Multicenter, open-label, phase 1, cohort dose escalation study to determine the MTD of OSI-906 in combination with erlotinib

The study will open with Schedule 1 (S1), in which OSI-906 is administered on Days 1-3 every 7 days. Erlotinib will be administered daily starting on Day 2. A treatment period is defined as 21 days. Initiation of Schedule 2 (S2), in which OSI-906 is administered daily starting on Day 1 and erlotinib is administered daily starting on Day 2, will occur after observation of clinically significant related toxicity >/= grade 2 in any patient on S1 or after > 2 dose levels in S1 have been examined without evidence of DLT. Once the recommended phase 2 dose has been established for S1 and S2, 3 expansion cohorts of up to 10 evaluable patients each will be opened.

• Experimental: Schedule 1 (S1): OSI-906 is administered on Days 1-3 every 7 days. Erlotinib will be administered daily starting on Day 2.
• Experimental: Schedule 2 (S2): OSI-906 is administered daily starting on Day 1 and erlotinib is administered daily starting on Day 2

Inclusion Criteria:

• Histologically or cytologically confirmed advanced solid tumor
• For Expansion Cohort C, a confirmed diagnosis of stage IIIB/IV NSCLC after failure of at least 1 prior chemotherapy regimen is required
• Age >/= 18 years
• ECOG PS 0-2
• Predicted life expectancy >/= 12 weeks
• Patients may have had prior therapy, providing certain conditions are met
• Fasting glucose </= 125 mg/dL (7 mmol/L) at baseline and on Day 1 prior to dosing
• Blood ketones </= ULN
• ANC >/= 1.5 x 10^9/L, Platelets >/= 100 x 10^9/L; bilirubin </= 1.5 x ULN, AST and/or ALT </= 2.5 x ULN or </= 5 x ULN if patient has documented liver metastases; serum creatinine </= 1.5 x ULN
• Patients must be nonsmokers (or former smokers who stopped smoking > 3 months previously) and have a negative cotinine test at baseline and on Day
• Patients in the expansion cohorts must have measurable disease per RECIST
• Patients must be accessible for repeat dosing and follow-up, including pharmacokinetic sampling
• Patients - both males and females - with reproductive potential must agree to practice effective contraceptive measures throughout the study. Women of childbearing potential must provide a negative pregnancy test at baseline and on Day 1
• Patients must provide verbal and written informed consent to participate in the study

Exclusion Criteria:

• Documented history of diabetes mellitus
• History of significant cardiac disease unless the disease is well-controlled
• History of cerebrovascular accident (CVA) within 12 months prior to registration or that is not stable
• Prior EGFR or IGFR inhibitor therapy
• History of any psychiatric condition that might impair the patient's ability to understand or to comply with the requirements of the study or to provide informed consent
• Pregnant or breast-feeding females GI abnormalities including inability to take oral medication, requirement for IV alimentation, active peptic ulcer, or prior surgical procedures affecting absorption
• Ocular inflammatory or infectious condition that is not completely resolved prior to registration
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to the study drug
• Any type of active seizure disorder
• Use of drugs that have a risk of causing QT interval prolongation within 14 days prior to Day 1 dosing
• Use of strong or moderate CYP3A4 or CYP1A2 inhibitors/inducers, with the exception of low-dose steroids, within 14 days prior to Day 1 dosing
• Use of proton pump inhibitors within 14 days prior to day 1 dosing
• Symptomatic brain metastases that are not stable, require steroids, or that have required radiation within the last 28 days
• Active or uncontrolled infections or serious illnesses or medical conditions that could interfere with the patient's ongoing participation in the study