A Study of RO5083945 in Combination With Chemotherapy Versus Chemotherapy Alone in Patients With Advanced or Recurrent Non-Small Cell Lung Cancer

• Part 1: Adverse event profile: adverse events, ECG, hematology, urinalysis, human anti-human antibodies (HAHA) [ Time Frame: 6 months ] [ Designated as safety issue: No ]
• Part 2: Progression-free survival, according to RECIST criteria by CT/MRI [ Time Frame: 23 months ] [ Designated as safety issue: No ]

• Pharmacokinetics of RO5083945 (AUC, Cmax and Cmin) in combination with cisplatin and gemcitabine/pemetrexed [ Time Frame: multiple sampling cycles 1-6 (18 weeks) ] [ Designated as safety issue: No ]
• Overall response rate (ORR), according to RECIST criteria by CT/MRI [ Time Frame: 23 months ] [ Designated as safety issue: No ]
• Duration of response, according to RECIST criteria by CT/MRI [ Time Frame: from response to disease progression ] [ Designated as safety issue: No ]
• Clinical benefit rate (complete response, partial response or stable disease for >/=6 weeks), according to RECIST criteria by CT/MRI [ Time Frame: 23 months ] [ Designated as safety issue: No ]
• Overall survival [ Time Frame: 23 months ] [ Designated as safety issue: No ]

This open label, 2-part study will evaluate the safety and efficacy of RO5083945 in combination with standard chemotherapy in patients with advanced or recurrent non-small cell lung cancer who have not received prior chemotherapy. In Part 1 patients will receive RO5083945 intravenously and standard chemotherapy (cisplatin plus either gemcitabine or pemetrexed) for up to 6 cycles of 3 weeks and then RO5083945 until disease progression. In Part 2 patients will be randomized to receive either RO5083945 in combination with standard chemotherapy or chemotherapy alone for up to 6 cycles. In the absence of disease progression, patients receiving RO503945 can continue treatment with RO5083945 as monotherapy.

• Drug: RO5083945
  intravenously, until disease progression
• Drug: cisplatin
  standard treatment, up to 6 cycles
• Drug: gemcitabine
  standard treatment, up to 6 cycles
• Drug: pemetrexed
  standard treatment, up to 6 cycles

• Experimental: A squamous
  Interventions:

  • Drug: RO5083945
  • Drug: cisplatin
  • Drug: gemcitabine
• Experimental: A non-squamous
  Interventions:

  • Drug: RO5083945
  • Drug: cisplatin
  • Drug: pemetrexed
• Active Comparator: B squamous
  Interventions:

  • Drug: cisplatin
  • Drug: gemcitabine
• Active Comparator: B non-squamous
  Interventions:

  • Drug: cisplatin
  • Drug: pemetrexed

Inclusion Criteria:

• Adult patients, >/=18 years of age
• Advanced (IIIb), metastatic (IV) or recurrent non-small cell lung cancer
• At least 1 measurable disease lesion as per RECIST criteria
• Confirmed presence of EGFR in tumor tissue
• ECOG performance status 0-1
• Adequate hematological, renal and liver function

Exclusion Criteria:

• Prior chemotherapy or treatment with another systemic anti-cancer agent
• Radiotherapy within the last 4 weeks, except for limited field palliative radiotherapy for bone pain relief
• Symptomatic or active CNS metastases
• Recent history of poorly controlled hypertension (systolic >180mmHg or diastolic >100mmHg)
• Requirement for steroids > 40 mg prednisolone