Trial Outcomes & Findings for MEDI-573 in Combination With SOC in Unresectable or Metastatic HCC. (NCT NCT01498952)

NCT ID: NCT01498952

Last Updated: 2019-02-19

Results Overview

The DLT was defined as any Grade 3 or higher hematologic or non-hematologic toxicity considered to be related to MEDI-573 that occurred during the DLT evaluation period (Days 1 to 21 of Cycle 1), with the exceptions of Grade 3 fever (occurred in the absence of neutropenia and resolved to normal or baseline within 24 hours of treatment and was not considered as SAE), Grade 3 rigors/chills that responded to optimal therapy, and Grade \< 4 hyperglycemia that resolved in \< 24 hours.

• Recruitment status: COMPLETED
• Study phase: PHASE1
• Target enrollment: 6 participants
• Primary outcome timeframe: Day 1 to Day 21 of Cycle 1
• Results posted on: 2019-02-19

Participant Flow

The study was conducted in the USA.

Phase 2 part of the study was not launched by the sponsor due to strategic business reasons. No participants were randomized in Phase 1b Cohort C part of the study as no dose limiting toxicity was observed in Phase 1b Cohort B.

Participant milestones

Measure	Phase 1b Cohort A Participants received MEDI-573 10 mg/kg intravenous infusion (IV) on Day 1 of each 21-day cycle and sorafenib 400 mg orally twice daily as background therapy until unacceptable toxicity, documentation of disease progression, initiation of alternative anticancer treatment, or withdrawal for other reasons.	Phase 1b Cohort B Participants received MEDI-573 45 mg/kg IV on Day 1 of each 21-day cycle and sorafenib 400 mg orally twice daily as background therapy until unacceptable toxicity, documentation of disease progression, initiation of alternative anticancer treatment, or withdrawal for other reasons.	Phase 1b Cohort C Participants were planned to receive MEDI-573 30 mg/kg IV on Day 1 of each 21-day cycle and sorafenib 400 mg orally twice daily as background therapy until unacceptable toxicity, documentation of disease progression, initiation of alternative anticancer treatment, or withdrawal for other reasons.	Phase 2 Arm 1 Participants were planned to receive recommended dose of MEDI-573 from Phase 1b IV on Day 1 of each 21-day cycle and sorafenib 400 mg orally twice daily until unacceptable toxicity, documentation of disease progression, initiation of alternative anticancer treatment, or withdrawal for other reasons.	Phase 2 Arm 2 Participants were planned to receive sorafenib 400 mg orally twice daily until unacceptable toxicity, documentation of disease progression, initiation of alternative anticancer treatment, or withdrawal for other reasons.
Overall Study STARTED	3	3	0	0	0
Overall Study COMPLETED	1	1	0	0	0
Overall Study NOT COMPLETED	2	2	0	0	0

Reasons for withdrawal

Measure	Phase 1b Cohort A Participants received MEDI-573 10 mg/kg intravenous infusion (IV) on Day 1 of each 21-day cycle and sorafenib 400 mg orally twice daily as background therapy until unacceptable toxicity, documentation of disease progression, initiation of alternative anticancer treatment, or withdrawal for other reasons.	Phase 1b Cohort B Participants received MEDI-573 45 mg/kg IV on Day 1 of each 21-day cycle and sorafenib 400 mg orally twice daily as background therapy until unacceptable toxicity, documentation of disease progression, initiation of alternative anticancer treatment, or withdrawal for other reasons.	Phase 1b Cohort C Participants were planned to receive MEDI-573 30 mg/kg IV on Day 1 of each 21-day cycle and sorafenib 400 mg orally twice daily as background therapy until unacceptable toxicity, documentation of disease progression, initiation of alternative anticancer treatment, or withdrawal for other reasons.	Phase 2 Arm 1 Participants were planned to receive recommended dose of MEDI-573 from Phase 1b IV on Day 1 of each 21-day cycle and sorafenib 400 mg orally twice daily until unacceptable toxicity, documentation of disease progression, initiation of alternative anticancer treatment, or withdrawal for other reasons.	Phase 2 Arm 2 Participants were planned to receive sorafenib 400 mg orally twice daily until unacceptable toxicity, documentation of disease progression, initiation of alternative anticancer treatment, or withdrawal for other reasons.
Overall Study Death	2	2	0	0	0

Baseline Characteristics

MEDI-573 in Combination With SOC in Unresectable or Metastatic HCC.

Baseline characteristics by cohort

Measure	Phase 1b Cohort A n=3 Participants Participants received MEDI-573 10 mg/kg IV on Day 1 of each 21-day cycle and sorafenib 400 mg orally twice daily as background therapy until unacceptable toxicity, documentation of disease progression, initiation of alternative anticancer treatment, or withdrawal for other reasons.	Phase 1b Cohort B n=3 Participants Participants received MEDI-573 45 mg/kg IV on Day 1 of each 21-day cycle and sorafenib 400 mg orally twice daily as background therapy until unacceptable toxicity, documentation of disease progression, initiation of alternative anticancer treatment, or withdrawal for other reasons.	Total n=6 Participants Total of all reporting groups
Age, Continuous	67.7 Years STANDARD_DEVIATION 1.2 • n=5 Participants	65.7 Years STANDARD_DEVIATION 11.6 • n=7 Participants	66.7 Years STANDARD_DEVIATION 7.4 • n=5 Participants
Sex: Female, Male Female	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Sex: Female, Male Male	3 Participants n=5 Participants	3 Participants n=7 Participants	6 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	2 Participants n=5 Participants	3 Participants n=7 Participants	5 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) White	2 Participants n=5 Participants	1 Participants n=7 Participants	3 Participants n=5 Participants
Race (NIH/OMB) More than one race	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants

PRIMARY outcome

Timeframe: Day 1 to Day 21 of Cycle 1

Population: Evaluable population included all participants enrolled in the Phase 1b who received at least 1 full dose of MEDI-573, received sorafenib treatment per standard practice during the DLT evaluation period, and completed safety follow-up through the DLT evaluation period or experienced any DLTs during the DLT evaluation period.

The DLT was defined as any Grade 3 or higher hematologic or non-hematologic toxicity considered to be related to MEDI-573 that occurred during the DLT evaluation period (Days 1 to 21 of Cycle 1), with the exceptions of Grade 3 fever (occurred in the absence of neutropenia and resolved to normal or baseline within 24 hours of treatment and was not considered as SAE), Grade 3 rigors/chills that responded to optimal therapy, and Grade < 4 hyperglycemia that resolved in < 24 hours.

Outcome measures

Measure	Phase 1b Cohort A n=3 Participants Participants received MEDI-573 10 mg/kg IV on Day 1 of each 21-day cycle and sorafenib 400 mg orally twice daily as background therapy until unacceptable toxicity, documentation of disease progression, initiation of alternative anticancer treatment, or withdrawal for other reasons.	Phase 1b Cohort B n=3 Participants Participants received MEDI-573 45 mg/kg IV on Day 1 of each 21-day cycle and sorafenib 400 mg orally twice daily as background therapy until unacceptable toxicity, documentation of disease progression, initiation of alternative anticancer treatment, or withdrawal for other reasons.	Phase 2 Arm 1 Participants were planned to receive the recommended dose of MEDI-573 from Phase 1b IV on Day 1 of each 21-day cycle and sorafenib 400 mg orally twice daily until unacceptable toxicity, documentation of disease progression, initiation of alternative anticancer treatment, or withdrawal for other reasons.	Phase 2 Arm 2 Participants were planned to receive sorafenib 400 mg orally twice daily until unacceptable toxicity, documentation of disease progression, initiation of alternative anticancer treatment, or withdrawal for other reasons
Phase 1b: Number of Participants With Dose-limiting Toxicities (DLTs)	1 Participants	0 Participants	—	—

PRIMARY outcome

Timeframe: From the start of study treatment (Day 1) through 60 days after the last dose of MEDI-573 or initiation of another anticancer therapy, whichever occurred first (approximately 15 months)

Population: Safety population included all participants who received any amount of study treatment.

An Adverse Event (AE) is any unfavourable and unintended sign, symptoms, or diseases temporally associated with use of study drug, whether or not considered related to study drug. A serious adverse event (SAE) is an AE that results in death, initial or prolonged inpatient hospitalization, life-threatening, persistent or significant disability/incapacity, congenital anomaly/birth defect, or an important medical event. The TEAEs are defined as AEs present at baseline that worsened in intensity after administration of study drug, or events absent at baseline that emerged after administration of study drug, up to 60 days after the last study drug or until the participants started another anticancer therapy, whichever occurred first (approximately 15 months).

Outcome measures

Measure	Phase 1b Cohort A n=3 Participants Participants received MEDI-573 10 mg/kg IV on Day 1 of each 21-day cycle and sorafenib 400 mg orally twice daily as background therapy until unacceptable toxicity, documentation of disease progression, initiation of alternative anticancer treatment, or withdrawal for other reasons.	Phase 1b Cohort B n=3 Participants Participants received MEDI-573 45 mg/kg IV on Day 1 of each 21-day cycle and sorafenib 400 mg orally twice daily as background therapy until unacceptable toxicity, documentation of disease progression, initiation of alternative anticancer treatment, or withdrawal for other reasons.	Phase 2 Arm 1 Participants were planned to receive the recommended dose of MEDI-573 from Phase 1b IV on Day 1 of each 21-day cycle and sorafenib 400 mg orally twice daily until unacceptable toxicity, documentation of disease progression, initiation of alternative anticancer treatment, or withdrawal for other reasons.	Phase 2 Arm 2 Participants were planned to receive sorafenib 400 mg orally twice daily until unacceptable toxicity, documentation of disease progression, initiation of alternative anticancer treatment, or withdrawal for other reasons
Phase 1b: Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (SAEs) Any TEAEs	3 Participants	3 Participants	—	—
Phase 1b: Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (SAEs) Any TESAEs	1 Participants	1 Participants	—	—

PRIMARY outcome

Timeframe: From the start of study treatment (Day 1) through 60 days after the last dose of MEDI-573 or initiation of another anticancer therapy, whichever occurred first (approximately 15 months)

Population: Safety population included all participants who received any amount of study treatment.

An abnormal laboratory finding which required an action or intervention by the investigator, or a finding judged by the investigator to represent a change beyond the range of normal physiologic fluctuation were reported as AEs. The TEAEs are defined as AEs present at baseline that worsened in intensity after administration of study drug, or events absent at baseline that emerged after administration of study drug, up to 60 days after the last study drug or until the participants started another anticancer therapy, whichever occurred first (approximately 15 months).

Outcome measures

Measure	Phase 1b Cohort A n=3 Participants Participants received MEDI-573 10 mg/kg IV on Day 1 of each 21-day cycle and sorafenib 400 mg orally twice daily as background therapy until unacceptable toxicity, documentation of disease progression, initiation of alternative anticancer treatment, or withdrawal for other reasons.	Phase 1b Cohort B n=3 Participants Participants received MEDI-573 45 mg/kg IV on Day 1 of each 21-day cycle and sorafenib 400 mg orally twice daily as background therapy until unacceptable toxicity, documentation of disease progression, initiation of alternative anticancer treatment, or withdrawal for other reasons.	Phase 2 Arm 1 Participants were planned to receive the recommended dose of MEDI-573 from Phase 1b IV on Day 1 of each 21-day cycle and sorafenib 400 mg orally twice daily until unacceptable toxicity, documentation of disease progression, initiation of alternative anticancer treatment, or withdrawal for other reasons.	Phase 2 Arm 2 Participants were planned to receive sorafenib 400 mg orally twice daily until unacceptable toxicity, documentation of disease progression, initiation of alternative anticancer treatment, or withdrawal for other reasons
Phase 1b: Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs Neutropenia	1 Participants	1 Participants	—	—
Phase 1b: Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs Blood bilirubin increased	2 Participants	2 Participants	—	—
Phase 1b: Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs Blood creatinine increased	0 Participants	1 Participants	—	—
Phase 1b: Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs Proteinuria	0 Participants	1 Participants	—	—
Phase 1b: Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs Hypophosphataemia	1 Participants	1 Participants	—	—
Phase 1b: Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs Hypoalbuminaemia	1 Participants	1 Participants	—	—
Phase 1b: Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs Alanine aminotransferase increased	1 Participants	0 Participants	—	—
Phase 1b: Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs Amylase increased	0 Participants	1 Participants	—	—
Phase 1b: Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs Blood alkaline phosphatase increased	1 Participants	0 Participants	—	—
Phase 1b: Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs Blood uric acid increased	0 Participants	1 Participants	—	—
Phase 1b: Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs Gamma-glutamyltransferase increased	1 Participants	0 Participants	—	—
Phase 1b: Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs Hypercholesterolaemia	1 Participants	0 Participants	—	—
Phase 1b: Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs Hypocalcaemia	1 Participants	0 Participants	—	—
Phase 1b: Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs Hypoglycaemia	0 Participants	1 Participants	—	—
Phase 1b: Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs Hypomagnesaemia	1 Participants	0 Participants	—	—
Phase 1b: Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs Hematuria	0 Participants	1 Participants	—	—
Phase 1b: Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs Thrombocytopenia	2 Participants	2 Participants	—	—
Phase 1b: Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs Anemia	0 Participants	1 Participants	—	—
Phase 1b: Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs Lipase increased	2 Participants	1 Participants	—	—
Phase 1b: Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs Hyperbilirubinemia	2 Participants	0 Participants	—	—
Phase 1b: Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs Aspartate aminotransferase increased	2 Participants	0 Participants	—	—

PRIMARY outcome

Timeframe: From the start of study treatment (Day 1) through 60 days after the last dose of MEDI-573 or initiation of another anticancer therapy, whichever occurred first (approximately 15 months)

Population: Safety population included all participants who received any amount of study treatment.

An abnormal vital signs that were judged by the investigator to be medically significant were reported as AEs. The TEAEs are defined as AEs present at baseline that worsened in intensity after administration of study drug, or events absent at baseline that emerged after administration of study drug, up to 60 days after the last study drug or until the participants started another anticancer therapy, whichever occurred first (approximately 15 months).

Outcome measures

Measure	Phase 1b Cohort A n=3 Participants Participants received MEDI-573 10 mg/kg IV on Day 1 of each 21-day cycle and sorafenib 400 mg orally twice daily as background therapy until unacceptable toxicity, documentation of disease progression, initiation of alternative anticancer treatment, or withdrawal for other reasons.	Phase 1b Cohort B n=3 Participants Participants received MEDI-573 45 mg/kg IV on Day 1 of each 21-day cycle and sorafenib 400 mg orally twice daily as background therapy until unacceptable toxicity, documentation of disease progression, initiation of alternative anticancer treatment, or withdrawal for other reasons.	Phase 2 Arm 1 Participants were planned to receive the recommended dose of MEDI-573 from Phase 1b IV on Day 1 of each 21-day cycle and sorafenib 400 mg orally twice daily until unacceptable toxicity, documentation of disease progression, initiation of alternative anticancer treatment, or withdrawal for other reasons.	Phase 2 Arm 2 Participants were planned to receive sorafenib 400 mg orally twice daily until unacceptable toxicity, documentation of disease progression, initiation of alternative anticancer treatment, or withdrawal for other reasons
Phase 1b: Number of Participants With Vital Signs Abnormalities Reported as TEAEs Hypertension	0 Participants	2 Participants	—	—
Phase 1b: Number of Participants With Vital Signs Abnormalities Reported as TEAEs Pyrexia	0 Participants	1 Participants	—	—
Phase 1b: Number of Participants With Vital Signs Abnormalities Reported as TEAEs Diastolic hypertension	0 Participants	1 Participants	—	—

PRIMARY outcome

Timeframe: From the start of study treatment (Day 1) through 60 days after the last dose of MEDI-573 or initiation of another anticancer therapy, whichever occurred first (approximately 15 months)

Population: Safety population included all participants who received any amount of study treatment.

An abnormal ECG findings that were judged by the investigator to be medically significant were reported as AEs. The TEAEs are defined as AEs present at baseline that worsened in intensity after administration of study drug, or events absent at baseline that emerged after administration of study drug, up to 60 days after the last study drug or until the participants started another anticancer therapy, whichever occurred first (approximately 15 months).

Outcome measures

Measure	Phase 1b Cohort A n=3 Participants Participants received MEDI-573 10 mg/kg IV on Day 1 of each 21-day cycle and sorafenib 400 mg orally twice daily as background therapy until unacceptable toxicity, documentation of disease progression, initiation of alternative anticancer treatment, or withdrawal for other reasons.	Phase 1b Cohort B n=3 Participants Participants received MEDI-573 45 mg/kg IV on Day 1 of each 21-day cycle and sorafenib 400 mg orally twice daily as background therapy until unacceptable toxicity, documentation of disease progression, initiation of alternative anticancer treatment, or withdrawal for other reasons.	Phase 2 Arm 1 Participants were planned to receive the recommended dose of MEDI-573 from Phase 1b IV on Day 1 of each 21-day cycle and sorafenib 400 mg orally twice daily until unacceptable toxicity, documentation of disease progression, initiation of alternative anticancer treatment, or withdrawal for other reasons.	Phase 2 Arm 2 Participants were planned to receive sorafenib 400 mg orally twice daily until unacceptable toxicity, documentation of disease progression, initiation of alternative anticancer treatment, or withdrawal for other reasons
Phase 1b: Number of Participants With Electrocardiogram (ECG) Abnormalities Reported as TEAEs	0 Participants	0 Participants	—	—

PRIMARY outcome

Timeframe: From Day 1 until documentation of progressive disease (approximately 15 months)

Population: Safety population included all participants who received any amount of study treatment.

Phase 2 part of the study was not launched by the sponsor due to strategic business reasons. Therefore, this outcome was not evaluated.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Predose on Day 1 of every treatment cycle; end of treatment; Days 30, 60 and 90 post treatment; every 3 months post treatrment till end of study (approximately 15 months)

Population: Safety population included all participants who received any amount of study treatment.

Participants with positive ADA to MEDI-573 are reported in the below table. This outcome was not evaluated for Phase 2 as it was not launched by the sponsor due to strategic business reasons.

Outcome measures

Measure	Phase 1b Cohort A n=3 Participants Participants received MEDI-573 10 mg/kg IV on Day 1 of each 21-day cycle and sorafenib 400 mg orally twice daily as background therapy until unacceptable toxicity, documentation of disease progression, initiation of alternative anticancer treatment, or withdrawal for other reasons.	Phase 1b Cohort B n=3 Participants Participants received MEDI-573 45 mg/kg IV on Day 1 of each 21-day cycle and sorafenib 400 mg orally twice daily as background therapy until unacceptable toxicity, documentation of disease progression, initiation of alternative anticancer treatment, or withdrawal for other reasons.	Phase 2 Arm 1 Participants were planned to receive the recommended dose of MEDI-573 from Phase 1b IV on Day 1 of each 21-day cycle and sorafenib 400 mg orally twice daily until unacceptable toxicity, documentation of disease progression, initiation of alternative anticancer treatment, or withdrawal for other reasons.	Phase 2 Arm 2 Participants were planned to receive sorafenib 400 mg orally twice daily until unacceptable toxicity, documentation of disease progression, initiation of alternative anticancer treatment, or withdrawal for other reasons
Phase 1b and Phase 2: Number of Participants With Positive Anti-drug Antibodies (ADA) to MEDI-573	0 Participants	0 Participants	—	—

SECONDARY outcome

Timeframe: From Day 1 until disease progression or death due to any cause, whichever occurred first (approximately 15 months)

Population: Safety population included all participants who received any amount of study treatment.

Phase 2 part of the study was not launched by the sponsor due to strategic business reasons. Therefore, this outcome was not evaluated.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: From Day 1 until disease progression or death due to any cause, whichever occurred first (approximately 15 months)

Population: Safety population included all participants who received any amount of study treatment.

Phase 2 part of the study was not launched by the sponsor due to strategic business reasons. Therefore, this outcome was not evaluated.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: From Day 1 until disease progression or death due to any cause, whichever occurred first (approximately 15 months)

Population: Safety population included all participants who received any amount of study treatment.

Phase 2 part of the study was not launched by the sponsor due to strategic business reasons. Therefore, this outcome was not evaluated.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: From Day 1 until disease progression or death due to any cause, whichever occurred first (approximately 15 months)

Population: Safety population included all participants who received any amount of study treatment.

Phase 2 part the study was not launched by the sponsor due to strategic business reasons. Therefore, this outcome was not evaluated.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Cycle 1 (pre-dose; and 5 minutes, 24 hours, Day 8, and Day 15 post-dose); and Cycle 2 Day 1 (pre-dose)

Population: Safety population included all participants who received any amount of study treatment.

The tmax is defined as actual sampling time to reach maximum observed serum concentration of the study drug. This outcome was not evaluated for Phase 2 as it was not launched by the sponsor due to strategic business reasons.

Outcome measures

Measure	Phase 1b Cohort A n=3 Participants Participants received MEDI-573 10 mg/kg IV on Day 1 of each 21-day cycle and sorafenib 400 mg orally twice daily as background therapy until unacceptable toxicity, documentation of disease progression, initiation of alternative anticancer treatment, or withdrawal for other reasons.	Phase 1b Cohort B n=3 Participants Participants received MEDI-573 45 mg/kg IV on Day 1 of each 21-day cycle and sorafenib 400 mg orally twice daily as background therapy until unacceptable toxicity, documentation of disease progression, initiation of alternative anticancer treatment, or withdrawal for other reasons.	Phase 2 Arm 1 Participants were planned to receive the recommended dose of MEDI-573 from Phase 1b IV on Day 1 of each 21-day cycle and sorafenib 400 mg orally twice daily until unacceptable toxicity, documentation of disease progression, initiation of alternative anticancer treatment, or withdrawal for other reasons.	Phase 2 Arm 2 Participants were planned to receive sorafenib 400 mg orally twice daily until unacceptable toxicity, documentation of disease progression, initiation of alternative anticancer treatment, or withdrawal for other reasons
Phase 1b and Phase 2: Time to Reach Maximum Observed Serum Concentration (Tmax) of MEDI-573 for Cycle 1	1.05 Hours Interval 1.05 to 1.08	1.55 Hours Interval 1.52 to 1.58	—	—

SECONDARY outcome

Timeframe: Cycle 1 (pre-dose; and 5 minutes, 24 hours, Day 8, and Day 15 post-dose); and Cycle 2 Day 1 (pre-dose)

Population: Safety population included all participants who received any amount of study treatment.

The Cmax is the maximum observed serum concentration of study drug. This outcome was not evaluated for Phase 2 as it was not launched by the sponsor due to strategic business reasons.

Outcome measures

Measure	Phase 1b Cohort A n=3 Participants Participants received MEDI-573 10 mg/kg IV on Day 1 of each 21-day cycle and sorafenib 400 mg orally twice daily as background therapy until unacceptable toxicity, documentation of disease progression, initiation of alternative anticancer treatment, or withdrawal for other reasons.	Phase 1b Cohort B n=3 Participants Participants received MEDI-573 45 mg/kg IV on Day 1 of each 21-day cycle and sorafenib 400 mg orally twice daily as background therapy until unacceptable toxicity, documentation of disease progression, initiation of alternative anticancer treatment, or withdrawal for other reasons.	Phase 2 Arm 1 Participants were planned to receive the recommended dose of MEDI-573 from Phase 1b IV on Day 1 of each 21-day cycle and sorafenib 400 mg orally twice daily until unacceptable toxicity, documentation of disease progression, initiation of alternative anticancer treatment, or withdrawal for other reasons.	Phase 2 Arm 2 Participants were planned to receive sorafenib 400 mg orally twice daily until unacceptable toxicity, documentation of disease progression, initiation of alternative anticancer treatment, or withdrawal for other reasons
Phase 1b and Phase 2: Maximum Observed Serum Concentration (Cmax) of MEDI-573 for Cycle 1	195 mcg/mL Standard Deviation 11.4	920 mcg/mL Standard Deviation 145	—	—

SECONDARY outcome

Timeframe: Cycle 1 (pre-dose; and 5 minutes, 24 hours, Day 8, and Day 15 post-dose); and Cycle 2 Day 1 (pre-dose)

Population: Safety population included all participants who received any amount of study treatment.

Area under the concentration-time curve from time zero to Day 22 is reported. This outcome was not evaluated for Phase 2 as it was not launched by the sponsor due to strategic business reasons.

Outcome measures

Measure	Phase 1b Cohort A n=3 Participants Participants received MEDI-573 10 mg/kg IV on Day 1 of each 21-day cycle and sorafenib 400 mg orally twice daily as background therapy until unacceptable toxicity, documentation of disease progression, initiation of alternative anticancer treatment, or withdrawal for other reasons.	Phase 1b Cohort B n=3 Participants Participants received MEDI-573 45 mg/kg IV on Day 1 of each 21-day cycle and sorafenib 400 mg orally twice daily as background therapy until unacceptable toxicity, documentation of disease progression, initiation of alternative anticancer treatment, or withdrawal for other reasons.	Phase 2 Arm 1 Participants were planned to receive the recommended dose of MEDI-573 from Phase 1b IV on Day 1 of each 21-day cycle and sorafenib 400 mg orally twice daily until unacceptable toxicity, documentation of disease progression, initiation of alternative anticancer treatment, or withdrawal for other reasons.	Phase 2 Arm 2 Participants were planned to receive sorafenib 400 mg orally twice daily until unacceptable toxicity, documentation of disease progression, initiation of alternative anticancer treatment, or withdrawal for other reasons
Phase 1b and Phase 2: Area Under Serum Concentration-time Curve From Time Zero to Day 22 (AUC0-Day22) of MEDI-573 for Cycle 1	887 day*mcg/mL Standard Deviation 231	6390 day*mcg/mL Standard Deviation 1440	—	—

Adverse Events

Phase 1b Cohort A

Serious events: 1 serious events

Other events: 3 other events

Deaths: 2 deaths

Phase 1b Cohort B

Serious events: 1 serious events

Other events: 3 other events

Deaths: 2 deaths

Serious adverse events

Measure	Phase 1b Cohort A n=3 participants at risk Participants received MEDI-573 10 mg/kg IV on Day 1 of each 21-day cycle and sorafenib 400 mg orally twice daily as background therapy until unacceptable toxicity, documentation of disease progression, initiation of alternative anticancer treatment, or withdrawal for other reasons.	Phase 1b Cohort B n=3 participants at risk Participants received MEDI-573 45 mg/kg IV on Day 1 of each 21-day cycle and sorafenib 400 mg orally twice daily as background therapy until unacceptable toxicity, documentation of disease progression, initiation of alternative anticancer treatment, or withdrawal for other reasons.
Nervous system disorders Hepatic encephalopathy	0.00% 0/3 • All AEs were reported during safety follow-up period (from the start of study treatment [Day 1] through 60 days after the last dose of MEDI-573 or initiation of another anticancer therapy, whichever occurred first) (approximately 15 months).	33.3% 1/3 • Number of events 1 • All AEs were reported during safety follow-up period (from the start of study treatment [Day 1] through 60 days after the last dose of MEDI-573 or initiation of another anticancer therapy, whichever occurred first) (approximately 15 months).
Respiratory, thoracic and mediastinal disorders Pneumothorax	33.3% 1/3 • Number of events 1 • All AEs were reported during safety follow-up period (from the start of study treatment [Day 1] through 60 days after the last dose of MEDI-573 or initiation of another anticancer therapy, whichever occurred first) (approximately 15 months).	0.00% 0/3 • All AEs were reported during safety follow-up period (from the start of study treatment [Day 1] through 60 days after the last dose of MEDI-573 or initiation of another anticancer therapy, whichever occurred first) (approximately 15 months).
Hepatobiliary disorders Hepatic failure	0.00% 0/3 • All AEs were reported during safety follow-up period (from the start of study treatment [Day 1] through 60 days after the last dose of MEDI-573 or initiation of another anticancer therapy, whichever occurred first) (approximately 15 months).	33.3% 1/3 • Number of events 1 • All AEs were reported during safety follow-up period (from the start of study treatment [Day 1] through 60 days after the last dose of MEDI-573 or initiation of another anticancer therapy, whichever occurred first) (approximately 15 months).
Investigations Lipase increased	0.00% 0/3 • All AEs were reported during safety follow-up period (from the start of study treatment [Day 1] through 60 days after the last dose of MEDI-573 or initiation of another anticancer therapy, whichever occurred first) (approximately 15 months).	33.3% 1/3 • Number of events 1 • All AEs were reported during safety follow-up period (from the start of study treatment [Day 1] through 60 days after the last dose of MEDI-573 or initiation of another anticancer therapy, whichever occurred first) (approximately 15 months).
Gastrointestinal disorders Abdominal pain	33.3% 1/3 • Number of events 2 • All AEs were reported during safety follow-up period (from the start of study treatment [Day 1] through 60 days after the last dose of MEDI-573 or initiation of another anticancer therapy, whichever occurred first) (approximately 15 months).	0.00% 0/3 • All AEs were reported during safety follow-up period (from the start of study treatment [Day 1] through 60 days after the last dose of MEDI-573 or initiation of another anticancer therapy, whichever occurred first) (approximately 15 months).
General disorders Asthenia	33.3% 1/3 • Number of events 1 • All AEs were reported during safety follow-up period (from the start of study treatment [Day 1] through 60 days after the last dose of MEDI-573 or initiation of another anticancer therapy, whichever occurred first) (approximately 15 months).	0.00% 0/3 • All AEs were reported during safety follow-up period (from the start of study treatment [Day 1] through 60 days after the last dose of MEDI-573 or initiation of another anticancer therapy, whichever occurred first) (approximately 15 months).
General disorders Non-cardiac chest pain	33.3% 1/3 • Number of events 1 • All AEs were reported during safety follow-up period (from the start of study treatment [Day 1] through 60 days after the last dose of MEDI-573 or initiation of another anticancer therapy, whichever occurred first) (approximately 15 months).	0.00% 0/3 • All AEs were reported during safety follow-up period (from the start of study treatment [Day 1] through 60 days after the last dose of MEDI-573 or initiation of another anticancer therapy, whichever occurred first) (approximately 15 months).

Other adverse events

Measure	Phase 1b Cohort A n=3 participants at risk Participants received MEDI-573 10 mg/kg IV on Day 1 of each 21-day cycle and sorafenib 400 mg orally twice daily as background therapy until unacceptable toxicity, documentation of disease progression, initiation of alternative anticancer treatment, or withdrawal for other reasons.	Phase 1b Cohort B n=3 participants at risk Participants received MEDI-573 45 mg/kg IV on Day 1 of each 21-day cycle and sorafenib 400 mg orally twice daily as background therapy until unacceptable toxicity, documentation of disease progression, initiation of alternative anticancer treatment, or withdrawal for other reasons.
Blood and lymphatic system disorders Anaemia	0.00% 0/3 • All AEs were reported during safety follow-up period (from the start of study treatment [Day 1] through 60 days after the last dose of MEDI-573 or initiation of another anticancer therapy, whichever occurred first) (approximately 15 months).	33.3% 1/3 • Number of events 1 • All AEs were reported during safety follow-up period (from the start of study treatment [Day 1] through 60 days after the last dose of MEDI-573 or initiation of another anticancer therapy, whichever occurred first) (approximately 15 months).
Blood and lymphatic system disorders Neutropenia	33.3% 1/3 • Number of events 1 • All AEs were reported during safety follow-up period (from the start of study treatment [Day 1] through 60 days after the last dose of MEDI-573 or initiation of another anticancer therapy, whichever occurred first) (approximately 15 months).	33.3% 1/3 • Number of events 1 • All AEs were reported during safety follow-up period (from the start of study treatment [Day 1] through 60 days after the last dose of MEDI-573 or initiation of another anticancer therapy, whichever occurred first) (approximately 15 months).
Blood and lymphatic system disorders Thrombocytopenia	66.7% 2/3 • Number of events 10 • All AEs were reported during safety follow-up period (from the start of study treatment [Day 1] through 60 days after the last dose of MEDI-573 or initiation of another anticancer therapy, whichever occurred first) (approximately 15 months).	66.7% 2/3 • Number of events 2 • All AEs were reported during safety follow-up period (from the start of study treatment [Day 1] through 60 days after the last dose of MEDI-573 or initiation of another anticancer therapy, whichever occurred first) (approximately 15 months).
Ear and labyrinth disorders Hypoacusis	0.00% 0/3 • All AEs were reported during safety follow-up period (from the start of study treatment [Day 1] through 60 days after the last dose of MEDI-573 or initiation of another anticancer therapy, whichever occurred first) (approximately 15 months).	33.3% 1/3 • Number of events 1 • All AEs were reported during safety follow-up period (from the start of study treatment [Day 1] through 60 days after the last dose of MEDI-573 or initiation of another anticancer therapy, whichever occurred first) (approximately 15 months).
Eye disorders Conjunctivitis	33.3% 1/3 • Number of events 1 • All AEs were reported during safety follow-up period (from the start of study treatment [Day 1] through 60 days after the last dose of MEDI-573 or initiation of another anticancer therapy, whichever occurred first) (approximately 15 months).	0.00% 0/3 • All AEs were reported during safety follow-up period (from the start of study treatment [Day 1] through 60 days after the last dose of MEDI-573 or initiation of another anticancer therapy, whichever occurred first) (approximately 15 months).
Eye disorders Scleral haemorrhage	33.3% 1/3 • Number of events 1 • All AEs were reported during safety follow-up period (from the start of study treatment [Day 1] through 60 days after the last dose of MEDI-573 or initiation of another anticancer therapy, whichever occurred first) (approximately 15 months).	0.00% 0/3 • All AEs were reported during safety follow-up period (from the start of study treatment [Day 1] through 60 days after the last dose of MEDI-573 or initiation of another anticancer therapy, whichever occurred first) (approximately 15 months).
Gastrointestinal disorders Abdominal pain	33.3% 1/3 • Number of events 1 • All AEs were reported during safety follow-up period (from the start of study treatment [Day 1] through 60 days after the last dose of MEDI-573 or initiation of another anticancer therapy, whichever occurred first) (approximately 15 months).	0.00% 0/3 • All AEs were reported during safety follow-up period (from the start of study treatment [Day 1] through 60 days after the last dose of MEDI-573 or initiation of another anticancer therapy, whichever occurred first) (approximately 15 months).
Gastrointestinal disorders Abdominal pain upper	0.00% 0/3 • All AEs were reported during safety follow-up period (from the start of study treatment [Day 1] through 60 days after the last dose of MEDI-573 or initiation of another anticancer therapy, whichever occurred first) (approximately 15 months).	33.3% 1/3 • Number of events 1 • All AEs were reported during safety follow-up period (from the start of study treatment [Day 1] through 60 days after the last dose of MEDI-573 or initiation of another anticancer therapy, whichever occurred first) (approximately 15 months).
Gastrointestinal disorders Ascites	33.3% 1/3 • Number of events 1 • All AEs were reported during safety follow-up period (from the start of study treatment [Day 1] through 60 days after the last dose of MEDI-573 or initiation of another anticancer therapy, whichever occurred first) (approximately 15 months).	0.00% 0/3 • All AEs were reported during safety follow-up period (from the start of study treatment [Day 1] through 60 days after the last dose of MEDI-573 or initiation of another anticancer therapy, whichever occurred first) (approximately 15 months).
Gastrointestinal disorders Diarrhoea	66.7% 2/3 • Number of events 3 • All AEs were reported during safety follow-up period (from the start of study treatment [Day 1] through 60 days after the last dose of MEDI-573 or initiation of another anticancer therapy, whichever occurred first) (approximately 15 months).	33.3% 1/3 • Number of events 1 • All AEs were reported during safety follow-up period (from the start of study treatment [Day 1] through 60 days after the last dose of MEDI-573 or initiation of another anticancer therapy, whichever occurred first) (approximately 15 months).
Gastrointestinal disorders Frequent bowel movements	33.3% 1/3 • Number of events 1 • All AEs were reported during safety follow-up period (from the start of study treatment [Day 1] through 60 days after the last dose of MEDI-573 or initiation of another anticancer therapy, whichever occurred first) (approximately 15 months).	0.00% 0/3 • All AEs were reported during safety follow-up period (from the start of study treatment [Day 1] through 60 days after the last dose of MEDI-573 or initiation of another anticancer therapy, whichever occurred first) (approximately 15 months).
Gastrointestinal disorders Inguinal hernia	33.3% 1/3 • Number of events 1 • All AEs were reported during safety follow-up period (from the start of study treatment [Day 1] through 60 days after the last dose of MEDI-573 or initiation of another anticancer therapy, whichever occurred first) (approximately 15 months).	0.00% 0/3 • All AEs were reported during safety follow-up period (from the start of study treatment [Day 1] through 60 days after the last dose of MEDI-573 or initiation of another anticancer therapy, whichever occurred first) (approximately 15 months).
Gastrointestinal disorders Nausea	33.3% 1/3 • Number of events 3 • All AEs were reported during safety follow-up period (from the start of study treatment [Day 1] through 60 days after the last dose of MEDI-573 or initiation of another anticancer therapy, whichever occurred first) (approximately 15 months).	66.7% 2/3 • Number of events 2 • All AEs were reported during safety follow-up period (from the start of study treatment [Day 1] through 60 days after the last dose of MEDI-573 or initiation of another anticancer therapy, whichever occurred first) (approximately 15 months).
Gastrointestinal disorders Retching	33.3% 1/3 • Number of events 1 • All AEs were reported during safety follow-up period (from the start of study treatment [Day 1] through 60 days after the last dose of MEDI-573 or initiation of another anticancer therapy, whichever occurred first) (approximately 15 months).	0.00% 0/3 • All AEs were reported during safety follow-up period (from the start of study treatment [Day 1] through 60 days after the last dose of MEDI-573 or initiation of another anticancer therapy, whichever occurred first) (approximately 15 months).
Gastrointestinal disorders Vomiting	66.7% 2/3 • Number of events 2 • All AEs were reported during safety follow-up period (from the start of study treatment [Day 1] through 60 days after the last dose of MEDI-573 or initiation of another anticancer therapy, whichever occurred first) (approximately 15 months).	33.3% 1/3 • Number of events 1 • All AEs were reported during safety follow-up period (from the start of study treatment [Day 1] through 60 days after the last dose of MEDI-573 or initiation of another anticancer therapy, whichever occurred first) (approximately 15 months).
General disorders Fatigue	33.3% 1/3 • Number of events 1 • All AEs were reported during safety follow-up period (from the start of study treatment [Day 1] through 60 days after the last dose of MEDI-573 or initiation of another anticancer therapy, whichever occurred first) (approximately 15 months).	66.7% 2/3 • Number of events 4 • All AEs were reported during safety follow-up period (from the start of study treatment [Day 1] through 60 days after the last dose of MEDI-573 or initiation of another anticancer therapy, whichever occurred first) (approximately 15 months).
General disorders Implant site pain	0.00% 0/3 • All AEs were reported during safety follow-up period (from the start of study treatment [Day 1] through 60 days after the last dose of MEDI-573 or initiation of another anticancer therapy, whichever occurred first) (approximately 15 months).	66.7% 2/3 • Number of events 2 • All AEs were reported during safety follow-up period (from the start of study treatment [Day 1] through 60 days after the last dose of MEDI-573 or initiation of another anticancer therapy, whichever occurred first) (approximately 15 months).
General disorders Oedema peripheral	33.3% 1/3 • Number of events 1 • All AEs were reported during safety follow-up period (from the start of study treatment [Day 1] through 60 days after the last dose of MEDI-573 or initiation of another anticancer therapy, whichever occurred first) (approximately 15 months).	0.00% 0/3 • All AEs were reported during safety follow-up period (from the start of study treatment [Day 1] through 60 days after the last dose of MEDI-573 or initiation of another anticancer therapy, whichever occurred first) (approximately 15 months).
General disorders Pyrexia	0.00% 0/3 • All AEs were reported during safety follow-up period (from the start of study treatment [Day 1] through 60 days after the last dose of MEDI-573 or initiation of another anticancer therapy, whichever occurred first) (approximately 15 months).	33.3% 1/3 • Number of events 1 • All AEs were reported during safety follow-up period (from the start of study treatment [Day 1] through 60 days after the last dose of MEDI-573 or initiation of another anticancer therapy, whichever occurred first) (approximately 15 months).
Hepatobiliary disorders Hyperbilirubinaemia	66.7% 2/3 • Number of events 3 • All AEs were reported during safety follow-up period (from the start of study treatment [Day 1] through 60 days after the last dose of MEDI-573 or initiation of another anticancer therapy, whichever occurred first) (approximately 15 months).	0.00% 0/3 • All AEs were reported during safety follow-up period (from the start of study treatment [Day 1] through 60 days after the last dose of MEDI-573 or initiation of another anticancer therapy, whichever occurred first) (approximately 15 months).
Hepatobiliary disorders Portal vein thrombosis	33.3% 1/3 • Number of events 1 • All AEs were reported during safety follow-up period (from the start of study treatment [Day 1] through 60 days after the last dose of MEDI-573 or initiation of another anticancer therapy, whichever occurred first) (approximately 15 months).	0.00% 0/3 • All AEs were reported during safety follow-up period (from the start of study treatment [Day 1] through 60 days after the last dose of MEDI-573 or initiation of another anticancer therapy, whichever occurred first) (approximately 15 months).
Infections and infestations Oral candidiasis	33.3% 1/3 • Number of events 1 • All AEs were reported during safety follow-up period (from the start of study treatment [Day 1] through 60 days after the last dose of MEDI-573 or initiation of another anticancer therapy, whichever occurred first) (approximately 15 months).	0.00% 0/3 • All AEs were reported during safety follow-up period (from the start of study treatment [Day 1] through 60 days after the last dose of MEDI-573 or initiation of another anticancer therapy, whichever occurred first) (approximately 15 months).
Infections and infestations Pneumonia	33.3% 1/3 • Number of events 1 • All AEs were reported during safety follow-up period (from the start of study treatment [Day 1] through 60 days after the last dose of MEDI-573 or initiation of another anticancer therapy, whichever occurred first) (approximately 15 months).	0.00% 0/3 • All AEs were reported during safety follow-up period (from the start of study treatment [Day 1] through 60 days after the last dose of MEDI-573 or initiation of another anticancer therapy, whichever occurred first) (approximately 15 months).
Infections and infestations Viral upper respiratory tract infection	0.00% 0/3 • All AEs were reported during safety follow-up period (from the start of study treatment [Day 1] through 60 days after the last dose of MEDI-573 or initiation of another anticancer therapy, whichever occurred first) (approximately 15 months).	33.3% 1/3 • Number of events 1 • All AEs were reported during safety follow-up period (from the start of study treatment [Day 1] through 60 days after the last dose of MEDI-573 or initiation of another anticancer therapy, whichever occurred first) (approximately 15 months).
Injury, poisoning and procedural complications Laceration	33.3% 1/3 • Number of events 1 • All AEs were reported during safety follow-up period (from the start of study treatment [Day 1] through 60 days after the last dose of MEDI-573 or initiation of another anticancer therapy, whichever occurred first) (approximately 15 months).	0.00% 0/3 • All AEs were reported during safety follow-up period (from the start of study treatment [Day 1] through 60 days after the last dose of MEDI-573 or initiation of another anticancer therapy, whichever occurred first) (approximately 15 months).
Investigations Alanine aminotransferase increased	33.3% 1/3 • Number of events 1 • All AEs were reported during safety follow-up period (from the start of study treatment [Day 1] through 60 days after the last dose of MEDI-573 or initiation of another anticancer therapy, whichever occurred first) (approximately 15 months).	0.00% 0/3 • All AEs were reported during safety follow-up period (from the start of study treatment [Day 1] through 60 days after the last dose of MEDI-573 or initiation of another anticancer therapy, whichever occurred first) (approximately 15 months).
Investigations Amylase increased	0.00% 0/3 • All AEs were reported during safety follow-up period (from the start of study treatment [Day 1] through 60 days after the last dose of MEDI-573 or initiation of another anticancer therapy, whichever occurred first) (approximately 15 months).	33.3% 1/3 • Number of events 1 • All AEs were reported during safety follow-up period (from the start of study treatment [Day 1] through 60 days after the last dose of MEDI-573 or initiation of another anticancer therapy, whichever occurred first) (approximately 15 months).
Investigations Aspartate aminotransferase increased	66.7% 2/3 • Number of events 3 • All AEs were reported during safety follow-up period (from the start of study treatment [Day 1] through 60 days after the last dose of MEDI-573 or initiation of another anticancer therapy, whichever occurred first) (approximately 15 months).	0.00% 0/3 • All AEs were reported during safety follow-up period (from the start of study treatment [Day 1] through 60 days after the last dose of MEDI-573 or initiation of another anticancer therapy, whichever occurred first) (approximately 15 months).
Investigations Blood alkaline phosphatase increased	33.3% 1/3 • Number of events 1 • All AEs were reported during safety follow-up period (from the start of study treatment [Day 1] through 60 days after the last dose of MEDI-573 or initiation of another anticancer therapy, whichever occurred first) (approximately 15 months).	0.00% 0/3 • All AEs were reported during safety follow-up period (from the start of study treatment [Day 1] through 60 days after the last dose of MEDI-573 or initiation of another anticancer therapy, whichever occurred first) (approximately 15 months).
Investigations Blood bilirubin increased	66.7% 2/3 • Number of events 2 • All AEs were reported during safety follow-up period (from the start of study treatment [Day 1] through 60 days after the last dose of MEDI-573 or initiation of another anticancer therapy, whichever occurred first) (approximately 15 months).	66.7% 2/3 • Number of events 2 • All AEs were reported during safety follow-up period (from the start of study treatment [Day 1] through 60 days after the last dose of MEDI-573 or initiation of another anticancer therapy, whichever occurred first) (approximately 15 months).
Investigations Blood creatinine increased	0.00% 0/3 • All AEs were reported during safety follow-up period (from the start of study treatment [Day 1] through 60 days after the last dose of MEDI-573 or initiation of another anticancer therapy, whichever occurred first) (approximately 15 months).	33.3% 1/3 • Number of events 1 • All AEs were reported during safety follow-up period (from the start of study treatment [Day 1] through 60 days after the last dose of MEDI-573 or initiation of another anticancer therapy, whichever occurred first) (approximately 15 months).
Investigations Blood uric acid increased	0.00% 0/3 • All AEs were reported during safety follow-up period (from the start of study treatment [Day 1] through 60 days after the last dose of MEDI-573 or initiation of another anticancer therapy, whichever occurred first) (approximately 15 months).	33.3% 1/3 • Number of events 1 • All AEs were reported during safety follow-up period (from the start of study treatment [Day 1] through 60 days after the last dose of MEDI-573 or initiation of another anticancer therapy, whichever occurred first) (approximately 15 months).
Investigations Gamma-glutamyltransferase increased	33.3% 1/3 • Number of events 5 • All AEs were reported during safety follow-up period (from the start of study treatment [Day 1] through 60 days after the last dose of MEDI-573 or initiation of another anticancer therapy, whichever occurred first) (approximately 15 months).	0.00% 0/3 • All AEs were reported during safety follow-up period (from the start of study treatment [Day 1] through 60 days after the last dose of MEDI-573 or initiation of another anticancer therapy, whichever occurred first) (approximately 15 months).
Investigations Lipase increased	66.7% 2/3 • Number of events 6 • All AEs were reported during safety follow-up period (from the start of study treatment [Day 1] through 60 days after the last dose of MEDI-573 or initiation of another anticancer therapy, whichever occurred first) (approximately 15 months).	33.3% 1/3 • Number of events 1 • All AEs were reported during safety follow-up period (from the start of study treatment [Day 1] through 60 days after the last dose of MEDI-573 or initiation of another anticancer therapy, whichever occurred first) (approximately 15 months).
Metabolism and nutrition disorders Decreased appetite	33.3% 1/3 • Number of events 1 • All AEs were reported during safety follow-up period (from the start of study treatment [Day 1] through 60 days after the last dose of MEDI-573 or initiation of another anticancer therapy, whichever occurred first) (approximately 15 months).	33.3% 1/3 • Number of events 1 • All AEs were reported during safety follow-up period (from the start of study treatment [Day 1] through 60 days after the last dose of MEDI-573 or initiation of another anticancer therapy, whichever occurred first) (approximately 15 months).
Metabolism and nutrition disorders Hypercholesterolaemia	33.3% 1/3 • Number of events 1 • All AEs were reported during safety follow-up period (from the start of study treatment [Day 1] through 60 days after the last dose of MEDI-573 or initiation of another anticancer therapy, whichever occurred first) (approximately 15 months).	0.00% 0/3 • All AEs were reported during safety follow-up period (from the start of study treatment [Day 1] through 60 days after the last dose of MEDI-573 or initiation of another anticancer therapy, whichever occurred first) (approximately 15 months).
Metabolism and nutrition disorders Hypoalbuminaemia	33.3% 1/3 • Number of events 1 • All AEs were reported during safety follow-up period (from the start of study treatment [Day 1] through 60 days after the last dose of MEDI-573 or initiation of another anticancer therapy, whichever occurred first) (approximately 15 months).	33.3% 1/3 • Number of events 1 • All AEs were reported during safety follow-up period (from the start of study treatment [Day 1] through 60 days after the last dose of MEDI-573 or initiation of another anticancer therapy, whichever occurred first) (approximately 15 months).
Metabolism and nutrition disorders Hypocalcaemia	33.3% 1/3 • Number of events 1 • All AEs were reported during safety follow-up period (from the start of study treatment [Day 1] through 60 days after the last dose of MEDI-573 or initiation of another anticancer therapy, whichever occurred first) (approximately 15 months).	0.00% 0/3 • All AEs were reported during safety follow-up period (from the start of study treatment [Day 1] through 60 days after the last dose of MEDI-573 or initiation of another anticancer therapy, whichever occurred first) (approximately 15 months).
Metabolism and nutrition disorders Hypoglycaemia	0.00% 0/3 • All AEs were reported during safety follow-up period (from the start of study treatment [Day 1] through 60 days after the last dose of MEDI-573 or initiation of another anticancer therapy, whichever occurred first) (approximately 15 months).	33.3% 1/3 • Number of events 1 • All AEs were reported during safety follow-up period (from the start of study treatment [Day 1] through 60 days after the last dose of MEDI-573 or initiation of another anticancer therapy, whichever occurred first) (approximately 15 months).
Metabolism and nutrition disorders Hypomagnesaemia	33.3% 1/3 • Number of events 1 • All AEs were reported during safety follow-up period (from the start of study treatment [Day 1] through 60 days after the last dose of MEDI-573 or initiation of another anticancer therapy, whichever occurred first) (approximately 15 months).	0.00% 0/3 • All AEs were reported during safety follow-up period (from the start of study treatment [Day 1] through 60 days after the last dose of MEDI-573 or initiation of another anticancer therapy, whichever occurred first) (approximately 15 months).
Metabolism and nutrition disorders Hypophosphataemia	33.3% 1/3 • Number of events 1 • All AEs were reported during safety follow-up period (from the start of study treatment [Day 1] through 60 days after the last dose of MEDI-573 or initiation of another anticancer therapy, whichever occurred first) (approximately 15 months).	33.3% 1/3 • Number of events 1 • All AEs were reported during safety follow-up period (from the start of study treatment [Day 1] through 60 days after the last dose of MEDI-573 or initiation of another anticancer therapy, whichever occurred first) (approximately 15 months).
Musculoskeletal and connective tissue disorders Arthralgia	33.3% 1/3 • Number of events 1 • All AEs were reported during safety follow-up period (from the start of study treatment [Day 1] through 60 days after the last dose of MEDI-573 or initiation of another anticancer therapy, whichever occurred first) (approximately 15 months).	0.00% 0/3 • All AEs were reported during safety follow-up period (from the start of study treatment [Day 1] through 60 days after the last dose of MEDI-573 or initiation of another anticancer therapy, whichever occurred first) (approximately 15 months).
Musculoskeletal and connective tissue disorders Back pain	0.00% 0/3 • All AEs were reported during safety follow-up period (from the start of study treatment [Day 1] through 60 days after the last dose of MEDI-573 or initiation of another anticancer therapy, whichever occurred first) (approximately 15 months).	33.3% 1/3 • Number of events 1 • All AEs were reported during safety follow-up period (from the start of study treatment [Day 1] through 60 days after the last dose of MEDI-573 or initiation of another anticancer therapy, whichever occurred first) (approximately 15 months).
Musculoskeletal and connective tissue disorders Musculoskeletal chest pain	33.3% 1/3 • Number of events 1 • All AEs were reported during safety follow-up period (from the start of study treatment [Day 1] through 60 days after the last dose of MEDI-573 or initiation of another anticancer therapy, whichever occurred first) (approximately 15 months).	0.00% 0/3 • All AEs were reported during safety follow-up period (from the start of study treatment [Day 1] through 60 days after the last dose of MEDI-573 or initiation of another anticancer therapy, whichever occurred first) (approximately 15 months).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Squamous cell carcinoma	33.3% 1/3 • Number of events 1 • All AEs were reported during safety follow-up period (from the start of study treatment [Day 1] through 60 days after the last dose of MEDI-573 or initiation of another anticancer therapy, whichever occurred first) (approximately 15 months).	0.00% 0/3 • All AEs were reported during safety follow-up period (from the start of study treatment [Day 1] through 60 days after the last dose of MEDI-573 or initiation of another anticancer therapy, whichever occurred first) (approximately 15 months).
Nervous system disorders Encephalopathy	33.3% 1/3 • Number of events 1 • All AEs were reported during safety follow-up period (from the start of study treatment [Day 1] through 60 days after the last dose of MEDI-573 or initiation of another anticancer therapy, whichever occurred first) (approximately 15 months).	0.00% 0/3 • All AEs were reported during safety follow-up period (from the start of study treatment [Day 1] through 60 days after the last dose of MEDI-573 or initiation of another anticancer therapy, whichever occurred first) (approximately 15 months).
Nervous system disorders Headache	33.3% 1/3 • Number of events 2 • All AEs were reported during safety follow-up period (from the start of study treatment [Day 1] through 60 days after the last dose of MEDI-573 or initiation of another anticancer therapy, whichever occurred first) (approximately 15 months).	0.00% 0/3 • All AEs were reported during safety follow-up period (from the start of study treatment [Day 1] through 60 days after the last dose of MEDI-573 or initiation of another anticancer therapy, whichever occurred first) (approximately 15 months).
Nervous system disorders Neuropathy peripheral	0.00% 0/3 • All AEs were reported during safety follow-up period (from the start of study treatment [Day 1] through 60 days after the last dose of MEDI-573 or initiation of another anticancer therapy, whichever occurred first) (approximately 15 months).	33.3% 1/3 • Number of events 1 • All AEs were reported during safety follow-up period (from the start of study treatment [Day 1] through 60 days after the last dose of MEDI-573 or initiation of another anticancer therapy, whichever occurred first) (approximately 15 months).
Psychiatric disorders Anxiety	0.00% 0/3 • All AEs were reported during safety follow-up period (from the start of study treatment [Day 1] through 60 days after the last dose of MEDI-573 or initiation of another anticancer therapy, whichever occurred first) (approximately 15 months).	66.7% 2/3 • Number of events 2 • All AEs were reported during safety follow-up period (from the start of study treatment [Day 1] through 60 days after the last dose of MEDI-573 or initiation of another anticancer therapy, whichever occurred first) (approximately 15 months).
Psychiatric disorders Confusional state	33.3% 1/3 • Number of events 1 • All AEs were reported during safety follow-up period (from the start of study treatment [Day 1] through 60 days after the last dose of MEDI-573 or initiation of another anticancer therapy, whichever occurred first) (approximately 15 months).	0.00% 0/3 • All AEs were reported during safety follow-up period (from the start of study treatment [Day 1] through 60 days after the last dose of MEDI-573 or initiation of another anticancer therapy, whichever occurred first) (approximately 15 months).
Psychiatric disorders Depression	0.00% 0/3 • All AEs were reported during safety follow-up period (from the start of study treatment [Day 1] through 60 days after the last dose of MEDI-573 or initiation of another anticancer therapy, whichever occurred first) (approximately 15 months).	33.3% 1/3 • Number of events 1 • All AEs were reported during safety follow-up period (from the start of study treatment [Day 1] through 60 days after the last dose of MEDI-573 or initiation of another anticancer therapy, whichever occurred first) (approximately 15 months).
Psychiatric disorders Insomnia	33.3% 1/3 • Number of events 1 • All AEs were reported during safety follow-up period (from the start of study treatment [Day 1] through 60 days after the last dose of MEDI-573 or initiation of another anticancer therapy, whichever occurred first) (approximately 15 months).	66.7% 2/3 • Number of events 2 • All AEs were reported during safety follow-up period (from the start of study treatment [Day 1] through 60 days after the last dose of MEDI-573 or initiation of another anticancer therapy, whichever occurred first) (approximately 15 months).
Renal and urinary disorders Anuria	0.00% 0/3 • All AEs were reported during safety follow-up period (from the start of study treatment [Day 1] through 60 days after the last dose of MEDI-573 or initiation of another anticancer therapy, whichever occurred first) (approximately 15 months).	33.3% 1/3 • Number of events 1 • All AEs were reported during safety follow-up period (from the start of study treatment [Day 1] through 60 days after the last dose of MEDI-573 or initiation of another anticancer therapy, whichever occurred first) (approximately 15 months).
Renal and urinary disorders Haematuria	0.00% 0/3 • All AEs were reported during safety follow-up period (from the start of study treatment [Day 1] through 60 days after the last dose of MEDI-573 or initiation of another anticancer therapy, whichever occurred first) (approximately 15 months).	33.3% 1/3 • Number of events 1 • All AEs were reported during safety follow-up period (from the start of study treatment [Day 1] through 60 days after the last dose of MEDI-573 or initiation of another anticancer therapy, whichever occurred first) (approximately 15 months).
Renal and urinary disorders Proteinuria	0.00% 0/3 • All AEs were reported during safety follow-up period (from the start of study treatment [Day 1] through 60 days after the last dose of MEDI-573 or initiation of another anticancer therapy, whichever occurred first) (approximately 15 months).	33.3% 1/3 • Number of events 1 • All AEs were reported during safety follow-up period (from the start of study treatment [Day 1] through 60 days after the last dose of MEDI-573 or initiation of another anticancer therapy, whichever occurred first) (approximately 15 months).
Respiratory, thoracic and mediastinal disorders Atelectasis	33.3% 1/3 • Number of events 1 • All AEs were reported during safety follow-up period (from the start of study treatment [Day 1] through 60 days after the last dose of MEDI-573 or initiation of another anticancer therapy, whichever occurred first) (approximately 15 months).	0.00% 0/3 • All AEs were reported during safety follow-up period (from the start of study treatment [Day 1] through 60 days after the last dose of MEDI-573 or initiation of another anticancer therapy, whichever occurred first) (approximately 15 months).
Respiratory, thoracic and mediastinal disorders Cough	66.7% 2/3 • Number of events 4 • All AEs were reported during safety follow-up period (from the start of study treatment [Day 1] through 60 days after the last dose of MEDI-573 or initiation of another anticancer therapy, whichever occurred first) (approximately 15 months).	0.00% 0/3 • All AEs were reported during safety follow-up period (from the start of study treatment [Day 1] through 60 days after the last dose of MEDI-573 or initiation of another anticancer therapy, whichever occurred first) (approximately 15 months).
Respiratory, thoracic and mediastinal disorders Hypoxia	33.3% 1/3 • Number of events 1 • All AEs were reported during safety follow-up period (from the start of study treatment [Day 1] through 60 days after the last dose of MEDI-573 or initiation of another anticancer therapy, whichever occurred first) (approximately 15 months).	0.00% 0/3 • All AEs were reported during safety follow-up period (from the start of study treatment [Day 1] through 60 days after the last dose of MEDI-573 or initiation of another anticancer therapy, whichever occurred first) (approximately 15 months).
Respiratory, thoracic and mediastinal disorders Pleural effusion	66.7% 2/3 • Number of events 2 • All AEs were reported during safety follow-up period (from the start of study treatment [Day 1] through 60 days after the last dose of MEDI-573 or initiation of another anticancer therapy, whichever occurred first) (approximately 15 months).	0.00% 0/3 • All AEs were reported during safety follow-up period (from the start of study treatment [Day 1] through 60 days after the last dose of MEDI-573 or initiation of another anticancer therapy, whichever occurred first) (approximately 15 months).
Skin and subcutaneous tissue disorders Dermatitis acneiform	33.3% 1/3 • Number of events 3 • All AEs were reported during safety follow-up period (from the start of study treatment [Day 1] through 60 days after the last dose of MEDI-573 or initiation of another anticancer therapy, whichever occurred first) (approximately 15 months).	33.3% 1/3 • Number of events 1 • All AEs were reported during safety follow-up period (from the start of study treatment [Day 1] through 60 days after the last dose of MEDI-573 or initiation of another anticancer therapy, whichever occurred first) (approximately 15 months).
Skin and subcutaneous tissue disorders Erythema	0.00% 0/3 • All AEs were reported during safety follow-up period (from the start of study treatment [Day 1] through 60 days after the last dose of MEDI-573 or initiation of another anticancer therapy, whichever occurred first) (approximately 15 months).	33.3% 1/3 • Number of events 1 • All AEs were reported during safety follow-up period (from the start of study treatment [Day 1] through 60 days after the last dose of MEDI-573 or initiation of another anticancer therapy, whichever occurred first) (approximately 15 months).
Skin and subcutaneous tissue disorders Palmar-plantar erythrodysaesthesia syndrome	0.00% 0/3 • All AEs were reported during safety follow-up period (from the start of study treatment [Day 1] through 60 days after the last dose of MEDI-573 or initiation of another anticancer therapy, whichever occurred first) (approximately 15 months).	33.3% 1/3 • Number of events 1 • All AEs were reported during safety follow-up period (from the start of study treatment [Day 1] through 60 days after the last dose of MEDI-573 or initiation of another anticancer therapy, whichever occurred first) (approximately 15 months).
Skin and subcutaneous tissue disorders Pruritus	0.00% 0/3 • All AEs were reported during safety follow-up period (from the start of study treatment [Day 1] through 60 days after the last dose of MEDI-573 or initiation of another anticancer therapy, whichever occurred first) (approximately 15 months).	66.7% 2/3 • Number of events 3 • All AEs were reported during safety follow-up period (from the start of study treatment [Day 1] through 60 days after the last dose of MEDI-573 or initiation of another anticancer therapy, whichever occurred first) (approximately 15 months).
Skin and subcutaneous tissue disorders Rash	0.00% 0/3 • All AEs were reported during safety follow-up period (from the start of study treatment [Day 1] through 60 days after the last dose of MEDI-573 or initiation of another anticancer therapy, whichever occurred first) (approximately 15 months).	33.3% 1/3 • Number of events 2 • All AEs were reported during safety follow-up period (from the start of study treatment [Day 1] through 60 days after the last dose of MEDI-573 or initiation of another anticancer therapy, whichever occurred first) (approximately 15 months).
Vascular disorders Diastolic hypertension	0.00% 0/3 • All AEs were reported during safety follow-up period (from the start of study treatment [Day 1] through 60 days after the last dose of MEDI-573 or initiation of another anticancer therapy, whichever occurred first) (approximately 15 months).	33.3% 1/3 • Number of events 1 • All AEs were reported during safety follow-up period (from the start of study treatment [Day 1] through 60 days after the last dose of MEDI-573 or initiation of another anticancer therapy, whichever occurred first) (approximately 15 months).
Vascular disorders Haematoma	33.3% 1/3 • Number of events 1 • All AEs were reported during safety follow-up period (from the start of study treatment [Day 1] through 60 days after the last dose of MEDI-573 or initiation of another anticancer therapy, whichever occurred first) (approximately 15 months).	0.00% 0/3 • All AEs were reported during safety follow-up period (from the start of study treatment [Day 1] through 60 days after the last dose of MEDI-573 or initiation of another anticancer therapy, whichever occurred first) (approximately 15 months).
Vascular disorders Hypertension	0.00% 0/3 • All AEs were reported during safety follow-up period (from the start of study treatment [Day 1] through 60 days after the last dose of MEDI-573 or initiation of another anticancer therapy, whichever occurred first) (approximately 15 months).	66.7% 2/3 • Number of events 2 • All AEs were reported during safety follow-up period (from the start of study treatment [Day 1] through 60 days after the last dose of MEDI-573 or initiation of another anticancer therapy, whichever occurred first) (approximately 15 months).

Additional Information

Mohammed Dar

MedImmune LLC

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Email: information.center@astrazeneca.com

Results disclosure agreements

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