Trial Outcomes & Findings for A Study of ZW25 (Zanidatamab) in Subjects With Advanced or Metastatic HER2-Amplified Biliary Tract Cancers (NCT NCT04466891)

Last Updated: 2025-09-15

Results Overview

Number of participants who achieved a confirmed best overall response (BOR) of either complete response (CR) or partial response (PR) during treatment per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. Complete response (CR) is defined as a disappearance of all target and non-target lesions and partial response (PR) is defined as at least a 30% decrease in the sum of diameters of all target lesions.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

87 participants

Primary outcome timeframe

Up to 34 months

Results posted on

2025-09-15

Participant Flow

A total of 87 participants who met all eligibility criteria were enrolled and received treatment.

Participants must have received at least 1 prior gemcitabine-containing systemic chemotherapy regimen for advanced disease and experienced disease progression after or developed intolerance to the most recent prior therapy.

Participant milestones

Participant milestones
Measure	Cohort I Participants with advanced or metastatic biliary tract cancer with HER2 amplification by in situ hybridization (ISH) and HER2 overexpression by immunohistochemistry (IHC) which includes IHC 2+ or 3+	Cohort II Participants with advanced or metastatic biliary tract cancer with HER2 amplification by ISH and HER2 IHC 0 or 1+.
Overall Study STARTED	80	7
Overall Study COMPLETED	0	0
Overall Study NOT COMPLETED	80	7

Reasons for withdrawal

Reasons for withdrawal
Measure	Cohort I Participants with advanced or metastatic biliary tract cancer with HER2 amplification by in situ hybridization (ISH) and HER2 overexpression by immunohistochemistry (IHC) which includes IHC 2+ or 3+	Cohort II Participants with advanced or metastatic biliary tract cancer with HER2 amplification by ISH and HER2 IHC 0 or 1+.
Overall Study Death	60	6
Overall Study Withdrawal by Subject	8	1
Overall Study Study terminated by sponsor	5	0
Overall Study Lost to Follow-up	2	0
Overall Study Transitioned to Named Patient Supply (NPS) program	5	0

Baseline Characteristics

A Study of ZW25 (Zanidatamab) in Subjects With Advanced or Metastatic HER2-Amplified Biliary Tract Cancers

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Cohort I n=80 Participants Participants with advanced or metastatic biliary tract cancer with HER2 amplification by in situ hybridization (ISH) and HER2 overexpression by immunohistochemistry (IHC) which includes IHC 2+ or 3+	Cohort II n=7 Participants Participants with advanced or metastatic biliary tract cancer with HER2 amplification by ISH and HER2 IHC 0 or 1+.	Total n=87 Participants Total of all reporting groups
Age, Continuous	62.5 years STANDARD_DEVIATION 9.56 • n=5 Participants	65.4 years STANDARD_DEVIATION 8.75 • n=7 Participants	62.7 years STANDARD_DEVIATION 9.48 • n=5 Participants
Sex: Female, Male Female	45 Participants n=5 Participants	2 Participants n=7 Participants	47 Participants n=5 Participants
Sex: Female, Male Male	35 Participants n=5 Participants	5 Participants n=7 Participants	40 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	5 Participants n=5 Participants	1 Participants n=7 Participants	6 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	72 Participants n=5 Participants	6 Participants n=7 Participants	78 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	3 Participants n=5 Participants	0 Participants n=7 Participants	3 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) Asian	52 Participants n=5 Participants	5 Participants n=7 Participants	57 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) White	23 Participants n=5 Participants	2 Participants n=7 Participants	25 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	4 Participants n=5 Participants	0 Participants n=7 Participants	4 Participants n=5 Participants

PRIMARY outcome

Timeframe: Up to 34 months

Population: Assessed in participants with available data in the Efficacy Analysis Set.

Outcome measures

Outcome measures
Measure	Cohort I n=80 Participants Participants with advanced or metastatic biliary tract cancer with HER2 amplification by in situ hybridization (ISH) and HER2 overexpression by immunohistochemistry (IHC) which includes IHC 2+ or 3+	Cohort II n=7 Participants Participants with advanced or metastatic biliary tract cancer with HER2 amplification by ISH and HER2 IHC 0 or 1+.
Confirmed Objective Response Rate (ORR) by Independent Central Review (ICR)	33 Participants	0 Participants

SECONDARY outcome

Timeframe: Up to 45 months

Population: Only participants with a response (a confirmed Complete Response (CR) or confirmed Partial Response (PR)), as evaluated by ICR, were evaluated for this outcome.

The time from the first confirmed objective response (CR or PR) to documented progressive disease (PD) per RECIST 1.1, or death from any cause

Outcome measures

Outcome measures
Measure	Cohort I n=33 Participants Participants with advanced or metastatic biliary tract cancer with HER2 amplification by in situ hybridization (ISH) and HER2 overexpression by immunohistochemistry (IHC) which includes IHC 2+ or 3+	Cohort II Participants with advanced or metastatic biliary tract cancer with HER2 amplification by ISH and HER2 IHC 0 or 1+.
Duration of Response (DOR) by ICR	14.92 months Interval 7.39 to 23.98	—

SECONDARY outcome

Timeframe: 24 weeks, up to 45 months

Population: Only participants with a response (a confirmed Complete Response (CR) or confirmed Partial Response (PR)), as evaluated by ICR, were evaluated for this outcome.

Proportion of subjects with a DOR ≥ 16 weeks per RECIST 1.1

Outcome measures

Outcome measures
Measure	Cohort I n=33 Participants Participants with advanced or metastatic biliary tract cancer with HER2 amplification by in situ hybridization (ISH) and HER2 overexpression by immunohistochemistry (IHC) which includes IHC 2+ or 3+	Cohort II Participants with advanced or metastatic biliary tract cancer with HER2 amplification by ISH and HER2 IHC 0 or 1+.
DOR ≥ 16 Weeks by ICR	28 Participants	—

SECONDARY outcome

Timeframe: Up to 45 months

Number of subjects who achieved a best overall response of stable disease (SD), non-CR/non-PD, or confirmed CR or PR per RECIST 1.1

Outcome measures

Outcome measures
Measure	Cohort I n=80 Participants Participants with advanced or metastatic biliary tract cancer with HER2 amplification by in situ hybridization (ISH) and HER2 overexpression by immunohistochemistry (IHC) which includes IHC 2+ or 3+	Cohort II n=7 Participants Participants with advanced or metastatic biliary tract cancer with HER2 amplification by ISH and HER2 IHC 0 or 1+.
Disease Control Rate (DCR) by ICR	55 Participants	3 Participants

SECONDARY outcome

Timeframe: Up to 45 months

The time from the first dose of study treatment to the date of documented disease progression (per RECIST 1.1), or death from any cause

Outcome measures

Outcome measures
Measure	Cohort I n=80 Participants Participants with advanced or metastatic biliary tract cancer with HER2 amplification by in situ hybridization (ISH) and HER2 overexpression by immunohistochemistry (IHC) which includes IHC 2+ or 3+	Cohort II n=7 Participants Participants with advanced or metastatic biliary tract cancer with HER2 amplification by ISH and HER2 IHC 0 or 1+.
Progression-free Survival (PFS) by ICR	5.49 months Interval 3.65 to 7.29	1.87 months Interval 1.22 to Upper Confidence Interval (CI) not estimable due to insufficient events

SECONDARY outcome

Timeframe: Up to 45 months

Number of subjects who achieved a confirmed BOR of either CR or PR during treatment per RECIST 1.1

Outcome measures

Outcome measures
Measure	Cohort I n=80 Participants Participants with advanced or metastatic biliary tract cancer with HER2 amplification by in situ hybridization (ISH) and HER2 overexpression by immunohistochemistry (IHC) which includes IHC 2+ or 3+	Cohort II n=7 Participants Participants with advanced or metastatic biliary tract cancer with HER2 amplification by ISH and HER2 IHC 0 or 1+.
ORR by Investigator Assessment	34 Participants	0 Participants

SECONDARY outcome

Timeframe: Up to 45 months

Population: Only participants with a response (a confirmed Complete Response (CR) or confirmed Partial Response (PR)) as per investigator assessment, were evaluated for this outcome.

The time from the first confirmed objective response (CR or PR) to documented progressive disease (PD) per RECIST 1.1, or death from any cause

Outcome measures

Outcome measures
Measure	Cohort I n=34 Participants Participants with advanced or metastatic biliary tract cancer with HER2 amplification by in situ hybridization (ISH) and HER2 overexpression by immunohistochemistry (IHC) which includes IHC 2+ or 3+	Cohort II Participants with advanced or metastatic biliary tract cancer with HER2 amplification by ISH and HER2 IHC 0 or 1+.
DOR by Investigator Assessment	11.10 months Interval 7.46 to 14.06	—

SECONDARY outcome

Timeframe: 24 weeks, up to 45 months

Population: Only participants with a response (a confirmed Complete Response (CR) or confirmed Partial Response (PR)) as per investigator assessment, were evaluated for this outcome.

Proportion of subjects with a DOR ≥ 16 weeks per RECIST 1.1

Outcome measures

Outcome measures
Measure	Cohort I n=34 Participants Participants with advanced or metastatic biliary tract cancer with HER2 amplification by in situ hybridization (ISH) and HER2 overexpression by immunohistochemistry (IHC) which includes IHC 2+ or 3+	Cohort II Participants with advanced or metastatic biliary tract cancer with HER2 amplification by ISH and HER2 IHC 0 or 1+.
DOR ≥ 16 Weeks by Investigator Assessment	31 Participants	—

SECONDARY outcome

Timeframe: Up to 45 months

Number of subjects who achieved a best overall response of stable disease (SD), non-CR/non-PD, or confirmed CR or PR per RECIST 1.1

Outcome measures

Outcome measures
Measure	Cohort I n=80 Participants Participants with advanced or metastatic biliary tract cancer with HER2 amplification by in situ hybridization (ISH) and HER2 overexpression by immunohistochemistry (IHC) which includes IHC 2+ or 3+	Cohort II n=7 Participants Participants with advanced or metastatic biliary tract cancer with HER2 amplification by ISH and HER2 IHC 0 or 1+.
DCR by Investigator Assessment	54 Participants	1 Participants

SECONDARY outcome

Timeframe: Up to 45 months

The time from the first dose of study treatment to the date of documented disease progression (per RECIST 1.1), or death from any cause

Outcome measures

Outcome measures
Measure	Cohort I n=80 Participants Participants with advanced or metastatic biliary tract cancer with HER2 amplification by in situ hybridization (ISH) and HER2 overexpression by immunohistochemistry (IHC) which includes IHC 2+ or 3+	Cohort II n=7 Participants Participants with advanced or metastatic biliary tract cancer with HER2 amplification by ISH and HER2 IHC 0 or 1+.
PFS by Investigator Assessment	5.37 months Interval 3.55 to 7.29	1.77 months Interval 0.79 to 1.94

SECONDARY outcome

Timeframe: Up to 45 months

The time from the first dose of study treatment until the date of death from any cause

Outcome measures

Outcome measures
Measure	Cohort I n=80 Participants Participants with advanced or metastatic biliary tract cancer with HER2 amplification by in situ hybridization (ISH) and HER2 overexpression by immunohistochemistry (IHC) which includes IHC 2+ or 3+	Cohort II n=7 Participants Participants with advanced or metastatic biliary tract cancer with HER2 amplification by ISH and HER2 IHC 0 or 1+.
Overall Survival	15.54 months Interval 10.38 to 18.66	5.52 months Interval 1.22 to Upper CI not estimable due to insufficient events

SECONDARY outcome

Timeframe: Up to 45 months

Number of subjects who experienced AEs or serious adverse events

Outcome measures

Outcome measures
Measure	Cohort I n=80 Participants Participants with advanced or metastatic biliary tract cancer with HER2 amplification by in situ hybridization (ISH) and HER2 overexpression by immunohistochemistry (IHC) which includes IHC 2+ or 3+	Cohort II n=7 Participants Participants with advanced or metastatic biliary tract cancer with HER2 amplification by ISH and HER2 IHC 0 or 1+.
Incidence of Adverse Events (AEs) Any Treatment Emergent Adverse Event (TEAE)	78 Participants	6 Participants
Incidence of Adverse Events (AEs) Zanidatamab related TEAE	61 Participants	2 Participants
Incidence of Adverse Events (AEs) Any Treatment Emergent Serious Adverse Event	43 Participants	3 Participants
Incidence of Adverse Events (AEs) Zanidatamab related serious TEAE	8 Participants	0 Participants
Incidence of Adverse Events (AEs) Zanidatamab related TEAE resulting in treatment discontinuation	2 Participants	0 Participants

SECONDARY outcome

Timeframe: Up to 45 months

Number of subjects who experienced a maximum severity of Grade 3 or higher post-baseline laboratory abnormality, including either hematology or chemistry. Grades are defined using National Cancer Institute's Common Terminology Criteria for Adverse Events (CTCAE), version 5.0

Outcome measures

Outcome measures
Measure	Cohort I n=80 Participants Participants with advanced or metastatic biliary tract cancer with HER2 amplification by in situ hybridization (ISH) and HER2 overexpression by immunohistochemistry (IHC) which includes IHC 2+ or 3+	Cohort II n=7 Participants Participants with advanced or metastatic biliary tract cancer with HER2 amplification by ISH and HER2 IHC 0 or 1+.
Incidence of Laboratory Abnormalities	37 Participants	7 Participants

SECONDARY outcome

Timeframe: Pre-dose, end of infusion, 2, 4, 8, 24 and 96 hours post dose

Population: All subjects who received any amount of zanidatamab and have at least 1 post-baseline PK assessment were included in this outcome

Outcome measures

Outcome measures
Measure	Cohort I n=80 Participants Participants with advanced or metastatic biliary tract cancer with HER2 amplification by in situ hybridization (ISH) and HER2 overexpression by immunohistochemistry (IHC) which includes IHC 2+ or 3+	Cohort II n=7 Participants Participants with advanced or metastatic biliary tract cancer with HER2 amplification by ISH and HER2 IHC 0 or 1+.
Maximum Serum Concentration of ZW25	457.6 micrograms per milliliter Geometric Coefficient of Variation 15.44	443.6 micrograms per milliliter Geometric Coefficient of Variation 24.10

SECONDARY outcome

Timeframe: Pre-dose, end of infusion, 2, 4, 8, 24 and 96 hours post dose

Population: All subjects who received any amount of zanidatamab and have at least 1 post-baseline pharmacokinetic (PK) assessment were included in this outcome.

Minimum observed serum concentration (trough)

Outcome measures

Outcome measures
Measure	Cohort I n=80 Participants Participants with advanced or metastatic biliary tract cancer with HER2 amplification by in situ hybridization (ISH) and HER2 overexpression by immunohistochemistry (IHC) which includes IHC 2+ or 3+	Cohort II n=7 Participants Participants with advanced or metastatic biliary tract cancer with HER2 amplification by ISH and HER2 IHC 0 or 1+.
Trough Concentration of ZW25	73.4 micrograms per milliliter Geometric Coefficient of Variation 42.10	46.5 micrograms per milliliter Geometric Coefficient of Variation 18.66

SECONDARY outcome

Timeframe: Up to 45 months

Population: All subjects who received any amount of zanidatamab and have both baseline anti-drug antibodies (ADA) and at least 1 post baseline ADA results available were included in this outcome

Number of subjects who develop ADAs

Outcome measures

Outcome measures
Measure	Cohort I n=78 Participants Participants with advanced or metastatic biliary tract cancer with HER2 amplification by in situ hybridization (ISH) and HER2 overexpression by immunohistochemistry (IHC) which includes IHC 2+ or 3+	Cohort II n=7 Participants Participants with advanced or metastatic biliary tract cancer with HER2 amplification by ISH and HER2 IHC 0 or 1+.
Incidence of Anti-drug Antibodies (ADAs)	1 Participants	0 Participants

Adverse Events

Cohort I

Serious events: 43 serious events

Other events: 78 other events

Deaths: 60 deaths

Cohort II

Serious events: 3 serious events

Other events: 5 other events

Deaths: 6 deaths

Serious adverse events

Other adverse events

Additional Information

Clinical Trial Disclosure & Transparency

Jazz Pharmaceuticals Inc.

Phone: 215-832-3750

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	Cohort I n=80 participants at risk Participants with advanced or metastatic biliary tract cancer with HER2 amplification by in situ hybridization (ISH) and HER2 overexpression by immunohistochemistry (IHC) which includes IHC 2+ or 3+	Cohort II n=7 participants at risk Participants with advanced or metastatic biliary tract cancer with HER2 amplification by ISH and HER2 IHC 0 or 1+.
Blood and lymphatic system disorders Anemia	22.5% 18/80 • Adverse events were collected from the start of dosing of any study drug up until 30 days after last study dose, up to approximately 45 months	42.9% 3/7 • Adverse events were collected from the start of dosing of any study drug up until 30 days after last study dose, up to approximately 45 months
Blood and lymphatic system disorders Leukocytosis	0.00% 0/80 • Adverse events were collected from the start of dosing of any study drug up until 30 days after last study dose, up to approximately 45 months	14.3% 1/7 • Adverse events were collected from the start of dosing of any study drug up until 30 days after last study dose, up to approximately 45 months
Cardiac disorders Palpitations	0.00% 0/80 • Adverse events were collected from the start of dosing of any study drug up until 30 days after last study dose, up to approximately 45 months	14.3% 1/7 • Adverse events were collected from the start of dosing of any study drug up until 30 days after last study dose, up to approximately 45 months
Gastrointestinal disorders Abdominal pain	20.0% 16/80 • Adverse events were collected from the start of dosing of any study drug up until 30 days after last study dose, up to approximately 45 months	0.00% 0/7 • Adverse events were collected from the start of dosing of any study drug up until 30 days after last study dose, up to approximately 45 months
Gastrointestinal disorders Abdominal pain upper	8.8% 7/80 • Adverse events were collected from the start of dosing of any study drug up until 30 days after last study dose, up to approximately 45 months	0.00% 0/7 • Adverse events were collected from the start of dosing of any study drug up until 30 days after last study dose, up to approximately 45 months
Gastrointestinal disorders Ascites	5.0% 4/80 • Adverse events were collected from the start of dosing of any study drug up until 30 days after last study dose, up to approximately 45 months	14.3% 1/7 • Adverse events were collected from the start of dosing of any study drug up until 30 days after last study dose, up to approximately 45 months
Gastrointestinal disorders Constipation	6.2% 5/80 • Adverse events were collected from the start of dosing of any study drug up until 30 days after last study dose, up to approximately 45 months	0.00% 0/7 • Adverse events were collected from the start of dosing of any study drug up until 30 days after last study dose, up to approximately 45 months
Gastrointestinal disorders Diarrhoea	48.8% 39/80 • Adverse events were collected from the start of dosing of any study drug up until 30 days after last study dose, up to approximately 45 months	0.00% 0/7 • Adverse events were collected from the start of dosing of any study drug up until 30 days after last study dose, up to approximately 45 months
Gastrointestinal disorders Duodenal ulcer	1.2% 1/80 • Adverse events were collected from the start of dosing of any study drug up until 30 days after last study dose, up to approximately 45 months	14.3% 1/7 • Adverse events were collected from the start of dosing of any study drug up until 30 days after last study dose, up to approximately 45 months
Gastrointestinal disorders Dyspepsia	6.2% 5/80 • Adverse events were collected from the start of dosing of any study drug up until 30 days after last study dose, up to approximately 45 months	0.00% 0/7 • Adverse events were collected from the start of dosing of any study drug up until 30 days after last study dose, up to approximately 45 months
Gastrointestinal disorders Nausea	17.5% 14/80 • Adverse events were collected from the start of dosing of any study drug up until 30 days after last study dose, up to approximately 45 months	0.00% 0/7 • Adverse events were collected from the start of dosing of any study drug up until 30 days after last study dose, up to approximately 45 months
Gastrointestinal disorders Vomiting	16.2% 13/80 • Adverse events were collected from the start of dosing of any study drug up until 30 days after last study dose, up to approximately 45 months	14.3% 1/7 • Adverse events were collected from the start of dosing of any study drug up until 30 days after last study dose, up to approximately 45 months
General disorders Asthenia	7.5% 6/80 • Adverse events were collected from the start of dosing of any study drug up until 30 days after last study dose, up to approximately 45 months	14.3% 1/7 • Adverse events were collected from the start of dosing of any study drug up until 30 days after last study dose, up to approximately 45 months
General disorders Fatigue	13.8% 11/80 • Adverse events were collected from the start of dosing of any study drug up until 30 days after last study dose, up to approximately 45 months	0.00% 0/7 • Adverse events were collected from the start of dosing of any study drug up until 30 days after last study dose, up to approximately 45 months
General disorders Oedema peripheral	6.2% 5/80 • Adverse events were collected from the start of dosing of any study drug up until 30 days after last study dose, up to approximately 45 months	0.00% 0/7 • Adverse events were collected from the start of dosing of any study drug up until 30 days after last study dose, up to approximately 45 months
General disorders Pyrexia	17.5% 14/80 • Adverse events were collected from the start of dosing of any study drug up until 30 days after last study dose, up to approximately 45 months	0.00% 0/7 • Adverse events were collected from the start of dosing of any study drug up until 30 days after last study dose, up to approximately 45 months
Immune system disorders Drug hypersensitivity	3.8% 3/80 • Adverse events were collected from the start of dosing of any study drug up until 30 days after last study dose, up to approximately 45 months	14.3% 1/7 • Adverse events were collected from the start of dosing of any study drug up until 30 days after last study dose, up to approximately 45 months
Infections and infestations Conjunctivitis	0.00% 0/80 • Adverse events were collected from the start of dosing of any study drug up until 30 days after last study dose, up to approximately 45 months	14.3% 1/7 • Adverse events were collected from the start of dosing of any study drug up until 30 days after last study dose, up to approximately 45 months
Infections and infestations Urinary tract infection	7.5% 6/80 • Adverse events were collected from the start of dosing of any study drug up until 30 days after last study dose, up to approximately 45 months	0.00% 0/7 • Adverse events were collected from the start of dosing of any study drug up until 30 days after last study dose, up to approximately 45 months
Injury, poisoning and procedural complications Fall	0.00% 0/80 • Adverse events were collected from the start of dosing of any study drug up until 30 days after last study dose, up to approximately 45 months	14.3% 1/7 • Adverse events were collected from the start of dosing of any study drug up until 30 days after last study dose, up to approximately 45 months
Injury, poisoning and procedural complications Infusion related reaction	33.8% 27/80 • Adverse events were collected from the start of dosing of any study drug up until 30 days after last study dose, up to approximately 45 months	14.3% 1/7 • Adverse events were collected from the start of dosing of any study drug up until 30 days after last study dose, up to approximately 45 months
Injury, poisoning and procedural complications Procedural pain	1.2% 1/80 • Adverse events were collected from the start of dosing of any study drug up until 30 days after last study dose, up to approximately 45 months	14.3% 1/7 • Adverse events were collected from the start of dosing of any study drug up until 30 days after last study dose, up to approximately 45 months
Investigations Alanine aminotransferase increased	20.0% 16/80 • Adverse events were collected from the start of dosing of any study drug up until 30 days after last study dose, up to approximately 45 months	14.3% 1/7 • Adverse events were collected from the start of dosing of any study drug up until 30 days after last study dose, up to approximately 45 months
Investigations Aspartate aminotransferase increased	18.8% 15/80 • Adverse events were collected from the start of dosing of any study drug up until 30 days after last study dose, up to approximately 45 months	14.3% 1/7 • Adverse events were collected from the start of dosing of any study drug up until 30 days after last study dose, up to approximately 45 months
Investigations Blood alkaline phosphatase increased	8.8% 7/80 • Adverse events were collected from the start of dosing of any study drug up until 30 days after last study dose, up to approximately 45 months	28.6% 2/7 • Adverse events were collected from the start of dosing of any study drug up until 30 days after last study dose, up to approximately 45 months
Investigations Blood bilirubin increased	12.5% 10/80 • Adverse events were collected from the start of dosing of any study drug up until 30 days after last study dose, up to approximately 45 months	0.00% 0/7 • Adverse events were collected from the start of dosing of any study drug up until 30 days after last study dose, up to approximately 45 months
Investigations Blood creatinine increased	7.5% 6/80 • Adverse events were collected from the start of dosing of any study drug up until 30 days after last study dose, up to approximately 45 months	14.3% 1/7 • Adverse events were collected from the start of dosing of any study drug up until 30 days after last study dose, up to approximately 45 months
Investigations Ejection fraction decreased	13.8% 11/80 • Adverse events were collected from the start of dosing of any study drug up until 30 days after last study dose, up to approximately 45 months	0.00% 0/7 • Adverse events were collected from the start of dosing of any study drug up until 30 days after last study dose, up to approximately 45 months
Investigations Gamma-glutamyltransferase increased	7.5% 6/80 • Adverse events were collected from the start of dosing of any study drug up until 30 days after last study dose, up to approximately 45 months	14.3% 1/7 • Adverse events were collected from the start of dosing of any study drug up until 30 days after last study dose, up to approximately 45 months
Investigations Neutrophil count increased	0.00% 0/80 • Adverse events were collected from the start of dosing of any study drug up until 30 days after last study dose, up to approximately 45 months	14.3% 1/7 • Adverse events were collected from the start of dosing of any study drug up until 30 days after last study dose, up to approximately 45 months
Investigations Platelet count decreased	3.8% 3/80 • Adverse events were collected from the start of dosing of any study drug up until 30 days after last study dose, up to approximately 45 months	14.3% 1/7 • Adverse events were collected from the start of dosing of any study drug up until 30 days after last study dose, up to approximately 45 months
Investigations Weight decreased	13.8% 11/80 • Adverse events were collected from the start of dosing of any study drug up until 30 days after last study dose, up to approximately 45 months	14.3% 1/7 • Adverse events were collected from the start of dosing of any study drug up until 30 days after last study dose, up to approximately 45 months
Metabolism and nutrition disorders Decreased appetite	16.2% 13/80 • Adverse events were collected from the start of dosing of any study drug up until 30 days after last study dose, up to approximately 45 months	0.00% 0/7 • Adverse events were collected from the start of dosing of any study drug up until 30 days after last study dose, up to approximately 45 months
Metabolism and nutrition disorders Hypoalbuminemia	7.5% 6/80 • Adverse events were collected from the start of dosing of any study drug up until 30 days after last study dose, up to approximately 45 months	0.00% 0/7 • Adverse events were collected from the start of dosing of any study drug up until 30 days after last study dose, up to approximately 45 months
Metabolism and nutrition disorders Hypochloraemia	1.2% 1/80 • Adverse events were collected from the start of dosing of any study drug up until 30 days after last study dose, up to approximately 45 months	14.3% 1/7 • Adverse events were collected from the start of dosing of any study drug up until 30 days after last study dose, up to approximately 45 months
Metabolism and nutrition disorders Hypokalemia	13.8% 11/80 • Adverse events were collected from the start of dosing of any study drug up until 30 days after last study dose, up to approximately 45 months	0.00% 0/7 • Adverse events were collected from the start of dosing of any study drug up until 30 days after last study dose, up to approximately 45 months
Metabolism and nutrition disorders Hypomagnesemia	6.2% 5/80 • Adverse events were collected from the start of dosing of any study drug up until 30 days after last study dose, up to approximately 45 months	0.00% 0/7 • Adverse events were collected from the start of dosing of any study drug up until 30 days after last study dose, up to approximately 45 months
Metabolism and nutrition disorders Hyponatremia	3.8% 3/80 • Adverse events were collected from the start of dosing of any study drug up until 30 days after last study dose, up to approximately 45 months	14.3% 1/7 • Adverse events were collected from the start of dosing of any study drug up until 30 days after last study dose, up to approximately 45 months
Metabolism and nutrition disorders Hypoproteinemia	1.2% 1/80 • Adverse events were collected from the start of dosing of any study drug up until 30 days after last study dose, up to approximately 45 months	14.3% 1/7 • Adverse events were collected from the start of dosing of any study drug up until 30 days after last study dose, up to approximately 45 months
Nervous system disorders Dizziness	8.8% 7/80 • Adverse events were collected from the start of dosing of any study drug up until 30 days after last study dose, up to approximately 45 months	0.00% 0/7 • Adverse events were collected from the start of dosing of any study drug up until 30 days after last study dose, up to approximately 45 months
Nervous system disorders Peripheral sesory neuropathy	7.5% 6/80 • Adverse events were collected from the start of dosing of any study drug up until 30 days after last study dose, up to approximately 45 months	0.00% 0/7 • Adverse events were collected from the start of dosing of any study drug up until 30 days after last study dose, up to approximately 45 months
Renal and urinary disorders Pollakiuria	1.2% 1/80 • Adverse events were collected from the start of dosing of any study drug up until 30 days after last study dose, up to approximately 45 months	14.3% 1/7 • Adverse events were collected from the start of dosing of any study drug up until 30 days after last study dose, up to approximately 45 months
Renal and urinary disorders Renal failure	0.00% 0/80 • Adverse events were collected from the start of dosing of any study drug up until 30 days after last study dose, up to approximately 45 months	14.3% 1/7 • Adverse events were collected from the start of dosing of any study drug up until 30 days after last study dose, up to approximately 45 months
Reproductive system and breast disorders Pelvic pain	0.00% 0/80 • Adverse events were collected from the start of dosing of any study drug up until 30 days after last study dose, up to approximately 45 months	14.3% 1/7 • Adverse events were collected from the start of dosing of any study drug up until 30 days after last study dose, up to approximately 45 months
Respiratory, thoracic and mediastinal disorders Epistaxis	2.5% 2/80 • Adverse events were collected from the start of dosing of any study drug up until 30 days after last study dose, up to approximately 45 months	14.3% 1/7 • Adverse events were collected from the start of dosing of any study drug up until 30 days after last study dose, up to approximately 45 months
Skin and subcutaneous tissue disorders Pruritis	13.8% 11/80 • Adverse events were collected from the start of dosing of any study drug up until 30 days after last study dose, up to approximately 45 months	0.00% 0/7 • Adverse events were collected from the start of dosing of any study drug up until 30 days after last study dose, up to approximately 45 months
Skin and subcutaneous tissue disorders Rash	8.8% 7/80 • Adverse events were collected from the start of dosing of any study drug up until 30 days after last study dose, up to approximately 45 months	0.00% 0/7 • Adverse events were collected from the start of dosing of any study drug up until 30 days after last study dose, up to approximately 45 months
Vascular disorders Hypertension	12.5% 10/80 • Adverse events were collected from the start of dosing of any study drug up until 30 days after last study dose, up to approximately 45 months	0.00% 0/7 • Adverse events were collected from the start of dosing of any study drug up until 30 days after last study dose, up to approximately 45 months
Infections and infestations COVID-19	6.2% 5/80 • Adverse events were collected from the start of dosing of any study drug up until 30 days after last study dose, up to approximately 45 months	14.3% 1/7 • Adverse events were collected from the start of dosing of any study drug up until 30 days after last study dose, up to approximately 45 months
Psychiatric disorders Insomnia	7.5% 6/80 • Adverse events were collected from the start of dosing of any study drug up until 30 days after last study dose, up to approximately 45 months	0.00% 0/7 • Adverse events were collected from the start of dosing of any study drug up until 30 days after last study dose, up to approximately 45 months