Trial Outcomes & Findings for MEDI4736 (Durvalumab) in Patients With Brain Metastasis From Epithelial-derived Tumors (NCT NCT02669914)

Last Updated: 2018-11-06

Results Overview

-% 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

Recruitment status

TERMINATED

Study phase

PHASE2

Target enrollment

4 participants

Primary outcome timeframe

Completion of treatment (estimated to be 6 months)

Results posted on

2018-11-06

Participant Flow

The study opened to participant enrollment on 09/12/2016 and closed to participant accrual on 11/16/2017.

Participant milestones

Participant milestones
Measure	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.	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.	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.
Overall Study STARTED	4	0	0
Overall Study COMPLETED	4	0	0
Overall Study NOT COMPLETED	0	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Cohort A: Non-small Cell Lung Cancer w/o Corticosteroids n=4 Participants -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.	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.	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.	Total n=4 Participants Total of all reporting groups
Age, Continuous	62 years n=5 Participants	—	—	62 years n=4 Participants
Sex: Female, Male Female	3 Participants n=5 Participants	—	—	3 Participants n=4 Participants
Sex: Female, Male Male	1 Participants n=5 Participants	—	—	1 Participants n=4 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants	—	—	0 Participants n=4 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	4 Participants n=5 Participants	—	—	4 Participants n=4 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	—	—	0 Participants n=4 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	—	—	0 Participants n=4 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	—	—	0 Participants n=4 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	—	—	0 Participants n=4 Participants
Race (NIH/OMB) Black or African American	1 Participants n=5 Participants	—	—	1 Participants n=4 Participants
Race (NIH/OMB) White	3 Participants n=5 Participants	—	—	3 Participants n=4 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	—	—	0 Participants n=4 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	—	—	0 Participants n=4 Participants
Region of Enrollment United States	4 Participants n=5 Participants	—	—	4 Participants n=4 Participants

PRIMARY outcome

Timeframe: Completion of treatment (estimated to be 6 months)

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

Outcome measures

Outcome measures
Measure	Cohort A: Non-small Cell Lung Cancer w/o Corticosteroids n=4 Participants -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.	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.	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.
Overall Response Rate of Intracranial Disease	0 Participants	—	—

SECONDARY outcome

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

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

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

Outcome measures

Outcome measures
Measure	Cohort A: Non-small Cell Lung Cancer w/o Corticosteroids n=4 Participants -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.	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.	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.
Safety of MEDI4736 in Advanced Solid Epithelial-derived Tumor Patients With Brain Metastases as Measured by Number of Participants With Treatment-emergent Adverse Events Grade 1 anemia	1 Participants	—	—
Safety of MEDI4736 in Advanced Solid Epithelial-derived Tumor Patients With Brain Metastases as Measured by Number of Participants With Treatment-emergent Adverse Events Grade 2 anemia	1 Participants	—	—
Safety of MEDI4736 in Advanced Solid Epithelial-derived Tumor Patients With Brain Metastases as Measured by Number of Participants With Treatment-emergent Adverse Events Grade 1 bloating	1 Participants	—	—
Safety of MEDI4736 in Advanced Solid Epithelial-derived Tumor Patients With Brain Metastases as Measured by Number of Participants With Treatment-emergent Adverse Events Grade 2 constipation	1 Participants	—	—
Safety of MEDI4736 in Advanced Solid Epithelial-derived Tumor Patients With Brain Metastases as Measured by Number of Participants With Treatment-emergent Adverse Events Grade 2 diarrhea	1 Participants	—	—
Safety of MEDI4736 in Advanced Solid Epithelial-derived Tumor Patients With Brain Metastases as Measured by Number of Participants With Treatment-emergent Adverse Events Grade 1 nausea	1 Participants	—	—
Safety of MEDI4736 in Advanced Solid Epithelial-derived Tumor Patients With Brain Metastases as Measured by Number of Participants With Treatment-emergent Adverse Events Grade 1 chills	1 Participants	—	—
Safety of MEDI4736 in Advanced Solid Epithelial-derived Tumor Patients With Brain Metastases as Measured by Number of Participants With Treatment-emergent Adverse Events Grade 2 weight loss	1 Participants	—	—
Safety of MEDI4736 in Advanced Solid Epithelial-derived Tumor Patients With Brain Metastases as Measured by Number of Participants With Treatment-emergent Adverse Events Grade 1 hypercalcemia	1 Participants	—	—
Safety of MEDI4736 in Advanced Solid Epithelial-derived Tumor Patients With Brain Metastases as Measured by Number of Participants With Treatment-emergent Adverse Events Grade 1 hyperhidrosis	1 Participants	—	—
Safety of MEDI4736 in Advanced Solid Epithelial-derived Tumor Patients With Brain Metastases as Measured by Number of Participants With Treatment-emergent Adverse Events Grade 1 pruritus	1 Participants	—	—
Safety of MEDI4736 in Advanced Solid Epithelial-derived Tumor Patients With Brain Metastases as Measured by Number of Participants With Treatment-emergent Adverse Events Grade 1 hypertension	1 Participants	—	—
Safety of MEDI4736 in Advanced Solid Epithelial-derived Tumor Patients With Brain Metastases as Measured by Number of Participants With Treatment-emergent Adverse Events Grade 2 fever	1 Participants	—	—
Safety of MEDI4736 in Advanced Solid Epithelial-derived Tumor Patients With Brain Metastases as Measured by Number of Participants With Treatment-emergent Adverse Events Grade 1 non-cardiac chest pain	1 Participants	—	—
Safety of MEDI4736 in Advanced Solid Epithelial-derived Tumor Patients With Brain Metastases as Measured by Number of Participants With Treatment-emergent Adverse Events Grade 1 night sweats	1 Participants	—	—
Safety of MEDI4736 in Advanced Solid Epithelial-derived Tumor Patients With Brain Metastases as Measured by Number of Participants With Treatment-emergent Adverse Events Grade 2 sinusitis	1 Participants	—	—
Safety of MEDI4736 in Advanced Solid Epithelial-derived Tumor Patients With Brain Metastases as Measured by Number of Participants With Treatment-emergent Adverse Events Grade 1 lymphocyte count decreased	1 Participants	—	—
Safety of MEDI4736 in Advanced Solid Epithelial-derived Tumor Patients With Brain Metastases as Measured by Number of Participants With Treatment-emergent Adverse Events Grade 2 lymphocyte count decreased	2 Participants	—	—
Safety of MEDI4736 in Advanced Solid Epithelial-derived Tumor Patients With Brain Metastases as Measured by Number of Participants With Treatment-emergent Adverse Events Grade 3 hypercalcemia	1 Participants	—	—
Safety of MEDI4736 in Advanced Solid Epithelial-derived Tumor Patients With Brain Metastases as Measured by Number of Participants With Treatment-emergent Adverse Events Grade 1 hyponatremia	1 Participants	—	—
Safety of MEDI4736 in Advanced Solid Epithelial-derived Tumor Patients With Brain Metastases as Measured by Number of Participants With Treatment-emergent Adverse Events Grade 1 arthralgia	1 Participants	—	—
Safety of MEDI4736 in Advanced Solid Epithelial-derived Tumor Patients With Brain Metastases as Measured by Number of Participants With Treatment-emergent Adverse Events Grade 3 paresthesia	1 Participants	—	—
Safety of MEDI4736 in Advanced Solid Epithelial-derived Tumor Patients With Brain Metastases as Measured by Number of Participants With Treatment-emergent Adverse Events Grade 1 productive cough	1 Participants	—	—
Safety of MEDI4736 in Advanced Solid Epithelial-derived Tumor Patients With Brain Metastases as Measured by Number of Participants With Treatment-emergent Adverse Events Grade 2 post nasal drip	1 Participants	—	—

SECONDARY outcome

Timeframe: Completion of treatment (estimated to be 6 months)

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

* 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

Outcome measures

Outcome measures
Measure	Cohort A: Non-small Cell Lung Cancer w/o Corticosteroids n=4 Participants -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.	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.	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.
Overall Disease Control Rate of Intracranial Disease	2 Participants	—	—

SECONDARY outcome

Timeframe: Completion of treatment (estimated to be 6 months)

Population: 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.

* 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

Outcome measures

Outcome measures
Measure	Cohort A: Non-small Cell Lung Cancer w/o Corticosteroids n=2 Participants -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.	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.	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.
Overall Response Rate of Extracranial Disease	0 Participants	—	—

SECONDARY outcome

Timeframe: Completion of treatment (estimated to be 6 months)

Population: 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.

* 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

Outcome measures

Outcome measures
Measure	Cohort A: Non-small Cell Lung Cancer w/o Corticosteroids n=2 Participants -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.	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.	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.
Overall Disease Control Rate of Extracranial Disease	1 Participants	—	—

SECONDARY outcome

Timeframe: Completion of treatment (estimated to be 6 months)

Population: 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.

* 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

Outcome measures

Outcome measures
Measure	Cohort A: Non-small Cell Lung Cancer w/o Corticosteroids n=2 Participants -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.	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.	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.
Overall Response Rate Considering Both Intracranial and Extracranial Disease	0 Participants	—	—

SECONDARY outcome

Timeframe: Completion of treatment (estimated to be 6 months)

Population: 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.

* 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)

Outcome measures

Outcome measures
Measure	Cohort A: Non-small Cell Lung Cancer w/o Corticosteroids n=2 Participants -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.	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.	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.
Overall Disease Control Rate Considering Both Intracranial and Extracranial Disease	1 Participants	—	—

SECONDARY outcome

Timeframe: Completion of treatment (estimated to be 6 months)

Population: 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.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Completion of treatment (estimated to be 6 months)

Population: 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.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Completion of treatment (estimated to be 6 months)

Population: 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.

* 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)

Outcome measures

Outcome data not reported

SECONDARY outcome

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

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

* 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.

Outcome measures

Outcome measures
Measure	Cohort A: Non-small Cell Lung Cancer w/o Corticosteroids n=4 Participants -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.	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.	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.
Progression-free Survival (PFS)	51.5 days Interval 18.0 to 64.0	—	—

SECONDARY outcome

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

Population: 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.

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

Outcome measures

Outcome measures
Measure	Cohort A: Non-small Cell Lung Cancer w/o Corticosteroids n=3 Participants -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.	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.	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.
Overall Survival (OS)	197 days Interval 130.0 to 262.0	—	—

Adverse Events

Cohort A: Non-small Cell Lung Cancer w/o Corticosteroids

Serious events: 1 serious events

Other events: 4 other events

Deaths: 2 deaths

Cohort B: Epithelial Origin Solid Tumors w/o Corticosteroids

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Cohort C: NSCLC or Non-NSCLC w/Corticosteroids

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Cohort A: Non-small Cell Lung Cancer w/o Corticosteroids n=4 participants at risk -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.	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.	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.
Nervous system disorders Parasthesia	25.0% 1/4 • Adverse events were collected starting at baseline and ending 30 days after the completion of treatment. There were no participants enrolled in Cohort B or C and that is why the number of participants at risk for All-Cause Mortality, Serious Adverse Events, and Other Adverse Events is zero.	— 0/0 • Adverse events were collected starting at baseline and ending 30 days after the completion of treatment. There were no participants enrolled in Cohort B or C and that is why the number of participants at risk for All-Cause Mortality, Serious Adverse Events, and Other Adverse Events is zero.	— 0/0 • Adverse events were collected starting at baseline and ending 30 days after the completion of treatment. There were no participants enrolled in Cohort B or C and that is why the number of participants at risk for All-Cause Mortality, Serious Adverse Events, and Other Adverse Events is zero.

Other adverse events

Additional Information

Ramaswamy Govindan, M.D.

Washington University School of Medicine

Phone: 314-362-5737

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place