GRN1005 in Non-Small Cell Lung Cancer (NSCLC) Patients With Brain Metastases (GRABM-L)

Key 1. Adult patients (≥ 18 years) 2. Histologically or cytologically-documented NSCLC (EGFR mutation status must be known) 3. Brain metastases from NSCLC, which: have radiologically-progressed after WBRT or are present without prior WBRT 4. At least one radiologically-confirmed and measurable lesion (≥ 1.0 cm in the longest diameter) within14 days prior to the first dose of GRN1005 (Cycle 1, Day 1), as follows: an intra-cranial disease lesion (≥ 1.0 cm in the longest diameter) confirmed by Gd-MRI, or an extra-cranial disease lesion (≥ 1.0 cm in the longest diameter) confirmed by MRI or CT scan with contrast Prior stereotactic radiosurgery (SRS) is allowed; however, metastatic brain lesions previously treated with SRS are not allowed as target or as non-target lesions. 5. Patients must be neurologically stable, defined as being on stable doses of corticosteroids and anticonvulsants (not EIAEDs, including phenytoin, phenobarbitol, carbamazepine, fosphenytoin, primidone, oxcarbazepine) for ≥ 5 days prior to obtaining the baseline Gd-MRI of the brain and ≥ 5 days prior to first dose of GRN1005 (Cycle 1, Day 1). 6. Karnofsky Performance Score (KPS) ≥ 80% 7. Completed WBRT for intra-cranial lesions ≥ 28 days prior to first dose of GRN1005 (with the exception of local radiation therapy for palliation to extra-cranial sites, i.e., bone). All clinically significant toxicities must have resolved to ≤ NCI CTCAE v4.0 Grade 1.0. Key

1. NCI CTCAE v4.0 Grade ≥ 2 neuropathy 2. CNS disease requiring immediate neurosurgical intervention (e.g., resection, shunt placement, etc.) 3. Known intra-cranial hemorrhage 4. Known leptomeningeal disease