MEDI4736 (Durvalumab) in Patients With Brain Metastasis From Epithelial-derived Tumors

Brief summary public domain (ClinicalTrials.gov)

Brain metastases are the most common intracranial malignancy occurring in 20-40% of all cancers, and the presence of CNS metastases is associated with a poor prognosis. As such, the median overall survival of patients with symptomatic brain lesions is a dismal 2-3 months regardless of tumor type. Because standard chemotherapy largely does not cross the blood brain barrier at a meaningful concentration, standard treatment is limited and usually involves surgical resection and/or stereotactic radiosurgery for isolated lesions and whole brain radiation for multiple lesions. Unfortunately, the median overall survival is only improved by about 6 months with this multimodality approach2, and there is a paucity of second-line therapies to treat recurrence. Furthermore, re-resection and re-radiation are often not feasible options due to concern for increasing complications or neurotoxicity, respectively. Thus, there is a dire clinical need for additional treatment options for this patient population. Checkpoint blockade therapy, in particular PD-1 and PD-L1 inhibition, has recently shown clinical efficacy in multiple types of solid tumors. The investigators propose to study the efficacy of checkpoint blockade therapy in patients with solid tumors and refractory/recurrent brain metastases. The investigators will assess the efficacy of MEDI4736, a novel PD-L1 inhibitory monoclonal antibody, in this study.

Posted results (ClinicalTrials.gov registry) · primary outcome public domain (ClinicalTrials.gov)

Overall Response Rate of Intracranial Disease [Completion of treatment (estimated to be 6 months)]. Count Of Participants, Participants. Cohort A: Non-small Cell Lung Cancer w/o Corticosteroids (n=4): 0.

Posted results (ClinicalTrials.gov registry) · secondary outcome public domain (ClinicalTrials.gov)

Safety of MEDI4736 in Advanced Solid Epithelial-derived Tumor Patients With Brain Metastases as Measured by Number of Participants With Treatment-emergent Adverse Events [30 days after completion of treatment (estimated to be 7 months)]. Count Of Participants, Participants. Grade 1 anemia: Cohort A: Non-small Cell Lung Cancer w/o Corticosteroids (n=4): 1. Grade 2 anemia: Cohort A: Non-small Cell Lung Cancer w/o Corticosteroids (n=4): 1. Grade 1 bloating: Cohort A: Non-small Cell Lung Cancer w/o Corticosteroids (n=4): 1. Grade 2 constipation: Cohort A: Non-small Cell Lung Cancer w/o Corticosteroids (n=4): 1. Grade 2 diarrhea: Cohort A: Non-small Cell Lung Cancer w/o Corticosteroids (n=4): 1. Grade 1 nausea: Cohort A: Non-small Cell Lung Cancer w/o Corticosteroids (n=4): 1. Grade 1 chills: Cohort A: Non-small Cell Lung Cancer w/o Corticosteroids (n=4): 1. Grade 2 fever: Cohort A: Non-small Cell Lung Cancer w/o Corticosteroids (n=4): 1. Grade 1 non-cardiac chest pain: Cohort A: Non-small Cell Lung Cancer w/o Corticosteroids (n=4): 1. Grade 1 night sweats: Cohort A: Non-small Cell Lung Cancer w/o Corticosteroids (n=4): 1. Grade 2 sinusitis: Cohort A: Non-small Cell Lung Cancer w/o Corticosteroids (n=4): 1. Grade 1 lymphocyte count decreased: Cohort A: Non-small Cell Lung Cancer w/o Corticosteroids (n=4): 1. Grade 2 lymphocyte count decreased: Cohort A: Non-small Cell Lung Cancer w/o Corticosteroids (n=4): 2. Grade 2 weight loss: Cohort A: Non-small Cell Lung Cancer w/o Corticosteroids (n=4): 1. Grade 1 hypercalcemia: Cohort A: Non-small Cell Lung Cancer w/o Corticosteroids (n=4): 1. Grade 3 hypercalcemia: Cohort A: Non-small Cell Lung Cancer w/o Corticosteroids (n=4): 1. Grade 1 hyponatremia: Cohort A: Non-small Cell Lung Cancer w/o Corticosteroids (n=4): 1. Grade 1 arthralgia: Cohort A: Non-small Cell Lung Cancer w/o Corticosteroids (n=4): 1. Grade 3 paresthesia: Cohort A: Non-small Cell Lung Cancer w/o Corticosteroids (n=4): 1. Grade 1 productive cough: Cohort A: Non-small Cell Lung Cancer w/o Corticosteroids (n=4): 1. Grade 2 post nasal drip: Cohort A: Non-small Cell Lung Cancer w/o Corticosteroids (n=4): 1. Grade 1 hyperhidrosis: Cohort A: Non-small Cell Lung Cancer w/o Corticosteroids (n=4): 1. Grade 1 pruritus: Cohort A: Non-small Cell Lung Cancer w/o Corticosteroids (n=4): 1. Grade 1 hypertension: Cohort A: Non-small Cell Lung Cancer w/o Corticosteroids (n=4): 1.

Posted results (ClinicalTrials.gov registry) · secondary outcome public domain (ClinicalTrials.gov)

Overall Disease Control Rate of Intracranial Disease [Completion of treatment (estimated to be 6 months)]. Count Of Participants, Participants. Cohort A: Non-small Cell Lung Cancer w/o Corticosteroids (n=4): 2.

Posted results (ClinicalTrials.gov registry) · secondary outcome public domain (ClinicalTrials.gov)

Overall Response Rate of Extracranial Disease [Completion of treatment (estimated to be 6 months)]. Count Of Participants, Participants. Cohort A: Non-small Cell Lung Cancer w/o Corticosteroids (n=2): 0.

Posted results (ClinicalTrials.gov registry) · secondary outcome public domain (ClinicalTrials.gov)

Overall Disease Control Rate of Extracranial Disease [Completion of treatment (estimated to be 6 months)]. Count Of Participants, Participants. Cohort A: Non-small Cell Lung Cancer w/o Corticosteroids (n=2): 1.

Posted results (ClinicalTrials.gov registry) · secondary outcome public domain (ClinicalTrials.gov)

Overall Response Rate Considering Both Intracranial and Extracranial Disease [Completion of treatment (estimated to be 6 months)]. Count Of Participants, Participants. Cohort A: Non-small Cell Lung Cancer w/o Corticosteroids (n=2): 0.

Posted results (ClinicalTrials.gov registry) · secondary outcome public domain (ClinicalTrials.gov)

Overall Disease Control Rate Considering Both Intracranial and Extracranial Disease [Completion of treatment (estimated to be 6 months)]. Count Of Participants, Participants. Cohort A: Non-small Cell Lung Cancer w/o Corticosteroids (n=2): 1.

Posted results (ClinicalTrials.gov registry) · secondary outcome public domain (ClinicalTrials.gov)

Duration of Response of Intracranial Disease [Completion of treatment (estimated to be 6 months)].

Posted results (ClinicalTrials.gov registry) · secondary outcome public domain (ClinicalTrials.gov)

Duration of Response of Extracranial Disease [Completion of treatment (estimated to be 6 months)].

Posted results (ClinicalTrials.gov registry) · secondary outcome public domain (ClinicalTrials.gov)

Duration of Response Considering Both Intracranial and Extracranial Disease [Completion of treatment (estimated to be 6 months)].

Posted results (ClinicalTrials.gov registry) · secondary outcome public domain (ClinicalTrials.gov)

Progression-free Survival (PFS) [Up to 2 years after completion of treatment (estimated to be 2 years and 6 months)]. Median, days (Full Range). Cohort A: Non-small Cell Lung Cancer w/o Corticosteroids (n=4): 51.5 (18 to 64).

Posted results (ClinicalTrials.gov registry) · secondary outcome public domain (ClinicalTrials.gov)

Overall Survival (OS) [Up to 2 years after completion of treatment (estimated to be 2 years and 6 months)]. Median, days (Full Range). Cohort A: Non-small Cell Lung Cancer w/o Corticosteroids (n=3): 197 (130 to 262).