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

Study Overview
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Brief Summary
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The purpose of this study is to assess the efficacy, safety, and tolerability of GRN1005 in patients with brain metastases from non-small cell lung cancer (NSCLC).

Official Title
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A Phase II, Multi-center, Open-label Study Evaluating the Efficacy and Safety of GRN1005 in Non-Small Cell Lung Cancer Patients With Brain Metastases

Conditions
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Non-small Cell Lung Cancer (NSCLC) With Brain Metastases

Intervention / Treatment
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* Drug: GRN1005


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: Adult patients (≥ 18 years) Histologically or cytologically-documented NSCLC (EGFR mutation status must be known) Brain metastases from NSCLC, which: have radiologically-progressed after WBRT or are present without prior WBRT 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. 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). Karnofsky Performance Score (KPS) ≥ 80% 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 Exclusion Criteria: NCI CTCAE v4.0 Grade ≥ 2 neuropathy CNS disease requiring immediate neurosurgical intervention (e.g., resection, shunt placement, etc.) Known intra-cranial hemorrhage Known leptomeningeal disease

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: GRN1005 alone<br>GRN1005 alone | Drug: GRN1005<br>* 650 mg/m2 IV every 3 weeks<br>* Other names: ANG1005;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall (Intra-cranial and Extra-cranial) Objective Response Rate in Non-small Cell Lung Cancer (NSCLC) Patients With Brain Metastasis | Tumor response was assessed by Gd-MRI for intracranial lesions and CT/MRI with contrast of chest, abdomen, pelvis for extracranial lesions using modified OVERALL RECIST v1.1 as follows: Complete Response (CR), disappearance of all target and non-target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions and non-target lesions stable or decreased; Stable Disease (SD), < 30% decrease but <20% increase in target lesions and non-target lesions stable or decreased; Progressive disease (PD), >= 20% (>= 5 mm) increase in the sum of diameters of the target lesions, taking as reference the smallest sum on study, non-target lesions increased or appearance of a new lesion; Overall Response (OR) = CR + PR. | upon enrollment through end of study period (1 year after last patient is enrolled) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Patients With Adverse Events as a Measure of Safety and Tolerability |  | Upon enrollment through end of study period (1 year after last patient is enrolled) | 
| Duration of Overall Objective Response |  | Upon enrollment through end of study period (1 year after last patient is enrolled) | 
| Duration of Overall Progression Free Survival |  | Upon enrollment through end of study period (1 year after last patient is enrolled) | 
| Six Month Overall Survival |  | Upon enrollment through end of study period (1 year after last patient is enrolled) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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GRN1005, ANG1005, LRP-1, Targeted Therapy, Brain Tumor, Blood Brain Barrier, Peptide-Drug Conjugate (PDC), Brain Metastases, Paclitaxel, Taxol, NSCLC, Non-Small Cell Lung Cancer