GRN1005 Alone or in Combination With Trastuzumab in Breast Cancer Patients With Brain Metastases (GRABM-B)

• Number of patients with adverse events as a measure of safety and tolerability of GRN1005 alone or in combination with Trastuzumab [ Time Frame: Upon enrollment through end of study period (1 year after last patient is enrolled) ] [ Designated as safety issue: Yes ]
• Intra-cranial objective response duration [ Time Frame: Upon enrollment through end of study period (1 year after last patient is enrolled) ] [ Designated as safety issue: No ]
• 3-month intra-cranial progression-free survival [ Time Frame: Upon enrollment through end of study period (1 year after last patient is enrolled) ] [ Designated as safety issue: No ]
• Six month overall survival (OS) [ Time Frame: Upon enrollment through end of study period (1 year after last patient is enrolled) ] [ Designated as safety issue: No ]

The purpose of this study is to assess the efficacy, safety, and tolerability of GRN1005 in patients with brain metastases from breast cancer. For patients with HER2 positive metastatic breast cancer, GRN1005 will be assessed in combination with Trastuzumab (Herceptin®) as per standard-of-care practice.

Please see Brief Summary section.

• Breast Cancer
• Brain Metastases

• Drug: GRN1005
  550 mg/m2 IV every 3 weeks
  Other Name: ANG1005
• Drug: Trastuzumab
  2 mg/kg IV every week or 6 mg/kg IV every 3 weeks per investigator choice
  Other Name: Herceptin

• Experimental: GRN1005 alone for HER2- MBC patients
  Please see above.
  Intervention: Drug: GRN1005
• Experimental: GRN1005 with trastuzumab
  GRN1005 in combination with trastuzumab in MBC patients with brain mets
  Interventions:

  • Drug: GRN1005
  • Drug: Trastuzumab

Key Inclusion Criteria:

1. Age ≥ 18 years
2. Histologically or cytologically-documented breast cancer (HER2 status and ER/PgR status must be known)
3. Brain metastasis from breast cancer with or without prior WBRT
4. At least one radiologically-confirmed and measurable metastatic brain lesion (≥ 1.0 cm in the longest diameter) by Gd-MRI of the brain < 14 days prior to first dose (Metastatic brain lesions previously treated with SRS may not be target or non-target lesions)
5. Patients must be neurologically stable: 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
6. KPS ≥ 70%
7. Completed WBRT for intra-cranial lesions ≥ 28 days prior to first dose

Key Exclusion Criteria:

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