Trial Outcomes & Findings for Moxetumomab Pasudotox for Advanced Hairy Cell Leukemia (NCT NCT01829711)

NCT ID: NCT01829711

Last Updated: 2020-04-08

Results Overview

Durable CR was defined as overall response that meets blood, bone marrow and imaging criteria for CR, followed by a \>180 day duration of hematologic remission (HR). CR requires all of the following to be present: No evidence of leukemic cells in peripheral blood and/or by routine H/E staining of bone marrow; Resolution of any hepatomegaly, splenomegaly, and abnormal (\>= 2 cm minimum length) lymphadenopathy by CT or MRI (maximum diameter of spleen should be either \< 17 cm or have decreased by \>25% from its baseline.); HR requires normal complete blood count (CBC) as exhibited by: Neutrophils \>= 1.5 x 10\^9/L, Platelets \>= 100 x 10\^9/L, and hemoglobin \>= 11.0 g/dL without transfusions or growth factors for at least 4 weeks.

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 80 participants
• Primary outcome timeframe: Full disease assessment (CBC, bone marrow and imaging) at end of treatment (EOT; up to 24 weeks) and post EOT Day 181; CBC monthly for 6 months post EOT, every 3 months post Day 181 for first 2 years and every 6 months thereafter (approximately 6 years)
• Results posted on: 2020-04-08

Participant Flow

The study was conducted across 14 countries (the USA, France, Italy, Germany, Belgium, Canada, Czech Republic, Ireland, Israel, Norway, Poland, Serbia, Spain, and United Kingdom).

Participant milestones

Measure	Moxetumomab Pasudotox 40 µg/kg Participants received intravenous infusion of moxetumomab pasudotox 40 µg/kg on Days 1, 3, and 5 of each 28-day cycle for up to 6 cycles, until documentation of complete response, progressive disease, initiation of alternate therapy, or unacceptable toxicity.
Overall Study STARTED	80
Overall Study COMPLETED	37
Overall Study NOT COMPLETED	43

Reasons for withdrawal

Measure	Moxetumomab Pasudotox 40 µg/kg Participants received intravenous infusion of moxetumomab pasudotox 40 µg/kg on Days 1, 3, and 5 of each 28-day cycle for up to 6 cycles, until documentation of complete response, progressive disease, initiation of alternate therapy, or unacceptable toxicity.
Overall Study Lost to Follow-up	2
Overall Study Withdrawal by Subject	3
Overall Study Death	4
Overall Study Started new therapies	17
Overall Study Adverse Event	3
Overall Study Due to progression of disease	13
Overall Study Due to lack of response	1

Baseline Characteristics

Moxetumomab Pasudotox for Advanced Hairy Cell Leukemia

Baseline characteristics by cohort

Measure	Moxetumomab Pasudotox 40 µg/kg n=80 Participants Participants received intravenous infusion of moxetumomab pasudotox 40 µg/kg on Days 1, 3, and 5 of each 28-day cycle for up to 6 cycles, until documentation of complete response, progressive disease, initiation of alternate therapy, or unacceptable toxicity.
Age, Continuous	60.3 Years STANDARD_DEVIATION 11.9 • n=5 Participants
Sex: Female, Male Female	17 Participants n=5 Participants
Sex: Female, Male Male	63 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	5 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	67 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	8 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants
Race (NIH/OMB) Asian	1 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	1 Participants n=5 Participants
Race (NIH/OMB) White	70 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	8 Participants n=5 Participants

PRIMARY outcome

Timeframe: Full disease assessment (CBC, bone marrow and imaging) at end of treatment (EOT; up to 24 weeks) and post EOT Day 181; CBC monthly for 6 months post EOT, every 3 months post Day 181 for first 2 years and every 6 months thereafter (approximately 6 years)

Population: The ITT population included participants who entered into the study and treated with moxetumomab pasudotox.

Durable CR was defined as overall response that meets blood, bone marrow and imaging criteria for CR, followed by a >180 day duration of hematologic remission (HR). CR requires all of the following to be present: No evidence of leukemic cells in peripheral blood and/or by routine H/E staining of bone marrow; Resolution of any hepatomegaly, splenomegaly, and abnormal (>= 2 cm minimum length) lymphadenopathy by CT or MRI (maximum diameter of spleen should be either < 17 cm or have decreased by >25% from its baseline.); HR requires normal complete blood count (CBC) as exhibited by: Neutrophils >= 1.5 x 10^9/L, Platelets >= 100 x 10^9/L, and hemoglobin >= 11.0 g/dL without transfusions or growth factors for at least 4 weeks.

Outcome measures

Measure	Moxetumomab Pasudotox 40 µg/kg n=80 Participants Participants received intravenous infusion of moxetumomab pasudotox 40 µg/kg on Days 1, 3, and 5 of each 28-day cycle for up to 6 cycles, until documentation of complete response, progressive disease, initiation of alternate therapy, or unacceptable toxicity.
Percentage of Participants With Durable Complete Response (CR) Assessed by Blinded Independent Central Review	36.3 Percentage of participants Interval 25.8 to 47.8

PRIMARY outcome

Timeframe: Full disease assessment (CBC, bone marrow and imaging) at end of treatment (EOT; up to 24 weeks) and post EOT Day 181; CBC monthly for 6 months post EOT, every 3 months post Day 181 for first 2 years and every 6 months thereafter (approximately 6 years)

Population: The ITT population included participants who entered into the study and treated with moxetumomab pasudotox.

Durable CR was defined as overall response that meets blood, bone marrow and imaging criteria for CR, followed by a >180 day duration of HR. CR requires all of the following to be present: No evidence of leukemic cells in peripheral blood and/or by routine H/E staining of bone marrow; Resolution of any hepatomegaly, splenomegaly, and abnormal (>= 2 cm minimum length) lymphadenopathy by CT or MRI (maximum diameter of spleen should be either < 17 cm or have decreased by >25% from its baseline.); HR requires normal complete blood count (CBC) as exhibited by: Neutrophils >= 1.5 x 10^9/L, Platelets >= 100 x 10^9/L, and hemoglobin >= 11.0 g/dL without transfusions or growth factors for at least 4 weeks.

Outcome measures

Measure	Moxetumomab Pasudotox 40 µg/kg n=80 Participants Participants received intravenous infusion of moxetumomab pasudotox 40 µg/kg on Days 1, 3, and 5 of each 28-day cycle for up to 6 cycles, until documentation of complete response, progressive disease, initiation of alternate therapy, or unacceptable toxicity.
Percentage of Participants With Durable CR by Investigator's Assessment	48.8 Percentage of participants Interval 37.4 to 60.2

SECONDARY outcome

Timeframe: Prior to each treatment cycle, EOT (up to 24 weeks), monthly from the EOT assessment until the Day 181 assessment (only for CBC), at follow-up visits every 3 months for the next 24 months, and every 6 months thereafter (approximately 6 years)

Population: The ITT population included participants who entered into the study and treated with moxetumomab pasudotox.

The MRD status by blinded independent review refers specifically to results of central pathologist read of bone marrow biopsy by immunohistochemistry.

The CR with Positive or Negative MRD requires all of the following to be present:

• No evidence of leukemic cells in the peripheral blood and/or by routine H/E staining of bone marrow. Minimal Residual Disease: CR with HCL evident in blood or in bone marrow biopsy by immunohistochemistry.
• Resolution of any hepatomegaly, splenomegaly, and abnormal (>= 2 cm minimum length) lymphadenopathy by CT or MRI. Although a normal spleen size is not defined, the maximum diameter of the spleen should be either < 17 cm or have decreased by >25% from its baseline.
• Normal CBC as exhibited by: Neutrophils >= 1.5 x 10^9/L, Platelets >= 100 x 10^9/L, and hemoglobin >= 11.0 g/dL without transfusions or growth factors for at least 4 weeks.

Outcome measures

Measure	Moxetumomab Pasudotox 40 µg/kg n=80 Participants Participants received intravenous infusion of moxetumomab pasudotox 40 µg/kg on Days 1, 3, and 5 of each 28-day cycle for up to 6 cycles, until documentation of complete response, progressive disease, initiation of alternate therapy, or unacceptable toxicity.
Percentage of Participants With Minimal Residual Disease (MRD) Positive or MRD Negative CR Assessed by Blinded Independent Central Review MRD negative CR	33.8 Percentage of participants Interval 23.6 to 45.2
Percentage of Participants With Minimal Residual Disease (MRD) Positive or MRD Negative CR Assessed by Blinded Independent Central Review MRD positive CR	7.5 Percentage of participants Interval 2.8 to 15.6

SECONDARY outcome

Timeframe: Prior to each treatment cycle, end of treatment, and at follow-up visits every 3 months for the next 24 months and every 6 months thereafter (Approximately 6 years)

Population: The ITT population included participants who entered into the study and treated with moxetumomab pasudotox.

The MRD status by investigator refers to results of investigator assessment of bone marrow biopsy or bone marrow aspirate by immunohistochemistry and/or flow cytometry.

The CR with Positive or Negative MRD requires all of the following to be present:

• No evidence of leukemic cells in the peripheral blood and/or by routine H/E staining of bone marrow. Minimal Residual Disease: CR with HCL evident in blood or marrow by flow cytometry.
• Resolution of any hepatomegaly, splenomegaly, and abnormal (>= 2 cm minimum length) lymphadenopathy by CT or MRI. Although a normal spleen size is not defined, the maximum diameter of the spleen should be either < 17 cm or have decreased by >25% from its baseline.
• Normal CBC as exhibited by: Neutrophils >= 1.5 x 10^9/L, Platelets >= 100 x 10^9/L, and hemoglobin >= 11.0 g/dL without transfusions or growth factors for at least 4 weeks.

Outcome measures

Measure	Moxetumomab Pasudotox 40 µg/kg n=80 Participants Participants received intravenous infusion of moxetumomab pasudotox 40 µg/kg on Days 1, 3, and 5 of each 28-day cycle for up to 6 cycles, until documentation of complete response, progressive disease, initiation of alternate therapy, or unacceptable toxicity.
Percentage of Participants With MRD Positive or MRD Negative CR by Investigator's Assessment MRD negative CR	32.5 Percentage of participants Interval 22.4 to 43.9
Percentage of Participants With MRD Positive or MRD Negative CR by Investigator's Assessment MRD positive CR	7.5 Percentage of participants Interval 2.8 to 15.6

SECONDARY outcome

Timeframe: Prior to each treatment cycle, EOT (up to 24 weeks), monthly from the EOT assessment until the Day 181 assessment (only for CBC), at follow-up visits every 3 months for the next 24 months, and every 6 months thereafter (approximately 6 years)

Population: The ITT population included participants who entered into the study and treated with moxetumomab pasudotox. Time to CR was evaluated for participants who achieved CR per independent central review.

Time to CR was defined as the time from the start of moxetumomab pasudotox administration to the first documentation of CR.

Outcome measures

Measure	Moxetumomab Pasudotox 40 µg/kg n=80 Participants Participants received intravenous infusion of moxetumomab pasudotox 40 µg/kg on Days 1, 3, and 5 of each 28-day cycle for up to 6 cycles, until documentation of complete response, progressive disease, initiation of alternate therapy, or unacceptable toxicity.
Time to CR Assessed by Blinded Independent Central Review	5.9 Months Interval 1.8 to 13.2

SECONDARY outcome

Timeframe: Prior to each treatment cycle, EOT (up to 24 weeks), monthly from the EOT assessment until the Day 181 assessment (only for CBC), at follow-up visits every 3 months for the next 24 months, and every 6 months thereafter (approximately 6 years)

Population: The ITT population included participants who entered into the study and treated with moxetumomab pasudotox. Duration of CR was evaluated for participants who achieved CR per independent central review.

Duration of CR was defined as the duration from documentation of CR to the time of relapse from CR. Relapse from CR was defined as any CR criteria (blood counts, imaging or bone marrow) no longer consistent with CR. CR requires all of the following to be present: No evidence of leukemic cells in peripheral blood and/or by routine H/E staining of bone marrow; Resolution of any hepatomegaly, splenomegaly, and abnormal (>= 2 cm minimum length) lymphadenopathy by CT or MRI (maximum diameter of spleen should be either < 17 cm or have decreased by >25% from its baseline); normal CBC as exhibited by: Neutrophils >= 1.5 x 10^9/L, Platelets >= 100 x 10^9/L, and hemoglobin >= 11.0 g/dL without transfusions or growth factors for at least 4 weeks.

Outcome measures

Measure	Moxetumomab Pasudotox 40 µg/kg n=80 Participants Participants received intravenous infusion of moxetumomab pasudotox 40 µg/kg on Days 1, 3, and 5 of each 28-day cycle for up to 6 cycles, until documentation of complete response, progressive disease, initiation of alternate therapy, or unacceptable toxicity.
Duration of CR Assessed by Blinded Independent Central Review	62.8 Months Interval 35.7 to 62.8

SECONDARY outcome

Timeframe: Prior to each treatment cycle, EOT (up to 24 weeks), monthly from the EOT assessment until the Day 181 assessment (only for CBC), at follow-up visits every 3 months for the next 24 months, and every 6 months thereafter (approximately 6 years)

Population: The ITT population included participants who entered into the study and treated with moxetumomab pasudotox. Duration of HR was evaluated for participants who achieved HR.

Duration of HR was defined as the duration from documentation of HR to the time of relapse. HR was defined as the blood counts required for CR as normal CBC as exhibited by: Neutrophils >= 1.5 x 10^9/L, Platelets >= 100 x 10^9/L, and hemoglobin >= 11.0 g/dL without transfusions or growth factors for at least 4 weeks.

Duration of HR was censored on the date of the last hematologic assessment for participants who have no documented relapse based on blood count prior to data cutoff, dropout, or initiation of alternative anticancer therapy.

Outcome measures

Measure	Moxetumomab Pasudotox 40 µg/kg n=80 Participants Participants received intravenous infusion of moxetumomab pasudotox 40 µg/kg on Days 1, 3, and 5 of each 28-day cycle for up to 6 cycles, until documentation of complete response, progressive disease, initiation of alternate therapy, or unacceptable toxicity.
Duration of Hematologic Remission	45.8 Months Interval 25.9 to 71.5

SECONDARY outcome

Timeframe: Prior to each treatment cycle, EOT (up to 24 weeks), monthly from the EOT assessment until the Day 181 assessment (only for CBC), at follow-up visits every 3 months for the next 24 months, and every 6 months thereafter (approximately 6 years)

Population: The ITT population included participants who entered into the study and treated with moxetumomab pasudotox. Time to HR was evaluated for participants in the ITT population who achieved HR.

Time to HR was defined as the time from the start of moxetumomab pasudotox administration to the first documentation of HR. HR was defined as the blood counts required for CR as normal CBC as exhibited by: Neutrophils >= 1.5 x 10^9/L, Platelets >= 100 x 10^9/L, and hemoglobin >= 11.0 g/dL without transfusions or growth factors for at least 4 weeks.

Outcome measures

Measure	Moxetumomab Pasudotox 40 µg/kg n=80 Participants Participants received intravenous infusion of moxetumomab pasudotox 40 µg/kg on Days 1, 3, and 5 of each 28-day cycle for up to 6 cycles, until documentation of complete response, progressive disease, initiation of alternate therapy, or unacceptable toxicity.
Time to Hematologic Remission	1.1 Months Interval 0.2 to 12.9

SECONDARY outcome

Timeframe: Prior to each treatment cycle, EOT (up to 24 weeks), monthly from the EOT assessment until the Day 181 assessment (only for CBC), at follow-up visits every 3 months for the next 24 months, and every 6 months thereafter (approximately 6 years)

Population: The ITT population included participants who entered into the study and treated with moxetumomab pasudotox.

The OR was defined as number of participants with a best response of CR or PR. CR requires all of following to be present: No evidence of leukemic cells in peripheral blood and/or by routine H/E staining of bone marrow; Resolution of any hepatomegaly, splenomegaly, and abnormal (>=2 cm minimum length) lymphadenopathy by CT or MRI (maximum diameter of spleen should be either <17 cm or have decreased by >25% from its baseline); normal CBC (Neutrophils >=1.5 x 10^9/L, Platelets >=100 x 10^9/L, and hemoglobin >=11.0 g/dL) without transfusions or growth factors for at least 4 weeks. PR requires all of following for a period of at least 4 weeks: >=50% decrease or normalization (<5.0 x 10^9/L) in peripheral blood lymphocyte count and >=50% reduction in lymphadenopathy and in abnormal haepatosplenomegaly by CT or MRI from pre-treatment baseline value; normal CBC as mentioned above or 50% improvement in CBC values over baseline without transfusions or growth factors for at least 4 weeks.

Outcome measures

Measure	Moxetumomab Pasudotox 40 µg/kg n=80 Participants Participants received intravenous infusion of moxetumomab pasudotox 40 µg/kg on Days 1, 3, and 5 of each 28-day cycle for up to 6 cycles, until documentation of complete response, progressive disease, initiation of alternate therapy, or unacceptable toxicity.
Percentage of Participants With Objective Response (OR) Assessed by Blinded Independent Central Review	75.0 Percentage of participants Interval 64.1 to 84.0

SECONDARY outcome

Timeframe: Prior to each treatment cycle, end of treatment, and at follow-up visits every 3 months for the next 24 months and every 6 months thereafter (Approximately 6 years)

Population: The ITT population included participants who entered into the study and treated with moxetumomab pasudotox.

The OR was defined as number of participants with a best response of CR or PR. CR requires all of following to be present: No evidence of leukemic cells in peripheral blood and/or by routine H/E staining of bone marrow; Resolution of any hepatomegaly, splenomegaly, and abnormal (>=2 cm minimum length) lymphadenopathy by CT or MRI (maximum diameter of spleen should be either <17 cm or have decreased by >25% from its baseline); normal CBC (Neutrophils >=1.5 x 10^9/L, Platelets >=100 x 10^9/L, and hemoglobin >=11.0 g/dL) without transfusions or growth factors for at least 4 weeks. PR requires all of following for a period of at least 4 weeks: >=50% decrease or normalization (<5.0 x 10^9/L) in peripheral blood lymphocyte count and >=50% reduction in lymphadenopathy and in abnormal haepatosplenomegaly by CT or MRI from pre-treatment baseline value; normal CBC as mentioned above or 50% improvement in CBC values over baseline without transfusions or growth factors for at least 4 weeks.

Outcome measures

Measure	Moxetumomab Pasudotox 40 µg/kg n=80 Participants Participants received intravenous infusion of moxetumomab pasudotox 40 µg/kg on Days 1, 3, and 5 of each 28-day cycle for up to 6 cycles, until documentation of complete response, progressive disease, initiation of alternate therapy, or unacceptable toxicity.
Percentage of Participants With Objective Response by Investigator's Assessment	78.8 Percentage of participants Interval 68.2 to 87.1

SECONDARY outcome

Timeframe: Prior to each treatment cycle, EOT (up to 24 weeks), monthly from the EOT assessment until the Day 181 assessment (only for CBC), at follow-up visits every 3 months for the next 24 months, and every 6 months thereafter (approximately 6 years)

Population: The ITT population included participants who entered into the study and treated with moxetumomab pasudotox. Time to OR was evaluated for participants who achieved OR per independent central review.

Time to OR was defined as the time from the start of moxetumomab pasudotox administration to the first documentation of OR (CR or PR).

Outcome measures

Measure	Moxetumomab Pasudotox 40 µg/kg n=80 Participants Participants received intravenous infusion of moxetumomab pasudotox 40 µg/kg on Days 1, 3, and 5 of each 28-day cycle for up to 6 cycles, until documentation of complete response, progressive disease, initiation of alternate therapy, or unacceptable toxicity.
Time to Objective Response Assessed by Blinded Independent Central Review	5.7 Months Interval 1.8 to 12.9

SECONDARY outcome

Timeframe: Prior to each treatment cycle, EOT (up to 24 weeks), monthly from the EOT assessment until the Day 181 assessment (only for CBC), at follow-up visits every 3 months for the next 24 months, and every 6 months thereafter (approximately 6 years)

Population: The ITT population included participants who entered into the study and treated with moxetumomab pasudotox. Duration of OR was evaluated for participants who achieved OR per independent central review.

Duration of OR was defined as the time from the first documentation of objective response (CR or PR) to the date of relapse.

Duration of OR was censored on the date of last disease assessment or hematologic assessment for participants who have no documented relapse prior to data cut-off, dropout, or the initiation of alternative anticancer therapy.

Outcome measures

Measure	Moxetumomab Pasudotox 40 µg/kg n=80 Participants Participants received intravenous infusion of moxetumomab pasudotox 40 µg/kg on Days 1, 3, and 5 of each 28-day cycle for up to 6 cycles, until documentation of complete response, progressive disease, initiation of alternate therapy, or unacceptable toxicity.
Duration of Objective Response Assessed by Blinded Independent Central Review	66.7 Months Interval 25.4 to 66.7

SECONDARY outcome

Timeframe: Prior to each treatment cycle, EOT (up to 24 weeks), monthly from the EOT assessment until the Day 181 assessment (only for CBC), at follow-up visits every 3 months for the next 24 months, and every 6 months thereafter (approximately 6 years)

Population: The ITT population included participants who entered into the study and treated with moxetumomab pasudotox.

The PFS was defined as the time from the start of moxetumomab pasudotox administration to the earliest date of a disease assessment showing a progressive disease/relapse, earliest date of hematologic relapse or date of death, whichever was earlier. The PFS was censored on the date of last disease assessment or hematologic assessment for participants who are alive with no documented relapse or PD prior to data cut-off, dropout, or the initiation of alternative anticancer therapy.

Outcome measures

Measure	Moxetumomab Pasudotox 40 µg/kg n=80 Participants Participants received intravenous infusion of moxetumomab pasudotox 40 µg/kg on Days 1, 3, and 5 of each 28-day cycle for up to 6 cycles, until documentation of complete response, progressive disease, initiation of alternate therapy, or unacceptable toxicity.
Progression-free Survival (PFS) Assessed by Blinded Independent Central Review	41.5 Months Interval 28.1 to 71.7

SECONDARY outcome

Timeframe: Prior to each treatment cycle, EOT (up to 24 weeks), monthly from the EOT assessment until the Day 181 assessment (only for CBC), at follow-up visits every 3 months for the next 24 months, and every 6 months thereafter (approximately 6 years)

Population: The ITT population included participants who entered into the study and treated with moxetumomab pasudotox.

The TTF was defined as the time from the start of moxetumomab pasudotox administration to the date of the first of relapse, progressive disease, initiation of alternative anticancer therapy, or death due to disease or disease-related complication. The TTF was censored on the date of last disease assessment or hematologic assessment for participants who are alive with no documented relapse or PD prior to data cut-off, dropout, or the initiation of alternative anticancer therapy and also censored for death not accompanied by relapse.

Outcome measures

Measure	Moxetumomab Pasudotox 40 µg/kg n=80 Participants Participants received intravenous infusion of moxetumomab pasudotox 40 µg/kg on Days 1, 3, and 5 of each 28-day cycle for up to 6 cycles, until documentation of complete response, progressive disease, initiation of alternate therapy, or unacceptable toxicity.
Time to Treatment Failure (TTF) Assessed by Blinded Independent Central Review	41.5 Months Interval 28.1 to 71.7

SECONDARY outcome

Timeframe: From the start of study treatment (Day 1) through 4-6 weeks after last dose of Cycle 6 (28-day cycle) (approximately 7 months)

Population: Safety population included participants who received at least 1 dose of moxetumomab pasudotox.

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. TEAEs and TESAEs are defined as AEs and SAEs present at baseline that worsened in intensity after administration of study drug, or events absent at baseline that emerged after administration of study drug.

Outcome measures

Measure	Moxetumomab Pasudotox 40 µg/kg n=80 Participants Participants received intravenous infusion of moxetumomab pasudotox 40 µg/kg on Days 1, 3, and 5 of each 28-day cycle for up to 6 cycles, until documentation of complete response, progressive disease, initiation of alternate therapy, or unacceptable toxicity.
Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs) Any TEAEs	79 Participants
Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs) Any TESAEs	28 Participants

SECONDARY outcome

Timeframe: From the start of study treatment (Day 1) through 4-6 weeks after last dose of Cycle 6 (28-day cycle) (approximately 7 months)

Population: Safety population included participants who received at least 1 dose of moxetumomab pasudotox.

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 30 days after the last dose of study drug (approximately 7 months).

Outcome measures

Measure	Moxetumomab Pasudotox 40 µg/kg n=80 Participants Participants received intravenous infusion of moxetumomab pasudotox 40 µg/kg on Days 1, 3, and 5 of each 28-day cycle for up to 6 cycles, until documentation of complete response, progressive disease, initiation of alternate therapy, or unacceptable toxicity.
Number of Participants With Abnormal Clinical Laboratory Results Reported as TEAEs Anaemia	17 Participants
Number of Participants With Abnormal Clinical Laboratory Results Reported as TEAEs Disseminated intravascular coagulation	1 Participants
Number of Participants With Abnormal Clinical Laboratory Results Reported as TEAEs Febrile neutropenia	5 Participants
Number of Participants With Abnormal Clinical Laboratory Results Reported as TEAEs Iron deficiency anaemia	1 Participants
Number of Participants With Abnormal Clinical Laboratory Results Reported as TEAEs Leukopenia	2 Participants
Number of Participants With Abnormal Clinical Laboratory Results Reported as TEAEs Lymphopenia	1 Participants
Number of Participants With Abnormal Clinical Laboratory Results Reported as TEAEs Neutropenia	4 Participants
Number of Participants With Abnormal Clinical Laboratory Results Reported as TEAEs Thrombocytopenia	3 Participants
Number of Participants With Abnormal Clinical Laboratory Results Reported as TEAEs Activated partial thromboplastin time prolonged	1 Participants
Number of Participants With Abnormal Clinical Laboratory Results Reported as TEAEs Lymphocyte count decreased	16 Participants
Number of Participants With Abnormal Clinical Laboratory Results Reported as TEAEs Lymphocyte count increased	1 Participants
Number of Participants With Abnormal Clinical Laboratory Results Reported as TEAEs Neutrophil count decreased	6 Participants
Number of Participants With Abnormal Clinical Laboratory Results Reported as TEAEs Platelet count decreased	9 Participants
Number of Participants With Abnormal Clinical Laboratory Results Reported as TEAEs White blood cell count decreased	8 Participants
Number of Participants With Abnormal Clinical Laboratory Results Reported as TEAEs Aspartate aminotransferase increased	15 Participants
Number of Participants With Abnormal Clinical Laboratory Results Reported as TEAEs Blood albumin decreased	1 Participants
Number of Participants With Abnormal Clinical Laboratory Results Reported as TEAEs Blood alkaline phosphatase increased	4 Participants
Number of Participants With Abnormal Clinical Laboratory Results Reported as TEAEs Blood bicarbonate decreased	2 Participants
Number of Participants With Abnormal Clinical Laboratory Results Reported as TEAEs Blood bilirubin increased	5 Participants
Number of Participants With Abnormal Clinical Laboratory Results Reported as TEAEs Blood creatinine increased	9 Participants
Number of Participants With Abnormal Clinical Laboratory Results Reported as TEAEs Blood triglycerides increased	1 Participants
Number of Participants With Abnormal Clinical Laboratory Results Reported as TEAEs Gamma-glutamyltransferase increased	1 Participants
Number of Participants With Abnormal Clinical Laboratory Results Reported as TEAEs Lipase increased	2 Participants
Number of Participants With Abnormal Clinical Laboratory Results Reported as TEAEs Hyperglycaemia	8 Participants
Number of Participants With Abnormal Clinical Laboratory Results Reported as TEAEs Hyperkalaemia	6 Participants
Number of Participants With Abnormal Clinical Laboratory Results Reported as TEAEs Hypermagnesaemia	3 Participants
Number of Participants With Abnormal Clinical Laboratory Results Reported as TEAEs Hypernatraemia	4 Participants
Number of Participants With Abnormal Clinical Laboratory Results Reported as TEAEs Hypertriglyceridaemia	2 Participants
Number of Participants With Abnormal Clinical Laboratory Results Reported as TEAEs Hypoalbuminaemia	16 Participants
Number of Participants With Abnormal Clinical Laboratory Results Reported as TEAEs Hypocalcaemia	19 Participants
Number of Participants With Abnormal Clinical Laboratory Results Reported as TEAEs Hypoglycaemia	2 Participants
Number of Participants With Abnormal Clinical Laboratory Results Reported as TEAEs Hypokalaemia	13 Participants
Number of Participants With Abnormal Clinical Laboratory Results Reported as TEAEs Hypomagnesaemia	6 Participants
Number of Participants With Abnormal Clinical Laboratory Results Reported as TEAEs Hyponatraemia	9 Participants
Number of Participants With Abnormal Clinical Laboratory Results Reported as TEAEs Haematuria	6 Participants
Number of Participants With Abnormal Clinical Laboratory Results Reported as TEAEs Haemoglobinuria	2 Participants
Number of Participants With Abnormal Clinical Laboratory Results Reported as TEAEs Proteinuria	1 Participants

SECONDARY outcome

Timeframe: From the start of study treatment (Day 1) through 4-6 weeks after last dose of Cycle 6 (28-day cycle) (approximately 7 months)

Population: Safety population included participants who received at least 1 dose of moxetumomab pasudotox.

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 30 days after the last dose of study drug (approximately 7 months).

Outcome measures

Measure	Moxetumomab Pasudotox 40 µg/kg n=80 Participants Participants received intravenous infusion of moxetumomab pasudotox 40 µg/kg on Days 1, 3, and 5 of each 28-day cycle for up to 6 cycles, until documentation of complete response, progressive disease, initiation of alternate therapy, or unacceptable toxicity.
Number of Participants With Abnormal Vital Signs Reported as TEAEs Dyspnoea	9 Participants
Number of Participants With Abnormal Vital Signs Reported as TEAEs Dyspnoea exertional	3 Participants
Number of Participants With Abnormal Vital Signs Reported as TEAEs Hypertension	12 Participants
Number of Participants With Abnormal Vital Signs Reported as TEAEs Hypotension	6 Participants
Number of Participants With Abnormal Vital Signs Reported as TEAEs Pyrexia	25 Participants

SECONDARY outcome

Timeframe: From the start of study treatment (Day 1) through 4-6 weeks after last dose of Cycle 6 (28-day cycle) (approximately 7 months)

Population: Safety population included participants who received at least 1 dose of moxetumomab pasudotox.

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 30 days after the last dose of study drug (approximately 7 months).

Outcome measures

Measure	Moxetumomab Pasudotox 40 µg/kg n=80 Participants Participants received intravenous infusion of moxetumomab pasudotox 40 µg/kg on Days 1, 3, and 5 of each 28-day cycle for up to 6 cycles, until documentation of complete response, progressive disease, initiation of alternate therapy, or unacceptable toxicity.
Number of Participants With Abnormal Electrocardiogram (ECG) Reported as TEAEs Sinus bradycardia	2 Participants
Number of Participants With Abnormal Electrocardiogram (ECG) Reported as TEAEs Sinus tachycardia	6 Participants
Number of Participants With Abnormal Electrocardiogram (ECG) Reported as TEAEs Angina pectoris	2 Participants
Number of Participants With Abnormal Electrocardiogram (ECG) Reported as TEAEs Atrial fibrillation	1 Participants
Number of Participants With Abnormal Electrocardiogram (ECG) Reported as TEAEs Atrioventricular block first degree	3 Participants
Number of Participants With Abnormal Electrocardiogram (ECG) Reported as TEAEs Bundle branch block left	1 Participants
Number of Participants With Abnormal Electrocardiogram (ECG) Reported as TEAEs Left ventricular dysfunction	1 Participants
Number of Participants With Abnormal Electrocardiogram (ECG) Reported as TEAEs Palpitations	1 Participants
Number of Participants With Abnormal Electrocardiogram (ECG) Reported as TEAEs Pericardial effusion	1 Participants
Number of Participants With Abnormal Electrocardiogram (ECG) Reported as TEAEs Supraventricular tachycardia	1 Participants
Number of Participants With Abnormal Electrocardiogram (ECG) Reported as TEAEs Tachycardia	1 Participants
Number of Participants With Abnormal Electrocardiogram (ECG) Reported as TEAEs Ventricular arrhythmia	1 Participants

SECONDARY outcome

Timeframe: Cycle 1 Day 1 (pre-dose; 5 mins and 3 hr post dose); Cycle 1 Day 5 (pre-dose; 5 mins, 1 hr, 3 hr, and 6 hrs post dose); and Cycle 2 Day 1 (pre-dose; 5 mins and 3 hr post dose)

Population: Pharmacokinetic (PK) population included all participants who received at least 1 dose of moxetumomab pasudotox and provided at least 1 baseline and post-baseline concentration-time data point.

The Tmax of moxetumomab pasudotox is reported.

Outcome measures

Measure	Moxetumomab Pasudotox 40 µg/kg n=80 Participants Participants received intravenous infusion of moxetumomab pasudotox 40 µg/kg on Days 1, 3, and 5 of each 28-day cycle for up to 6 cycles, until documentation of complete response, progressive disease, initiation of alternate therapy, or unacceptable toxicity.
Time to Reach Maximum Observed Plasma Concentration (Tmax) of Moxetumomab Pasudotox Cycle 1 Day 1	0.567 Hours Interval 0.433 to 1.3
Time to Reach Maximum Observed Plasma Concentration (Tmax) of Moxetumomab Pasudotox Cycle 1 Day 5	0.550 Hours Interval 0.417 to 2.45
Time to Reach Maximum Observed Plasma Concentration (Tmax) of Moxetumomab Pasudotox Cycle 2 Day 1	0.583 Hours Interval 0.5 to 1.75

SECONDARY outcome

Timeframe: Cycle 1 Day 1 (pre-dose; 5 mins and 3 hr post dose); Cycle 1 Day 5 (pre-dose; 5 mins, 1 hr, 3 hr, and 6 hrs post dose); and Cycle 2 Day 1 (pre-dose; 5 mins and 3 hr post dose)

Population: The PK population included all participants who received at least 1 dose of moxetumomab pasudotox and provided at least 1 baseline and post-baseline concentration-time data point.

The Cmax of moxetumomab pasudotox is reported.

Outcome measures

Measure	Moxetumomab Pasudotox 40 µg/kg n=80 Participants Participants received intravenous infusion of moxetumomab pasudotox 40 µg/kg on Days 1, 3, and 5 of each 28-day cycle for up to 6 cycles, until documentation of complete response, progressive disease, initiation of alternate therapy, or unacceptable toxicity.
Maximum Observed Plasma Concentration (Cmax) of Moxetumomab Pasudotox Cycle 1 Day 1	192 ng/mL Standard Deviation 162
Maximum Observed Plasma Concentration (Cmax) of Moxetumomab Pasudotox Cycle 1 Day 5	435 ng/mL Standard Deviation 233
Maximum Observed Plasma Concentration (Cmax) of Moxetumomab Pasudotox Cycle 2 Day 1	379 ng/mL Standard Deviation 262

SECONDARY outcome

Timeframe: Cycle 1 Day 1 (pre-dose; 5 mins and 3 hr post dose); Cycle 1 Day 5 (pre-dose; 5 mins, 1 hr, 3 hr, and 6 hrs post dose); and Cycle 2 Day 1 (pre-dose; 5 mins and 3 hr post dose)

Population: The PK population included all participants who received at least 1 dose of moxetumomab pasudotox and provided at least 1 baseline and post-baseline concentration-time data point.

The Tlast of moxetumomab pasudotox is reported.

Outcome measures

Measure	Moxetumomab Pasudotox 40 µg/kg n=80 Participants Participants received intravenous infusion of moxetumomab pasudotox 40 µg/kg on Days 1, 3, and 5 of each 28-day cycle for up to 6 cycles, until documentation of complete response, progressive disease, initiation of alternate therapy, or unacceptable toxicity.
Time of Last (Tlast) Measurable Concentration of Moxetumomab Pasudotox Cycle 1 Day 1	0.841 Hours Standard Deviation 0.866
Time of Last (Tlast) Measurable Concentration of Moxetumomab Pasudotox Cycle 1 Day 5	3.37 Hours Standard Deviation 2.38
Time of Last (Tlast) Measurable Concentration of Moxetumomab Pasudotox Cycle 2 Day 1	2.16 Hours Standard Deviation 1.43

SECONDARY outcome

Timeframe: Cycle 1 Day 1 (pre-dose; 5 mins and 3 hr post dose); Cycle 1 Day 5 (pre-dose; 5 mins, 1 hr, 3 hr, and 6 hrs post dose); and Cycle 2 Day 1 (pre-dose; 5 mins and 3 hr post dose)

Population: The PK population included all participants who received at least 1 dose of moxetumomab pasudotox and provided at least 1 baseline and post-baseline concentration-time data point.

The AUC0-last of moxetumomab pasudotox is reported.

Outcome measures

Measure	Moxetumomab Pasudotox 40 µg/kg n=80 Participants Participants received intravenous infusion of moxetumomab pasudotox 40 µg/kg on Days 1, 3, and 5 of each 28-day cycle for up to 6 cycles, until documentation of complete response, progressive disease, initiation of alternate therapy, or unacceptable toxicity.
Area Under the Plasma Concentration-time Curve From Time Zero to Time of the Last Quantifiable Concentration (AUC0-last) of Moxetumomab Pasudotox Cycle 1 Day 1	120 ng*hr/mL Standard Deviation 261
Area Under the Plasma Concentration-time Curve From Time Zero to Time of the Last Quantifiable Concentration (AUC0-last) of Moxetumomab Pasudotox Cycle 1 Day 5	820 ng*hr/mL Standard Deviation 721
Area Under the Plasma Concentration-time Curve From Time Zero to Time of the Last Quantifiable Concentration (AUC0-last) of Moxetumomab Pasudotox Cycle 2 Day 1	626 ng*hr/mL Standard Deviation 610

SECONDARY outcome

Timeframe: Cycle 1 Day 1 (pre-dose; 5 mins and 3 hr post dose); Cycle 1 Day 5 (pre-dose; 5 mins, 1 hr, and 3 hr post dose); and Cycle 2 Day 1 (pre-dose; 5 mins and 3 hr post dose)

Population: The PK population included all participants who received at least 1 dose of moxetumomab pasudotox and provided at least 1 baseline and post-baseline concentration-time data point.

The AUC0-3hr of moxetumomab pasudotox is reported.

Outcome measures

Measure	Moxetumomab Pasudotox 40 µg/kg n=80 Participants Participants received intravenous infusion of moxetumomab pasudotox 40 µg/kg on Days 1, 3, and 5 of each 28-day cycle for up to 6 cycles, until documentation of complete response, progressive disease, initiation of alternate therapy, or unacceptable toxicity.
Area Under the Plasma Concentration-time Curve From Time Zero to 3 Hours (AUC0-3hr) Post End of Moxetumomab Pasudotox Cycle 2 Day 1	1030 ng*hr/mL Standard Deviation 333
Area Under the Plasma Concentration-time Curve From Time Zero to 3 Hours (AUC0-3hr) Post End of Moxetumomab Pasudotox Cycle 1 Day 1	869 ng*hr/mL Standard Deviation 200
Area Under the Plasma Concentration-time Curve From Time Zero to 3 Hours (AUC0-3hr) Post End of Moxetumomab Pasudotox Cycle 1 Day 5	856 ng*hr/mL Standard Deviation 370

SECONDARY outcome

Timeframe: Cycle 1 Day 1 (pre-dose; 5 mins and 3 hr post dose); Cycle 1 Day 5 (pre-dose; 5 mins, 1 hr, 3 hr, and 6 hrs post dose); and Cycle 2 Day 1 (pre-dose; 5 mins and 3 hr post dose)

Population: The PK population included all participants who received at least 1 dose of moxetumomab pasudotox and provided at least 1 baseline and post-baseline concentration-time data point. Data for Cycle 1 Day 1 was not reported as no evaluable participants for the calculation of the concerned parameters (ie., data were not sufficient).

The AUC0-inf of moxetumomab pasudotox is reported.

Outcome measures

Measure	Moxetumomab Pasudotox 40 µg/kg n=80 Participants Participants received intravenous infusion of moxetumomab pasudotox 40 µg/kg on Days 1, 3, and 5 of each 28-day cycle for up to 6 cycles, until documentation of complete response, progressive disease, initiation of alternate therapy, or unacceptable toxicity.
Area Under the Plasma Concentration-time Curve From Time Zero to Infinity (AUC0-inf) of Moxetumomab Pasudotox Cycle 1 Day 5	1300 ng*hr/mL Standard Deviation 742
Area Under the Plasma Concentration-time Curve From Time Zero to Infinity (AUC0-inf) of Moxetumomab Pasudotox Cycle 2 Day 1	1470 ng*hr/mL Standard Deviation 541

SECONDARY outcome

Timeframe: Cycle 1 Day 1 (pre-dose; 5 mins and 3 hr post dose); Cycle 1 Day 5 (pre-dose; 5 mins, 1 hr, 3 hr, and 6 hrs post dose); and Cycle 2 Day 1 (pre-dose; 5 mins and 3 hr post dose)

Population: The PK population included all participants who received at least 1 dose of moxetumomab pasudotox and provided at least 1 baseline and post-baseline concentration-time data point.

The AUCExt of moxetumomab pasudotox is reported.

Outcome measures

Measure	Moxetumomab Pasudotox 40 µg/kg n=80 Participants Participants received intravenous infusion of moxetumomab pasudotox 40 µg/kg on Days 1, 3, and 5 of each 28-day cycle for up to 6 cycles, until documentation of complete response, progressive disease, initiation of alternate therapy, or unacceptable toxicity.
Area Under the Plasma Concentration-time Curve Extrapolated (AUCExt) of Moxetumomab Pasudotox Cycle 1 Day 1	13.2 ng*hr/mL Standard Deviation 3.04
Area Under the Plasma Concentration-time Curve Extrapolated (AUCExt) of Moxetumomab Pasudotox Cycle 1 Day 5	14.3 ng*hr/mL Standard Deviation 5.72
Area Under the Plasma Concentration-time Curve Extrapolated (AUCExt) of Moxetumomab Pasudotox Cycle 2 Day 1	20.2 ng*hr/mL Standard Deviation 7.62

SECONDARY outcome

Timeframe: Cycle 1 Day 1 (pre-dose; 5 mins and 3 hr post dose); Cycle 1 Day 5 (pre-dose; 5 mins, 1 hr, 3 hr, and 6 hrs post dose); and Cycle 2 Day 1 (pre-dose; 5 mins and 3 hr post dose)

Population: The PK population included all participants who received at least 1 dose of moxetumomab pasudotox and provided at least 1 baseline and post-baseline concentration-time data point. Data for Cycle 1 Day 1 was not reported as no evaluable participants for the calculation of the concerned parameters (ie., data were not sufficient).

The CL of moxetumomab pasudotox is reported.

Outcome measures

Measure	Moxetumomab Pasudotox 40 µg/kg n=80 Participants Participants received intravenous infusion of moxetumomab pasudotox 40 µg/kg on Days 1, 3, and 5 of each 28-day cycle for up to 6 cycles, until documentation of complete response, progressive disease, initiation of alternate therapy, or unacceptable toxicity.
Systemic Clearance (CL) of Moxetumomab Pasudotox Cycle 1 Day 5	44.6 mL/hr/kg Standard Deviation 30.5
Systemic Clearance (CL) of Moxetumomab Pasudotox Cycle 2 Day 1	31.8 mL/hr/kg Standard Deviation 13.7

SECONDARY outcome

Timeframe: Cycle 1 Day 1 (pre-dose; 5 mins and 3 hr post dose); Cycle 1 Day 5 (pre-dose; 5 mins, 1 hr, 3 hr, and 6 hrs post dose); and Cycle 2 Day 1 (pre-dose; 5 mins and 3 hr post dose)

Population: The PK population included all participants who received at least 1 dose of moxetumomab pasudotox and provided at least 1 baseline and post-baseline concentration-time data point. Data for Cycle 1 Day 1 was not reported as no evaluable participants for the calculation of the concerned parameters (ie., data were not sufficient).

The t1/2 of moxetumomab pasudotox is reported.

Outcome measures

Measure	Moxetumomab Pasudotox 40 µg/kg n=80 Participants Participants received intravenous infusion of moxetumomab pasudotox 40 µg/kg on Days 1, 3, and 5 of each 28-day cycle for up to 6 cycles, until documentation of complete response, progressive disease, initiation of alternate therapy, or unacceptable toxicity.
Terminal Half Life (t1/2) of Moxetumomab Pasudotox Cycle 1 Day 5	1.38 Hours Standard Deviation 0.632
Terminal Half Life (t1/2) of Moxetumomab Pasudotox Cycle 2 Day 1	1.39 Hours Standard Deviation 0.351

SECONDARY outcome

Timeframe: Pre-infusion on Day 1 of Cycles 1, 2, 3, and 5; at the End of Treatment (4 to 6 weeks after the last dose; approximately 7 months)

Population: Safety population included participants who received at least 1 dose of moxetumomab pasudotox.

Participants with ADA positive, nAb positive, cluster of differentiation 22 (CD22) positive of ADA positive/NAb positive, and pseudomonas exotoxin 38 (PE38) positive of ADA positive/NAb positive to moxetumomab pasudotox at any visit are reported.

Outcome measures

Measure	Moxetumomab Pasudotox 40 µg/kg n=80 Participants Participants received intravenous infusion of moxetumomab pasudotox 40 µg/kg on Days 1, 3, and 5 of each 28-day cycle for up to 6 cycles, until documentation of complete response, progressive disease, initiation of alternate therapy, or unacceptable toxicity.
Percentage of Participants With Positive Anti-drug Antibodies (ADA), Neutralizing Anti-drug Antibodies (nAb) and Specificity (CD22 and PE38) Positive to Moxetumomab Pasudotox ADA positive	87.5 Percentage of Participants
Percentage of Participants With Positive Anti-drug Antibodies (ADA), Neutralizing Anti-drug Antibodies (nAb) and Specificity (CD22 and PE38) Positive to Moxetumomab Pasudotox ADA and NAb positive	83.8 Percentage of Participants
Percentage of Participants With Positive Anti-drug Antibodies (ADA), Neutralizing Anti-drug Antibodies (nAb) and Specificity (CD22 and PE38) Positive to Moxetumomab Pasudotox Specificity CD22 positive of ADA+/NAb+	55.2 Percentage of Participants
Percentage of Participants With Positive Anti-drug Antibodies (ADA), Neutralizing Anti-drug Antibodies (nAb) and Specificity (CD22 and PE38) Positive to Moxetumomab Pasudotox Specificity PE38 positive of ADA+/NAb+	98.5 Percentage of Participants

Adverse Events

Moxetumomab Pasudotox 40 µg/kg

Serious events: 28 serious events

Other events: 77 other events

Deaths: 4 deaths

Serious adverse events

Measure	Moxetumomab Pasudotox 40 µg/kg n=80 participants at risk Participants received intravenous infusion of moxetumomab pasudotox 40 µg/kg on Days 1, 3, and 5 of each 28-day cycle for up to 6 cycles, until documentation of complete response, progressive disease, initiation of alternate therapy, or unacceptable toxicity.
Blood and lymphatic system disorders Febrile neutropenia	2.5% 2/80 • Number of events 3 • For TEAEs and TESAEs: From the start of study treatment (Day 1) through 4-6 weeks after last dose of Cycle 6 (28-day cycle) (approximately 7 months) All-cause mortality data: From the start of study treatment (Day 1) through end of study (approximately 6 years)
Blood and lymphatic system disorders Haemolytic uraemic syndrome	7.5% 6/80 • Number of events 6 • For TEAEs and TESAEs: From the start of study treatment (Day 1) through 4-6 weeks after last dose of Cycle 6 (28-day cycle) (approximately 7 months) All-cause mortality data: From the start of study treatment (Day 1) through end of study (approximately 6 years)
Cardiac disorders Left ventricular dysfunction	1.2% 1/80 • Number of events 1 • For TEAEs and TESAEs: From the start of study treatment (Day 1) through 4-6 weeks after last dose of Cycle 6 (28-day cycle) (approximately 7 months) All-cause mortality data: From the start of study treatment (Day 1) through end of study (approximately 6 years)
Gastrointestinal disorders Diarrhoea	1.2% 1/80 • Number of events 1 • For TEAEs and TESAEs: From the start of study treatment (Day 1) through 4-6 weeks after last dose of Cycle 6 (28-day cycle) (approximately 7 months) All-cause mortality data: From the start of study treatment (Day 1) through end of study (approximately 6 years)
Gastrointestinal disorders Nausea	1.2% 1/80 • Number of events 1 • For TEAEs and TESAEs: From the start of study treatment (Day 1) through 4-6 weeks after last dose of Cycle 6 (28-day cycle) (approximately 7 months) All-cause mortality data: From the start of study treatment (Day 1) through end of study (approximately 6 years)
Gastrointestinal disorders Neutropenic colitis	1.2% 1/80 • Number of events 1 • For TEAEs and TESAEs: From the start of study treatment (Day 1) through 4-6 weeks after last dose of Cycle 6 (28-day cycle) (approximately 7 months) All-cause mortality data: From the start of study treatment (Day 1) through end of study (approximately 6 years)
Gastrointestinal disorders Vomiting	1.2% 1/80 • Number of events 1 • For TEAEs and TESAEs: From the start of study treatment (Day 1) through 4-6 weeks after last dose of Cycle 6 (28-day cycle) (approximately 7 months) All-cause mortality data: From the start of study treatment (Day 1) through end of study (approximately 6 years)
General disorders Fatigue	1.2% 1/80 • Number of events 1 • For TEAEs and TESAEs: From the start of study treatment (Day 1) through 4-6 weeks after last dose of Cycle 6 (28-day cycle) (approximately 7 months) All-cause mortality data: From the start of study treatment (Day 1) through end of study (approximately 6 years)
General disorders Multiple organ dysfunction syndrome	1.2% 1/80 • Number of events 1 • For TEAEs and TESAEs: From the start of study treatment (Day 1) through 4-6 weeks after last dose of Cycle 6 (28-day cycle) (approximately 7 months) All-cause mortality data: From the start of study treatment (Day 1) through end of study (approximately 6 years)
General disorders Pain	1.2% 1/80 • Number of events 1 • For TEAEs and TESAEs: From the start of study treatment (Day 1) through 4-6 weeks after last dose of Cycle 6 (28-day cycle) (approximately 7 months) All-cause mortality data: From the start of study treatment (Day 1) through end of study (approximately 6 years)
General disorders Pyrexia	6.2% 5/80 • Number of events 5 • For TEAEs and TESAEs: From the start of study treatment (Day 1) through 4-6 weeks after last dose of Cycle 6 (28-day cycle) (approximately 7 months) All-cause mortality data: From the start of study treatment (Day 1) through end of study (approximately 6 years)
Infections and infestations Clostridium difficile colitis	1.2% 1/80 • Number of events 1 • For TEAEs and TESAEs: From the start of study treatment (Day 1) through 4-6 weeks after last dose of Cycle 6 (28-day cycle) (approximately 7 months) All-cause mortality data: From the start of study treatment (Day 1) through end of study (approximately 6 years)
Infections and infestations Erysipelas	1.2% 1/80 • Number of events 1 • For TEAEs and TESAEs: From the start of study treatment (Day 1) through 4-6 weeks after last dose of Cycle 6 (28-day cycle) (approximately 7 months) All-cause mortality data: From the start of study treatment (Day 1) through end of study (approximately 6 years)
Infections and infestations Infection	1.2% 1/80 • Number of events 1 • For TEAEs and TESAEs: From the start of study treatment (Day 1) through 4-6 weeks after last dose of Cycle 6 (28-day cycle) (approximately 7 months) All-cause mortality data: From the start of study treatment (Day 1) through end of study (approximately 6 years)
Infections and infestations Lung infection	1.2% 1/80 • Number of events 1 • For TEAEs and TESAEs: From the start of study treatment (Day 1) through 4-6 weeks after last dose of Cycle 6 (28-day cycle) (approximately 7 months) All-cause mortality data: From the start of study treatment (Day 1) through end of study (approximately 6 years)
Infections and infestations Pneumonia	1.2% 1/80 • Number of events 1 • For TEAEs and TESAEs: From the start of study treatment (Day 1) through 4-6 weeks after last dose of Cycle 6 (28-day cycle) (approximately 7 months) All-cause mortality data: From the start of study treatment (Day 1) through end of study (approximately 6 years)
Infections and infestations Pneumonia fungal	1.2% 1/80 • Number of events 1 • For TEAEs and TESAEs: From the start of study treatment (Day 1) through 4-6 weeks after last dose of Cycle 6 (28-day cycle) (approximately 7 months) All-cause mortality data: From the start of study treatment (Day 1) through end of study (approximately 6 years)
Infections and infestations Sepsis syndrome	1.2% 1/80 • Number of events 1 • For TEAEs and TESAEs: From the start of study treatment (Day 1) through 4-6 weeks after last dose of Cycle 6 (28-day cycle) (approximately 7 months) All-cause mortality data: From the start of study treatment (Day 1) through end of study (approximately 6 years)
Infections and infestations Septic shock	1.2% 1/80 • Number of events 1 • For TEAEs and TESAEs: From the start of study treatment (Day 1) through 4-6 weeks after last dose of Cycle 6 (28-day cycle) (approximately 7 months) All-cause mortality data: From the start of study treatment (Day 1) through end of study (approximately 6 years)
Infections and infestations Upper respiratory tract infection	2.5% 2/80 • Number of events 2 • For TEAEs and TESAEs: From the start of study treatment (Day 1) through 4-6 weeks after last dose of Cycle 6 (28-day cycle) (approximately 7 months) All-cause mortality data: From the start of study treatment (Day 1) through end of study (approximately 6 years)
Injury, poisoning and procedural complications Infusion related reaction	2.5% 2/80 • Number of events 2 • For TEAEs and TESAEs: From the start of study treatment (Day 1) through 4-6 weeks after last dose of Cycle 6 (28-day cycle) (approximately 7 months) All-cause mortality data: From the start of study treatment (Day 1) through end of study (approximately 6 years)
Investigations Blood creatinine increased	1.2% 1/80 • Number of events 1 • For TEAEs and TESAEs: From the start of study treatment (Day 1) through 4-6 weeks after last dose of Cycle 6 (28-day cycle) (approximately 7 months) All-cause mortality data: From the start of study treatment (Day 1) through end of study (approximately 6 years)
Investigations Haptoglobin decreased	1.2% 1/80 • Number of events 1 • For TEAEs and TESAEs: From the start of study treatment (Day 1) through 4-6 weeks after last dose of Cycle 6 (28-day cycle) (approximately 7 months) All-cause mortality data: From the start of study treatment (Day 1) through end of study (approximately 6 years)
Investigations Neutrophil count decreased	1.2% 1/80 • Number of events 1 • For TEAEs and TESAEs: From the start of study treatment (Day 1) through 4-6 weeks after last dose of Cycle 6 (28-day cycle) (approximately 7 months) All-cause mortality data: From the start of study treatment (Day 1) through end of study (approximately 6 years)
Investigations Platelet count decreased	1.2% 1/80 • Number of events 1 • For TEAEs and TESAEs: From the start of study treatment (Day 1) through 4-6 weeks after last dose of Cycle 6 (28-day cycle) (approximately 7 months) All-cause mortality data: From the start of study treatment (Day 1) through end of study (approximately 6 years)
Investigations Weight increased	1.2% 1/80 • Number of events 1 • For TEAEs and TESAEs: From the start of study treatment (Day 1) through 4-6 weeks after last dose of Cycle 6 (28-day cycle) (approximately 7 months) All-cause mortality data: From the start of study treatment (Day 1) through end of study (approximately 6 years)
Musculoskeletal and connective tissue disorders Rhabdomyolysis	1.2% 1/80 • Number of events 1 • For TEAEs and TESAEs: From the start of study treatment (Day 1) through 4-6 weeks after last dose of Cycle 6 (28-day cycle) (approximately 7 months) All-cause mortality data: From the start of study treatment (Day 1) through end of study (approximately 6 years)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Glioblastoma	1.2% 1/80 • Number of events 1 • For TEAEs and TESAEs: From the start of study treatment (Day 1) through 4-6 weeks after last dose of Cycle 6 (28-day cycle) (approximately 7 months) All-cause mortality data: From the start of study treatment (Day 1) through end of study (approximately 6 years)
Psychiatric disorders Mental status changes	1.2% 1/80 • Number of events 1 • For TEAEs and TESAEs: From the start of study treatment (Day 1) through 4-6 weeks after last dose of Cycle 6 (28-day cycle) (approximately 7 months) All-cause mortality data: From the start of study treatment (Day 1) through end of study (approximately 6 years)
Renal and urinary disorders Acute kidney injury	1.2% 1/80 • Number of events 1 • For TEAEs and TESAEs: From the start of study treatment (Day 1) through 4-6 weeks after last dose of Cycle 6 (28-day cycle) (approximately 7 months) All-cause mortality data: From the start of study treatment (Day 1) through end of study (approximately 6 years)
Renal and urinary disorders Haematuria	1.2% 1/80 • Number of events 1 • For TEAEs and TESAEs: From the start of study treatment (Day 1) through 4-6 weeks after last dose of Cycle 6 (28-day cycle) (approximately 7 months) All-cause mortality data: From the start of study treatment (Day 1) through end of study (approximately 6 years)
Renal and urinary disorders Renal failure	1.2% 1/80 • Number of events 1 • For TEAEs and TESAEs: From the start of study treatment (Day 1) through 4-6 weeks after last dose of Cycle 6 (28-day cycle) (approximately 7 months) All-cause mortality data: From the start of study treatment (Day 1) through end of study (approximately 6 years)
Respiratory, thoracic and mediastinal disorders Cough	1.2% 1/80 • Number of events 1 • For TEAEs and TESAEs: From the start of study treatment (Day 1) through 4-6 weeks after last dose of Cycle 6 (28-day cycle) (approximately 7 months) All-cause mortality data: From the start of study treatment (Day 1) through end of study (approximately 6 years)
Respiratory, thoracic and mediastinal disorders Dyspnoea	1.2% 1/80 • Number of events 1 • For TEAEs and TESAEs: From the start of study treatment (Day 1) through 4-6 weeks after last dose of Cycle 6 (28-day cycle) (approximately 7 months) All-cause mortality data: From the start of study treatment (Day 1) through end of study (approximately 6 years)
Respiratory, thoracic and mediastinal disorders Hypoxia	2.5% 2/80 • Number of events 2 • For TEAEs and TESAEs: From the start of study treatment (Day 1) through 4-6 weeks after last dose of Cycle 6 (28-day cycle) (approximately 7 months) All-cause mortality data: From the start of study treatment (Day 1) through end of study (approximately 6 years)
Respiratory, thoracic and mediastinal disorders Pharyngeal cyst	1.2% 1/80 • Number of events 1 • For TEAEs and TESAEs: From the start of study treatment (Day 1) through 4-6 weeks after last dose of Cycle 6 (28-day cycle) (approximately 7 months) All-cause mortality data: From the start of study treatment (Day 1) through end of study (approximately 6 years)
Respiratory, thoracic and mediastinal disorders Respiratory failure	1.2% 1/80 • Number of events 1 • For TEAEs and TESAEs: From the start of study treatment (Day 1) through 4-6 weeks after last dose of Cycle 6 (28-day cycle) (approximately 7 months) All-cause mortality data: From the start of study treatment (Day 1) through end of study (approximately 6 years)
Respiratory, thoracic and mediastinal disorders Tachypnoea	1.2% 1/80 • Number of events 1 • For TEAEs and TESAEs: From the start of study treatment (Day 1) through 4-6 weeks after last dose of Cycle 6 (28-day cycle) (approximately 7 months) All-cause mortality data: From the start of study treatment (Day 1) through end of study (approximately 6 years)
Skin and subcutaneous tissue disorders Rash	1.2% 1/80 • Number of events 1 • For TEAEs and TESAEs: From the start of study treatment (Day 1) through 4-6 weeks after last dose of Cycle 6 (28-day cycle) (approximately 7 months) All-cause mortality data: From the start of study treatment (Day 1) through end of study (approximately 6 years)
Vascular disorders Capillary leak syndrome	5.0% 4/80 • Number of events 5 • For TEAEs and TESAEs: From the start of study treatment (Day 1) through 4-6 weeks after last dose of Cycle 6 (28-day cycle) (approximately 7 months) All-cause mortality data: From the start of study treatment (Day 1) through end of study (approximately 6 years)

Other adverse events

Measure	Moxetumomab Pasudotox 40 µg/kg n=80 participants at risk Participants received intravenous infusion of moxetumomab pasudotox 40 µg/kg on Days 1, 3, and 5 of each 28-day cycle for up to 6 cycles, until documentation of complete response, progressive disease, initiation of alternate therapy, or unacceptable toxicity.
Blood and lymphatic system disorders Anaemia	21.2% 17/80 • Number of events 41 • For TEAEs and TESAEs: From the start of study treatment (Day 1) through 4-6 weeks after last dose of Cycle 6 (28-day cycle) (approximately 7 months) All-cause mortality data: From the start of study treatment (Day 1) through end of study (approximately 6 years)
Blood and lymphatic system disorders Neutropenia	5.0% 4/80 • Number of events 5 • For TEAEs and TESAEs: From the start of study treatment (Day 1) through 4-6 weeks after last dose of Cycle 6 (28-day cycle) (approximately 7 months) All-cause mortality data: From the start of study treatment (Day 1) through end of study (approximately 6 years)
Cardiac disorders Sinus tachycardia	7.5% 6/80 • Number of events 6 • For TEAEs and TESAEs: From the start of study treatment (Day 1) through 4-6 weeks after last dose of Cycle 6 (28-day cycle) (approximately 7 months) All-cause mortality data: From the start of study treatment (Day 1) through end of study (approximately 6 years)
Eye disorders Cataract	5.0% 4/80 • Number of events 4 • For TEAEs and TESAEs: From the start of study treatment (Day 1) through 4-6 weeks after last dose of Cycle 6 (28-day cycle) (approximately 7 months) All-cause mortality data: From the start of study treatment (Day 1) through end of study (approximately 6 years)
Eye disorders Dry eye	7.5% 6/80 • Number of events 6 • For TEAEs and TESAEs: From the start of study treatment (Day 1) through 4-6 weeks after last dose of Cycle 6 (28-day cycle) (approximately 7 months) All-cause mortality data: From the start of study treatment (Day 1) through end of study (approximately 6 years)
Eye disorders Vision blurred	8.8% 7/80 • Number of events 8 • For TEAEs and TESAEs: From the start of study treatment (Day 1) through 4-6 weeks after last dose of Cycle 6 (28-day cycle) (approximately 7 months) All-cause mortality data: From the start of study treatment (Day 1) through end of study (approximately 6 years)
Gastrointestinal disorders Abdominal distension	12.5% 10/80 • Number of events 12 • For TEAEs and TESAEs: From the start of study treatment (Day 1) through 4-6 weeks after last dose of Cycle 6 (28-day cycle) (approximately 7 months) All-cause mortality data: From the start of study treatment (Day 1) through end of study (approximately 6 years)
Gastrointestinal disorders Abdominal pain	8.8% 7/80 • Number of events 7 • For TEAEs and TESAEs: From the start of study treatment (Day 1) through 4-6 weeks after last dose of Cycle 6 (28-day cycle) (approximately 7 months) All-cause mortality data: From the start of study treatment (Day 1) through end of study (approximately 6 years)
Gastrointestinal disorders Abdominal pain upper	5.0% 4/80 • Number of events 5 • For TEAEs and TESAEs: From the start of study treatment (Day 1) through 4-6 weeks after last dose of Cycle 6 (28-day cycle) (approximately 7 months) All-cause mortality data: From the start of study treatment (Day 1) through end of study (approximately 6 years)
Gastrointestinal disorders Constipation	22.5% 18/80 • Number of events 21 • For TEAEs and TESAEs: From the start of study treatment (Day 1) through 4-6 weeks after last dose of Cycle 6 (28-day cycle) (approximately 7 months) All-cause mortality data: From the start of study treatment (Day 1) through end of study (approximately 6 years)
Gastrointestinal disorders Diarrhoea	21.2% 17/80 • Number of events 20 • For TEAEs and TESAEs: From the start of study treatment (Day 1) through 4-6 weeks after last dose of Cycle 6 (28-day cycle) (approximately 7 months) All-cause mortality data: From the start of study treatment (Day 1) through end of study (approximately 6 years)
Gastrointestinal disorders Dyspepsia	5.0% 4/80 • Number of events 5 • For TEAEs and TESAEs: From the start of study treatment (Day 1) through 4-6 weeks after last dose of Cycle 6 (28-day cycle) (approximately 7 months) All-cause mortality data: From the start of study treatment (Day 1) through end of study (approximately 6 years)
Gastrointestinal disorders Flatulence	6.2% 5/80 • Number of events 5 • For TEAEs and TESAEs: From the start of study treatment (Day 1) through 4-6 weeks after last dose of Cycle 6 (28-day cycle) (approximately 7 months) All-cause mortality data: From the start of study treatment (Day 1) through end of study (approximately 6 years)
Gastrointestinal disorders Nausea	35.0% 28/80 • Number of events 48 • For TEAEs and TESAEs: From the start of study treatment (Day 1) through 4-6 weeks after last dose of Cycle 6 (28-day cycle) (approximately 7 months) All-cause mortality data: From the start of study treatment (Day 1) through end of study (approximately 6 years)
Gastrointestinal disorders Vomiting	17.5% 14/80 • Number of events 17 • For TEAEs and TESAEs: From the start of study treatment (Day 1) through 4-6 weeks after last dose of Cycle 6 (28-day cycle) (approximately 7 months) All-cause mortality data: From the start of study treatment (Day 1) through end of study (approximately 6 years)
General disorders Asthenia	12.5% 10/80 • Number of events 30 • For TEAEs and TESAEs: From the start of study treatment (Day 1) through 4-6 weeks after last dose of Cycle 6 (28-day cycle) (approximately 7 months) All-cause mortality data: From the start of study treatment (Day 1) through end of study (approximately 6 years)
General disorders Chills	18.8% 15/80 • Number of events 18 • For TEAEs and TESAEs: From the start of study treatment (Day 1) through 4-6 weeks after last dose of Cycle 6 (28-day cycle) (approximately 7 months) All-cause mortality data: From the start of study treatment (Day 1) through end of study (approximately 6 years)
General disorders Face oedema	13.8% 11/80 • Number of events 16 • For TEAEs and TESAEs: From the start of study treatment (Day 1) through 4-6 weeks after last dose of Cycle 6 (28-day cycle) (approximately 7 months) All-cause mortality data: From the start of study treatment (Day 1) through end of study (approximately 6 years)
General disorders Fatigue	32.5% 26/80 • Number of events 40 • For TEAEs and TESAEs: From the start of study treatment (Day 1) through 4-6 weeks after last dose of Cycle 6 (28-day cycle) (approximately 7 months) All-cause mortality data: From the start of study treatment (Day 1) through end of study (approximately 6 years)
General disorders Non-cardiac chest pain	5.0% 4/80 • Number of events 4 • For TEAEs and TESAEs: From the start of study treatment (Day 1) through 4-6 weeks after last dose of Cycle 6 (28-day cycle) (approximately 7 months) All-cause mortality data: From the start of study treatment (Day 1) through end of study (approximately 6 years)
General disorders Oedema	5.0% 4/80 • Number of events 5 • For TEAEs and TESAEs: From the start of study treatment (Day 1) through 4-6 weeks after last dose of Cycle 6 (28-day cycle) (approximately 7 months) All-cause mortality data: From the start of study treatment (Day 1) through end of study (approximately 6 years)
General disorders Oedema peripheral	38.8% 31/80 • Number of events 47 • For TEAEs and TESAEs: From the start of study treatment (Day 1) through 4-6 weeks after last dose of Cycle 6 (28-day cycle) (approximately 7 months) All-cause mortality data: From the start of study treatment (Day 1) through end of study (approximately 6 years)
General disorders Peripheral swelling	5.0% 4/80 • Number of events 5 • For TEAEs and TESAEs: From the start of study treatment (Day 1) through 4-6 weeks after last dose of Cycle 6 (28-day cycle) (approximately 7 months) All-cause mortality data: From the start of study treatment (Day 1) through end of study (approximately 6 years)
General disorders Pyrexia	27.5% 22/80 • Number of events 35 • For TEAEs and TESAEs: From the start of study treatment (Day 1) through 4-6 weeks after last dose of Cycle 6 (28-day cycle) (approximately 7 months) All-cause mortality data: From the start of study treatment (Day 1) through end of study (approximately 6 years)
Infections and infestations Nasopharyngitis	5.0% 4/80 • Number of events 4 • For TEAEs and TESAEs: From the start of study treatment (Day 1) through 4-6 weeks after last dose of Cycle 6 (28-day cycle) (approximately 7 months) All-cause mortality data: From the start of study treatment (Day 1) through end of study (approximately 6 years)
Infections and infestations Rhinitis	5.0% 4/80 • Number of events 4 • For TEAEs and TESAEs: From the start of study treatment (Day 1) through 4-6 weeks after last dose of Cycle 6 (28-day cycle) (approximately 7 months) All-cause mortality data: From the start of study treatment (Day 1) through end of study (approximately 6 years)
Infections and infestations Sinusitis	5.0% 4/80 • Number of events 4 • For TEAEs and TESAEs: From the start of study treatment (Day 1) through 4-6 weeks after last dose of Cycle 6 (28-day cycle) (approximately 7 months) All-cause mortality data: From the start of study treatment (Day 1) through end of study (approximately 6 years)
Infections and infestations Upper respiratory tract infection	6.2% 5/80 • Number of events 5 • For TEAEs and TESAEs: From the start of study treatment (Day 1) through 4-6 weeks after last dose of Cycle 6 (28-day cycle) (approximately 7 months) All-cause mortality data: From the start of study treatment (Day 1) through end of study (approximately 6 years)
Injury, poisoning and procedural complications Infusion related reaction	6.2% 5/80 • Number of events 6 • For TEAEs and TESAEs: From the start of study treatment (Day 1) through 4-6 weeks after last dose of Cycle 6 (28-day cycle) (approximately 7 months) All-cause mortality data: From the start of study treatment (Day 1) through end of study (approximately 6 years)
Investigations Alanine aminotransferase increased	21.2% 17/80 • Number of events 43 • For TEAEs and TESAEs: From the start of study treatment (Day 1) through 4-6 weeks after last dose of Cycle 6 (28-day cycle) (approximately 7 months) All-cause mortality data: From the start of study treatment (Day 1) through end of study (approximately 6 years)
Investigations Aspartate aminotransferase increased	18.8% 15/80 • Number of events 38 • For TEAEs and TESAEs: From the start of study treatment (Day 1) through 4-6 weeks after last dose of Cycle 6 (28-day cycle) (approximately 7 months) All-cause mortality data: From the start of study treatment (Day 1) through end of study (approximately 6 years)
Investigations Blood alkaline phosphatase increased	5.0% 4/80 • Number of events 8 • For TEAEs and TESAEs: From the start of study treatment (Day 1) through 4-6 weeks after last dose of Cycle 6 (28-day cycle) (approximately 7 months) All-cause mortality data: From the start of study treatment (Day 1) through end of study (approximately 6 years)
Investigations Blood bilirubin increased	6.2% 5/80 • Number of events 14 • For TEAEs and TESAEs: From the start of study treatment (Day 1) through 4-6 weeks after last dose of Cycle 6 (28-day cycle) (approximately 7 months) All-cause mortality data: From the start of study treatment (Day 1) through end of study (approximately 6 years)
Investigations Blood creatinine increased	10.0% 8/80 • Number of events 15 • For TEAEs and TESAEs: From the start of study treatment (Day 1) through 4-6 weeks after last dose of Cycle 6 (28-day cycle) (approximately 7 months) All-cause mortality data: From the start of study treatment (Day 1) through end of study (approximately 6 years)
Investigations Haptoglobin decreased	7.5% 6/80 • Number of events 6 • For TEAEs and TESAEs: From the start of study treatment (Day 1) through 4-6 weeks after last dose of Cycle 6 (28-day cycle) (approximately 7 months) All-cause mortality data: From the start of study treatment (Day 1) through end of study (approximately 6 years)
Investigations Lymphocyte count decreased	20.0% 16/80 • Number of events 73 • For TEAEs and TESAEs: From the start of study treatment (Day 1) through 4-6 weeks after last dose of Cycle 6 (28-day cycle) (approximately 7 months) All-cause mortality data: From the start of study treatment (Day 1) through end of study (approximately 6 years)
Investigations Neutrophil count decreased	6.2% 5/80 • Number of events 10 • For TEAEs and TESAEs: From the start of study treatment (Day 1) through 4-6 weeks after last dose of Cycle 6 (28-day cycle) (approximately 7 months) All-cause mortality data: From the start of study treatment (Day 1) through end of study (approximately 6 years)
Investigations Platelet count decreased	11.2% 9/80 • Number of events 18 • For TEAEs and TESAEs: From the start of study treatment (Day 1) through 4-6 weeks after last dose of Cycle 6 (28-day cycle) (approximately 7 months) All-cause mortality data: From the start of study treatment (Day 1) through end of study (approximately 6 years)
Investigations Weight increased	7.5% 6/80 • Number of events 7 • For TEAEs and TESAEs: From the start of study treatment (Day 1) through 4-6 weeks after last dose of Cycle 6 (28-day cycle) (approximately 7 months) All-cause mortality data: From the start of study treatment (Day 1) through end of study (approximately 6 years)
Investigations White blood cell count decreased	10.0% 8/80 • Number of events 15 • For TEAEs and TESAEs: From the start of study treatment (Day 1) through 4-6 weeks after last dose of Cycle 6 (28-day cycle) (approximately 7 months) All-cause mortality data: From the start of study treatment (Day 1) through end of study (approximately 6 years)
Metabolism and nutrition disorders Decreased appetite	13.8% 11/80 • Number of events 12 • For TEAEs and TESAEs: From the start of study treatment (Day 1) through 4-6 weeks after last dose of Cycle 6 (28-day cycle) (approximately 7 months) All-cause mortality data: From the start of study treatment (Day 1) through end of study (approximately 6 years)
Metabolism and nutrition disorders Hyperglycaemia	10.0% 8/80 • Number of events 15 • For TEAEs and TESAEs: From the start of study treatment (Day 1) through 4-6 weeks after last dose of Cycle 6 (28-day cycle) (approximately 7 months) All-cause mortality data: From the start of study treatment (Day 1) through end of study (approximately 6 years)
Metabolism and nutrition disorders Hyperkalaemia	7.5% 6/80 • Number of events 8 • For TEAEs and TESAEs: From the start of study treatment (Day 1) through 4-6 weeks after last dose of Cycle 6 (28-day cycle) (approximately 7 months) All-cause mortality data: From the start of study treatment (Day 1) through end of study (approximately 6 years)
Metabolism and nutrition disorders Hypernatraemia	5.0% 4/80 • Number of events 5 • For TEAEs and TESAEs: From the start of study treatment (Day 1) through 4-6 weeks after last dose of Cycle 6 (28-day cycle) (approximately 7 months) All-cause mortality data: From the start of study treatment (Day 1) through end of study (approximately 6 years)
Metabolism and nutrition disorders Hypoalbuminaemia	20.0% 16/80 • Number of events 51 • For TEAEs and TESAEs: From the start of study treatment (Day 1) through 4-6 weeks after last dose of Cycle 6 (28-day cycle) (approximately 7 months) All-cause mortality data: From the start of study treatment (Day 1) through end of study (approximately 6 years)
Metabolism and nutrition disorders Hypocalcaemia	23.8% 19/80 • Number of events 39 • For TEAEs and TESAEs: From the start of study treatment (Day 1) through 4-6 weeks after last dose of Cycle 6 (28-day cycle) (approximately 7 months) All-cause mortality data: From the start of study treatment (Day 1) through end of study (approximately 6 years)
Metabolism and nutrition disorders Hypokalaemia	16.2% 13/80 • Number of events 22 • For TEAEs and TESAEs: From the start of study treatment (Day 1) through 4-6 weeks after last dose of Cycle 6 (28-day cycle) (approximately 7 months) All-cause mortality data: From the start of study treatment (Day 1) through end of study (approximately 6 years)
Metabolism and nutrition disorders Hypomagnesaemia	7.5% 6/80 • Number of events 8 • For TEAEs and TESAEs: From the start of study treatment (Day 1) through 4-6 weeks after last dose of Cycle 6 (28-day cycle) (approximately 7 months) All-cause mortality data: From the start of study treatment (Day 1) through end of study (approximately 6 years)
Metabolism and nutrition disorders Hyponatraemia	11.2% 9/80 • Number of events 17 • For TEAEs and TESAEs: From the start of study treatment (Day 1) through 4-6 weeks after last dose of Cycle 6 (28-day cycle) (approximately 7 months) All-cause mortality data: From the start of study treatment (Day 1) through end of study (approximately 6 years)
Metabolism and nutrition disorders Hypophosphataemia	23.8% 19/80 • Number of events 47 • For TEAEs and TESAEs: From the start of study treatment (Day 1) through 4-6 weeks after last dose of Cycle 6 (28-day cycle) (approximately 7 months) All-cause mortality data: From the start of study treatment (Day 1) through end of study (approximately 6 years)
Musculoskeletal and connective tissue disorders Arthralgia	16.2% 13/80 • Number of events 22 • For TEAEs and TESAEs: From the start of study treatment (Day 1) through 4-6 weeks after last dose of Cycle 6 (28-day cycle) (approximately 7 months) All-cause mortality data: From the start of study treatment (Day 1) through end of study (approximately 6 years)
Musculoskeletal and connective tissue disorders Back pain	15.0% 12/80 • Number of events 12 • For TEAEs and TESAEs: From the start of study treatment (Day 1) through 4-6 weeks after last dose of Cycle 6 (28-day cycle) (approximately 7 months) All-cause mortality data: From the start of study treatment (Day 1) through end of study (approximately 6 years)
Musculoskeletal and connective tissue disorders Musculoskeletal chest pain	5.0% 4/80 • Number of events 4 • For TEAEs and TESAEs: From the start of study treatment (Day 1) through 4-6 weeks after last dose of Cycle 6 (28-day cycle) (approximately 7 months) All-cause mortality data: From the start of study treatment (Day 1) through end of study (approximately 6 years)
Musculoskeletal and connective tissue disorders Musculoskeletal pain	6.2% 5/80 • Number of events 7 • For TEAEs and TESAEs: From the start of study treatment (Day 1) through 4-6 weeks after last dose of Cycle 6 (28-day cycle) (approximately 7 months) All-cause mortality data: From the start of study treatment (Day 1) through end of study (approximately 6 years)
Musculoskeletal and connective tissue disorders Myalgia	13.8% 11/80 • Number of events 16 • For TEAEs and TESAEs: From the start of study treatment (Day 1) through 4-6 weeks after last dose of Cycle 6 (28-day cycle) (approximately 7 months) All-cause mortality data: From the start of study treatment (Day 1) through end of study (approximately 6 years)
Musculoskeletal and connective tissue disorders Pain in extremity	15.0% 12/80 • Number of events 14 • For TEAEs and TESAEs: From the start of study treatment (Day 1) through 4-6 weeks after last dose of Cycle 6 (28-day cycle) (approximately 7 months) All-cause mortality data: From the start of study treatment (Day 1) through end of study (approximately 6 years)
Nervous system disorders Dizziness	10.0% 8/80 • Number of events 12 • For TEAEs and TESAEs: From the start of study treatment (Day 1) through 4-6 weeks after last dose of Cycle 6 (28-day cycle) (approximately 7 months) All-cause mortality data: From the start of study treatment (Day 1) through end of study (approximately 6 years)
Nervous system disorders Dysgeusia	6.2% 5/80 • Number of events 5 • For TEAEs and TESAEs: From the start of study treatment (Day 1) through 4-6 weeks after last dose of Cycle 6 (28-day cycle) (approximately 7 months) All-cause mortality data: From the start of study treatment (Day 1) through end of study (approximately 6 years)
Nervous system disorders Headache	32.5% 26/80 • Number of events 37 • For TEAEs and TESAEs: From the start of study treatment (Day 1) through 4-6 weeks after last dose of Cycle 6 (28-day cycle) (approximately 7 months) All-cause mortality data: From the start of study treatment (Day 1) through end of study (approximately 6 years)
Nervous system disorders Paraesthesia	8.8% 7/80 • Number of events 8 • For TEAEs and TESAEs: From the start of study treatment (Day 1) through 4-6 weeks after last dose of Cycle 6 (28-day cycle) (approximately 7 months) All-cause mortality data: From the start of study treatment (Day 1) through end of study (approximately 6 years)
Psychiatric disorders Anxiety	11.2% 9/80 • Number of events 9 • For TEAEs and TESAEs: From the start of study treatment (Day 1) through 4-6 weeks after last dose of Cycle 6 (28-day cycle) (approximately 7 months) All-cause mortality data: From the start of study treatment (Day 1) through end of study (approximately 6 years)
Psychiatric disorders Insomnia	10.0% 8/80 • Number of events 9 • For TEAEs and TESAEs: From the start of study treatment (Day 1) through 4-6 weeks after last dose of Cycle 6 (28-day cycle) (approximately 7 months) All-cause mortality data: From the start of study treatment (Day 1) through end of study (approximately 6 years)
Renal and urinary disorders Haematuria	6.2% 5/80 • Number of events 5 • For TEAEs and TESAEs: From the start of study treatment (Day 1) through 4-6 weeks after last dose of Cycle 6 (28-day cycle) (approximately 7 months) All-cause mortality data: From the start of study treatment (Day 1) through end of study (approximately 6 years)
Respiratory, thoracic and mediastinal disorders Cough	8.8% 7/80 • Number of events 8 • For TEAEs and TESAEs: From the start of study treatment (Day 1) through 4-6 weeks after last dose of Cycle 6 (28-day cycle) (approximately 7 months) All-cause mortality data: From the start of study treatment (Day 1) through end of study (approximately 6 years)
Respiratory, thoracic and mediastinal disorders Dyspnoea	10.0% 8/80 • Number of events 10 • For TEAEs and TESAEs: From the start of study treatment (Day 1) through 4-6 weeks after last dose of Cycle 6 (28-day cycle) (approximately 7 months) All-cause mortality data: From the start of study treatment (Day 1) through end of study (approximately 6 years)
Respiratory, thoracic and mediastinal disorders Nasal congestion	6.2% 5/80 • Number of events 5 • For TEAEs and TESAEs: From the start of study treatment (Day 1) through 4-6 weeks after last dose of Cycle 6 (28-day cycle) (approximately 7 months) All-cause mortality data: From the start of study treatment (Day 1) through end of study (approximately 6 years)
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	7.5% 6/80 • Number of events 8 • For TEAEs and TESAEs: From the start of study treatment (Day 1) through 4-6 weeks after last dose of Cycle 6 (28-day cycle) (approximately 7 months) All-cause mortality data: From the start of study treatment (Day 1) through end of study (approximately 6 years)
Respiratory, thoracic and mediastinal disorders Pleural effusion	6.2% 5/80 • Number of events 6 • For TEAEs and TESAEs: From the start of study treatment (Day 1) through 4-6 weeks after last dose of Cycle 6 (28-day cycle) (approximately 7 months) All-cause mortality data: From the start of study treatment (Day 1) through end of study (approximately 6 years)
Skin and subcutaneous tissue disorders Pruritus	7.5% 6/80 • Number of events 12 • For TEAEs and TESAEs: From the start of study treatment (Day 1) through 4-6 weeks after last dose of Cycle 6 (28-day cycle) (approximately 7 months) All-cause mortality data: From the start of study treatment (Day 1) through end of study (approximately 6 years)
Skin and subcutaneous tissue disorders Rash	5.0% 4/80 • Number of events 4 • For TEAEs and TESAEs: From the start of study treatment (Day 1) through 4-6 weeks after last dose of Cycle 6 (28-day cycle) (approximately 7 months) All-cause mortality data: From the start of study treatment (Day 1) through end of study (approximately 6 years)
Skin and subcutaneous tissue disorders Rash maculo-papular	5.0% 4/80 • Number of events 5 • For TEAEs and TESAEs: From the start of study treatment (Day 1) through 4-6 weeks after last dose of Cycle 6 (28-day cycle) (approximately 7 months) All-cause mortality data: From the start of study treatment (Day 1) through end of study (approximately 6 years)
Vascular disorders Flushing	5.0% 4/80 • Number of events 4 • For TEAEs and TESAEs: From the start of study treatment (Day 1) through 4-6 weeks after last dose of Cycle 6 (28-day cycle) (approximately 7 months) All-cause mortality data: From the start of study treatment (Day 1) through end of study (approximately 6 years)
Vascular disorders Hypertension	15.0% 12/80 • Number of events 38 • For TEAEs and TESAEs: From the start of study treatment (Day 1) through 4-6 weeks after last dose of Cycle 6 (28-day cycle) (approximately 7 months) All-cause mortality data: From the start of study treatment (Day 1) through end of study (approximately 6 years)
Vascular disorders Hypotension	7.5% 6/80 • Number of events 8 • For TEAEs and TESAEs: From the start of study treatment (Day 1) through 4-6 weeks after last dose of Cycle 6 (28-day cycle) (approximately 7 months) All-cause mortality data: From the start of study treatment (Day 1) through end of study (approximately 6 years)

Additional Information

Priti Patel

MedImmune, LLC

Phone: +1-650-264-9079

Email: information.center@astrazeneca.com

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