse events are located in the Reported Adverse Event Section.

The duration of a complete response (CR) or partial response (PR) was defined as the time from the first objective status assessment of CR or PR to the first date of progression or death as a result of any cause: CR was achieved if all tumor lesions disappeared; PR was achieved if there was >=30% decrease in sum of the longest diameter (LD) of target lesions (reference: baseline sum LDs) or complete disappearance of target lesions with persistence (but not worsening) of >=1 nontarget lesions and no appearance of new lesions.

PFS was from date of study enrollment to first date of objectively determined progressive disease (PD) or death from any cause. For participants who did not die as of data cut-off date and who did not have objective PD, PFS was censored at date of last objective progression-free disease assessment. For participants who received subsequent systemic anticancer therapy (after discontinuation from study drug) before objectively determined disease progression or death, PFS was censored at date of last objective progression-free disease assessment, before post-discontinuation chemotherapy.

OS was the duration from enrollment to death. For participants who lived, OS was censored at the last contact.

Complete response (CR): all tumor lesions disappear. Partial response (PR): >=30% decrease in sum of the longest diameter (LD) of target lesions (reference: baseline sum LDs) or complete disappearance of target lesions, with persistence (but not worsening) of >=1 nontarget lesions; no appearance of new lesions. Stable disease: neither sufficient shrinkage for PR nor sufficient increase for PD; references: smallest sum LD. Progressive disease (PD): >=20% increase in the sum of LD of target lesions (references: smallest sum LD recorded since treatment started) or appearance of >=1 new lesions.

0: fully active, able to carry on all pre-disease performance without restriction; 1: restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature; 2: ambulatory and capable of all self-care but unable to carry out any work activities, up and about more than 50% of waking hours; 3: capable of only limited self-care, confined to bed or chair more than 50% of waking hours; 4: completely disabled, cannot carry on any self-care, totally confined to bed or chair; 5: dead.

Target lesions: all measurable lesions up to a maximum of 5 lesions per organ and 10 lesions in total, representative of all involved organs; selected on the basis of size (those lesions with the longest diameter) and suitability for accurate repeated measurements (either by imaging techniques or clinically). If the measurable disease is restricted to a solitary lesion, the neoplastic nature of the lesion was confirmed by cytology/histology.

All lesions that do not meet the criteria for target lesions, including small lesions (longest diameter <20 millimeter [mm] with conventional computed tomography [CT] scan, <10 mm with spiral CT scan) and other non-measurable lesions.

When the protocol was written, time to treatment failure (TTTF) was included as a secondary endpoint. However, it was subsequently realized that due to the design of the study, participants are treated until disease progression or discontinuation from study treatment, not for a fixed number of cycles. Therefore, it was concluded that analysis of TTTF was inappropriate with the current study design and the analysis was not conducted, since it would be essentially the same as Progression-Free Survival.

Since this outcome measure was not analyzed due to the study design, zero participants were analyzed.

It was planned to examine methylthioadenosine phosphorylase (MTAP) gene deletion, folate receptor alpha (FRα) and folylpoly-gamma-glutamate synthetase (FPGS) expression, and to correlate the results with the clinical data to determine the association between these factors and clinical outcome to treatment. However, due to the small number of participants with partial response (n=1), the planned statistical analyses that would correlate responders/non responders with pharmacogenomics data are no longer valid and the analyses were not conducted.

Since this outcome measure was not analyzed due to the inadequate number of responders, zero participants were analyzed.

Pharmacology toxicity was defined as serious and non-serious adverse events. Summaries of these adverse events are located in the Reported Adverse Event Section.

Full analysis population: all participants who were treated with at least one dose of the study regimen

The duration of a complete response (CR) or partial response (PR) was defined as the time from the first objective status assessment of CR or PR to the first date of progression or death as a result of any cause: CR was achieved if all tumor lesions disappeared; PR was achieved if there was >=30% decrease in sum of the longest diameter (LD) of target lesions (reference: baseline sum LDs) or complete disappearance of target lesions with persistence (but not worsening) of >=1 nontarget lesions and no appearance of new lesions.

Tumor response population: participants with best overall response of complete response (CR) and partial response (PR).

PFS was from date of study enrollment to first date of objectively determined progressive disease (PD) or death from any cause. For participants who did not die as of data cut-off date and who did not have objective PD, PFS was censored at date of last objective progression-free disease assessment. For participants who received subsequent systemic anticancer therapy (after discontinuation from study drug) before objectively determined disease progression or death, PFS was censored at date of last objective progression-free disease assessment, before post-discontinuation chemotherapy.

Full analysis population: all participants who were treated with at least one dose of the study regimen.

OS was the duration from enrollment to death. For participants who lived, OS was censored at the last contact.

Full analysis population: all participants who were treated with at least one dose of the study regimen.

Resulted in death due to multiorgan failure possibly related to study drug.

Cause of death could not be established.