• Time to death on the combination of ZD4054 plus pemetrexed compared to pemetrexed alone in patients with locally advanced or metastatic NSCLC after failure of first line anti-cancer therapy [ Time Frame: Patients will be followed up every week for the first 3 weeks then every 3 weeks whilst on study medication until the data cut-off (DCO) for survival, estimated to be 12 months after the last patient is randomised. ] [ Designated as safety issue: Yes ]
  

• Progression-free survival; progression is defined as objective disease progression using Response Evaluation Criteria In Solid Tumours (RECIST), clinical progression on or before the Mandatory Tumour Assessment Visit (MTAV), or death from any cause. [ Time Frame: Tumour assessment at screening, every 3 weeks, MTAV, treatment discontinuation ] [ Designated as safety issue: No ]
  
• Safety and tolerability of ZD4054 in combination with pemetrexed for the treatment of NSCLC by review of adverse events (AEs) and laboratory parameters [ Time Frame: Predose until post-study medical ] [ Designated as safety issue: Yes ]
  

Inclusion Criteria:

• Histologically or cytologically confirmed locally advanced or metastatic NSCLC on entry into study suitable for pemetrexed therapy
• Patients that meet one of the following criteria: - progressed following one prior platinum-based chemotherapy regimen for locally advanced or metastatic disease; -progressed within 6 months of adjuvant platinum-based chemotherapy
• Life expectancy of > 12 weeks

Exclusion Criteria:

• Prior treatment with pemetrexed in the last 12 months.
• Prior therapy with an ET receptor antagonist
• Any recent surgery, unhealed surgical incision, severe concomitant medical condition (eg, unstable cardiac, hepatic or renal disease) or significant laboratory finding which makes it undesirable for the patient to participate