Trial Outcomes & Findings for Testing the Addition of Copanlisib to Eribulin in Metastatic Triple Negative Breast Cancer (NCT NCT04345913)

Last Updated: 2025-12-18

Results Overview

MTD is defined as the highest dose level of copanlisib at which at most 1 of 6 patients experience a dose limiting toxicity during the observation window.

Recruitment status

ACTIVE_NOT_RECRUITING

Study phase

PHASE1/PHASE2

Target enrollment

24 participants

Primary outcome timeframe

Up to 28 days

Results posted on

2025-12-18

Participant Flow

24 patients received study treatment (8 patients in Phase I and 16 patients in Phase II). There were 9 additional patients that signed consent and were never treated. This includes 6 screen fails and 3 patients that were not treated and withdrawn prior to receiving study therapy.

Participant milestones

Participant milestones
Measure	Phase I, DL1 (Eribulin, Copanlisib) Phase I, DL1: Patients receive copanlisib (45 mg) IV over 1 hour and eribulin (1.1 mg/m\^2) IV over 2 to 5 minutes on days 1 and 8 of each cycle. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. Additionally, patients undergo a CT scan and/or MRI at screening, cycle 3 day 1, and every 9 weeks thereafter. Patients also undergo a biopsy at baseline, cycle 2 day 1, and at time of disease progression as well as blood sample collection at baseline, cycle 2 day 1, every 9 weeks and at time of disease progression.	Phase I, DL2 (Eribulin, Copanlisib) Phase I, DL2: Patients receive copanlisib (45 mg) IV over 1 hour and eribulin (1.4 mg/m\^2) IV over 2 to 5 minutes on days 1 and 8 of each cycle. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. Additionally, patients undergo a CT scan and/or MRI at screening, cycle 3 day 1, and every 9 weeks thereafter. Patients also undergo a biopsy at baseline, cycle 2 day 1, and at time of disease progression as well as blood sample collection at baseline, cycle 2 day 1, every 9 weeks and at time of disease progression.	Group I (Phase II, Eribulin) Group I (Phase II): Patients receive eribulin (1.4 mg/m\^2) IV over 2 to 5 minutes on days 1 and 8 of each cycle. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. Additionally, patients undergo a CT scan and/or MRI at screening, cycle 3 day 1, and every 9 weeks thereafter. Patients also undergo a biopsy at baseline, cycle 2 day 1, and at time of disease progression as well as blood sample collection at baseline, cycle 2 day 1, every 9 weeks and at time of disease progression.	Group II (Phase II, DL1, Eribulin, Copanlisib) Group II (Phase II, DL1): Patients receive copanlisib (45 mg) IV over 1 hour and eribulin (1.1 mg/m\^2) IV over 2 to 5 minutes on days 1 and 8 of each cycle. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. Additionally, patients undergo a CT scan and/or MRI at screening, cycle 3 day 1, and every 9 weeks thereafter. Patients also undergo a biopsy at baseline, cycle 2 day 1, and at time of disease progression as well as blood sample collection at baseline, cycle 2 day 1, every 9 weeks and at time of disease progression.
Overall Study STARTED	6	2	8	8
Overall Study COMPLETED	6	2	8	8
Overall Study NOT COMPLETED	0	0	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Testing the Addition of Copanlisib to Eribulin in Metastatic Triple Negative Breast Cancer

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Phase I, DL1 (Eribulin, Copanlisib) n=6 Participants Phase I, DL1: Patients receive copanlisib (45 mg) IV over 1 hour and eribulin (1.1 mg/m\^2) IV over 2 to 5 minutes on days 1 and 8 of each cycle. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. Additionally, patients undergo a CT scan and/or MRI at screening, cycle 3 day 1, and every 9 weeks thereafter. Patients also undergo a biopsy at baseline, cycle 2 day 1, and at time of disease progression as well as blood sample collection at baseline, cycle 2 day 1, every 9 weeks and at time of disease progression.	Phase I, DL2 (Eribulin, Copanlisib) n=2 Participants Phase I, DL2: Patients receive copanlisib (45 mg) IV over 1 hour and eribulin (1.4 mg/m\^2) IV over 2 to 5 minutes on days 1 and 8 of each cycle. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. Additionally, patients undergo a CT scan and/or MRI at screening, cycle 3 day 1, and every 9 weeks thereafter. Patients also undergo a biopsy at baseline, cycle 2 day 1, and at time of disease progression as well as blood sample collection at baseline, cycle 2 day 1, every 9 weeks and at time of disease progression.	Group I (Phase II, Eribulin) n=8 Participants Group I (Phase II): Patients receive eribulin (1.4 mg/m\^2) IV over 2 to 5 minutes on days 1 and 8 of each cycle. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. Additionally, patients undergo a CT scan and/or MRI at screening, cycle 3 day 1, and every 9 weeks thereafter. Patients also undergo a biopsy at baseline, cycle 2 day 1, and at time of disease progression as well as blood sample collection at baseline, cycle 2 day 1, every 9 weeks and at time of disease progression.	Group II (Phase II, DL1, Eribulin, Copanlisib) n=8 Participants Group II (Phase II, DL1): Patients receive copanlisib (45 mg) IV over 1 hour and eribulin (1.1 mg/m\^2) IV over 2 to 5 minutes on days 1 and 8 of each cycle. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. Additionally, patients undergo a CT scan and/or MRI at screening, cycle 3 day 1, and every 9 weeks thereafter. Patients also undergo a biopsy at baseline, cycle 2 day 1, and at time of disease progression as well as blood sample collection at baseline, cycle 2 day 1, every 9 weeks and at time of disease progression.	Total n=24 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=47 Participants	0 Participants n=41 Participants	0 Participants n=88 Participants	0 Participants n=9 Participants	0 Participants n=3 Participants
Age, Categorical Between 18 and 65 years	5 Participants n=47 Participants	2 Participants n=41 Participants	6 Participants n=88 Participants	8 Participants n=9 Participants	21 Participants n=3 Participants
Age, Categorical >=65 years	1 Participants n=47 Participants	0 Participants n=41 Participants	2 Participants n=88 Participants	0 Participants n=9 Participants	3 Participants n=3 Participants
Age, Continuous	50.33 years STANDARD_DEVIATION 11.02 • n=47 Participants	42.5 years STANDARD_DEVIATION 23.33 • n=41 Participants	58.00 years STANDARD_DEVIATION 7.73 • n=88 Participants	50.13 years STANDARD_DEVIATION 6.22 • n=9 Participants	52.17 years STANDARD_DEVIATION 10.12 • n=3 Participants
Sex: Female, Male Female	6 Participants n=47 Participants	2 Participants n=41 Participants	8 Participants n=88 Participants	8 Participants n=9 Participants	24 Participants n=3 Participants
Sex: Female, Male Male	0 Participants n=47 Participants	0 Participants n=41 Participants	0 Participants n=88 Participants	0 Participants n=9 Participants	0 Participants n=3 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	1 Participants n=47 Participants	1 Participants n=41 Participants	0 Participants n=88 Participants	1 Participants n=9 Participants	3 Participants n=3 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	4 Participants n=47 Participants	1 Participants n=41 Participants	8 Participants n=88 Participants	7 Participants n=9 Participants	20 Participants n=3 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	1 Participants n=47 Participants	0 Participants n=41 Participants	0 Participants n=88 Participants	0 Participants n=9 Participants	1 Participants n=3 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=47 Participants	0 Participants n=41 Participants	0 Participants n=88 Participants	0 Participants n=9 Participants	0 Participants n=3 Participants
Race (NIH/OMB) Asian	0 Participants n=47 Participants	0 Participants n=41 Participants	0 Participants n=88 Participants	1 Participants n=9 Participants	1 Participants n=3 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=47 Participants	0 Participants n=41 Participants	0 Participants n=88 Participants	0 Participants n=9 Participants	0 Participants n=3 Participants
Race (NIH/OMB) Black or African American	1 Participants n=47 Participants	0 Participants n=41 Participants	5 Participants n=88 Participants	3 Participants n=9 Participants	9 Participants n=3 Participants
Race (NIH/OMB) White	3 Participants n=47 Participants	1 Participants n=41 Participants	3 Participants n=88 Participants	4 Participants n=9 Participants	11 Participants n=3 Participants
Race (NIH/OMB) More than one race	0 Participants n=47 Participants	0 Participants n=41 Participants	0 Participants n=88 Participants	0 Participants n=9 Participants	0 Participants n=3 Participants
Race (NIH/OMB) Unknown or Not Reported	2 Participants n=47 Participants	1 Participants n=41 Participants	0 Participants n=88 Participants	0 Participants n=9 Participants	3 Participants n=3 Participants
Region of Enrollment United States	6 participants n=47 Participants	2 participants n=41 Participants	8 participants n=88 Participants	8 participants n=9 Participants	24 participants n=3 Participants
Eastern Cooperative Oncology Score (ECOG) Performance Status ECOG 0	2 Participants n=47 Participants	0 Participants n=41 Participants	6 Participants n=88 Participants	2 Participants n=9 Participants	10 Participants n=3 Participants
Eastern Cooperative Oncology Score (ECOG) Performance Status ECOG 1	4 Participants n=47 Participants	2 Participants n=41 Participants	2 Participants n=88 Participants	6 Participants n=9 Participants	14 Participants n=3 Participants
PTEN/PIK3CA Mutation No Mutation	4 Participants n=47 Participants	2 Participants n=41 Participants	6 Participants n=88 Participants	7 Participants n=9 Participants	19 Participants n=3 Participants
PTEN/PIK3CA Mutation Yes Mutation	2 Participants n=47 Participants	0 Participants n=41 Participants	2 Participants n=88 Participants	1 Participants n=9 Participants	5 Participants n=3 Participants

PRIMARY outcome

Timeframe: Up to 28 days

Population: 6 patients in DL1 and 2 patients in DL2.

MTD is defined as the highest dose level of eribulin at which at most 1 of 6 patients experience a dose limiting toxicity during the observation window.

Outcome measures

Outcome measures
Measure	Phase I, DL and DL2 (Eribulin, Copanlisib) n=8 Participants Phase I, DL1 and DL2: DL1 patients receive copanlisib (45 mg) IV over 1 hour and eribulin (1.1 mg/m\^2) IV over 2 to 5 minutes on days 1 and 8 of each cycle. DL2 patients receive copanlisib (45 mg) IV over 1 hour and eribulin (1.4 mg/m\^2) IV over 2 to 5 minutes on days 1 and 8 of each cycle. Cycles for both dose levels repeat every 21 days in the absence off disease progression or unacceptable toxicity. Additionally, patients undergo a CT scan and/or MRI at screening, cycle 3 day 1, and every 9 weeks thereafter. Patients also undergo a biopsy at baseline, cycle 2 day 1, and at time of disease progression as well as blood sample collection at baseline, cycle 2 day 1, every 9 weeks and at time of disease progression.	Group II (Phase II, DL1, Eribulin, Copanlisib) Group II (Phase II, DL1): Patients receive copanlisib (45 mg) IV over 1 hour and eribulin (1.1 mg/m\^2) IV over 2 to 5 minutes on days 1 and 8 of each cycle. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. Additionally, patients undergo a CT scan and/or MRI at screening, cycle 3 day 1, and every 9 weeks thereafter. Patients also undergo a biopsy at baseline, cycle 2 day 1, and at time of disease progression as well as blood sample collection at baseline, cycle 2 day 1, every 9 weeks and at time of disease progression.
Maximum Tolerated Dose of Eribulin (MTD) (Phase I)	1.1 mg/m^2	—

PRIMARY outcome

Timeframe: Up to 28 days

Population: 6 patients in DL1 and 2 patients in DL2

RP2D is the maximum tolerated dose of eribulin at which at most 1 of 6 patients experience a dose limiting toxicity during the observation window.

Outcome measures

Outcome measures
Measure	Phase I, DL and DL2 (Eribulin, Copanlisib) n=8 Participants Phase I, DL1 and DL2: DL1 patients receive copanlisib (45 mg) IV over 1 hour and eribulin (1.1 mg/m\^2) IV over 2 to 5 minutes on days 1 and 8 of each cycle. DL2 patients receive copanlisib (45 mg) IV over 1 hour and eribulin (1.4 mg/m\^2) IV over 2 to 5 minutes on days 1 and 8 of each cycle. Cycles for both dose levels repeat every 21 days in the absence off disease progression or unacceptable toxicity. Additionally, patients undergo a CT scan and/or MRI at screening, cycle 3 day 1, and every 9 weeks thereafter. Patients also undergo a biopsy at baseline, cycle 2 day 1, and at time of disease progression as well as blood sample collection at baseline, cycle 2 day 1, every 9 weeks and at time of disease progression.	Group II (Phase II, DL1, Eribulin, Copanlisib) Group II (Phase II, DL1): Patients receive copanlisib (45 mg) IV over 1 hour and eribulin (1.1 mg/m\^2) IV over 2 to 5 minutes on days 1 and 8 of each cycle. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. Additionally, patients undergo a CT scan and/or MRI at screening, cycle 3 day 1, and every 9 weeks thereafter. Patients also undergo a biopsy at baseline, cycle 2 day 1, and at time of disease progression as well as blood sample collection at baseline, cycle 2 day 1, every 9 weeks and at time of disease progression.
Recommended Phase 2 Dose of Eribulin (RP2D) (Phase I)	1.1 mg/m^2	—

PRIMARY outcome

Timeframe: Up to 28 days

Population: 6 patients in DL1 and 2 patients in DL2

MTD is defined as the highest dose level of copanlisib at which at most 1 of 6 patients experience a dose limiting toxicity during the observation window.

Outcome measures

Outcome measures
Measure	Phase I, DL and DL2 (Eribulin, Copanlisib) n=8 Participants Phase I, DL1 and DL2: DL1 patients receive copanlisib (45 mg) IV over 1 hour and eribulin (1.1 mg/m\^2) IV over 2 to 5 minutes on days 1 and 8 of each cycle. DL2 patients receive copanlisib (45 mg) IV over 1 hour and eribulin (1.4 mg/m\^2) IV over 2 to 5 minutes on days 1 and 8 of each cycle. Cycles for both dose levels repeat every 21 days in the absence off disease progression or unacceptable toxicity. Additionally, patients undergo a CT scan and/or MRI at screening, cycle 3 day 1, and every 9 weeks thereafter. Patients also undergo a biopsy at baseline, cycle 2 day 1, and at time of disease progression as well as blood sample collection at baseline, cycle 2 day 1, every 9 weeks and at time of disease progression.	Group II (Phase II, DL1, Eribulin, Copanlisib) Group II (Phase II, DL1): Patients receive copanlisib (45 mg) IV over 1 hour and eribulin (1.1 mg/m\^2) IV over 2 to 5 minutes on days 1 and 8 of each cycle. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. Additionally, patients undergo a CT scan and/or MRI at screening, cycle 3 day 1, and every 9 weeks thereafter. Patients also undergo a biopsy at baseline, cycle 2 day 1, and at time of disease progression as well as blood sample collection at baseline, cycle 2 day 1, every 9 weeks and at time of disease progression.
Maximum Tolerated Dose of Copanlisib (MTD) (Phase I)	45 mg	—

PRIMARY outcome

Timeframe: Up to 28 days

Population: 6 patients in DL1 and 2 patients in DL2

RP2D is the maximum tolerated dose of copanlisib at which at most 1 of 6 patients experience a dose limiting toxicity during the observation window.

Outcome measures

Outcome measures
Measure	Phase I, DL and DL2 (Eribulin, Copanlisib) n=8 Participants Phase I, DL1 and DL2: DL1 patients receive copanlisib (45 mg) IV over 1 hour and eribulin (1.1 mg/m\^2) IV over 2 to 5 minutes on days 1 and 8 of each cycle. DL2 patients receive copanlisib (45 mg) IV over 1 hour and eribulin (1.4 mg/m\^2) IV over 2 to 5 minutes on days 1 and 8 of each cycle. Cycles for both dose levels repeat every 21 days in the absence off disease progression or unacceptable toxicity. Additionally, patients undergo a CT scan and/or MRI at screening, cycle 3 day 1, and every 9 weeks thereafter. Patients also undergo a biopsy at baseline, cycle 2 day 1, and at time of disease progression as well as blood sample collection at baseline, cycle 2 day 1, every 9 weeks and at time of disease progression.	Group II (Phase II, DL1, Eribulin, Copanlisib) Group II (Phase II, DL1): Patients receive copanlisib (45 mg) IV over 1 hour and eribulin (1.1 mg/m\^2) IV over 2 to 5 minutes on days 1 and 8 of each cycle. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. Additionally, patients undergo a CT scan and/or MRI at screening, cycle 3 day 1, and every 9 weeks thereafter. Patients also undergo a biopsy at baseline, cycle 2 day 1, and at time of disease progression as well as blood sample collection at baseline, cycle 2 day 1, every 9 weeks and at time of disease progression.
Recommended Phase 2 Dose of Copanlisib (RP2D) (Phase I)	45 mg	—

PRIMARY outcome

Timeframe: From date of treatment start to date of progression or death, assessed up to 36 months

Population: Phase II patients only.

Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1), as a 20% increase in the sum of the longest diameter of measurable target lesions, a measurable increase in a non-target lesion, or the appearance of new lesions. Patients who have not experienced progression or death will be censored at last follow up. PFS will be estimated using the Kaplan-Meier product limit estimator.

Outcome measures

Outcome measures
Measure	Phase I, DL and DL2 (Eribulin, Copanlisib) n=8 Participants Phase I, DL1 and DL2: DL1 patients receive copanlisib (45 mg) IV over 1 hour and eribulin (1.1 mg/m\^2) IV over 2 to 5 minutes on days 1 and 8 of each cycle. DL2 patients receive copanlisib (45 mg) IV over 1 hour and eribulin (1.4 mg/m\^2) IV over 2 to 5 minutes on days 1 and 8 of each cycle. Cycles for both dose levels repeat every 21 days in the absence off disease progression or unacceptable toxicity. Additionally, patients undergo a CT scan and/or MRI at screening, cycle 3 day 1, and every 9 weeks thereafter. Patients also undergo a biopsy at baseline, cycle 2 day 1, and at time of disease progression as well as blood sample collection at baseline, cycle 2 day 1, every 9 weeks and at time of disease progression.	Group II (Phase II, DL1, Eribulin, Copanlisib) n=8 Participants Group II (Phase II, DL1): Patients receive copanlisib (45 mg) IV over 1 hour and eribulin (1.1 mg/m\^2) IV over 2 to 5 minutes on days 1 and 8 of each cycle. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. Additionally, patients undergo a CT scan and/or MRI at screening, cycle 3 day 1, and every 9 weeks thereafter. Patients also undergo a biopsy at baseline, cycle 2 day 1, and at time of disease progression as well as blood sample collection at baseline, cycle 2 day 1, every 9 weeks and at time of disease progression.
Progression Free Survival (PFS) (Phase II)	3.9 months Interval 0.4 to When fewer than half of participants have experienced disease progression, the median PFS and its upper CI bound may not be estimable. Even when the median is reached, the upper bound can still be NE (NA) if there are too few events beyond that point.	3.3 months Interval 1.7 to 5.4

SECONDARY outcome

Timeframe: Up to 36 months

Population: Phase I patients only

ORR is defined as the proportion of patients with complete response, partial response by Response Evaluation Criteria in Solid Tumors (RECIST) version (v)1.1. Per RECIST 1.1, target lesions and assessed by CT/MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions. Overall Response (OR) = CR + PR.

Outcome measures

Outcome measures
Measure	Phase I, DL and DL2 (Eribulin, Copanlisib) n=6 Participants Phase I, DL1 and DL2: DL1 patients receive copanlisib (45 mg) IV over 1 hour and eribulin (1.1 mg/m\^2) IV over 2 to 5 minutes on days 1 and 8 of each cycle. DL2 patients receive copanlisib (45 mg) IV over 1 hour and eribulin (1.4 mg/m\^2) IV over 2 to 5 minutes on days 1 and 8 of each cycle. Cycles for both dose levels repeat every 21 days in the absence off disease progression or unacceptable toxicity. Additionally, patients undergo a CT scan and/or MRI at screening, cycle 3 day 1, and every 9 weeks thereafter. Patients also undergo a biopsy at baseline, cycle 2 day 1, and at time of disease progression as well as blood sample collection at baseline, cycle 2 day 1, every 9 weeks and at time of disease progression.	Group II (Phase II, DL1, Eribulin, Copanlisib) n=2 Participants Group II (Phase II, DL1): Patients receive copanlisib (45 mg) IV over 1 hour and eribulin (1.1 mg/m\^2) IV over 2 to 5 minutes on days 1 and 8 of each cycle. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. Additionally, patients undergo a CT scan and/or MRI at screening, cycle 3 day 1, and every 9 weeks thereafter. Patients also undergo a biopsy at baseline, cycle 2 day 1, and at time of disease progression as well as blood sample collection at baseline, cycle 2 day 1, every 9 weeks and at time of disease progression.
Objective Response Rate (ORR) (Phase I)	0 Participants	1 Participants

SECONDARY outcome

Timeframe: Up to 36 months

Population: Phase I patients only

CBR defined as the proportion of patients with clinical benefit (complete response, partial response and stable disease lasting \> 24 weeks) per RECIST v1.1 in the overall population, and by PTEN/PIK3CA mutation status based on archival tumor tissue next generation sequencing. Per RECIST 1.1, target lesions and assessed by CT/MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Stable Disease (SD), Neither 30% shrinkage of longest diameter of target lesions to qualify for PR nor 20% increase in longest diameter of target lesion to qualify for PD, for a period of time greater than 24 weeks.

Outcome measures

Outcome measures
Measure	Phase I, DL and DL2 (Eribulin, Copanlisib) n=6 Participants Phase I, DL1 and DL2: DL1 patients receive copanlisib (45 mg) IV over 1 hour and eribulin (1.1 mg/m\^2) IV over 2 to 5 minutes on days 1 and 8 of each cycle. DL2 patients receive copanlisib (45 mg) IV over 1 hour and eribulin (1.4 mg/m\^2) IV over 2 to 5 minutes on days 1 and 8 of each cycle. Cycles for both dose levels repeat every 21 days in the absence off disease progression or unacceptable toxicity. Additionally, patients undergo a CT scan and/or MRI at screening, cycle 3 day 1, and every 9 weeks thereafter. Patients also undergo a biopsy at baseline, cycle 2 day 1, and at time of disease progression as well as blood sample collection at baseline, cycle 2 day 1, every 9 weeks and at time of disease progression.	Group II (Phase II, DL1, Eribulin, Copanlisib) n=2 Participants Group II (Phase II, DL1): Patients receive copanlisib (45 mg) IV over 1 hour and eribulin (1.1 mg/m\^2) IV over 2 to 5 minutes on days 1 and 8 of each cycle. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. Additionally, patients undergo a CT scan and/or MRI at screening, cycle 3 day 1, and every 9 weeks thereafter. Patients also undergo a biopsy at baseline, cycle 2 day 1, and at time of disease progression as well as blood sample collection at baseline, cycle 2 day 1, every 9 weeks and at time of disease progression.
Clinical Benefit Rate (CBR) (Phase I)	0 Participants	1 Participants

SECONDARY outcome

Timeframe: Up to 36 months

Population: Phase II patients only

Outcome measures

Outcome measures
Measure	Phase I, DL and DL2 (Eribulin, Copanlisib) n=8 Participants Phase I, DL1 and DL2: DL1 patients receive copanlisib (45 mg) IV over 1 hour and eribulin (1.1 mg/m\^2) IV over 2 to 5 minutes on days 1 and 8 of each cycle. DL2 patients receive copanlisib (45 mg) IV over 1 hour and eribulin (1.4 mg/m\^2) IV over 2 to 5 minutes on days 1 and 8 of each cycle. Cycles for both dose levels repeat every 21 days in the absence off disease progression or unacceptable toxicity. Additionally, patients undergo a CT scan and/or MRI at screening, cycle 3 day 1, and every 9 weeks thereafter. Patients also undergo a biopsy at baseline, cycle 2 day 1, and at time of disease progression as well as blood sample collection at baseline, cycle 2 day 1, every 9 weeks and at time of disease progression.	Group II (Phase II, DL1, Eribulin, Copanlisib) n=8 Participants Group II (Phase II, DL1): Patients receive copanlisib (45 mg) IV over 1 hour and eribulin (1.1 mg/m\^2) IV over 2 to 5 minutes on days 1 and 8 of each cycle. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. Additionally, patients undergo a CT scan and/or MRI at screening, cycle 3 day 1, and every 9 weeks thereafter. Patients also undergo a biopsy at baseline, cycle 2 day 1, and at time of disease progression as well as blood sample collection at baseline, cycle 2 day 1, every 9 weeks and at time of disease progression.
ORR (Phase II)	0 Participants	2 Participants

SECONDARY outcome

Timeframe: Up to 36 months

Population: Phase II patients only

CBR is defined as the proportion of patients with clinical benefit (complete response, partial response, and stable disease lasting ≥ 24 weeks) per RECIST v1.1 in each arm. Per RECIST 1.1, target lesions and assessed by CT/MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Stable Disease (SD), Neither 30% shrinkage of longest diameter of target lesions to qualify for PR nor 20% increase in longest diameter of target lesion to qualify for PD, for a period of time greater than 24 weeks.

Outcome measures

Outcome measures
Measure	Phase I, DL and DL2 (Eribulin, Copanlisib) n=8 Participants Phase I, DL1 and DL2: DL1 patients receive copanlisib (45 mg) IV over 1 hour and eribulin (1.1 mg/m\^2) IV over 2 to 5 minutes on days 1 and 8 of each cycle. DL2 patients receive copanlisib (45 mg) IV over 1 hour and eribulin (1.4 mg/m\^2) IV over 2 to 5 minutes on days 1 and 8 of each cycle. Cycles for both dose levels repeat every 21 days in the absence off disease progression or unacceptable toxicity. Additionally, patients undergo a CT scan and/or MRI at screening, cycle 3 day 1, and every 9 weeks thereafter. Patients also undergo a biopsy at baseline, cycle 2 day 1, and at time of disease progression as well as blood sample collection at baseline, cycle 2 day 1, every 9 weeks and at time of disease progression.	Group II (Phase II, DL1, Eribulin, Copanlisib) n=8 Participants Group II (Phase II, DL1): Patients receive copanlisib (45 mg) IV over 1 hour and eribulin (1.1 mg/m\^2) IV over 2 to 5 minutes on days 1 and 8 of each cycle. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. Additionally, patients undergo a CT scan and/or MRI at screening, cycle 3 day 1, and every 9 weeks thereafter. Patients also undergo a biopsy at baseline, cycle 2 day 1, and at time of disease progression as well as blood sample collection at baseline, cycle 2 day 1, every 9 weeks and at time of disease progression.
CBR (Phase II)	0 Participants	3 Participants

SECONDARY outcome

Timeframe: From start of treatment to time of progression or death, whichever occurs first, assessed up to 36 months

Population: Phase I patients only

PFS is defined from date of treatment start to date of progression or death. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1), as a 20% increase in the sum of the longest diameter of measurable target lesions, a measurable increase in a non-target lesion, or the appearance of new lesions. Patients who have not experienced progression or death will be censored at last follow up. PFS will be estimated using the Kaplan-Meier product limit estimator.

Outcome measures

Outcome measures
Measure	Phase I, DL and DL2 (Eribulin, Copanlisib) n=6 Participants Phase I, DL1 and DL2: DL1 patients receive copanlisib (45 mg) IV over 1 hour and eribulin (1.1 mg/m\^2) IV over 2 to 5 minutes on days 1 and 8 of each cycle. DL2 patients receive copanlisib (45 mg) IV over 1 hour and eribulin (1.4 mg/m\^2) IV over 2 to 5 minutes on days 1 and 8 of each cycle. Cycles for both dose levels repeat every 21 days in the absence off disease progression or unacceptable toxicity. Additionally, patients undergo a CT scan and/or MRI at screening, cycle 3 day 1, and every 9 weeks thereafter. Patients also undergo a biopsy at baseline, cycle 2 day 1, and at time of disease progression as well as blood sample collection at baseline, cycle 2 day 1, every 9 weeks and at time of disease progression.	Group II (Phase II, DL1, Eribulin, Copanlisib) n=2 Participants Group II (Phase II, DL1): Patients receive copanlisib (45 mg) IV over 1 hour and eribulin (1.1 mg/m\^2) IV over 2 to 5 minutes on days 1 and 8 of each cycle. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. Additionally, patients undergo a CT scan and/or MRI at screening, cycle 3 day 1, and every 9 weeks thereafter. Patients also undergo a biopsy at baseline, cycle 2 day 1, and at time of disease progression as well as blood sample collection at baseline, cycle 2 day 1, every 9 weeks and at time of disease progression.
PFS (Phase I)	2.3 months Interval 1.2 to When fewer than half of participants have experienced disease progression, the median PFS and its upper CI bound may not be estimable. Even when the median is reached, the upper bound can still be NE (NA) if there are too few events beyond that point.	2.6 months Interval 2.0 to When fewer than half of participants have experienced disease progression, the median PFS and its upper CI bound may not be estimable. Even when the median is reached, the upper bound can still be NE (NA) if there are too few events beyond that point.

OTHER_PRE_SPECIFIED outcome

Timeframe: Up to 36 months

Outcome measures

Outcome data not reported

Serious events: 2 serious events

Other events: 2 other events

Deaths: 2 deaths

Group I (Phase II, Eribulin)

Serious events: 1 serious events

Other events: 8 other events

Deaths: 5 deaths

Group II (Phase II, DL1, Eribulin, Copanlisib)

Serious events: 5 serious events

Other events: 8 other events

Deaths: 8 deaths

Serious adverse events

Other adverse events

Additional Information

Nusayba Bagegni

Washington University in St. Louis School of Medicine

Phone: 3142733022

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: LTE60

Serious adverse events
Measure	Phase I, DL1 (Eribulin, Copanlisib) n=6 participants at risk Phase I, DL1: Patients receive copanlisib (45 mg) IV over 1 hour and eribulin (1.1 mg/m\^2) IV over 2 to 5 minutes on days 1 and 8 of each cycle. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. Additionally, patients undergo a CT scan and/or MRI at screening, cycle 3 day 1, and every 9 weeks thereafter. Patients also undergo a biopsy at baseline, cycle 2 day 1, and at time of disease progression as well as blood sample collection at baseline, cycle 2 day 1, every 9 weeks and at time of disease progression. Biopsy Procedure: Undergo biopsy Biospecimen Collection: Undergo blood sample collection Computed Tomography: Undergo CT scan Copanlisib Hydrochloride: Given IV Eribulin Mesylate: Given IV Magnetic Resonance Imaging: Undergo MRI	Phase I, DL2 (Eribulin, Copanlisib) n=2 participants at risk Phase I, DL2: Patients receive copanlisib (45 mg) IV over 1 hour and eribulin (1.4 mg/m\^2) IV over 2 to 5 minutes on days 1 and 8 of each cycle. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. Additionally, patients undergo a CT scan and/or MRI at screening, cycle 3 day 1, and every 9 weeks thereafter. Patients also undergo a biopsy at baseline, cycle 2 day 1, and at time of disease progression as well as blood sample collection at baseline, cycle 2 day 1, every 9 weeks and at time of disease progression. Biopsy Procedure: Undergo biopsy Biospecimen Collection: Undergo blood sample collection Computed Tomography: Undergo CT scan Copanlisib Hydrochloride: Given IV Eribulin Mesylate: Given IV Magnetic Resonance Imaging: Undergo MRI	Group I (Phase II, Eribulin) n=8 participants at risk Group I (Phase II): Patients receive eribulin (1.4 mg/m\^2) IV over 2 to 5 minutes on days 1 and 8 of each cycle. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. Additionally, patients undergo a CT scan and/or MRI at screening, cycle 3 day 1, and every 9 weeks thereafter. Patients also undergo a biopsy at baseline, cycle 2 day 1, and at time of disease progression as well as blood sample collection at baseline, cycle 2 day 1, every 9 weeks and at time of disease progression. Biopsy Procedure: Undergo biopsy Biospecimen Collection: Undergo blood sample collection Computed Tomography: Undergo CT scan Eribulin Mesylate: Given IV Magnetic Resonance Imaging: Undergo MRI	Group II (Phase II, DL1, Eribulin, Copanlisib) n=8 participants at risk Group II (Phase II, DL1): Patients receive copanlisib (45 mg) IV over 1 hour and eribulin (1.1 mg/m\^2) IV over 2 to 5 minutes on days 1 and 8 of each cycle. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. Additionally, patients undergo a CT scan and/or MRI at screening, cycle 3 day 1, and every 9 weeks thereafter. Patients also undergo a biopsy at baseline, cycle 2 day 1, and at time of disease progression as well as blood sample collection at baseline, cycle 2 day 1, every 9 weeks and at time of disease progression. Biopsy Procedure: Undergo biopsy Biospecimen Collection: Undergo blood sample collection Computed Tomography: Undergo CT scan Copanlisib Hydrochloride: Given IV Eribulin Mesylate: Given IV Magnetic Resonance Imaging: Undergo MRI
Blood and lymphatic system disorders Anemia	0.00% 0/6 • Adverse events (AEs) were collected from start of treatment through follow up. Patients removed due to unacceptable AE(s), were followed until resolution or stabilization of the AE. Median AE length of follow-up was 62.5 days (full range 7-244 days). All-cause mortality was collected from start of treatment through completion of follow-up. Overall median length of follow-up was 268 days (full range 7-771 days).	50.0% 1/2 • Adverse events (AEs) were collected from start of treatment through follow up. Patients removed due to unacceptable AE(s), were followed until resolution or stabilization of the AE. Median AE length of follow-up was 62.5 days (full range 7-244 days). All-cause mortality was collected from start of treatment through completion of follow-up. Overall median length of follow-up was 268 days (full range 7-771 days).	0.00% 0/8 • Adverse events (AEs) were collected from start of treatment through follow up. Patients removed due to unacceptable AE(s), were followed until resolution or stabilization of the AE. Median AE length of follow-up was 62.5 days (full range 7-244 days). All-cause mortality was collected from start of treatment through completion of follow-up. Overall median length of follow-up was 268 days (full range 7-771 days).	12.5% 1/8 • Adverse events (AEs) were collected from start of treatment through follow up. Patients removed due to unacceptable AE(s), were followed until resolution or stabilization of the AE. Median AE length of follow-up was 62.5 days (full range 7-244 days). All-cause mortality was collected from start of treatment through completion of follow-up. Overall median length of follow-up was 268 days (full range 7-771 days).
Gastrointestinal disorders Abdominal pain	0.00% 0/6 • Adverse events (AEs) were collected from start of treatment through follow up. Patients removed due to unacceptable AE(s), were followed until resolution or stabilization of the AE. Median AE length of follow-up was 62.5 days (full range 7-244 days). All-cause mortality was collected from start of treatment through completion of follow-up. Overall median length of follow-up was 268 days (full range 7-771 days).	0.00% 0/2 • Adverse events (AEs) were collected from start of treatment through follow up. Patients removed due to unacceptable AE(s), were followed until resolution or stabilization of the AE. Median AE length of follow-up was 62.5 days (full range 7-244 days). All-cause mortality was collected from start of treatment through completion of follow-up. Overall median length of follow-up was 268 days (full range 7-771 days).	12.5% 1/8 • Adverse events (AEs) were collected from start of treatment through follow up. Patients removed due to unacceptable AE(s), were followed until resolution or stabilization of the AE. Median AE length of follow-up was 62.5 days (full range 7-244 days). All-cause mortality was collected from start of treatment through completion of follow-up. Overall median length of follow-up was 268 days (full range 7-771 days).	0.00% 0/8 • Adverse events (AEs) were collected from start of treatment through follow up. Patients removed due to unacceptable AE(s), were followed until resolution or stabilization of the AE. Median AE length of follow-up was 62.5 days (full range 7-244 days). All-cause mortality was collected from start of treatment through completion of follow-up. Overall median length of follow-up was 268 days (full range 7-771 days).
Gastrointestinal disorders Colitis	0.00% 0/6 • Adverse events (AEs) were collected from start of treatment through follow up. Patients removed due to unacceptable AE(s), were followed until resolution or stabilization of the AE. Median AE length of follow-up was 62.5 days (full range 7-244 days). All-cause mortality was collected from start of treatment through completion of follow-up. Overall median length of follow-up was 268 days (full range 7-771 days).	0.00% 0/2 • Adverse events (AEs) were collected from start of treatment through follow up. Patients removed due to unacceptable AE(s), were followed until resolution or stabilization of the AE. Median AE length of follow-up was 62.5 days (full range 7-244 days). All-cause mortality was collected from start of treatment through completion of follow-up. Overall median length of follow-up was 268 days (full range 7-771 days).	12.5% 1/8 • Adverse events (AEs) were collected from start of treatment through follow up. Patients removed due to unacceptable AE(s), were followed until resolution or stabilization of the AE. Median AE length of follow-up was 62.5 days (full range 7-244 days). All-cause mortality was collected from start of treatment through completion of follow-up. Overall median length of follow-up was 268 days (full range 7-771 days).	0.00% 0/8 • Adverse events (AEs) were collected from start of treatment through follow up. Patients removed due to unacceptable AE(s), were followed until resolution or stabilization of the AE. Median AE length of follow-up was 62.5 days (full range 7-244 days). All-cause mortality was collected from start of treatment through completion of follow-up. Overall median length of follow-up was 268 days (full range 7-771 days).
Gastrointestinal disorders Nausea	0.00% 0/6 • Adverse events (AEs) were collected from start of treatment through follow up. Patients removed due to unacceptable AE(s), were followed until resolution or stabilization of the AE. Median AE length of follow-up was 62.5 days (full range 7-244 days). All-cause mortality was collected from start of treatment through completion of follow-up. Overall median length of follow-up was 268 days (full range 7-771 days).	50.0% 1/2 • Adverse events (AEs) were collected from start of treatment through follow up. Patients removed due to unacceptable AE(s), were followed until resolution or stabilization of the AE. Median AE length of follow-up was 62.5 days (full range 7-244 days). All-cause mortality was collected from start of treatment through completion of follow-up. Overall median length of follow-up was 268 days (full range 7-771 days).	0.00% 0/8 • Adverse events (AEs) were collected from start of treatment through follow up. Patients removed due to unacceptable AE(s), were followed until resolution or stabilization of the AE. Median AE length of follow-up was 62.5 days (full range 7-244 days). All-cause mortality was collected from start of treatment through completion of follow-up. Overall median length of follow-up was 268 days (full range 7-771 days).	0.00% 0/8 • Adverse events (AEs) were collected from start of treatment through follow up. Patients removed due to unacceptable AE(s), were followed until resolution or stabilization of the AE. Median AE length of follow-up was 62.5 days (full range 7-244 days). All-cause mortality was collected from start of treatment through completion of follow-up. Overall median length of follow-up was 268 days (full range 7-771 days).
Gastrointestinal disorders Vomiting	0.00% 0/6 • Adverse events (AEs) were collected from start of treatment through follow up. Patients removed due to unacceptable AE(s), were followed until resolution or stabilization of the AE. Median AE length of follow-up was 62.5 days (full range 7-244 days). All-cause mortality was collected from start of treatment through completion of follow-up. Overall median length of follow-up was 268 days (full range 7-771 days).	50.0% 1/2 • Adverse events (AEs) were collected from start of treatment through follow up. Patients removed due to unacceptable AE(s), were followed until resolution or stabilization of the AE. Median AE length of follow-up was 62.5 days (full range 7-244 days). All-cause mortality was collected from start of treatment through completion of follow-up. Overall median length of follow-up was 268 days (full range 7-771 days).	0.00% 0/8 • Adverse events (AEs) were collected from start of treatment through follow up. Patients removed due to unacceptable AE(s), were followed until resolution or stabilization of the AE. Median AE length of follow-up was 62.5 days (full range 7-244 days). All-cause mortality was collected from start of treatment through completion of follow-up. Overall median length of follow-up was 268 days (full range 7-771 days).	0.00% 0/8 • Adverse events (AEs) were collected from start of treatment through follow up. Patients removed due to unacceptable AE(s), were followed until resolution or stabilization of the AE. Median AE length of follow-up was 62.5 days (full range 7-244 days). All-cause mortality was collected from start of treatment through completion of follow-up. Overall median length of follow-up was 268 days (full range 7-771 days).
General disorders Fever	0.00% 0/6 • Adverse events (AEs) were collected from start of treatment through follow up. Patients removed due to unacceptable AE(s), were followed until resolution or stabilization of the AE. Median AE length of follow-up was 62.5 days (full range 7-244 days). All-cause mortality was collected from start of treatment through completion of follow-up. Overall median length of follow-up was 268 days (full range 7-771 days).	0.00% 0/2 • Adverse events (AEs) were collected from start of treatment through follow up. Patients removed due to unacceptable AE(s), were followed until resolution or stabilization of the AE. Median AE length of follow-up was 62.5 days (full range 7-244 days). All-cause mortality was collected from start of treatment through completion of follow-up. Overall median length of follow-up was 268 days (full range 7-771 days).	0.00% 0/8 • Adverse events (AEs) were collected from start of treatment through follow up. Patients removed due to unacceptable AE(s), were followed until resolution or stabilization of the AE. Median AE length of follow-up was 62.5 days (full range 7-244 days). All-cause mortality was collected from start of treatment through completion of follow-up. Overall median length of follow-up was 268 days (full range 7-771 days).	12.5% 1/8 • Adverse events (AEs) were collected from start of treatment through follow up. Patients removed due to unacceptable AE(s), were followed until resolution or stabilization of the AE. Median AE length of follow-up was 62.5 days (full range 7-244 days). All-cause mortality was collected from start of treatment through completion of follow-up. Overall median length of follow-up was 268 days (full range 7-771 days).
General disorders Non-cardiac chest pain	16.7% 1/6 • Adverse events (AEs) were collected from start of treatment through follow up. Patients removed due to unacceptable AE(s), were followed until resolution or stabilization of the AE. Median AE length of follow-up was 62.5 days (full range 7-244 days). All-cause mortality was collected from start of treatment through completion of follow-up. Overall median length of follow-up was 268 days (full range 7-771 days).	0.00% 0/2 • Adverse events (AEs) were collected from start of treatment through follow up. Patients removed due to unacceptable AE(s), were followed until resolution or stabilization of the AE. Median AE length of follow-up was 62.5 days (full range 7-244 days). All-cause mortality was collected from start of treatment through completion of follow-up. Overall median length of follow-up was 268 days (full range 7-771 days).	0.00% 0/8 • Adverse events (AEs) were collected from start of treatment through follow up. Patients removed due to unacceptable AE(s), were followed until resolution or stabilization of the AE. Median AE length of follow-up was 62.5 days (full range 7-244 days). All-cause mortality was collected from start of treatment through completion of follow-up. Overall median length of follow-up was 268 days (full range 7-771 days).	12.5% 1/8 • Adverse events (AEs) were collected from start of treatment through follow up. Patients removed due to unacceptable AE(s), were followed until resolution or stabilization of the AE. Median AE length of follow-up was 62.5 days (full range 7-244 days). All-cause mortality was collected from start of treatment through completion of follow-up. Overall median length of follow-up was 268 days (full range 7-771 days).
Infections and infestations Rhinovirus	0.00% 0/6 • Adverse events (AEs) were collected from start of treatment through follow up. Patients removed due to unacceptable AE(s), were followed until resolution or stabilization of the AE. Median AE length of follow-up was 62.5 days (full range 7-244 days). All-cause mortality was collected from start of treatment through completion of follow-up. Overall median length of follow-up was 268 days (full range 7-771 days).	0.00% 0/2 • Adverse events (AEs) were collected from start of treatment through follow up. Patients removed due to unacceptable AE(s), were followed until resolution or stabilization of the AE. Median AE length of follow-up was 62.5 days (full range 7-244 days). All-cause mortality was collected from start of treatment through completion of follow-up. Overall median length of follow-up was 268 days (full range 7-771 days).	0.00% 0/8 • Adverse events (AEs) were collected from start of treatment through follow up. Patients removed due to unacceptable AE(s), were followed until resolution or stabilization of the AE. Median AE length of follow-up was 62.5 days (full range 7-244 days). All-cause mortality was collected from start of treatment through completion of follow-up. Overall median length of follow-up was 268 days (full range 7-771 days).	12.5% 1/8 • Adverse events (AEs) were collected from start of treatment through follow up. Patients removed due to unacceptable AE(s), were followed until resolution or stabilization of the AE. Median AE length of follow-up was 62.5 days (full range 7-244 days). All-cause mortality was collected from start of treatment through completion of follow-up. Overall median length of follow-up was 268 days (full range 7-771 days).
Infections and infestations Sepsis	0.00% 0/6 • Adverse events (AEs) were collected from start of treatment through follow up. Patients removed due to unacceptable AE(s), were followed until resolution or stabilization of the AE. Median AE length of follow-up was 62.5 days (full range 7-244 days). All-cause mortality was collected from start of treatment through completion of follow-up. Overall median length of follow-up was 268 days (full range 7-771 days).	0.00% 0/2 • Adverse events (AEs) were collected from start of treatment through follow up. Patients removed due to unacceptable AE(s), were followed until resolution or stabilization of the AE. Median AE length of follow-up was 62.5 days (full range 7-244 days). All-cause mortality was collected from start of treatment through completion of follow-up. Overall median length of follow-up was 268 days (full range 7-771 days).	12.5% 1/8 • Adverse events (AEs) were collected from start of treatment through follow up. Patients removed due to unacceptable AE(s), were followed until resolution or stabilization of the AE. Median AE length of follow-up was 62.5 days (full range 7-244 days). All-cause mortality was collected from start of treatment through completion of follow-up. Overall median length of follow-up was 268 days (full range 7-771 days).	0.00% 0/8 • Adverse events (AEs) were collected from start of treatment through follow up. Patients removed due to unacceptable AE(s), were followed until resolution or stabilization of the AE. Median AE length of follow-up was 62.5 days (full range 7-244 days). All-cause mortality was collected from start of treatment through completion of follow-up. Overall median length of follow-up was 268 days (full range 7-771 days).
Investigations Activated partial thromboplastin time prolonged	16.7% 1/6 • Adverse events (AEs) were collected from start of treatment through follow up. Patients removed due to unacceptable AE(s), were followed until resolution or stabilization of the AE. Median AE length of follow-up was 62.5 days (full range 7-244 days). All-cause mortality was collected from start of treatment through completion of follow-up. Overall median length of follow-up was 268 days (full range 7-771 days).	0.00% 0/2 • Adverse events (AEs) were collected from start of treatment through follow up. Patients removed due to unacceptable AE(s), were followed until resolution or stabilization of the AE. Median AE length of follow-up was 62.5 days (full range 7-244 days). All-cause mortality was collected from start of treatment through completion of follow-up. Overall median length of follow-up was 268 days (full range 7-771 days).	0.00% 0/8 • Adverse events (AEs) were collected from start of treatment through follow up. Patients removed due to unacceptable AE(s), were followed until resolution or stabilization of the AE. Median AE length of follow-up was 62.5 days (full range 7-244 days). All-cause mortality was collected from start of treatment through completion of follow-up. Overall median length of follow-up was 268 days (full range 7-771 days).	0.00% 0/8 • Adverse events (AEs) were collected from start of treatment through follow up. Patients removed due to unacceptable AE(s), were followed until resolution or stabilization of the AE. Median AE length of follow-up was 62.5 days (full range 7-244 days). All-cause mortality was collected from start of treatment through completion of follow-up. Overall median length of follow-up was 268 days (full range 7-771 days).
Investigations Lymphocyte count decreased	0.00% 0/6 • Adverse events (AEs) were collected from start of treatment through follow up. Patients removed due to unacceptable AE(s), were followed until resolution or stabilization of the AE. Median AE length of follow-up was 62.5 days (full range 7-244 days). All-cause mortality was collected from start of treatment through completion of follow-up. Overall median length of follow-up was 268 days (full range 7-771 days).	0.00% 0/2 • Adverse events (AEs) were collected from start of treatment through follow up. Patients removed due to unacceptable AE(s), were followed until resolution or stabilization of the AE. Median AE length of follow-up was 62.5 days (full range 7-244 days). All-cause mortality was collected from start of treatment through completion of follow-up. Overall median length of follow-up was 268 days (full range 7-771 days).	0.00% 0/8 • Adverse events (AEs) were collected from start of treatment through follow up. Patients removed due to unacceptable AE(s), were followed until resolution or stabilization of the AE. Median AE length of follow-up was 62.5 days (full range 7-244 days). All-cause mortality was collected from start of treatment through completion of follow-up. Overall median length of follow-up was 268 days (full range 7-771 days).	12.5% 1/8 • Adverse events (AEs) were collected from start of treatment through follow up. Patients removed due to unacceptable AE(s), were followed until resolution or stabilization of the AE. Median AE length of follow-up was 62.5 days (full range 7-244 days). All-cause mortality was collected from start of treatment through completion of follow-up. Overall median length of follow-up was 268 days (full range 7-771 days).
Investigations Neutrophil count decreased	0.00% 0/6 • Adverse events (AEs) were collected from start of treatment through follow up. Patients removed due to unacceptable AE(s), were followed until resolution or stabilization of the AE. Median AE length of follow-up was 62.5 days (full range 7-244 days). All-cause mortality was collected from start of treatment through completion of follow-up. Overall median length of follow-up was 268 days (full range 7-771 days).	0.00% 0/2 • Adverse events (AEs) were collected from start of treatment through follow up. Patients removed due to unacceptable AE(s), were followed until resolution or stabilization of the AE. Median AE length of follow-up was 62.5 days (full range 7-244 days). All-cause mortality was collected from start of treatment through completion of follow-up. Overall median length of follow-up was 268 days (full range 7-771 days).	0.00% 0/8 • Adverse events (AEs) were collected from start of treatment through follow up. Patients removed due to unacceptable AE(s), were followed until resolution or stabilization of the AE. Median AE length of follow-up was 62.5 days (full range 7-244 days). All-cause mortality was collected from start of treatment through completion of follow-up. Overall median length of follow-up was 268 days (full range 7-771 days).	25.0% 2/8 • Adverse events (AEs) were collected from start of treatment through follow up. Patients removed due to unacceptable AE(s), were followed until resolution or stabilization of the AE. Median AE length of follow-up was 62.5 days (full range 7-244 days). All-cause mortality was collected from start of treatment through completion of follow-up. Overall median length of follow-up was 268 days (full range 7-771 days).
Investigations White blood cell decreased	0.00% 0/6 • Adverse events (AEs) were collected from start of treatment through follow up. Patients removed due to unacceptable AE(s), were followed until resolution or stabilization of the AE. Median AE length of follow-up was 62.5 days (full range 7-244 days). All-cause mortality was collected from start of treatment through completion of follow-up. Overall median length of follow-up was 268 days (full range 7-771 days).	0.00% 0/2 • Adverse events (AEs) were collected from start of treatment through follow up. Patients removed due to unacceptable AE(s), were followed until resolution or stabilization of the AE. Median AE length of follow-up was 62.5 days (full range 7-244 days). All-cause mortality was collected from start of treatment through completion of follow-up. Overall median length of follow-up was 268 days (full range 7-771 days).	0.00% 0/8 • Adverse events (AEs) were collected from start of treatment through follow up. Patients removed due to unacceptable AE(s), were followed until resolution or stabilization of the AE. Median AE length of follow-up was 62.5 days (full range 7-244 days). All-cause mortality was collected from start of treatment through completion of follow-up. Overall median length of follow-up was 268 days (full range 7-771 days).	12.5% 1/8 • Adverse events (AEs) were collected from start of treatment through follow up. Patients removed due to unacceptable AE(s), were followed until resolution or stabilization of the AE. Median AE length of follow-up was 62.5 days (full range 7-244 days). All-cause mortality was collected from start of treatment through completion of follow-up. Overall median length of follow-up was 268 days (full range 7-771 days).
Metabolism and nutrition disorders Anorexia	0.00% 0/6 • Adverse events (AEs) were collected from start of treatment through follow up. Patients removed due to unacceptable AE(s), were followed until resolution or stabilization of the AE. Median AE length of follow-up was 62.5 days (full range 7-244 days). All-cause mortality was collected from start of treatment through completion of follow-up. Overall median length of follow-up was 268 days (full range 7-771 days).	50.0% 1/2 • Adverse events (AEs) were collected from start of treatment through follow up. Patients removed due to unacceptable AE(s), were followed until resolution or stabilization of the AE. Median AE length of follow-up was 62.5 days (full range 7-244 days). All-cause mortality was collected from start of treatment through completion of follow-up. Overall median length of follow-up was 268 days (full range 7-771 days).	0.00% 0/8 • Adverse events (AEs) were collected from start of treatment through follow up. Patients removed due to unacceptable AE(s), were followed until resolution or stabilization of the AE. Median AE length of follow-up was 62.5 days (full range 7-244 days). All-cause mortality was collected from start of treatment through completion of follow-up. Overall median length of follow-up was 268 days (full range 7-771 days).	0.00% 0/8 • Adverse events (AEs) were collected from start of treatment through follow up. Patients removed due to unacceptable AE(s), were followed until resolution or stabilization of the AE. Median AE length of follow-up was 62.5 days (full range 7-244 days). All-cause mortality was collected from start of treatment through completion of follow-up. Overall median length of follow-up was 268 days (full range 7-771 days).
Musculoskeletal and connective tissue disorders Myalgia	0.00% 0/6 • Adverse events (AEs) were collected from start of treatment through follow up. Patients removed due to unacceptable AE(s), were followed until resolution or stabilization of the AE. Median AE length of follow-up was 62.5 days (full range 7-244 days). All-cause mortality was collected from start of treatment through completion of follow-up. Overall median length of follow-up was 268 days (full range 7-771 days).	50.0% 1/2 • Adverse events (AEs) were collected from start of treatment through follow up. Patients removed due to unacceptable AE(s), were followed until resolution or stabilization of the AE. Median AE length of follow-up was 62.5 days (full range 7-244 days). All-cause mortality was collected from start of treatment through completion of follow-up. Overall median length of follow-up was 268 days (full range 7-771 days).	0.00% 0/8 • Adverse events (AEs) were collected from start of treatment through follow up. Patients removed due to unacceptable AE(s), were followed until resolution or stabilization of the AE. Median AE length of follow-up was 62.5 days (full range 7-244 days). All-cause mortality was collected from start of treatment through completion of follow-up. Overall median length of follow-up was 268 days (full range 7-771 days).	0.00% 0/8 • Adverse events (AEs) were collected from start of treatment through follow up. Patients removed due to unacceptable AE(s), were followed until resolution or stabilization of the AE. Median AE length of follow-up was 62.5 days (full range 7-244 days). All-cause mortality was collected from start of treatment through completion of follow-up. Overall median length of follow-up was 268 days (full range 7-771 days).
Nervous system disorders Headache	0.00% 0/6 • Adverse events (AEs) were collected from start of treatment through follow up. Patients removed due to unacceptable AE(s), were followed until resolution or stabilization of the AE. Median AE length of follow-up was 62.5 days (full range 7-244 days). All-cause mortality was collected from start of treatment through completion of follow-up. Overall median length of follow-up was 268 days (full range 7-771 days).	50.0% 1/2 • Adverse events (AEs) were collected from start of treatment through follow up. Patients removed due to unacceptable AE(s), were followed until resolution or stabilization of the AE. Median AE length of follow-up was 62.5 days (full range 7-244 days). All-cause mortality was collected from start of treatment through completion of follow-up. Overall median length of follow-up was 268 days (full range 7-771 days).	0.00% 0/8 • Adverse events (AEs) were collected from start of treatment through follow up. Patients removed due to unacceptable AE(s), were followed until resolution or stabilization of the AE. Median AE length of follow-up was 62.5 days (full range 7-244 days). All-cause mortality was collected from start of treatment through completion of follow-up. Overall median length of follow-up was 268 days (full range 7-771 days).	0.00% 0/8 • Adverse events (AEs) were collected from start of treatment through follow up. Patients removed due to unacceptable AE(s), were followed until resolution or stabilization of the AE. Median AE length of follow-up was 62.5 days (full range 7-244 days). All-cause mortality was collected from start of treatment through completion of follow-up. Overall median length of follow-up was 268 days (full range 7-771 days).
Renal and urinary disorders Acute renal failure	0.00% 0/6 • Adverse events (AEs) were collected from start of treatment through follow up. Patients removed due to unacceptable AE(s), were followed until resolution or stabilization of the AE. Median AE length of follow-up was 62.5 days (full range 7-244 days). All-cause mortality was collected from start of treatment through completion of follow-up. Overall median length of follow-up was 268 days (full range 7-771 days).	50.0% 1/2 • Adverse events (AEs) were collected from start of treatment through follow up. Patients removed due to unacceptable AE(s), were followed until resolution or stabilization of the AE. Median AE length of follow-up was 62.5 days (full range 7-244 days). All-cause mortality was collected from start of treatment through completion of follow-up. Overall median length of follow-up was 268 days (full range 7-771 days).	0.00% 0/8 • Adverse events (AEs) were collected from start of treatment through follow up. Patients removed due to unacceptable AE(s), were followed until resolution or stabilization of the AE. Median AE length of follow-up was 62.5 days (full range 7-244 days). All-cause mortality was collected from start of treatment through completion of follow-up. Overall median length of follow-up was 268 days (full range 7-771 days).	0.00% 0/8 • Adverse events (AEs) were collected from start of treatment through follow up. Patients removed due to unacceptable AE(s), were followed until resolution or stabilization of the AE. Median AE length of follow-up was 62.5 days (full range 7-244 days). All-cause mortality was collected from start of treatment through completion of follow-up. Overall median length of follow-up was 268 days (full range 7-771 days).
Respiratory, thoracic and mediastinal disorders Dyspnea	16.7% 1/6 • Adverse events (AEs) were collected from start of treatment through follow up. Patients removed due to unacceptable AE(s), were followed until resolution or stabilization of the AE. Median AE length of follow-up was 62.5 days (full range 7-244 days). All-cause mortality was collected from start of treatment through completion of follow-up. Overall median length of follow-up was 268 days (full range 7-771 days).	0.00% 0/2 • Adverse events (AEs) were collected from start of treatment through follow up. Patients removed due to unacceptable AE(s), were followed until resolution or stabilization of the AE. Median AE length of follow-up was 62.5 days (full range 7-244 days). All-cause mortality was collected from start of treatment through completion of follow-up. Overall median length of follow-up was 268 days (full range 7-771 days).	0.00% 0/8 • Adverse events (AEs) were collected from start of treatment through follow up. Patients removed due to unacceptable AE(s), were followed until resolution or stabilization of the AE. Median AE length of follow-up was 62.5 days (full range 7-244 days). All-cause mortality was collected from start of treatment through completion of follow-up. Overall median length of follow-up was 268 days (full range 7-771 days).	12.5% 1/8 • Adverse events (AEs) were collected from start of treatment through follow up. Patients removed due to unacceptable AE(s), were followed until resolution or stabilization of the AE. Median AE length of follow-up was 62.5 days (full range 7-244 days). All-cause mortality was collected from start of treatment through completion of follow-up. Overall median length of follow-up was 268 days (full range 7-771 days).
Respiratory, thoracic and mediastinal disorders Hypoxia	0.00% 0/6 • Adverse events (AEs) were collected from start of treatment through follow up. Patients removed due to unacceptable AE(s), were followed until resolution or stabilization of the AE. Median AE length of follow-up was 62.5 days (full range 7-244 days). All-cause mortality was collected from start of treatment through completion of follow-up. Overall median length of follow-up was 268 days (full range 7-771 days).	0.00% 0/2 • Adverse events (AEs) were collected from start of treatment through follow up. Patients removed due to unacceptable AE(s), were followed until resolution or stabilization of the AE. Median AE length of follow-up was 62.5 days (full range 7-244 days). All-cause mortality was collected from start of treatment through completion of follow-up. Overall median length of follow-up was 268 days (full range 7-771 days).	0.00% 0/8 • Adverse events (AEs) were collected from start of treatment through follow up. Patients removed due to unacceptable AE(s), were followed until resolution or stabilization of the AE. Median AE length of follow-up was 62.5 days (full range 7-244 days). All-cause mortality was collected from start of treatment through completion of follow-up. Overall median length of follow-up was 268 days (full range 7-771 days).	12.5% 1/8 • Adverse events (AEs) were collected from start of treatment through follow up. Patients removed due to unacceptable AE(s), were followed until resolution or stabilization of the AE. Median AE length of follow-up was 62.5 days (full range 7-244 days). All-cause mortality was collected from start of treatment through completion of follow-up. Overall median length of follow-up was 268 days (full range 7-771 days).
Respiratory, thoracic and mediastinal disorders Pleural effusion	0.00% 0/6 • Adverse events (AEs) were collected from start of treatment through follow up. Patients removed due to unacceptable AE(s), were followed until resolution or stabilization of the AE. Median AE length of follow-up was 62.5 days (full range 7-244 days). All-cause mortality was collected from start of treatment through completion of follow-up. Overall median length of follow-up was 268 days (full range 7-771 days).	0.00% 0/2 • Adverse events (AEs) were collected from start of treatment through follow up. Patients removed due to unacceptable AE(s), were followed until resolution or stabilization of the AE. Median AE length of follow-up was 62.5 days (full range 7-244 days). All-cause mortality was collected from start of treatment through completion of follow-up. Overall median length of follow-up was 268 days (full range 7-771 days).	0.00% 0/8 • Adverse events (AEs) were collected from start of treatment through follow up. Patients removed due to unacceptable AE(s), were followed until resolution or stabilization of the AE. Median AE length of follow-up was 62.5 days (full range 7-244 days). All-cause mortality was collected from start of treatment through completion of follow-up. Overall median length of follow-up was 268 days (full range 7-771 days).	25.0% 2/8 • Adverse events (AEs) were collected from start of treatment through follow up. Patients removed due to unacceptable AE(s), were followed until resolution or stabilization of the AE. Median AE length of follow-up was 62.5 days (full range 7-244 days). All-cause mortality was collected from start of treatment through completion of follow-up. Overall median length of follow-up was 268 days (full range 7-771 days).
Respiratory, thoracic and mediastinal disorders Pneumonitis	0.00% 0/6 • Adverse events (AEs) were collected from start of treatment through follow up. Patients removed due to unacceptable AE(s), were followed until resolution or stabilization of the AE. Median AE length of follow-up was 62.5 days (full range 7-244 days). All-cause mortality was collected from start of treatment through completion of follow-up. Overall median length of follow-up was 268 days (full range 7-771 days).	0.00% 0/2 • Adverse events (AEs) were collected from start of treatment through follow up. Patients removed due to unacceptable AE(s), were followed until resolution or stabilization of the AE. Median AE length of follow-up was 62.5 days (full range 7-244 days). All-cause mortality was collected from start of treatment through completion of follow-up. Overall median length of follow-up was 268 days (full range 7-771 days).	0.00% 0/8 • Adverse events (AEs) were collected from start of treatment through follow up. Patients removed due to unacceptable AE(s), were followed until resolution or stabilization of the AE. Median AE length of follow-up was 62.5 days (full range 7-244 days). All-cause mortality was collected from start of treatment through completion of follow-up. Overall median length of follow-up was 268 days (full range 7-771 days).	12.5% 1/8 • Adverse events (AEs) were collected from start of treatment through follow up. Patients removed due to unacceptable AE(s), were followed until resolution or stabilization of the AE. Median AE length of follow-up was 62.5 days (full range 7-244 days). All-cause mortality was collected from start of treatment through completion of follow-up. Overall median length of follow-up was 268 days (full range 7-771 days).
Respiratory, thoracic and mediastinal disorders Respiratory failure	0.00% 0/6 • Adverse events (AEs) were collected from start of treatment through follow up. Patients removed due to unacceptable AE(s), were followed until resolution or stabilization of the AE. Median AE length of follow-up was 62.5 days (full range 7-244 days). All-cause mortality was collected from start of treatment through completion of follow-up. Overall median length of follow-up was 268 days (full range 7-771 days).	0.00% 0/2 • Adverse events (AEs) were collected from start of treatment through follow up. Patients removed due to unacceptable AE(s), were followed until resolution or stabilization of the AE. Median AE length of follow-up was 62.5 days (full range 7-244 days). All-cause mortality was collected from start of treatment through completion of follow-up. Overall median length of follow-up was 268 days (full range 7-771 days).	0.00% 0/8 • Adverse events (AEs) were collected from start of treatment through follow up. Patients removed due to unacceptable AE(s), were followed until resolution or stabilization of the AE. Median AE length of follow-up was 62.5 days (full range 7-244 days). All-cause mortality was collected from start of treatment through completion of follow-up. Overall median length of follow-up was 268 days (full range 7-771 days).	12.5% 1/8 • Adverse events (AEs) were collected from start of treatment through follow up. Patients removed due to unacceptable AE(s), were followed until resolution or stabilization of the AE. Median AE length of follow-up was 62.5 days (full range 7-244 days). All-cause mortality was collected from start of treatment through completion of follow-up. Overall median length of follow-up was 268 days (full range 7-771 days).
Skin and subcutaneous tissue disorders Rash maculo-papular	0.00% 0/6 • Adverse events (AEs) were collected from start of treatment through follow up. Patients removed due to unacceptable AE(s), were followed until resolution or stabilization of the AE. Median AE length of follow-up was 62.5 days (full range 7-244 days). All-cause mortality was collected from start of treatment through completion of follow-up. Overall median length of follow-up was 268 days (full range 7-771 days).	0.00% 0/2 • Adverse events (AEs) were collected from start of treatment through follow up. Patients removed due to unacceptable AE(s), were followed until resolution or stabilization of the AE. Median AE length of follow-up was 62.5 days (full range 7-244 days). All-cause mortality was collected from start of treatment through completion of follow-up. Overall median length of follow-up was 268 days (full range 7-771 days).	0.00% 0/8 • Adverse events (AEs) were collected from start of treatment through follow up. Patients removed due to unacceptable AE(s), were followed until resolution or stabilization of the AE. Median AE length of follow-up was 62.5 days (full range 7-244 days). All-cause mortality was collected from start of treatment through completion of follow-up. Overall median length of follow-up was 268 days (full range 7-771 days).	12.5% 1/8 • Adverse events (AEs) were collected from start of treatment through follow up. Patients removed due to unacceptable AE(s), were followed until resolution or stabilization of the AE. Median AE length of follow-up was 62.5 days (full range 7-244 days). All-cause mortality was collected from start of treatment through completion of follow-up. Overall median length of follow-up was 268 days (full range 7-771 days).
Vascular disorders Hypertension	0.00% 0/6 • Adverse events (AEs) were collected from start of treatment through follow up. Patients removed due to unacceptable AE(s), were followed until resolution or stabilization of the AE. Median AE length of follow-up was 62.5 days (full range 7-244 days). All-cause mortality was collected from start of treatment through completion of follow-up. Overall median length of follow-up was 268 days (full range 7-771 days).	0.00% 0/2 • Adverse events (AEs) were collected from start of treatment through follow up. Patients removed due to unacceptable AE(s), were followed until resolution or stabilization of the AE. Median AE length of follow-up was 62.5 days (full range 7-244 days). All-cause mortality was collected from start of treatment through completion of follow-up. Overall median length of follow-up was 268 days (full range 7-771 days).	0.00% 0/8 • Adverse events (AEs) were collected from start of treatment through follow up. Patients removed due to unacceptable AE(s), were followed until resolution or stabilization of the AE. Median AE length of follow-up was 62.5 days (full range 7-244 days). All-cause mortality was collected from start of treatment through completion of follow-up. Overall median length of follow-up was 268 days (full range 7-771 days).	12.5% 1/8 • Adverse events (AEs) were collected from start of treatment through follow up. Patients removed due to unacceptable AE(s), were followed until resolution or stabilization of the AE. Median AE length of follow-up was 62.5 days (full range 7-244 days). All-cause mortality was collected from start of treatment through completion of follow-up. Overall median length of follow-up was 268 days (full range 7-771 days).
Vascular disorders Thromboembolic event	16.7% 1/6 • Adverse events (AEs) were collected from start of treatment through follow up. Patients removed due to unacceptable AE(s), were followed until resolution or stabilization of the AE. Median AE length of follow-up was 62.5 days (full range 7-244 days). All-cause mortality was collected from start of treatment through completion of follow-up. Overall median length of follow-up was 268 days (full range 7-771 days).	0.00% 0/2 • Adverse events (AEs) were collected from start of treatment through follow up. Patients removed due to unacceptable AE(s), were followed until resolution or stabilization of the AE. Median AE length of follow-up was 62.5 days (full range 7-244 days). All-cause mortality was collected from start of treatment through completion of follow-up. Overall median length of follow-up was 268 days (full range 7-771 days).	0.00% 0/8 • Adverse events (AEs) were collected from start of treatment through follow up. Patients removed due to unacceptable AE(s), were followed until resolution or stabilization of the AE. Median AE length of follow-up was 62.5 days (full range 7-244 days). All-cause mortality was collected from start of treatment through completion of follow-up. Overall median length of follow-up was 268 days (full range 7-771 days).	0.00% 0/8 • Adverse events (AEs) were collected from start of treatment through follow up. Patients removed due to unacceptable AE(s), were followed until resolution or stabilization of the AE. Median AE length of follow-up was 62.5 days (full range 7-244 days). All-cause mortality was collected from start of treatment through completion of follow-up. Overall median length of follow-up was 268 days (full range 7-771 days).

Other adverse events
Measure	Phase I, DL1 (Eribulin, Copanlisib) n=6 participants at risk Phase I, DL1: Patients receive copanlisib (45 mg) IV over 1 hour and eribulin (1.1 mg/m\^2) IV over 2 to 5 minutes on days 1 and 8 of each cycle. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. Additionally, patients undergo a CT scan and/or MRI at screening, cycle 3 day 1, and every 9 weeks thereafter. Patients also undergo a biopsy at baseline, cycle 2 day 1, and at time of disease progression as well as blood sample collection at baseline, cycle 2 day 1, every 9 weeks and at time of disease progression. Biopsy Procedure: Undergo biopsy Biospecimen Collection: Undergo blood sample collection Computed Tomography: Undergo CT scan Copanlisib Hydrochloride: Given IV Eribulin Mesylate: Given IV Magnetic Resonance Imaging: Undergo MRI	Phase I, DL2 (Eribulin, Copanlisib) n=2 participants at risk Phase I, DL2: Patients receive copanlisib (45 mg) IV over 1 hour and eribulin (1.4 mg/m\^2) IV over 2 to 5 minutes on days 1 and 8 of each cycle. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. Additionally, patients undergo a CT scan and/or MRI at screening, cycle 3 day 1, and every 9 weeks thereafter. Patients also undergo a biopsy at baseline, cycle 2 day 1, and at time of disease progression as well as blood sample collection at baseline, cycle 2 day 1, every 9 weeks and at time of disease progression. Biopsy Procedure: Undergo biopsy Biospecimen Collection: Undergo blood sample collection Computed Tomography: Undergo CT scan Copanlisib Hydrochloride: Given IV Eribulin Mesylate: Given IV Magnetic Resonance Imaging: Undergo MRI	Group I (Phase II, Eribulin) n=8 participants at risk Group I (Phase II): Patients receive eribulin (1.4 mg/m\^2) IV over 2 to 5 minutes on days 1 and 8 of each cycle. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. Additionally, patients undergo a CT scan and/or MRI at screening, cycle 3 day 1, and every 9 weeks thereafter. Patients also undergo a biopsy at baseline, cycle 2 day 1, and at time of disease progression as well as blood sample collection at baseline, cycle 2 day 1, every 9 weeks and at time of disease progression. Biopsy Procedure: Undergo biopsy Biospecimen Collection: Undergo blood sample collection Computed Tomography: Undergo CT scan Eribulin Mesylate: Given IV Magnetic Resonance Imaging: Undergo MRI	Group II (Phase II, DL1, Eribulin, Copanlisib) n=8 participants at risk Group II (Phase II, DL1): Patients receive copanlisib (45 mg) IV over 1 hour and eribulin (1.1 mg/m\^2) IV over 2 to 5 minutes on days 1 and 8 of each cycle. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. Additionally, patients undergo a CT scan and/or MRI at screening, cycle 3 day 1, and every 9 weeks thereafter. Patients also undergo a biopsy at baseline, cycle 2 day 1, and at time of disease progression as well as blood sample collection at baseline, cycle 2 day 1, every 9 weeks and at time of disease progression. Biopsy Procedure: Undergo biopsy Biospecimen Collection: Undergo blood sample collection Computed Tomography: Undergo CT scan Copanlisib Hydrochloride: Given IV Eribulin Mesylate: Given IV Magnetic Resonance Imaging: Undergo MRI
Blood and lymphatic system disorders Anemia	50.0% 3/6 • Adverse events (AEs) were collected from start of treatment through follow up. Patients removed due to unacceptable AE(s), were followed until resolution or stabilization of the AE. Median AE length of follow-up was 62.5 days (full range 7-244 days). All-cause mortality was collected from start of treatment through completion of follow-up. Overall median length of follow-up was 268 days (full range 7-771 days).	100.0% 2/2 • Adverse events (AEs) were collected from start of treatment through follow up. Patients removed due to unacceptable AE(s), were followed until resolution or stabilization of the AE. Median AE length of follow-up was 62.5 days (full range 7-244 days). All-cause mortality was collected from start of treatment through completion of follow-up. Overall median length of follow-up was 268 days (full range 7-771 days).	37.5% 3/8 • Adverse events (AEs) were collected from start of treatment through follow up. Patients removed due to unacceptable AE(s), were followed until resolution or stabilization of the AE. Median AE length of follow-up was 62.5 days (full range 7-244 days). All-cause mortality was collected from start of treatment through completion of follow-up. Overall median length of follow-up was 268 days (full range 7-771 days).	75.0% 6/8 • Adverse events (AEs) were collected from start of treatment through follow up. Patients removed due to unacceptable AE(s), were followed until resolution or stabilization of the AE. Median AE length of follow-up was 62.5 days (full range 7-244 days). All-cause mortality was collected from start of treatment through completion of follow-up. Overall median length of follow-up was 268 days (full range 7-771 days).
Blood and lymphatic system disorders Eosiniphilia	16.7% 1/6 • Adverse events (AEs) were collected from start of treatment through follow up. Patients removed due to unacceptable AE(s), were followed until resolution or stabilization of the AE. Median AE length of follow-up was 62.5 days (full range 7-244 days). All-cause mortality was collected from start of treatment through completion of follow-up. Overall median length of follow-up was 268 days (full range 7-771 days).	0.00% 0/2 • Adverse events (AEs) were collected from start of treatment through follow up. Patients removed due to unacceptable AE(s), were followed until resolution or stabilization of the AE. Median AE length of follow-up was 62.5 days (full range 7-244 days). All-cause mortality was collected from start of treatment through completion of follow-up. Overall median length of follow-up was 268 days (full range 7-771 days).	0.00% 0/8 • Adverse events (AEs) were collected from start of treatment through follow up. Patients removed due to unacceptable AE(s), were followed until resolution or stabilization of the AE. Median AE length of follow-up was 62.5 days (full range 7-244 days). All-cause mortality was collected from start of treatment through completion of follow-up. Overall median length of follow-up was 268 days (full range 7-771 days).	0.00% 0/8 • Adverse events (AEs) were collected from start of treatment through follow up. Patients removed due to unacceptable AE(s), were followed until resolution or stabilization of the AE. Median AE length of follow-up was 62.5 days (full range 7-244 days). All-cause mortality was collected from start of treatment through completion of follow-up. Overall median length of follow-up was 268 days (full range 7-771 days).
Cardiac disorders Sinus bradycardia	0.00% 0/6 • Adverse events (AEs) were collected from start of treatment through follow up. Patients removed due to unacceptable AE(s), were followed until resolution or stabilization of the AE. Median AE length of follow-up was 62.5 days (full range 7-244 days). All-cause mortality was collected from start of treatment through completion of follow-up. Overall median length of follow-up was 268 days (full range 7-771 days).	0.00% 0/2 • Adverse events (AEs) were collected from start of treatment through follow up. Patients removed due to unacceptable AE(s), were followed until resolution or stabilization of the AE. Median AE length of follow-up was 62.5 days (full range 7-244 days). All-cause mortality was collected from start of treatment through completion of follow-up. Overall median length of follow-up was 268 days (full range 7-771 days).	0.00% 0/8 • Adverse events (AEs) were collected from start of treatment through follow up. Patients removed due to unacceptable AE(s), were followed until resolution or stabilization of the AE. Median AE length of follow-up was 62.5 days (full range 7-244 days). All-cause mortality was collected from start of treatment through completion of follow-up. Overall median length of follow-up was 268 days (full range 7-771 days).	12.5% 1/8 • Adverse events (AEs) were collected from start of treatment through follow up. Patients removed due to unacceptable AE(s), were followed until resolution or stabilization of the AE. Median AE length of follow-up was 62.5 days (full range 7-244 days). All-cause mortality was collected from start of treatment through completion of follow-up. Overall median length of follow-up was 268 days (full range 7-771 days).
Cardiac disorders Sinus tachycardia	0.00% 0/6 • Adverse events (AEs) were collected from start of treatment through follow up. Patients removed due to unacceptable AE(s), were followed until resolution or stabilization of the AE. Median AE length of follow-up was 62.5 days (full range 7-244 days). All-cause mortality was collected from start of treatment through completion of follow-up. Overall median length of follow-up was 268 days (full range 7-771 days).	0.00% 0/2 • Adverse events (AEs) were collected from start of treatment through follow up. Patients removed due to unacceptable AE(s), were followed until resolution or stabilization of the AE. Median AE length of follow-up was 62.5 days (full range 7-244 days). All-cause mortality was collected from start of treatment through completion of follow-up. Overall median length of follow-up was 268 days (full range 7-771 days).	25.0% 2/8 • Adverse events (AEs) were collected from start of treatment through follow up. Patients removed due to unacceptable AE(s), were followed until resolution or stabilization of the AE. Median AE length of follow-up was 62.5 days (full range 7-244 days). All-cause mortality was collected from start of treatment through completion of follow-up. Overall median length of follow-up was 268 days (full range 7-771 days).	12.5% 1/8 • Adverse events (AEs) were collected from start of treatment through follow up. Patients removed due to unacceptable AE(s), were followed until resolution or stabilization of the AE. Median AE length of follow-up was 62.5 days (full range 7-244 days). All-cause mortality was collected from start of treatment through completion of follow-up. Overall median length of follow-up was 268 days (full range 7-771 days).
Cardiac disorders Ventricular arrhythmia	0.00% 0/6 • Adverse events (AEs) were collected from start of treatment through follow up. Patients removed due to unacceptable AE(s), were followed until resolution or stabilization of the AE. Median AE length of follow-up was 62.5 days (full range 7-244 days). All-cause mortality was collected from start of treatment through completion of follow-up. Overall median length of follow-up was 268 days (full range 7-771 days).	0.00% 0/2 • Adverse events (AEs) were collected from start of treatment through follow up. Patients removed due to unacceptable AE(s), were followed until resolution or stabilization of the AE. Median AE length of follow-up was 62.5 days (full range 7-244 days). All-cause mortality was collected from start of treatment through completion of follow-up. Overall median length of follow-up was 268 days (full range 7-771 days).	0.00% 0/8 • Adverse events (AEs) were collected from start of treatment through follow up. Patients removed due to unacceptable AE(s), were followed until resolution or stabilization of the AE. Median AE length of follow-up was 62.5 days (full range 7-244 days). All-cause mortality was collected from start of treatment through completion of follow-up. Overall median length of follow-up was 268 days (full range 7-771 days).	12.5% 1/8 • Adverse events (AEs) were collected from start of treatment through follow up. Patients removed due to unacceptable AE(s), were followed until resolution or stabilization of the AE. Median AE length of follow-up was 62.5 days (full range 7-244 days). All-cause mortality was collected from start of treatment through completion of follow-up. Overall median length of follow-up was 268 days (full range 7-771 days).
Ear and labyrinth disorders Fluid in ears	16.7% 1/6 • Adverse events (AEs) were collected from start of treatment through follow up. Patients removed due to unacceptable AE(s), were followed until resolution or stabilization of the AE. Median AE length of follow-up was 62.5 days (full range 7-244 days). All-cause mortality was collected from start of treatment through completion of follow-up. Overall median length of follow-up was 268 days (full range 7-771 days).	0.00% 0/2 • Adverse events (AEs) were collected from start of treatment through follow up. Patients removed due to unacceptable AE(s), were followed until resolution or stabilization of the AE. Median AE length of follow-up was 62.5 days (full range 7-244 days). All-cause mortality was collected from start of treatment through completion of follow-up. Overall median length of follow-up was 268 days (full range 7-771 days).	0.00% 0/8 • Adverse events (AEs) were collected from start of treatment through follow up. Patients removed due to unacceptable AE(s), were followed until resolution or stabilization of the AE. Median AE length of follow-up was 62.5 days (full range 7-244 days). All-cause mortality was collected from start of treatment through completion of follow-up. Overall median length of follow-up was 268 days (full range 7-771 days).	0.00% 0/8 • Adverse events (AEs) were collected from start of treatment through follow up. Patients removed due to unacceptable AE(s), were followed until resolution or stabilization of the AE. Median AE length of follow-up was 62.5 days (full range 7-244 days). All-cause mortality was collected from start of treatment through completion of follow-up. Overall median length of follow-up was 268 days (full range 7-771 days).
Ear and labyrinth disorders Vertigo	0.00% 0/6 • Adverse events (AEs) were collected from start of treatment through follow up. Patients removed due to unacceptable AE(s), were followed until resolution or stabilization of the AE. Median AE length of follow-up was 62.5 days (full range 7-244 days). All-cause mortality was collected from start of treatment through completion of follow-up. Overall median length of follow-up was 268 days (full range 7-771 days).	0.00% 0/2 • Adverse events (AEs) were collected from start of treatment through follow up. Patients removed due to unacceptable AE(s), were followed until resolution or stabilization of the AE. Median AE length of follow-up was 62.5 days (full range 7-244 days). All-cause mortality was collected from start of treatment through completion of follow-up. Overall median length of follow-up was 268 days (full range 7-771 days).	0.00% 0/8 • Adverse events (AEs) were collected from start of treatment through follow up. Patients removed due to unacceptable AE(s), were followed until resolution or stabilization of the AE. Median AE length of follow-up was 62.5 days (full range 7-244 days). All-cause mortality was collected from start of treatment through completion of follow-up. Overall median length of follow-up was 268 days (full range 7-771 days).	12.5% 1/8 • Adverse events (AEs) were collected from start of treatment through follow up. Patients removed due to unacceptable AE(s), were followed until resolution or stabilization of the AE. Median AE length of follow-up was 62.5 days (full range 7-244 days). All-cause mortality was collected from start of treatment through completion of follow-up. Overall median length of follow-up was 268 days (full range 7-771 days).
Endocrine disorders Hypothyroidism	0.00% 0/6 • Adverse events (AEs) were collected from start of treatment through follow up. Patients removed due to unacceptable AE(s), were followed until resolution or stabilization of the AE. Median AE length of follow-up was 62.5 days (full range 7-244 days). All-cause mortality was collected from start of treatment through completion of follow-up. Overall median length of follow-up was 268 days (full range 7-771 days).	50.0% 1/2 • Adverse events (AEs) were collected from start of treatment through follow up. Patients removed due to unacceptable AE(s), were followed until resolution or stabilization of the AE. Median AE length of follow-up was 62.5 days (full range 7-244 days). All-cause mortality was collected from start of treatment through completion of follow-up. Overall median length of follow-up was 268 days (full range 7-771 days).	0.00% 0/8 • Adverse events (AEs) were collected from start of treatment through follow up. Patients removed due to unacceptable AE(s), were followed until resolution or stabilization of the AE. Median AE length of follow-up was 62.5 days (full range 7-244 days). All-cause mortality was collected from start of treatment through completion of follow-up. Overall median length of follow-up was 268 days (full range 7-771 days).	0.00% 0/8 • Adverse events (AEs) were collected from start of treatment through follow up. Patients removed due to unacceptable AE(s), were followed until resolution or stabilization of the AE. Median AE length of follow-up was 62.5 days (full range 7-244 days). All-cause mortality was collected from start of treatment through completion of follow-up. Overall median length of follow-up was 268 days (full range 7-771 days).
Eye disorders Periorbital edema	16.7% 1/6 • Adverse events (AEs) were collected from start of treatment through follow up. Patients removed due to unacceptable AE(s), were followed until resolution or stabilization of the AE. Median AE length of follow-up was 62.5 days (full range 7-244 days). All-cause mortality was collected from start of treatment through completion of follow-up. Overall median length of follow-up was 268 days (full range 7-771 days).	0.00% 0/2 • Adverse events (AEs) were collected from start of treatment through follow up. Patients removed due to unacceptable AE(s), were followed until resolution or stabilization of the AE. Median AE length of follow-up was 62.5 days (full range 7-244 days). All-cause mortality was collected from start of treatment through completion of follow-up. Overall median length of follow-up was 268 days (full range 7-771 days).	0.00% 0/8 • Adverse events (AEs) were collected from start of treatment through follow up. Patients removed due to unacceptable AE(s), were followed until resolution or stabilization of the AE. Median AE length of follow-up was 62.5 days (full range 7-244 days). All-cause mortality was collected from start of treatment through completion of follow-up. Overall median length of follow-up was 268 days (full range 7-771 days).	0.00% 0/8 • Adverse events (AEs) were collected from start of treatment through follow up. Patients removed due to unacceptable AE(s), were followed until resolution or stabilization of the AE. Median AE length of follow-up was 62.5 days (full range 7-244 days). All-cause mortality was collected from start of treatment through completion of follow-up. Overall median length of follow-up was 268 days (full range 7-771 days).
Eye disorders itching/discharge from R eye	16.7% 1/6 • Adverse events (AEs) were collected from start of treatment through follow up. Patients removed due to unacceptable AE(s), were followed until resolution or stabilization of the AE. Median AE length of follow-up was 62.5 days (full range 7-244 days). All-cause mortality was collected from start of treatment through completion of follow-up. Overall median length of follow-up was 268 days (full range 7-771 days).	0.00% 0/2 • Adverse events (AEs) were collected from start of treatment through follow up. Patients removed due to unacceptable AE(s), were followed until resolution or stabilization of the AE. Median AE length of follow-up was 62.5 days (full range 7-244 days). All-cause mortality was collected from start of treatment through completion of follow-up. Overall median length of follow-up was 268 days (full range 7-771 days).	0.00% 0/8 • Adverse events (AEs) were collected from start of treatment through follow up. Patients removed due to unacceptable AE(s), were followed until resolution or stabilization of the AE. Median AE length of follow-up was 62.5 days (full range 7-244 days). All-cause mortality was collected from start of treatment through completion of follow-up. Overall median length of follow-up was 268 days (full range 7-771 days).	0.00% 0/8 • Adverse events (AEs) were collected from start of treatment through follow up. Patients removed due to unacceptable AE(s), were followed until resolution or stabilization of the AE. Median AE length of follow-up was 62.5 days (full range 7-244 days). All-cause mortality was collected from start of treatment through completion of follow-up. Overall median length of follow-up was 268 days (full range 7-771 days).
Gastrointestinal disorders Abdominal pain	0.00% 0/6 • Adverse events (AEs) were collected from start of treatment through follow up. Patients removed due to unacceptable AE(s), were followed until resolution or stabilization of the AE. Median AE length of follow-up was 62.5 days (full range 7-244 days). All-cause mortality was collected from start of treatment through completion of follow-up. Overall median length of follow-up was 268 days (full range 7-771 days).	0.00% 0/2 • Adverse events (AEs) were collected from start of treatment through follow up. Patients removed due to unacceptable AE(s), were followed until resolution or stabilization of the AE. Median AE length of follow-up was 62.5 days (full range 7-244 days). All-cause mortality was collected from start of treatment through completion of follow-up. Overall median length of follow-up was 268 days (full range 7-771 days).	12.5% 1/8 • Adverse events (AEs) were collected from start of treatment through follow up. Patients removed due to unacceptable AE(s), were followed until resolution or stabilization of the AE. Median AE length of follow-up was 62.5 days (full range 7-244 days). All-cause mortality was collected from start of treatment through completion of follow-up. Overall median length of follow-up was 268 days (full range 7-771 days).	25.0% 2/8 • Adverse events (AEs) were collected from start of treatment through follow up. Patients removed due to unacceptable AE(s), were followed until resolution or stabilization of the AE. Median AE length of follow-up was 62.5 days (full range 7-244 days). All-cause mortality was collected from start of treatment through completion of follow-up. Overall median length of follow-up was 268 days (full range 7-771 days).
Gastrointestinal disorders Colitis	0.00% 0/6 • Adverse events (AEs) were collected from start of treatment through follow up. Patients removed due to unacceptable AE(s), were followed until resolution or stabilization of the AE. Median AE length of follow-up was 62.5 days (full range 7-244 days). All-cause mortality was collected from start of treatment through completion of follow-up. Overall median length of follow-up was 268 days (full range 7-771 days).	0.00% 0/2 • Adverse events (AEs) were collected from start of treatment through follow up. Patients removed due to unacceptable AE(s), were followed until resolution or stabilization of the AE. Median AE length of follow-up was 62.5 days (full range 7-244 days). All-cause mortality was collected from start of treatment through completion of follow-up. Overall median length of follow-up was 268 days (full range 7-771 days).	12.5% 1/8 • Adverse events (AEs) were collected from start of treatment through follow up. Patients removed due to unacceptable AE(s), were followed until resolution or stabilization of the AE. Median AE length of follow-up was 62.5 days (full range 7-244 days). All-cause mortality was collected from start of treatment through completion of follow-up. Overall median length of follow-up was 268 days (full range 7-771 days).	0.00% 0/8 • Adverse events (AEs) were collected from start of treatment through follow up. Patients removed due to unacceptable AE(s), were followed until resolution or stabilization of the AE. Median AE length of follow-up was 62.5 days (full range 7-244 days). All-cause mortality was collected from start of treatment through completion of follow-up. Overall median length of follow-up was 268 days (full range 7-771 days).
Gastrointestinal disorders Constipation	16.7% 1/6 • Adverse events (AEs) were collected from start of treatment through follow up. Patients removed due to unacceptable AE(s), were followed until resolution or stabilization of the AE. Median AE length of follow-up was 62.5 days (full range 7-244 days). All-cause mortality was collected from start of treatment through completion of follow-up. Overall median length of follow-up was 268 days (full range 7-771 days).	0.00% 0/2 • Adverse events (AEs) were collected from start of treatment through follow up. Patients removed due to unacceptable AE(s), were followed until resolution or stabilization of the AE. Median AE length of follow-up was 62.5 days (full range 7-244 days). All-cause mortality was collected from start of treatment through completion of follow-up. Overall median length of follow-up was 268 days (full range 7-771 days).	37.5% 3/8 • Adverse events (AEs) were collected from start of treatment through follow up. Patients removed due to unacceptable AE(s), were followed until resolution or stabilization of the AE. Median AE length of follow-up was 62.5 days (full range 7-244 days). All-cause mortality was collected from start of treatment through completion of follow-up. Overall median length of follow-up was 268 days (full range 7-771 days).	25.0% 2/8 • Adverse events (AEs) were collected from start of treatment through follow up. Patients removed due to unacceptable AE(s), were followed until resolution or stabilization of the AE. Median AE length of follow-up was 62.5 days (full range 7-244 days). All-cause mortality was collected from start of treatment through completion of follow-up. Overall median length of follow-up was 268 days (full range 7-771 days).
Gastrointestinal disorders Diarrhea	16.7% 1/6 • Adverse events (AEs) were collected from start of treatment through follow up. Patients removed due to unacceptable AE(s), were followed until resolution or stabilization of the AE. Median AE length of follow-up was 62.5 days (full range 7-244 days). All-cause mortality was collected from start of treatment through completion of follow-up. Overall median length of follow-up was 268 days (full range 7-771 days).	50.0% 1/2 • Adverse events (AEs) were collected from start of treatment through follow up. Patients removed due to unacceptable AE(s), were followed until resolution or stabilization of the AE. Median AE length of follow-up was 62.5 days (full range 7-244 days). All-cause mortality was collected from start of treatment through completion of follow-up. Overall median length of follow-up was 268 days (full range 7-771 days).	25.0% 2/8 • Adverse events (AEs) were collected from start of treatment through follow up. Patients removed due to unacceptable AE(s), were followed until resolution or stabilization of the AE. Median AE length of follow-up was 62.5 days (full range 7-244 days). All-cause mortality was collected from start of treatment through completion of follow-up. Overall median length of follow-up was 268 days (full range 7-771 days).	37.5% 3/8 • Adverse events (AEs) were collected from start of treatment through follow up. Patients removed due to unacceptable AE(s), were followed until resolution or stabilization of the AE. Median AE length of follow-up was 62.5 days (full range 7-244 days). All-cause mortality was collected from start of treatment through completion of follow-up. Overall median length of follow-up was 268 days (full range 7-771 days).
Gastrointestinal disorders Dry mouth	0.00% 0/6 • Adverse events (AEs) were collected from start of treatment through follow up. Patients removed due to unacceptable AE(s), were followed until resolution or stabilization of the AE. Median AE length of follow-up was 62.5 days (full range 7-244 days). All-cause mortality was collected from start of treatment through completion of follow-up. Overall median length of follow-up was 268 days (full range 7-771 days).	0.00% 0/2 • Adverse events (AEs) were collected from start of treatment through follow up. Patients removed due to unacceptable AE(s), were followed until resolution or stabilization of the AE. Median AE length of follow-up was 62.5 days (full range 7-244 days). All-cause mortality was collected from start of treatment through completion of follow-up. Overall median length of follow-up was 268 days (full range 7-771 days).	12.5% 1/8 • Adverse events (AEs) were collected from start of treatment through follow up. Patients removed due to unacceptable AE(s), were followed until resolution or stabilization of the AE. Median AE length of follow-up was 62.5 days (full range 7-244 days). All-cause mortality was collected from start of treatment through completion of follow-up. Overall median length of follow-up was 268 days (full range 7-771 days).	12.5% 1/8 • Adverse events (AEs) were collected from start of treatment through follow up. Patients removed due to unacceptable AE(s), were followed until resolution or stabilization of the AE. Median AE length of follow-up was 62.5 days (full range 7-244 days). All-cause mortality was collected from start of treatment through completion of follow-up. Overall median length of follow-up was 268 days (full range 7-771 days).
Gastrointestinal disorders Dyspepsia	0.00% 0/6 • Adverse events (AEs) were collected from start of treatment through follow up. Patients removed due to unacceptable AE(s), were followed until resolution or stabilization of the AE. Median AE length of follow-up was 62.5 days (full range 7-244 days). All-cause mortality was collected from start of treatment through completion of follow-up. Overall median length of follow-up was 268 days (full range 7-771 days).	50.0% 1/2 • Adverse events (AEs) were collected from start of treatment through follow up. Patients removed due to unacceptable AE(s), were followed until resolution or stabilization of the AE. Median AE length of follow-up was 62.5 days (full range 7-244 days). All-cause mortality was collected from start of treatment through completion of follow-up. Overall median length of follow-up was 268 days (full range 7-771 days).	0.00% 0/8 • Adverse events (AEs) were collected from start of treatment through follow up. Patients removed due to unacceptable AE(s), were followed until resolution or stabilization of the AE. Median AE length of follow-up was 62.5 days (full range 7-244 days). All-cause mortality was collected from start of treatment through completion of follow-up. Overall median length of follow-up was 268 days (full range 7-771 days).	12.5% 1/8 • Adverse events (AEs) were collected from start of treatment through follow up. Patients removed due to unacceptable AE(s), were followed until resolution or stabilization of the AE. Median AE length of follow-up was 62.5 days (full range 7-244 days). All-cause mortality was collected from start of treatment through completion of follow-up. Overall median length of follow-up was 268 days (full range 7-771 days).
Gastrointestinal disorders Dysphagia	0.00% 0/6 • Adverse events (AEs) were collected from start of treatment through follow up. Patients removed due to unacceptable AE(s), were followed until resolution or stabilization of the AE. Median AE length of follow-up was 62.5 days (full range 7-244 days). All-cause mortality was collected from start of treatment through completion of follow-up. Overall median length of follow-up was 268 days (full range 7-771 days).	0.00% 0/2 • Adverse events (AEs) were collected from start of treatment through follow up. Patients removed due to unacceptable AE(s), were followed until resolution or stabilization of the AE. Median AE length of follow-up was 62.5 days (full range 7-244 days). All-cause mortality was collected from start of treatment through completion of follow-up. Overall median length of follow-up was 268 days (full range 7-771 days).	12.5% 1/8 • Adverse events (AEs) were collected from start of treatment through follow up. Patients removed due to unacceptable AE(s), were followed until resolution or stabilization of the AE. Median AE length of follow-up was 62.5 days (full range 7-244 days). All-cause mortality was collected from start of treatment through completion of follow-up. Overall median length of follow-up was 268 days (full range 7-771 days).	0.00% 0/8 • Adverse events (AEs) were collected from start of treatment through follow up. Patients removed due to unacceptable AE(s), were followed until resolution or stabilization of the AE. Median AE length of follow-up was 62.5 days (full range 7-244 days). All-cause mortality was collected from start of treatment through completion of follow-up. Overall median length of follow-up was 268 days (full range 7-771 days).
Gastrointestinal disorders Esophageal pain	0.00% 0/6 • Adverse events (AEs) were collected from start of treatment through follow up. Patients removed due to unacceptable AE(s), were followed until resolution or stabilization of the AE. Median AE length of follow-up was 62.5 days (full range 7-244 days). All-cause mortality was collected from start of treatment through completion of follow-up. Overall median length of follow-up was 268 days (full range 7-771 days).	0.00% 0/2 • Adverse events (AEs) were collected from start of treatment through follow up. Patients removed due to unacceptable AE(s), were followed until resolution or stabilization of the AE. Median AE length of follow-up was 62.5 days (full range 7-244 days). All-cause mortality was collected from start of treatment through completion of follow-up. Overall median length of follow-up was 268 days (full range 7-771 days).	12.5% 1/8 • Adverse events (AEs) were collected from start of treatment through follow up. Patients removed due to unacceptable AE(s), were followed until resolution or stabilization of the AE. Median AE length of follow-up was 62.5 days (full range 7-244 days). All-cause mortality was collected from start of treatment through completion of follow-up. Overall median length of follow-up was 268 days (full range 7-771 days).	0.00% 0/8 • Adverse events (AEs) were collected from start of treatment through follow up. Patients removed due to unacceptable AE(s), were followed until resolution or stabilization of the AE. Median AE length of follow-up was 62.5 days (full range 7-244 days). All-cause mortality was collected from start of treatment through completion of follow-up. Overall median length of follow-up was 268 days (full range 7-771 days).
Gastrointestinal disorders Fecal incontinence	0.00% 0/6 • Adverse events (AEs) were collected from start of treatment through follow up. Patients removed due to unacceptable AE(s), were followed until resolution or stabilization of the AE. Median AE length of follow-up was 62.5 days (full range 7-244 days). All-cause mortality was collected from start of treatment through completion of follow-up. Overall median length of follow-up was 268 days (full range 7-771 days).	0.00% 0/2 • Adverse events (AEs) were collected from start of treatment through follow up. Patients removed due to unacceptable AE(s), were followed until resolution or stabilization of the AE. Median AE length of follow-up was 62.5 days (full range 7-244 days). All-cause mortality was collected from start of treatment through completion of follow-up. Overall median length of follow-up was 268 days (full range 7-771 days).	0.00% 0/8 • Adverse events (AEs) were collected from start of treatment through follow up. Patients removed due to unacceptable AE(s), were followed until resolution or stabilization of the AE. Median AE length of follow-up was 62.5 days (full range 7-244 days). All-cause mortality was collected from start of treatment through completion of follow-up. Overall median length of follow-up was 268 days (full range 7-771 days).	12.5% 1/8 • Adverse events (AEs) were collected from start of treatment through follow up. Patients removed due to unacceptable AE(s), were followed until resolution or stabilization of the AE. Median AE length of follow-up was 62.5 days (full range 7-244 days). All-cause mortality was collected from start of treatment through completion of follow-up. Overall median length of follow-up was 268 days (full range 7-771 days).
Gastrointestinal disorders Gastroesophageal reflux disease	16.7% 1/6 • Adverse events (AEs) were collected from start of treatment through follow up. Patients removed due to unacceptable AE(s), were followed until resolution or stabilization of the AE. Median AE length of follow-up was 62.5 days (full range 7-244 days). All-cause mortality was collected from start of treatment through completion of follow-up. Overall median length of follow-up was 268 days (full range 7-771 days).	0.00% 0/2 • Adverse events (AEs) were collected from start of treatment through follow up. Patients removed due to unacceptable AE(s), were followed until resolution or stabilization of the AE. Median AE length of follow-up was 62.5 days (full range 7-244 days). All-cause mortality was collected from start of treatment through completion of follow-up. Overall median length of follow-up was 268 days (full range 7-771 days).	12.5% 1/8 • Adverse events (AEs) were collected from start of treatment through follow up. Patients removed due to unacceptable AE(s), were followed until resolution or stabilization of the AE. Median AE length of follow-up was 62.5 days (full range 7-244 days). All-cause mortality was collected from start of treatment through completion of follow-up. Overall median length of follow-up was 268 days (full range 7-771 days).	0.00% 0/8 • Adverse events (AEs) were collected from start of treatment through follow up. Patients removed due to unacceptable AE(s), were followed until resolution or stabilization of the AE. Median AE length of follow-up was 62.5 days (full range 7-244 days). All-cause mortality was collected from start of treatment through completion of follow-up. Overall median length of follow-up was 268 days (full range 7-771 days).
Gastrointestinal disorders Hemorrhoidal hemorhage	16.7% 1/6 • Adverse events (AEs) were collected from start of treatment through follow up. Patients removed due to unacceptable AE(s), were followed until resolution or stabilization of the AE. Median AE length of follow-up was 62.5 days (full range 7-244 days). All-cause mortality was collected from start of treatment through completion of follow-up. Overall median length of follow-up was 268 days (full range 7-771 days).	0.00% 0/2 • Adverse events (AEs) were collected from start of treatment through follow up. Patients removed due to unacceptable AE(s), were followed until resolution or stabilization of the AE. Median AE length of follow-up was 62.5 days (full range 7-244 days). All-cause mortality was collected from start of treatment through completion of follow-up. Overall median length of follow-up was 268 days (full range 7-771 days).	0.00% 0/8 • Adverse events (AEs) were collected from start of treatment through follow up. Patients removed due to unacceptable AE(s), were followed until resolution or stabilization of the AE. Median AE length of follow-up was 62.5 days (full range 7-244 days). All-cause mortality was collected from start of treatment through completion of follow-up. Overall median length of follow-up was 268 days (full range 7-771 days).	0.00% 0/8 • Adverse events (AEs) were collected from start of treatment through follow up. Patients removed due to unacceptable AE(s), were followed until resolution or stabilization of the AE. Median AE length of follow-up was 62.5 days (full range 7-244 days). All-cause mortality was collected from start of treatment through completion of follow-up. Overall median length of follow-up was 268 days (full range 7-771 days).
Gastrointestinal disorders Mucositis oral	0.00% 0/6 • Adverse events (AEs) were collected from start of treatment through follow up. Patients removed due to unacceptable AE(s), were followed until resolution or stabilization of the AE. Median AE length of follow-up was 62.5 days (full range 7-244 days). All-cause mortality was collected from start of treatment through completion of follow-up. Overall median length of follow-up was 268 days (full range 7-771 days).	0.00% 0/2 • Adverse events (AEs) were collected from start of treatment through follow up. Patients removed due to unacceptable AE(s), were followed until resolution or stabilization of the AE. Median AE length of follow-up was 62.5 days (full range 7-244 days). All-cause mortality was collected from start of treatment through completion of follow-up. Overall median length of follow-up was 268 days (full range 7-771 days).	12.5% 1/8 • Adverse events (AEs) were collected from start of treatment through follow up. Patients removed due to unacceptable AE(s), were followed until resolution or stabilization of the AE. Median AE length of follow-up was 62.5 days (full range 7-244 days). All-cause mortality was collected from start of treatment through completion of follow-up. Overall median length of follow-up was 268 days (full range 7-771 days).	25.0% 2/8 • Adverse events (AEs) were collected from start of treatment through follow up. Patients removed due to unacceptable AE(s), were followed until resolution or stabilization of the AE. Median AE length of follow-up was 62.5 days (full range 7-244 days). All-cause mortality was collected from start of treatment through completion of follow-up. Overall median length of follow-up was 268 days (full range 7-771 days).
Gastrointestinal disorders Nausea	16.7% 1/6 • Adverse events (AEs) were collected from start of treatment through follow up. Patients removed due to unacceptable AE(s), were followed until resolution or stabilization of the AE. Median AE length of follow-up was 62.5 days (full range 7-244 days). All-cause mortality was collected from start of treatment through completion of follow-up. Overall median length of follow-up was 268 days (full range 7-771 days).	100.0% 2/2 • Adverse events (AEs) were collected from start of treatment through follow up. Patients removed due to unacceptable AE(s), were followed until resolution or stabilization of the AE. Median AE length of follow-up was 62.5 days (full range 7-244 days). All-cause mortality was collected from start of treatment through completion of follow-up. Overall median length of follow-up was 268 days (full range 7-771 days).	12.5% 1/8 • Adverse events (AEs) were collected from start of treatment through follow up. Patients removed due to unacceptable AE(s), were followed until resolution or stabilization of the AE. Median AE length of follow-up was 62.5 days (full range 7-244 days). All-cause mortality was collected from start of treatment through completion of follow-up. Overall median length of follow-up was 268 days (full range 7-771 days).	87.5% 7/8 • Adverse events (AEs) were collected from start of treatment through follow up. Patients removed due to unacceptable AE(s), were followed until resolution or stabilization of the AE. Median AE length of follow-up was 62.5 days (full range 7-244 days). All-cause mortality was collected from start of treatment through completion of follow-up. Overall median length of follow-up was 268 days (full range 7-771 days).
Gastrointestinal disorders Rectal hemorrhage	16.7% 1/6 • Adverse events (AEs) were collected from start of treatment through follow up. Patients removed due to unacceptable AE(s), were followed until resolution or stabilization of the AE. Median AE length of follow-up was 62.5 days (full range 7-244 days). All-cause mortality was collected from start of treatment through completion of follow-up. Overall median length of follow-up was 268 days (full range 7-771 days).	0.00% 0/2 • Adverse events (AEs) were collected from start of treatment through follow up. Patients removed due to unacceptable AE(s), were followed until resolution or stabilization of the AE. Median AE length of follow-up was 62.5 days (full range 7-244 days). All-cause mortality was collected from start of treatment through completion of follow-up. Overall median length of follow-up was 268 days (full range 7-771 days).	0.00% 0/8 • Adverse events (AEs) were collected from start of treatment through follow up. Patients removed due to unacceptable AE(s), were followed until resolution or stabilization of the AE. Median AE length of follow-up was 62.5 days (full range 7-244 days). All-cause mortality was collected from start of treatment through completion of follow-up. Overall median length of follow-up was 268 days (full range 7-771 days).	0.00% 0/8 • Adverse events (AEs) were collected from start of treatment through follow up. Patients removed due to unacceptable AE(s), were followed until resolution or stabilization of the AE. Median AE length of follow-up was 62.5 days (full range 7-244 days). All-cause mortality was collected from start of treatment through completion of follow-up. Overall median length of follow-up was 268 days (full range 7-771 days).
Gastrointestinal disorders Vomiting	0.00% 0/6 • Adverse events (AEs) were collected from start of treatment through follow up. Patients removed due to unacceptable AE(s), were followed until resolution or stabilization of the AE. Median AE length of follow-up was 62.5 days (full range 7-244 days). All-cause mortality was collected from start of treatment through completion of follow-up. Overall median length of follow-up was 268 days (full range 7-771 days).	50.0% 1/2 • Adverse events (AEs) were collected from start of treatment through follow up. Patients removed due to unacceptable AE(s), were followed until resolution or stabilization of the AE. Median AE length of follow-up was 62.5 days (full range 7-244 days). All-cause mortality was collected from start of treatment through completion of follow-up. Overall median length of follow-up was 268 days (full range 7-771 days).	12.5% 1/8 • Adverse events (AEs) were collected from start of treatment through follow up. Patients removed due to unacceptable AE(s), were followed until resolution or stabilization of the AE. Median AE length of follow-up was 62.5 days (full range 7-244 days). All-cause mortality was collected from start of treatment through completion of follow-up. Overall median length of follow-up was 268 days (full range 7-771 days).	25.0% 2/8 • Adverse events (AEs) were collected from start of treatment through follow up. Patients removed due to unacceptable AE(s), were followed until resolution or stabilization of the AE. Median AE length of follow-up was 62.5 days (full range 7-244 days). All-cause mortality was collected from start of treatment through completion of follow-up. Overall median length of follow-up was 268 days (full range 7-771 days).
General disorders Axillary lymphadenopathy	0.00% 0/6 • Adverse events (AEs) were collected from start of treatment through follow up. Patients removed due to unacceptable AE(s), were followed until resolution or stabilization of the AE. Median AE length of follow-up was 62.5 days (full range 7-244 days). All-cause mortality was collected from start of treatment through completion of follow-up. Overall median length of follow-up was 268 days (full range 7-771 days).	0.00% 0/2 • Adverse events (AEs) were collected from start of treatment through follow up. Patients removed due to unacceptable AE(s), were followed until resolution or stabilization of the AE. Median AE length of follow-up was 62.5 days (full range 7-244 days). All-cause mortality was collected from start of treatment through completion of follow-up. Overall median length of follow-up was 268 days (full range 7-771 days).	12.5% 1/8 • Adverse events (AEs) were collected from start of treatment through follow up. Patients removed due to unacceptable AE(s), were followed until resolution or stabilization of the AE. Median AE length of follow-up was 62.5 days (full range 7-244 days). All-cause mortality was collected from start of treatment through completion of follow-up. Overall median length of follow-up was 268 days (full range 7-771 days).	0.00% 0/8 • Adverse events (AEs) were collected from start of treatment through follow up. Patients removed due to unacceptable AE(s), were followed until resolution or stabilization of the AE. Median AE length of follow-up was 62.5 days (full range 7-244 days). All-cause mortality was collected from start of treatment through completion of follow-up. Overall median length of follow-up was 268 days (full range 7-771 days).
General disorders Chills	16.7% 1/6 • Adverse events (AEs) were collected from start of treatment through follow up. Patients removed due to unacceptable AE(s), were followed until resolution or stabilization of the AE. Median AE length of follow-up was 62.5 days (full range 7-244 days). All-cause mortality was collected from start of treatment through completion of follow-up. Overall median length of follow-up was 268 days (full range 7-771 days).	0.00% 0/2 • Adverse events (AEs) were collected from start of treatment through follow up. Patients removed due to unacceptable AE(s), were followed until resolution or stabilization of the AE. Median AE length of follow-up was 62.5 days (full range 7-244 days). All-cause mortality was collected from start of treatment through completion of follow-up. Overall median length of follow-up was 268 days (full range 7-771 days).	0.00% 0/8 • Adverse events (AEs) were collected from start of treatment through follow up. Patients removed due to unacceptable AE(s), were followed until resolution or stabilization of the AE. Median AE length of follow-up was 62.5 days (full range 7-244 days). All-cause mortality was collected from start of treatment through completion of follow-up. Overall median length of follow-up was 268 days (full range 7-771 days).	12.5% 1/8 • Adverse events (AEs) were collected from start of treatment through follow up. Patients removed due to unacceptable AE(s), were followed until resolution or stabilization of the AE. Median AE length of follow-up was 62.5 days (full range 7-244 days). All-cause mortality was collected from start of treatment through completion of follow-up. Overall median length of follow-up was 268 days (full range 7-771 days).
General disorders Edema limbs	0.00% 0/6 • Adverse events (AEs) were collected from start of treatment through follow up. Patients removed due to unacceptable AE(s), were followed until resolution or stabilization of the AE. Median AE length of follow-up was 62.5 days (full range 7-244 days). All-cause mortality was collected from start of treatment through completion of follow-up. Overall median length of follow-up was 268 days (full range 7-771 days).	0.00% 0/2 • Adverse events (AEs) were collected from start of treatment through follow up. Patients removed due to unacceptable AE(s), were followed until resolution or stabilization of the AE. Median AE length of follow-up was 62.5 days (full range 7-244 days). All-cause mortality was collected from start of treatment through completion of follow-up. Overall median length of follow-up was 268 days (full range 7-771 days).	0.00% 0/8 • Adverse events (AEs) were collected from start of treatment through follow up. Patients removed due to unacceptable AE(s), were followed until resolution or stabilization of the AE. Median AE length of follow-up was 62.5 days (full range 7-244 days). All-cause mortality was collected from start of treatment through completion of follow-up. Overall median length of follow-up was 268 days (full range 7-771 days).	25.0% 2/8 • Adverse events (AEs) were collected from start of treatment through follow up. Patients removed due to unacceptable AE(s), were followed until resolution or stabilization of the AE. Median AE length of follow-up was 62.5 days (full range 7-244 days). All-cause mortality was collected from start of treatment through completion of follow-up. Overall median length of follow-up was 268 days (full range 7-771 days).
General disorders Fatigue	50.0% 3/6 • Adverse events (AEs) were collected from start of treatment through follow up. Patients removed due to unacceptable AE(s), were followed until resolution or stabilization of the AE. Median AE length of follow-up was 62.5 days (full range 7-244 days). All-cause mortality was collected from start of treatment through completion of follow-up. Overall median length of follow-up was 268 days (full range 7-771 days).	0.00% 0/2 • Adverse events (AEs) were collected from start of treatment through follow up. Patients removed due to unacceptable AE(s), were followed until resolution or stabilization of the AE. Median AE length of follow-up was 62.5 days (full range 7-244 days). All-cause mortality was collected from start of treatment through completion of follow-up. Overall median length of follow-up was 268 days (full range 7-771 days).	50.0% 4/8 • Adverse events (AEs) were collected from start of treatment through follow up. Patients removed due to unacceptable AE(s), were followed until resolution or stabilization of the AE. Median AE length of follow-up was 62.5 days (full range 7-244 days). All-cause mortality was collected from start of treatment through completion of follow-up. Overall median length of follow-up was 268 days (full range 7-771 days).	62.5% 5/8 • Adverse events (AEs) were collected from start of treatment through follow up. Patients removed due to unacceptable AE(s), were followed until resolution or stabilization of the AE. Median AE length of follow-up was 62.5 days (full range 7-244 days). All-cause mortality was collected from start of treatment through completion of follow-up. Overall median length of follow-up was 268 days (full range 7-771 days).
General disorders Fever	0.00% 0/6 • Adverse events (AEs) were collected from start of treatment through follow up. Patients removed due to unacceptable AE(s), were followed until resolution or stabilization of the AE. Median AE length of follow-up was 62.5 days (full range 7-244 days). All-cause mortality was collected from start of treatment through completion of follow-up. Overall median length of follow-up was 268 days (full range 7-771 days).	0.00% 0/2 • Adverse events (AEs) were collected from start of treatment through follow up. Patients removed due to unacceptable AE(s), were followed until resolution or stabilization of the AE. Median AE length of follow-up was 62.5 days (full range 7-244 days). All-cause mortality was collected from start of treatment through completion of follow-up. Overall median length of follow-up was 268 days (full range 7-771 days).	0.00% 0/8 • Adverse events (AEs) were collected from start of treatment through follow up. Patients removed due to unacceptable AE(s), were followed until resolution or stabilization of the AE. Median AE length of follow-up was 62.5 days (full range 7-244 days). All-cause mortality was collected from start of treatment through completion of follow-up. Overall median length of follow-up was 268 days (full range 7-771 days).	25.0% 2/8 • Adverse events (AEs) were collected from start of treatment through follow up. Patients removed due to unacceptable AE(s), were followed until resolution or stabilization of the AE. Median AE length of follow-up was 62.5 days (full range 7-244 days). All-cause mortality was collected from start of treatment through completion of follow-up. Overall median length of follow-up was 268 days (full range 7-771 days).
General disorders Flu-like symptoms	16.7% 1/6 • Adverse events (AEs) were collected from start of treatment through follow up. Patients removed due to unacceptable AE(s), were followed until resolution or stabilization of the AE. Median AE length of follow-up was 62.5 days (full range 7-244 days). All-cause mortality was collected from start of treatment through completion of follow-up. Overall median length of follow-up was 268 days (full range 7-771 days).	0.00% 0/2 • Adverse events (AEs) were collected from start of treatment through follow up. Patients removed due to unacceptable AE(s), were followed until resolution or stabilization of the AE. Median AE length of follow-up was 62.5 days (full range 7-244 days). All-cause mortality was collected from start of treatment through completion of follow-up. Overall median length of follow-up was 268 days (full range 7-771 days).	12.5% 1/8 • Adverse events (AEs) were collected from start of treatment through follow up. Patients removed due to unacceptable AE(s), were followed until resolution or stabilization of the AE. Median AE length of follow-up was 62.5 days (full range 7-244 days). All-cause mortality was collected from start of treatment through completion of follow-up. Overall median length of follow-up was 268 days (full range 7-771 days).	12.5% 1/8 • Adverse events (AEs) were collected from start of treatment through follow up. Patients removed due to unacceptable AE(s), were followed until resolution or stabilization of the AE. Median AE length of follow-up was 62.5 days (full range 7-244 days). All-cause mortality was collected from start of treatment through completion of follow-up. Overall median length of follow-up was 268 days (full range 7-771 days).
General disorders Gait disturbance	0.00% 0/6 • Adverse events (AEs) were collected from start of treatment through follow up. Patients removed due to unacceptable AE(s), were followed until resolution or stabilization of the AE. Median AE length of follow-up was 62.5 days (full range 7-244 days). All-cause mortality was collected from start of treatment through completion of follow-up. Overall median length of follow-up was 268 days (full range 7-771 days).	0.00% 0/2 • Adverse events (AEs) were collected from start of treatment through follow up. Patients removed due to unacceptable AE(s), were followed until resolution or stabilization of the AE. Median AE length of follow-up was 62.5 days (full range 7-244 days). All-cause mortality was collected from start of treatment through completion of follow-up. Overall median length of follow-up was 268 days (full range 7-771 days).	0.00% 0/8 • Adverse events (AEs) were collected from start of treatment through follow up. Patients removed due to unacceptable AE(s), were followed until resolution or stabilization of the AE. Median AE length of follow-up was 62.5 days (full range 7-244 days). All-cause mortality was collected from start of treatment through completion of follow-up. Overall median length of follow-up was 268 days (full range 7-771 days).	12.5% 1/8 • Adverse events (AEs) were collected from start of treatment through follow up. Patients removed due to unacceptable AE(s), were followed until resolution or stabilization of the AE. Median AE length of follow-up was 62.5 days (full range 7-244 days). All-cause mortality was collected from start of treatment through completion of follow-up. Overall median length of follow-up was 268 days (full range 7-771 days).
General disorders Malaise	0.00% 0/6 • Adverse events (AEs) were collected from start of treatment through follow up. Patients removed due to unacceptable AE(s), were followed until resolution or stabilization of the AE. Median AE length of follow-up was 62.5 days (full range 7-244 days). All-cause mortality was collected from start of treatment through completion of follow-up. Overall median length of follow-up was 268 days (full range 7-771 days).	0.00% 0/2 • Adverse events (AEs) were collected from start of treatment through follow up. Patients removed due to unacceptable AE(s), were followed until resolution or stabilization of the AE. Median AE length of follow-up was 62.5 days (full range 7-244 days). All-cause mortality was collected from start of treatment through completion of follow-up. Overall median length of follow-up was 268 days (full range 7-771 days).	0.00% 0/8 • Adverse events (AEs) were collected from start of treatment through follow up. Patients removed due to unacceptable AE(s), were followed until resolution or stabilization of the AE. Median AE length of follow-up was 62.5 days (full range 7-244 days). All-cause mortality was collected from start of treatment through completion of follow-up. Overall median length of follow-up was 268 days (full range 7-771 days).	12.5% 1/8 • Adverse events (AEs) were collected from start of treatment through follow up. Patients removed due to unacceptable AE(s), were followed until resolution or stabilization of the AE. Median AE length of follow-up was 62.5 days (full range 7-244 days). All-cause mortality was collected from start of treatment through completion of follow-up. Overall median length of follow-up was 268 days (full range 7-771 days).
General disorders Multi-organ failure	0.00% 0/6 • Adverse events (AEs) were collected from start of treatment through follow up. Patients removed due to unacceptable AE(s), were followed until resolution or stabilization of the AE. Median AE length of follow-up was 62.5 days (full range 7-244 days). All-cause mortality was collected from start of treatment through completion of follow-up. Overall median length of follow-up was 268 days (full range 7-771 days).	50.0% 1/2 • Adverse events (AEs) were collected from start of treatment through follow up. Patients removed due to unacceptable AE(s), were followed until resolution or stabilization of the AE. Median AE length of follow-up was 62.5 days (full range 7-244 days). All-cause mortality was collected from start of treatment through completion of follow-up. Overall median length of follow-up was 268 days (full range 7-771 days).	0.00% 0/8 • Adverse events (AEs) were collected from start of treatment through follow up. Patients removed due to unacceptable AE(s), were followed until resolution or stabilization of the AE. Median AE length of follow-up was 62.5 days (full range 7-244 days). All-cause mortality was collected from start of treatment through completion of follow-up. Overall median length of follow-up was 268 days (full range 7-771 days).	0.00% 0/8 • Adverse events (AEs) were collected from start of treatment through follow up. Patients removed due to unacceptable AE(s), were followed until resolution or stabilization of the AE. Median AE length of follow-up was 62.5 days (full range 7-244 days). All-cause mortality was collected from start of treatment through completion of follow-up. Overall median length of follow-up was 268 days (full range 7-771 days).
General disorders Non-cardiac chest pain	0.00% 0/6 • Adverse events (AEs) were collected from start of treatment through follow up. Patients removed due to unacceptable AE(s), were followed until resolution or stabilization of the AE. Median AE length of follow-up was 62.5 days (full range 7-244 days). All-cause mortality was collected from start of treatment through completion of follow-up. Overall median length of follow-up was 268 days (full range 7-771 days).	0.00% 0/2 • Adverse events (AEs) were collected from start of treatment through follow up. Patients removed due to unacceptable AE(s), were followed until resolution or stabilization of the AE. Median AE length of follow-up was 62.5 days (full range 7-244 days). All-cause mortality was collected from start of treatment through completion of follow-up. Overall median length of follow-up was 268 days (full range 7-771 days).	12.5% 1/8 • Adverse events (AEs) were collected from start of treatment through follow up. Patients removed due to unacceptable AE(s), were followed until resolution or stabilization of the AE. Median AE length of follow-up was 62.5 days (full range 7-244 days). All-cause mortality was collected from start of treatment through completion of follow-up. Overall median length of follow-up was 268 days (full range 7-771 days).	0.00% 0/8 • Adverse events (AEs) were collected from start of treatment through follow up. Patients removed due to unacceptable AE(s), were followed until resolution or stabilization of the AE. Median AE length of follow-up was 62.5 days (full range 7-244 days). All-cause mortality was collected from start of treatment through completion of follow-up. Overall median length of follow-up was 268 days (full range 7-771 days).
General disorders Pain	0.00% 0/6 • Adverse events (AEs) were collected from start of treatment through follow up. Patients removed due to unacceptable AE(s), were followed until resolution or stabilization of the AE. Median AE length of follow-up was 62.5 days (full range 7-244 days). All-cause mortality was collected from start of treatment through completion of follow-up. Overall median length of follow-up was 268 days (full range 7-771 days).	0.00% 0/2 • Adverse events (AEs) were collected from start of treatment through follow up. Patients removed due to unacceptable AE(s), were followed until resolution or stabilization of the AE. Median AE length of follow-up was 62.5 days (full range 7-244 days). All-cause mortality was collected from start of treatment through completion of follow-up. Overall median length of follow-up was 268 days (full range 7-771 days).	12.5% 1/8 • Adverse events (AEs) were collected from start of treatment through follow up. Patients removed due to unacceptable AE(s), were followed until resolution or stabilization of the AE. Median AE length of follow-up was 62.5 days (full range 7-244 days). All-cause mortality was collected from start of treatment through completion of follow-up. Overall median length of follow-up was 268 days (full range 7-771 days).	25.0% 2/8 • Adverse events (AEs) were collected from start of treatment through follow up. Patients removed due to unacceptable AE(s), were followed until resolution or stabilization of the AE. Median AE length of follow-up was 62.5 days (full range 7-244 days). All-cause mortality was collected from start of treatment through completion of follow-up. Overall median length of follow-up was 268 days (full range 7-771 days).
Infections and infestations Herpes simplex reactivation	0.00% 0/6 • Adverse events (AEs) were collected from start of treatment through follow up. Patients removed due to unacceptable AE(s), were followed until resolution or stabilization of the AE. Median AE length of follow-up was 62.5 days (full range 7-244 days). All-cause mortality was collected from start of treatment through completion of follow-up. Overall median length of follow-up was 268 days (full range 7-771 days).	0.00% 0/2 • Adverse events (AEs) were collected from start of treatment through follow up. Patients removed due to unacceptable AE(s), were followed until resolution or stabilization of the AE. Median AE length of follow-up was 62.5 days (full range 7-244 days). All-cause mortality was collected from start of treatment through completion of follow-up. Overall median length of follow-up was 268 days (full range 7-771 days).	0.00% 0/8 • Adverse events (AEs) were collected from start of treatment through follow up. Patients removed due to unacceptable AE(s), were followed until resolution or stabilization of the AE. Median AE length of follow-up was 62.5 days (full range 7-244 days). All-cause mortality was collected from start of treatment through completion of follow-up. Overall median length of follow-up was 268 days (full range 7-771 days).	12.5% 1/8 • Adverse events (AEs) were collected from start of treatment through follow up. Patients removed due to unacceptable AE(s), were followed until resolution or stabilization of the AE. Median AE length of follow-up was 62.5 days (full range 7-244 days). All-cause mortality was collected from start of treatment through completion of follow-up. Overall median length of follow-up was 268 days (full range 7-771 days).
Infections and infestations Papulopustular rash	0.00% 0/6 • Adverse events (AEs) were collected from start of treatment through follow up. Patients removed due to unacceptable AE(s), were followed until resolution or stabilization of the AE. Median AE length of follow-up was 62.5 days (full range 7-244 days). All-cause mortality was collected from start of treatment through completion of follow-up. Overall median length of follow-up was 268 days (full range 7-771 days).	0.00% 0/2 • Adverse events (AEs) were collected from start of treatment through follow up. Patients removed due to unacceptable AE(s), were followed until resolution or stabilization of the AE. Median AE length of follow-up was 62.5 days (full range 7-244 days). All-cause mortality was collected from start of treatment through completion of follow-up. Overall median length of follow-up was 268 days (full range 7-771 days).	0.00% 0/8 • Adverse events (AEs) were collected from start of treatment through follow up. Patients removed due to unacceptable AE(s), were followed until resolution or stabilization of the AE. Median AE length of follow-up was 62.5 days (full range 7-244 days). All-cause mortality was collected from start of treatment through completion of follow-up. Overall median length of follow-up was 268 days (full range 7-771 days).	12.5% 1/8 • Adverse events (AEs) were collected from start of treatment through follow up. Patients removed due to unacceptable AE(s), were followed until resolution or stabilization of the AE. Median AE length of follow-up was 62.5 days (full range 7-244 days). All-cause mortality was collected from start of treatment through completion of follow-up. Overall median length of follow-up was 268 days (full range 7-771 days).
Infections and infestations Shingles	0.00% 0/6 • Adverse events (AEs) were collected from start of treatment through follow up. Patients removed due to unacceptable AE(s), were followed until resolution or stabilization of the AE. Median AE length of follow-up was 62.5 days (full range 7-244 days). All-cause mortality was collected from start of treatment through completion of follow-up. Overall median length of follow-up was 268 days (full range 7-771 days).	0.00% 0/2 • Adverse events (AEs) were collected from start of treatment through follow up. Patients removed due to unacceptable AE(s), were followed until resolution or stabilization of the AE. Median AE length of follow-up was 62.5 days (full range 7-244 days). All-cause mortality was collected from start of treatment through completion of follow-up. Overall median length of follow-up was 268 days (full range 7-771 days).	0.00% 0/8 • Adverse events (AEs) were collected from start of treatment through follow up. Patients removed due to unacceptable AE(s), were followed until resolution or stabilization of the AE. Median AE length of follow-up was 62.5 days (full range 7-244 days). All-cause mortality was collected from start of treatment through completion of follow-up. Overall median length of follow-up was 268 days (full range 7-771 days).	12.5% 1/8 • Adverse events (AEs) were collected from start of treatment through follow up. Patients removed due to unacceptable AE(s), were followed until resolution or stabilization of the AE. Median AE length of follow-up was 62.5 days (full range 7-244 days). All-cause mortality was collected from start of treatment through completion of follow-up. Overall median length of follow-up was 268 days (full range 7-771 days).
Infections and infestations Sinusitis	16.7% 1/6 • Adverse events (AEs) were collected from start of treatment through follow up. Patients removed due to unacceptable AE(s), were followed until resolution or stabilization of the AE. Median AE length of follow-up was 62.5 days (full range 7-244 days). All-cause mortality was collected from start of treatment through completion of follow-up. Overall median length of follow-up was 268 days (full range 7-771 days).	0.00% 0/2 • Adverse events (AEs) were collected from start of treatment through follow up. Patients removed due to unacceptable AE(s), were followed until resolution or stabilization of the AE. Median AE length of follow-up was 62.5 days (full range 7-244 days). All-cause mortality was collected from start of treatment through completion of follow-up. Overall median length of follow-up was 268 days (full range 7-771 days).	0.00% 0/8 • Adverse events (AEs) were collected from start of treatment through follow up. Patients removed due to unacceptable AE(s), were followed until resolution or stabilization of the AE. Median AE length of follow-up was 62.5 days (full range 7-244 days). All-cause mortality was collected from start of treatment through completion of follow-up. Overall median length of follow-up was 268 days (full range 7-771 days).	0.00% 0/8 • Adverse events (AEs) were collected from start of treatment through follow up. Patients removed due to unacceptable AE(s), were followed until resolution or stabilization of the AE. Median AE length of follow-up was 62.5 days (full range 7-244 days). All-cause mortality was collected from start of treatment through completion of follow-up. Overall median length of follow-up was 268 days (full range 7-771 days).