A Study of XL184 (Cabozantinib) With or Without Erlotinib in Subjects With Non-Small Cell Lung Cancer (NSCLC)

Inclusion Criteria

• •Subjects had pathologically confirmed NSCLC and currently have Stage IIIb or IV NSCLC
• •Subjects had failed treatment with erlotinib at 150 mg qd
• •Subjects had tolerated erlotinib at the dose of the cohort in which they were enrolled (or at a higher dose) for at least 6 weeks (or for the duration of treatment if disease progression had occurred during treatment with erlotinib for less than 6 weeks)
• •The subject was at least 18 years old
• •The subject had an ECOG performance status of \< 2
• •The subject had organ and marrow function as follows: - absolute neutrophil count ≥ 1500/mm3, platelets ≥ 100,000/mm3, hemoglobin ≥ 9 g/dL, bilirubin ≤ 1.5 times the upper limit of normal, serum creatinine ≤ 1.5 mg/dL or if serum creatinine \> 1.5 mg/dL calculated creatinine clearance ≥ 60 mL/min, alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2.5 times the upper limit of normal, amylase and lipase \< 1.5 times the upper limit of normal
• •Sexually active subjects had to agree to use medically accepted methods of contraception during the course of the study and for 3 months following discontinuation of study treatments (excluding women who are not of child bearing potential and men who have been sterilized)
• •Female subjects of childbearing potential had to have a negative pregnancy test at enrollment. Females of childbearing potential were defined as sexually mature women without prior hysterectomy or who had evidence of menses in the past 12 months. However, women who had been amenorrheic for 12 or more months were still considered to be of childbearing potential if the amenorrhea was possibly due to prior chemotherapy, antiestrogens, or ovarian suppression
• •The subject had no other diagnosis of malignancy (unless non-melanoma skin cancer, carcinoma in situ of the cervix, or a malignancy diagnosed ≥ 2 years previously, and currently with no evidence of disease)
• •Subjects had pathologically confirmed NSCLC and currently have Stage IIIb or IV NSCLC
• •Subjects had: Documented radiological PD, following a prior response, per investigator assessment, to monotherapy with erlotinib, OR; Documented radiological PD, per investigator assessment, following stable disease of at least 6 months on monotherapy with erlotinib
• •Subjects who had received subsequent anti-cancer therapy after having progressed on erlotinib (as defined above) also had to have documented radiological PD per investigator assessment to their most recent anti-cancer therapy. If the most recent anti-cancer therapy was erlotinib after having previously progressed on erlotinib (as defined above) the subject also had to have documented radiological PD per investigator assessment to their most recent course of erlotinib
• •Subjects had to have tolerated erlotinib at the maximal dose that would be administered in Phase 2 (or at a higher dose) for a minimum of 6 weeks
• •Subjects had measurable disease per RECIST
• •Subjects had to have 15 unstained consecutive slides of archival or fresh tumor tissue (from one tumor block, frozen tumor tissue, or a paraffin block) identified and designated for shipment to the sponsor if permitted by local regulations (including IRB \[Institutional Review Board\] policies). The eligibility of subjects with \< 15 unstained slides of available archival tissue was discussed with the sponsor
• •The subject was at least 18 years old
• •The subject had an ECOG performance status of \< 1
• •The subject had organ and marrow function as follows: absolute neutrophil count ≥ 1500/mm3, platelets ≥ 100,000/mm3, hemoglobin ≥ 9 g/dL, bilirubin ≤ 1.5 times the upper limit of normal, serum creatinine ≤ 1.5 mg/dL or if serum creatinine \> 1.5 mg/dL calculated creatinine clearance ≥ 60 mL/min, ALT and AST ≤ 2.5 times the upper limit of normal, amylase and lipase \< 1.5 times the upper limit of normal
• •Sexually active subjects had to agree to use medically accepted methods of contraception during the course of the study and for 3 months following discontinuation of study treatments (excluding women who are not of child bearing potential and men who have been sterilized)
• •Female subjects of childbearing potential had to have a negative pregnancy test at enrollment. Females of childbearing potential were defined as sexually mature women without prior hysterectomy or who had evidence of menses in the past 12 months. However, women who had been amenorrheic for 12 or more months were still considered to be of childbearing potential if the amenorrhea was possibly due to prior chemotherapy, antiestrogens, or ovarian suppression
• •The subject had no other diagnosis of malignancy (unless non-melanoma skin cancer, carcinoma in situ of the cervix, or a malignancy diagnosed ≥ 2 years previously, and currently with no evidence of disease)