MEDI4736 (Durvalumab) in Patients With Brain Metastasis F... | NCT02669914

Name	Class
AstraZeneca	INDUSTRY

Description Module

Brief Summary

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.

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
Cohort A: Non-small cell lung cancer w/o corticosteroids	Experimental	-MEDI4736 will be given to all patients > 30 kg actual body weight intravenously at a fixed dose 750 mg every 2 weeks over the course of 60 minutes on an outpatient basis on Days 1 and 15 of each 28-day cycle. Patients < 30 kg actual body weight will be dosed at 10 mg/kg every 2 weeks.	Drug: MEDI4736
Cohort B: Epithelial origin solid tumors w/o corticosteroids	Experimental	-MEDI4736 will be given to all patients > 30 kg actual body weight intravenously at a fixed dose 750 mg every 2 weeks over the course of 60 minutes on an outpatient basis on Days 1 and 15 of each 28-day cycle. Patients < 30 kg actual body weight will be dosed at 10 mg/kg every 2 weeks.	Drug: MEDI4736
Cohort C: NSCLC or non-NSCLC w/corticosteroids	Experimental	-MEDI4736 will be given to all patients > 30 kg actual body weight intravenously at a fixed dose 750 mg every 2 weeks over the course of 60 minutes on an outpatient basis on Days 1 and 15 of each 28-day cycle. Patients < 30 kg actual body weight will be dosed at 10 mg/kg every 2 weeks.	Drug: MEDI4736

Interventions

Name	Type	Description	Arm Group Labels	Other Names
MEDI4736	Drug		Cohort A: Non-small cell lung cancer w/o corticosteroids Cohort B: Epithelial origin solid tumors w/o corticosteroids Cohort C: NSCLC or non-NSCLC w/corticosteroids

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Overall Response Rate of Intracranial Disease	-% of subjects who achieve a complete response (CR) or partial response (CR) based on assessment of brain lesions CR: Requires: complete disappearance of all enhancing measurable and nonmeasurable disease sustained for at least 4 weeks; No new lesions; stable or improved nonenhancing (T2/FLAIR) lesions.; off corticosteroids (or on physiologic replacement doses only) and stable or improved clinically. PR: Requires:• ≥ 50% decrease compared with baseline in the sum of products of perpendicular diameters of all measurable enhancing lesions sustained for at least 4 weeks. • No progression of nonmeasurable disease. • Stable or improved nonenhancing (T2/FLAIR) lesions on same or lower dose of corticosteroids compared with baseline scan; the corticosteroid dose at the time of the scan evaluation should be no greater than the dose at time of baseline scan. • Stable or improved clinically	Completion of treatment (estimated to be 6 months)

Secondary Outcomes

Measure	Description	Time Frame
Safety of MEDI4736 in Advanced Solid Epithelial-derived Tumor Patients With Brain Metastases as Measured by Number of Participants With Treatment-emergent Adverse Events	-The severity of AEs will be graded by the investigator according to the CTCAE, Version 4.03	30 days after completion of treatment (estimated to be 7 months)

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

Cohort A: Histologically confirmed metastatic non-small cell lung cancer (all histologic subtypes allowed) with radiographic evidence by MRI of at least one measurable brain lesion as defined by RANO criteria that does not require corticosteroids for symptomatic control.
Cohort B: Histologically confirmed metastatic solid tumor of epithelial origin, excluding NSCLC, including but not limited to ovarian cancer, colorectal cancer, pancreatic cancer, gastric cancer, renal cancer, bladder cancer, or breast cancer with radiographic evidence by MRI of at least one measurable brain lesion as defined by RANO criteria that does not require corticosteroids for symptomatic control.
Cohort C: Histologically confirmed metastatic solid tumor of epithelial origin, including both NSCLC and non-NSCLC, with radiographic evidence by MRI of at least one measurable brain lesion as defined by RANO criteria that requires corticosteroids for symptomatic control.
At least one prior treatment to a CNS-based lesion is required. Prior therapy must be completed > 2 weeks prior to enrollment. A previously treated lesion must be demonstrated by MRI to have progressed following treatment in order to be eligible. The subsequent development of a new CNS lesion that was not previously treated will be permitted and dose not require treatment followed by progression prior to enrollment. Treatment of a single CNS lesion with local therapy in the context of multifocal disease is permitted as long as at least one untreated lesions meets criteria for measurable disease. Patients should have received minimum of one line of systemic therapy.
At least 18 years of age.
ECOG performance status of 0 to 2
Adequate bone marrow and organ function as defined below:
- Absolute neutrophil count ≥ 1,500/mcL
- Platelets ≥ 100,000/mcL
- Hemoglobin ≥ 8.0 g/dL
- Serum bilirubin ≤ 1.5 x IULN
- AST(SGOT)/ALT(SGPT) ≤ 2.5 x IULN
- Creatinine clearance ≥ 40 mL/min/1.73 m2 by the Cockcroft-Gault formula or by 24-hour urine collection for determination of creatinine clearance
Negative antiviral serology:
- Negative human immunodeficiency virus (HIV) antibody.
- Negative hepatitis B surface antigen (HBsAg) and negative hepatitis B core (HBc) antibody or undetectable hepatitis B (HBV) DNA by quantitative polymerase chain reaction (PCR) testing.
- Negative hepatitis C virus (HCV) antibody or negative HCV ribonucleic acid (RNA) by quantitative PCR.
Mean QT interval corrected for heart rate (QTc) < 470 msec calculated from 3 ECGs performed at least 2 minutes apart using Frediricia's Correction.
Female subjects must either be of non-reproductive potential (i.e., post-menopausal by history: ≥60 years old and no menses for 1 year without an alternative medical cause; OR history of hysterectomy, OR history of bilateral tubal ligation, OR history of bilateral oophorectomy) or must have a negative serum pregnancy test upon study entry.
Ability to understand and willingness to sign an IRB approved written informed consent document (or that of legally authorized representative, if applicable).

Exclusion Criteria:

Diagnosis of leptomeningeal carcinomatosis.
Diagnosis of melanoma or other non-epithelial based malignancy such as sarcoma, neuroendocrine tumor, small cell lung cancer.
Presence of unstable systemic disease (e.g., visceral crisis or rapid progression) in the judgment of the investigator.
A history of other malignancy ≤ 5 years previous with the exception of basal cell or squamous cell carcinoma of the skin which were treated with local resection only or carcinoma in situ of the cervix.
Currently receiving any other investigational agents.
A history of allergic reactions attributed to compounds of similar chemical or biologic composition to MEDI4736 or other agents used in the study.
Previous treatment with a PD-1 or PD-L1 inhibitor, including MEDI4736, or a CTLA-4 inhibitory agent.
Current or prior use of immunosuppressive medication within 28 days before the first dose of MEDI4736 with the exceptions of intranasal and inhaled corticosteroids, or systemic corticosteroids in Cohort C.
Receipt of the last dose of anti-cancer therapy (chemotherapy, immunotherapy, endocrine therapy, targeted therapy, biologic therapy, tumor embolization, monoclonal antibodies, other investigational agent) 21 days prior to the first dose of study drug.
Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, uncontrolled hypertension (>180/110), unstable angina pectoris, cardiac arrhythmia, active peptic ulcer disease or gastritis, active bleeding diatheses, or psychiatric illness/social situations that would limit compliance with study requirements.
Active or prior documented autoimmune disease within the past 2 years (Note: subjects with vitiligo, Grave's disease, or psoriasis not requiring systemic treatment (within the past 2 years) are not excluded).
Active or prior documented inflammatory bowel disease (e.g., Crohn's disease, ulcerative colitis).
History of prior immunodeficiency.
History of allogeneic organ transplant.
Known history of previous clinical diagnosis of tuberculosis.
Receipt of live attenuated vaccination within 30 days prior to first dose of MEDI4736.
Pregnant and/or breastfeeding or female patients of reproductive potential who are not employing an effective method of birth control.
Any condition that, in the opinion of the investigator, would interfere with evaluation of study treatment or interpretation of patient safety or study results

Name	Affiliation	Role
Ramaswamy Govindan, M.D.	Washington University School of Medicine	Principal Investigator

Facility	Status	City	State	ZIP	Country	Contacts
Washington University School of Medicine		St Louis	Missouri	63110	United States

Label	URL
Alvin J. Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine	View source

ID	Title	Description
FG000	Cohort A: Non-small Cell Lung Cancer w/o Corticosteroids	-MEDI4736 will be given to all patients > 30 kg actual body weight intravenously at a fixed dose 750 mg every 2 weeks over the course of 60 minutes on an outpatient basis on Days 1 and 15 of each 28-day cycle. Patients < 30 kg actual body weight will be dosed at 10 mg/kg every 2 weeks.

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot_SAP	Yes	Yes	No	Study Protocol and Statistical Analysis Plan	Feb 23, 2016

ID	Title	Description
BG000	Cohort A: Non-small Cell Lung Cancer w/o Corticosteroids	-MEDI4736 will be given to all patients > 30 kg actual body weight intravenously at a fixed dose 750 mg every 2 weeks over the course of 60 minutes on an outpatient basis on Days 1 and 15 of each 28-day cycle. Patients < 30 kg actual body weight will be dosed at 10 mg/kg every 2 weeks.
BG001	Cohort B: Epithelial Origin Solid Tumors w/o Corticosteroids	-MEDI4736 will be given to all patients > 30 kg actual body weight intravenously at a fixed dose 750 mg every 2 weeks over the course of 60 minutes on an outpatient basis on Days 1 and 15 of each 28-day cycle. Patients < 30 kg actual body weight will be dosed at 10 mg/kg every 2 weeks.
BG002	Cohort C: NSCLC or Non-NSCLC w/Corticosteroids	-MEDI4736 will be given to all patients > 30 kg actual body weight intravenously at a fixed dose 750 mg every 2 weeks over the course of 60 minutes on an outpatient basis on Days 1 and 15 of each 28-day cycle. Patients < 30 kg actual body weight will be dosed at 10 mg/kg every 2 weeks.
BG003	Total	Total of all reporting groups

Units	Counts
Participants	BG0004 BG0010 BG0020 BG0034

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Anticipated Posting Date

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Calculate Percentage

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Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Overall Response Rate of Intracranial Disease

-% of subjects who achieve a complete response (CR) or partial response (CR) based on assessment of brain lesions

CR: Requires: complete disappearance of all enhancing measurable and nonmeasurable disease sustained for at least 4 weeks; No new lesions; stable or improved nonenhancing (T2/FLAIR) lesions.; off corticosteroids (or on physiologic replacement doses only) and stable or improved clinically.
PR: Requires:• ≥ 50% decrease compared with baseline in the sum of products of perpendicular diameters of all measurable enhancing lesions sustained for at least 4 weeks. • No progression of nonmeasurable disease. • Stable or improved nonenhancing (T2/FLAIR) lesions on same or lower dose of corticosteroids compared with baseline scan; the corticosteroid dose at the time of the scan evaluation should be no greater than the dose at time of baseline scan. • Stable or improved clinically

There were not any participants enrolled in Cohort B or Cohort C.

Posted

Count of Participants

Participants

Completion of treatment (estimated to be 6 months)

ID	Title	Description
OG000	Cohort A: Non-small Cell Lung Cancer w/o Corticosteroids	-MEDI4736 will be given to all patients > 30 kg actual body weight intravenously at a fixed dose 750 mg every 2 weeks over the course of 60 minutes on an outpatient basis on Days 1 and 15 of each 28-day cycle. Patients < 30 kg actual body weight will be dosed at 10 mg/kg every 2 weeks.
OG001	Cohort B: Epithelial Origin Solid Tumors w/o Corticosteroids	-MEDI4736 will be given to all patients > 30 kg actual body weight intravenously at a fixed dose 750 mg every 2 weeks over the course of 60 minutes on an outpatient basis on Days 1 and 15 of each 28-day cycle. Patients < 30 kg actual body weight will be dosed at 10 mg/kg every 2 weeks.
OG002	Cohort C: NSCLC or Non-NSCLC w/Corticosteroids	-MEDI4736 will be given to all patients > 30 kg actual body weight intravenously at a fixed dose 750 mg every 2 weeks over the course of 60 minutes on an outpatient basis on Days 1 and 15 of each 28-day cycle. Patients < 30 kg actual body weight will be dosed at 10 mg/kg every 2 weeks.

Units	Counts
Participants	OG0004 OG0010 OG0020

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	OG0000

Secondary

Safety of MEDI4736 in Advanced Solid Epithelial-derived Tumor Patients With Brain Metastases as Measured by Number of Participants With Treatment-emergent Adverse Events

-The severity of AEs will be graded by the investigator according to the CTCAE, Version 4.03

There were not any participants enrolled in Cohort B or Cohort C.

Posted

Count of Participants

Participants

30 days after completion of treatment (estimated to be 7 months)

ID	Title	Description
OG000	Cohort A: Non-small Cell Lung Cancer w/o Corticosteroids	-MEDI4736 will be given to all patients > 30 kg actual body weight intravenously at a fixed dose 750 mg every 2 weeks over the course of 60 minutes on an outpatient basis on Days 1 and 15 of each 28-day cycle. Patients < 30 kg actual body weight will be dosed at 10 mg/kg every 2 weeks.
OG001	Cohort B: Epithelial Origin Solid Tumors w/o Corticosteroids	-MEDI4736 will be given to all patients > 30 kg actual body weight intravenously at a fixed dose 750 mg every 2 weeks over the course of 60 minutes on an outpatient basis on Days 1 and 15 of each 28-day cycle. Patients < 30 kg actual body weight will be dosed at 10 mg/kg every 2 weeks.
OG002	Cohort C: NSCLC or Non-NSCLC w/Corticosteroids

Secondary

Overall Disease Control Rate of Intracranial Disease

Defined as the percentage of patients who achieve a complete response, partial response, or stable disease based on assessment of brain lesions
CR: Requires: complete disappearance of all enhancing measurable and nonmeasurable disease sustained for at least 4 weeks; No new lesions; stable or improved nonenhancing (T2/FLAIR) lesions.; off corticosteroids (or on physiologic replacement doses only) and stable or improved clinically.
PR: Requires:• ≥ 50% decrease compared with baseline in the sum of products of perpendicular diameters of all measurable enhancing lesions sustained for at least 4 weeks. • No progression of nonmeasurable disease. • Stable or improved nonenhancing (T2/FLAIR) lesions on same or lower dose of corticosteroids compared with baseline scan; the corticosteroid dose at the time of the scan evaluation should be no greater than the dose at time of baseline scan. • Stable or improved clinically

There were not any participants enrolled in Cohort B or Cohort C.

Posted

Count of Participants

Participants

Completion of treatment (estimated to be 6 months)

ID	Title	Description
OG000	Cohort A: Non-small Cell Lung Cancer w/o Corticosteroids	-MEDI4736 will be given to all patients > 30 kg actual body weight intravenously at a fixed dose 750 mg every 2 weeks over the course of 60 minutes on an outpatient basis on Days 1 and 15 of each 28-day cycle. Patients < 30 kg actual body weight will be dosed at 10 mg/kg every 2 weeks.
OG001	Cohort B: Epithelial Origin Solid Tumors w/o Corticosteroids

Secondary

Overall Response Rate of Extracranial Disease

Defined as the percentage of patients who achieve a complete response or partial response based on assessment of systemic lesions
Complete response: Disappearance of all target lesions, non-target lesions, and normalization of tumor marker level. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm.
Partial response: At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters

Two participants were not evaluable in Cohort A as the extracranial response per RECIST was not done. There were not any participants enrolled in Cohort B or Cohort C.

Posted

Count of Participants

Participants

Completion of treatment (estimated to be 6 months)

ID	Title	Description
OG000	Cohort A: Non-small Cell Lung Cancer w/o Corticosteroids	-MEDI4736 will be given to all patients > 30 kg actual body weight intravenously at a fixed dose 750 mg every 2 weeks over the course of 60 minutes on an outpatient basis on Days 1 and 15 of each 28-day cycle. Patients < 30 kg actual body weight will be dosed at 10 mg/kg every 2 weeks.
OG001	Cohort B: Epithelial Origin Solid Tumors w/o Corticosteroids	-MEDI4736 will be given to all patients > 30 kg actual body weight intravenously at a fixed dose 750 mg every 2 weeks over the course of 60 minutes on an outpatient basis on Days 1 and 15 of each 28-day cycle. Patients < 30 kg actual body weight will be dosed at 10 mg/kg every 2 weeks.

Secondary

Overall Disease Control Rate of Extracranial Disease

Defined as the percentage of patients who achieve a complete response, partial response, or stable disease based on assessment of systemic lesions
Complete response: Disappearance of all target lesions, non-target lesions, and normalization of tumor marker level. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm.
Partial response: At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters
Stable disease: Neither sufficient shrinkage to qualify for partial response nor sufficient increase to qualify for progressive disease, taking as reference the smallest sum diameters while on study

Two participants were not evaluable in Cohort A as the extracranial response per RECIST was not done. There were not any participants enrolled in Cohort B or Cohort C.

Posted

Count of Participants

Participants

Completion of treatment (estimated to be 6 months)

ID	Title	Description
OG000	Cohort A: Non-small Cell Lung Cancer w/o Corticosteroids	-MEDI4736 will be given to all patients > 30 kg actual body weight intravenously at a fixed dose 750 mg every 2 weeks over the course of 60 minutes on an outpatient basis on Days 1 and 15 of each 28-day cycle. Patients < 30 kg actual body weight will be dosed at 10 mg/kg every 2 weeks.
OG001	Cohort B: Epithelial Origin Solid Tumors w/o Corticosteroids

Secondary

Overall Response Rate Considering Both Intracranial and Extracranial Disease

Defined as the percentage of patients who achieve a complete response or partial response based on assessment of brain and systemic lesions
Intracranial disease
- Complete response: Disappearance of all target lesions, non-target lesions, and normalization of tumor marker level. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm.
- Partial response: At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters
Extracranial disease
- Complete response: Disappearance of all target lesions, non-target lesions, and normalization of tumor marker level. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm.
- Partial response: At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters

Two participants were not evaluable in Cohort A as the extracranial response per RECIST was not done. There were not any participants enrolled in Cohort B or Cohort C.

Posted

Count of Participants

Participants

Completion of treatment (estimated to be 6 months)

ID	Title	Description
OG000	Cohort A: Non-small Cell Lung Cancer w/o Corticosteroids	-MEDI4736 will be given to all patients > 30 kg actual body weight intravenously at a fixed dose 750 mg every 2 weeks over the course of 60 minutes on an outpatient basis on Days 1 and 15 of each 28-day cycle. Patients < 30 kg actual body weight will be dosed at 10 mg/kg every 2 weeks.

Secondary

Overall Disease Control Rate Considering Both Intracranial and Extracranial Disease

Defined as the percentage of subjects who achieve a complete response, partial response, or stable disease based on assessment of brain and systemic lesions
Intracranial disease: response and progression will be evaluated using the updated response assessment criteria for high-grade gliomas: Response Assessment in Neuro-Oncology (RANO) working group guideline
Extracranial disease: response and progression will be evaluated using the new international criteria proposed by the revised Response Evaluation Criteria in Solid Tumors (RECIST) guideline (version 1.1)

Two participants were not evaluable in Cohort A as the extracranial response per RECIST was not done. There were not any participants enrolled in Cohort B or Cohort C.

Posted

Count of Participants

Participants

Completion of treatment (estimated to be 6 months)

ID	Title	Description
OG000	Cohort A: Non-small Cell Lung Cancer w/o Corticosteroids	-MEDI4736 will be given to all patients > 30 kg actual body weight intravenously at a fixed dose 750 mg every 2 weeks over the course of 60 minutes on an outpatient basis on Days 1 and 15 of each 28-day cycle. Patients < 30 kg actual body weight will be dosed at 10 mg/kg every 2 weeks.
OG001	Cohort B: Epithelial Origin Solid Tumors w/o Corticosteroids	-MEDI4736 will be given to all patients > 30 kg actual body weight intravenously at a fixed dose 750 mg every 2 weeks over the course of 60 minutes on an outpatient basis on Days 1 and 15 of each 28-day cycle. Patients < 30 kg actual body weight will be dosed at 10 mg/kg every 2 weeks.

Secondary

Duration of Response of Intracranial Disease

Defined as the interval from the first documentation of objective response (complete response or partial response) to the earlier of the first documentation of disease progression or death from any cause
Intracranial disease: response and progression will be evaluated using the updated response assessment criteria for high-grade gliomas: Response Assessment in Neuro-Oncology (RANO) working group guideline

None of the participants in Cohort A were evaluable for this outcome measure as they did not have an objective response per RANO guidelines. There were not any participants enrolled to Cohort B or Cohort C.

Posted

Completion of treatment (estimated to be 6 months)

ID	Title	Description
OG000	Cohort A: Non-small Cell Lung Cancer w/o Corticosteroids	-MEDI4736 will be given to all patients > 30 kg actual body weight intravenously at a fixed dose 750 mg every 2 weeks over the course of 60 minutes on an outpatient basis on Days 1 and 15 of each 28-day cycle. Patients < 30 kg actual body weight will be dosed at 10 mg/kg every 2 weeks.
OG001	Cohort B: Epithelial Origin Solid Tumors w/o Corticosteroids	-MEDI4736 will be given to all patients > 30 kg actual body weight intravenously at a fixed dose 750 mg every 2 weeks over the course of 60 minutes on an outpatient basis on Days 1 and 15 of each 28-day cycle. Patients < 30 kg actual body weight will be dosed at 10 mg/kg every 2 weeks.

Secondary

Duration of Response of Extracranial Disease

Defined as the interval from the first documentation of objective response (complete response or partial response) to the earlier of the first documentation of disease progression or death from any cause
Extracranial disease: response and progression will be evaluated using the new international criteria proposed by the revised Response Evaluation Criteria in Solid Tumors (RECIST) guideline (version 1.1)

Two participants were not evaluable in Cohort A as the extracranial response per RECIST was not done. The remaining two participants were not evaluable for this outcome measure because they didn't have an objective response per RECIST. There were not any participants enrolled in Cohort B or Cohort C.

Posted

Completion of treatment (estimated to be 6 months)

ID	Title	Description
OG000	Cohort A: Non-small Cell Lung Cancer w/o Corticosteroids	-MEDI4736 will be given to all patients > 30 kg actual body weight intravenously at a fixed dose 750 mg every 2 weeks over the course of 60 minutes on an outpatient basis on Days 1 and 15 of each 28-day cycle. Patients < 30 kg actual body weight will be dosed at 10 mg/kg every 2 weeks.
OG001	Cohort B: Epithelial Origin Solid Tumors w/o Corticosteroids	-MEDI4736 will be given to all patients > 30 kg actual body weight intravenously at a fixed dose 750 mg every 2 weeks over the course of 60 minutes on an outpatient basis on Days 1 and 15 of each 28-day cycle. Patients < 30 kg actual body weight will be dosed at 10 mg/kg every 2 weeks.

Secondary

Duration of Response Considering Both Intracranial and Extracranial Disease

Defined as the interval from the first documentation of objective response (complete response or partial response) to the earlier of the first documentation of disease progression or death from any cause
Intracranial disease: response and progression will be evaluated using the updated response assessment criteria for high-grade gliomas: Response Assessment in Neuro-Oncology (RANO) working group guideline
Extracranial disease: response and progression will be evaluated using the new international criteria proposed by the revised Response Evaluation Criteria in Solid Tumors (RECIST) guideline (version 1.1)

Two participants were not evaluable in Cohort A as the extracranial response per RECIST was not done. The remaining two participants were not evaluable for this outcome measure because they didn't have an objective response. There were not any participants enrolled in Cohort B or Cohort C.

Posted

Completion of treatment (estimated to be 6 months)

ID	Title	Description
OG000	Cohort A: Non-small Cell Lung Cancer w/o Corticosteroids	-MEDI4736 will be given to all patients > 30 kg actual body weight intravenously at a fixed dose 750 mg every 2 weeks over the course of 60 minutes on an outpatient basis on Days 1 and 15 of each 28-day cycle. Patients < 30 kg actual body weight will be dosed at 10 mg/kg every 2 weeks.
OG001	Cohort B: Epithelial Origin Solid Tumors w/o Corticosteroids

Secondary

Progression-free Survival (PFS)

PFS is defined as the duration of time from start of treatment to time of progression or death, whichever occurs first.
At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. (Note: the appearance of one or more new lesions is also considered progression). Unequivocal progression of existing non-target lesions.

There were not any participants enrolled in Cohort B or Cohort C.

Posted

Median

Full Range

days

Up to 2 years after completion of treatment (estimated to be 2 years and 6 months)

ID	Title	Description
OG000	Cohort A: Non-small Cell Lung Cancer w/o Corticosteroids	-MEDI4736 will be given to all patients > 30 kg actual body weight intravenously at a fixed dose 750 mg every 2 weeks over the course of 60 minutes on an outpatient basis on Days 1 and 15 of each 28-day cycle. Patients < 30 kg actual body weight will be dosed at 10 mg/kg every 2 weeks.
OG001	Cohort B: Epithelial Origin Solid Tumors w/o Corticosteroids	-MEDI4736 will be given to all patients > 30 kg actual body weight intravenously at a fixed dose 750 mg every 2 weeks over the course of 60 minutes on an outpatient basis on Days 1 and 15 of each 28-day cycle. Patients < 30 kg actual body weight will be dosed at 10 mg/kg every 2 weeks.

Secondary

Overall Survival (OS)

-Defined as the interval from the start of study therapy to death from any cause

One participant in Cohort A was lost to follow-up and is not evaluable for this outcome measure. There were not any participants enrolled to Cohort B or Cohort C.

Posted

Median

Full Range

days

Up to 2 years after completion of treatment (estimated to be 2 years and 6 months)

ID	Title	Description
OG000	Cohort A: Non-small Cell Lung Cancer w/o Corticosteroids	-MEDI4736 will be given to all patients > 30 kg actual body weight intravenously at a fixed dose 750 mg every 2 weeks over the course of 60 minutes on an outpatient basis on Days 1 and 15 of each 28-day cycle. Patients < 30 kg actual body weight will be dosed at 10 mg/kg every 2 weeks.
OG001	Cohort B: Epithelial Origin Solid Tumors w/o Corticosteroids	-MEDI4736 will be given to all patients > 30 kg actual body weight intravenously at a fixed dose 750 mg every 2 weeks over the course of 60 minutes on an outpatient basis on Days 1 and 15 of each 28-day cycle. Patients < 30 kg actual body weight will be dosed at 10 mg/kg every 2 weeks.
OG002	Cohort C: NSCLC or Non-NSCLC w/Corticosteroids	-MEDI4736 will be given to all patients > 30 kg actual body weight intravenously at a fixed dose 750 mg every 2 weeks over the course of 60 minutes on an outpatient basis on Days 1 and 15 of each 28-day cycle. Patients < 30 kg actual body weight will be dosed at 10 mg/kg every 2 weeks.

Arm/Groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Cohort A: Non-small Cell Lung Cancer w/o Corticosteroids	-MEDI4736 will be given to all patients > 30 kg actual body weight intravenously at a fixed dose 750 mg every 2 weeks over the course of 60 minutes on an outpatient basis on Days 1 and 15 of each 28-day cycle. Patients < 30 kg actual body weight will be dosed at 10 mg/kg every 2 weeks.	2	4	1	4	4	4
EG001	Cohort B: Epithelial Origin Solid Tumors w/o Corticosteroids	-MEDI4736 will be given to all patients > 30 kg actual body weight intravenously at a fixed dose 750 mg every 2 weeks over the course of 60 minutes on an outpatient basis on Days 1 and 15 of each 28-day cycle. Patients < 30 kg actual body weight will be dosed at 10 mg/kg every 2 weeks.	0	0	0	0	0	0
EG002	Cohort C: NSCLC or Non-NSCLC w/Corticosteroids	-MEDI4736 will be given to all patients > 30 kg actual body weight intravenously at a fixed dose 750 mg every 2 weeks over the course of 60 minutes on an outpatient basis on Days 1 and 15 of each 28-day cycle. Patients < 30 kg actual body weight will be dosed at 10 mg/kg every 2 weeks.	0	0	0	0	0	0

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Anemia	Blood and lymphatic system disorders	CTCAE (4.0)	Systematic Assessment	EG0002 affected4 at risk EG0010 affected0 at risk EG0020 affected0 at risk
Bloating	Gastrointestinal disorders	CTCAE (4.0)	Systematic Assessment	EG0001 affected4 at risk EG0010 affected0 at risk EG0020 affected0 at risk
Constipation	Gastrointestinal disorders	CTCAE (4.0)	Systematic Assessment	EG0001 affected4 at risk EG0010 affected0 at risk EG0020 affected0 at risk
Diarrhea	Gastrointestinal disorders	CTCAE (4.0)	Systematic Assessment	EG0001 affected4 at risk EG0010 affected0 at risk EG0020 affected0 at risk
Nausea	Gastrointestinal disorders	CTCAE (4.0)	Systematic Assessment	EG0001 affected4 at risk EG0010 affected0 at risk EG0020 affected0 at risk
Chills	General disorders	CTCAE (4.0)	Systematic Assessment	EG0001 affected4 at risk EG0010 affected0 at risk EG0020 affected0 at risk
Fatigue	General disorders	CTCAE (4.0)	Systematic Assessment	EG0001 affected4 at risk EG0010 affected0 at risk EG0020 affected0 at risk
Non-cardiac chest pain	General disorders	CTCAE (4.0)	Systematic Assessment	EG0001 affected4 at risk EG0010 affected0 at risk EG0020 affected0 at risk
Night sweats	General disorders	CTCAE (4.0)	Systematic Assessment	EG0001 affected4 at risk EG0010 affected0 at risk EG0020 affected0 at risk
Sinusitis	Infections and infestations	CTCAE (4.0)	Systematic Assessment	EG0001 affected4 at risk EG0010 affected0 at risk EG0020 affected0 at risk
Lymphocyte count decreased	Investigations	CTCAE (4.0)	Systematic Assessment	EG0003 affected4 at risk EG0010 affected0 at risk EG0020 affected0 at risk
Weight loss	Investigations	CTCAE (4.0)	Systematic Assessment	EG0001 affected4 at risk EG0010 affected0 at risk EG0020 affected0 at risk
Hypercalcemia	Metabolism and nutrition disorders	CTCAE (4.0)	Systematic Assessment	EG0001 affected4 at risk EG0010 affected0 at risk EG0020 affected0 at risk
Hyperglycemia	Metabolism and nutrition disorders	CTCAE (4.0)	Systematic Assessment	EG0001 affected4 at risk EG0010 affected0 at risk EG0020 affected0 at risk
Hyponatremia	Metabolism and nutrition disorders	CTCAE (4.0)	Systematic Assessment	EG0001 affected4 at risk EG0010 affected0 at risk EG0020 affected0 at risk
Arthralgia	Musculoskeletal and connective tissue disorders	CTCAE (4.0)	Systematic Assessment	EG0001 affected4 at risk EG0010 affected0 at risk EG0020 affected0 at risk
Productive cough	Respiratory, thoracic and mediastinal disorders	CTCAE (4.0)	Systematic Assessment	EG0001 affected4 at risk EG0010 affected0 at risk EG0020 affected0 at risk
Post nasal drip	Respiratory, thoracic and mediastinal disorders	CTCAE (4.0)	Systematic Assessment	EG0001 affected4 at risk EG0010 affected0 at risk EG0020 affected0 at risk
Hyperhidrosis	Skin and subcutaneous tissue disorders	CTCAE (4.0)	Systematic Assessment	EG0001 affected4 at risk EG0010 affected0 at risk EG0020 affected0 at risk
Pruritus	Skin and subcutaneous tissue disorders	CTCAE (4.0)	Systematic Assessment	EG0001 affected4 at risk EG0010 affected0 at risk EG0020 affected0 at risk
Hypertension	Vascular disorders	CTCAE (4.0)	Systematic Assessment	EG0001 affected4 at risk EG0010 affected0 at risk EG0020 affected0 at risk

ID	Term
D002289	Carcinoma, Non-Small-Cell Lung
D001943	Breast Neoplasms
D010190	Pancreatic Neoplasms
D015179	Colorectal Neoplasms
D007680	Kidney Neoplasms
D010051	Ovarian Neoplasms

ID	Term
D002283	Carcinoma, Bronchogenic
D001984	Bronchial Neoplasms
D008175	Lung Neoplasms
D012142	Respiratory Tract Neoplasms
D013899	Thoracic Neoplasms
D009371	Neoplasms by Site
D009369	Neoplasms
D008171	Lung Diseases
D012140	Respiratory Tract Diseases
D001941	Breast Diseases
D012871	Skin Diseases
D017437	Skin and Connective Tissue Diseases
D004067	Digestive System Neoplasms
D004701	Endocrine Gland Neoplasms
D004066	Digestive System Diseases
D010182	Pancreatic Diseases
D004700	Endocrine System Diseases
D007414	Intestinal Neoplasms
D005770	Gastrointestinal Neoplasms
D005767	Gastrointestinal Diseases
D003108	Colonic Diseases
D007410	Intestinal Diseases
D012002	Rectal Diseases
D014571	Urologic Neoplasms
D014565	Urogenital Neoplasms
D052776	Female Urogenital Diseases
D005261	Female Urogenital Diseases and Pregnancy Complications
D000091642	Urogenital Diseases
D007674	Kidney Diseases
D014570	Urologic Diseases
D052801	Male Urogenital Diseases
D010049	Ovarian Diseases
D000291	Adnexal Diseases
D005831	Genital Diseases, Female
D005833	Genital Neoplasms, Female
D000091662	Genital Diseases
D006058	Gonadal Disorders