Trial Outcomes & Findings for A Study to Determine Best Tumor Response With Trastuzumab Emtansine in Human Epidermal Growth Factor Receptor 2 (HER2) Overexpressing Solid Tumors (NCT NCT02999672)

NCT ID: NCT02999672

Last Updated: 2019-08-28

Results Overview

BOR was defined as having best objective response as complete response (CR) or partial response (PR), as assessed by investigator and confirmed at least 28 days after initial response, according to the Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST 1.1). CR was defined as the disappearance of all target and non-target lesions. Any pathological lymph nodes (whether target or non-target) must decrease to normal (short axis less than \[\<\] 10 millimeter \[mm\]). PR was defined as a 30% decrease in the sum of the diameters of the target lesions taking as a reference the baseline sum diameter. Percentage of participants with best overall response of CR or PR are reported.

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 20 participants
• Primary outcome timeframe: Baseline up to PD/recurrence or death, whichever occurs first (up to approximately 18 months)
• Results posted on: 2019-08-28

Participant Flow

Participant milestones

Measure	Cohort 1 (UBC) First six participants with locally advanced (unresectable and not treatable with curative intent) or metastatic UBC initially received Regimen A (trastuzumab emtansine at a dose of 2.4 mg/kg qw). An iDMC assessed the safety among the first six participants and decided whether dose would be switched to Regimen B (trastuzumab emtansine at a dose of 3.6 mg/kg q3w).	Cohort 2 (Pancreatic Cancer/Cholangiocarcinoma) First six participants with metastatic pancreatic cancer/cholangiocarcinoma received Regimen A (trastuzumab emtansine at a dose of 2.4 mg/kg qw). An iDMC assessed the safety among the first six participants and decided whether dose would be switched to Regimen B (trastuzumab emtansine at a dose of 3.6 mg/kg q3w).
Overall Study STARTED	13	7
Overall Study COMPLETED	0	0
Overall Study NOT COMPLETED	13	7

Reasons for withdrawal

Measure	Cohort 1 (UBC) First six participants with locally advanced (unresectable and not treatable with curative intent) or metastatic UBC initially received Regimen A (trastuzumab emtansine at a dose of 2.4 mg/kg qw). An iDMC assessed the safety among the first six participants and decided whether dose would be switched to Regimen B (trastuzumab emtansine at a dose of 3.6 mg/kg q3w).	Cohort 2 (Pancreatic Cancer/Cholangiocarcinoma) First six participants with metastatic pancreatic cancer/cholangiocarcinoma received Regimen A (trastuzumab emtansine at a dose of 2.4 mg/kg qw). An iDMC assessed the safety among the first six participants and decided whether dose would be switched to Regimen B (trastuzumab emtansine at a dose of 3.6 mg/kg q3w).
Overall Study Death	0	1
Overall Study Study Terminated by Sponsor	0	1
Overall Study Progressive Disease	9	5
Overall Study Adverse Event	4	0

Baseline Characteristics

A Study to Determine Best Tumor Response With Trastuzumab Emtansine in Human Epidermal Growth Factor Receptor 2 (HER2) Overexpressing Solid Tumors

Baseline characteristics by cohort

Measure	Cohort 1 (UBC) n=13 Participants First six participants with locally advanced (unresectable and not treatable with curative intent) or metastatic UBC initially received Regimen A (trastuzumab emtansine at a dose of 2.4 mg/kg qw). An iDMC assessed the safety among the first six participants and decided whether dose would be switched to Regimen B (trastuzumab emtansine at a dose of 3.6 mg/kg q3w).	Cohort 2 (Pancreatic Cancer/Cholangiocarcinoma) n=7 Participants First six participants with metastatic pancreatic cancer/cholangiocarcinoma received Regimen A (trastuzumab emtansine at a dose of 2.4 mg/kg qw). An iDMC assessed the safety among the first six participants and decided whether dose would be switched to Regimen B (trastuzumab emtansine at a dose of 3.6 mg/kg q3w).	Total n=20 Participants Total of all reporting groups
Age, Continuous	57.4 Years STANDARD_DEVIATION 14.1 • n=5 Participants	62.9 Years STANDARD_DEVIATION 7.2 • n=7 Participants	59.3 Years STANDARD_DEVIATION 12.2 • n=5 Participants
Sex: Female, Male Female	1 Participants n=5 Participants	3 Participants n=7 Participants	4 Participants n=5 Participants
Sex: Female, Male Male	12 Participants n=5 Participants	4 Participants n=7 Participants	16 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	2 Participants n=5 Participants	0 Participants n=7 Participants	2 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	9 Participants n=5 Participants	7 Participants n=7 Participants	16 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	2 Participants n=5 Participants	0 Participants n=7 Participants	2 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	0 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	12 Participants n=5 Participants	7 Participants n=7 Participants	19 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	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline up to PD/recurrence or death, whichever occurs first (up to approximately 18 months)

Population: Urothelial bladder cancer (UBC) and Pancreatic Cancer/Cholangiocarcinoma cohorts

BOR was defined as having best objective response as complete response (CR) or partial response (PR), as assessed by investigator and confirmed at least 28 days after initial response, according to the Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST 1.1). CR was defined as the disappearance of all target and non-target lesions. Any pathological lymph nodes (whether target or non-target) must decrease to normal (short axis less than [<] 10 millimeter [mm]). PR was defined as a 30% decrease in the sum of the diameters of the target lesions taking as a reference the baseline sum diameter. Percentage of participants with best overall response of CR or PR are reported.

Outcome measures

Measure	Cohort 1 (UBC) n=13 Participants First six participants with locally advanced (unresectable and not treatable with curative intent) or metastatic UBC initially received Regimen A (trastuzumab emtansine at a dose of 2.4 mg/kg qw). An iDMC assessed the safety among the first six participants and decided whether dose would be switched to Regimen B (trastuzumab emtansine at a dose of 3.6 mg/kg q3w).	Cohort 2 (Pancreatic Cancer/Cholangiocarcinoma) n=7 Participants First six participants with metastatic pancreatic cancer/cholangiocarcinoma received Regimen A (trastuzumab emtansine at a dose of 2.4 mg/kg qw). An iDMC assessed the safety among the first six participants and decided whether dose would be switched to Regimen B (trastuzumab emtansine at a dose of 3.6 mg/kg q3w).
Best Overall Response (BOR) Assessed by the Investigator Using Response Evaluation Criteria in Solid Tumors [RECIST] 1.1). CR	0 Percentage of Treated Participants	0 Percentage of Treated Participants
Best Overall Response (BOR) Assessed by the Investigator Using Response Evaluation Criteria in Solid Tumors [RECIST] 1.1). PR	38.5 Percentage of Treated Participants	14.3 Percentage of Treated Participants

SECONDARY outcome

Timeframe: Baseline up to PD/recurrence or death, whichever occurs first (up to approximately 18 months)

Population: Urothelial bladder cancer (UBC) and Pancreatic Cancer/Cholangiocarcinoma cohorts

PFS was the time from inclusion in the study to the date of first documented PD or death from any cause, whichever occurred first. Participants without event were censored at the date of the last tumor assessment where non-progression was documented. If a participant received a second anti-cancer therapy without prior documentation of disease progression, the participant was censored at the date of last tumor assessment before starting new chemotherapy. PD was defined as at least a 20% increase in the sum of longest diameter (LD) of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of 1 or more new lesions.

Outcome measures

Measure	Cohort 1 (UBC) n=13 Participants First six participants with locally advanced (unresectable and not treatable with curative intent) or metastatic UBC initially received Regimen A (trastuzumab emtansine at a dose of 2.4 mg/kg qw). An iDMC assessed the safety among the first six participants and decided whether dose would be switched to Regimen B (trastuzumab emtansine at a dose of 3.6 mg/kg q3w).	Cohort 2 (Pancreatic Cancer/Cholangiocarcinoma) n=7 Participants First six participants with metastatic pancreatic cancer/cholangiocarcinoma received Regimen A (trastuzumab emtansine at a dose of 2.4 mg/kg qw). An iDMC assessed the safety among the first six participants and decided whether dose would be switched to Regimen B (trastuzumab emtansine at a dose of 3.6 mg/kg q3w).
Progression-Free Survival (PFS)	2.20 Months Interval 1.18 to 4.3	2.58 Months Interval 1.31 to 9.99

SECONDARY outcome

Timeframe: Baseline up to PD/recurrence or death, whichever occurs first (up to approximately 18 months)

Population: Urothelial bladder cancer (UBC) and Pancreatic Cancer/Cholangiocarcinoma cohorts

OS was determined as the time from beginning of treatment to death from any cause.

Outcome measures

Measure	Cohort 1 (UBC) n=13 Participants First six participants with locally advanced (unresectable and not treatable with curative intent) or metastatic UBC initially received Regimen A (trastuzumab emtansine at a dose of 2.4 mg/kg qw). An iDMC assessed the safety among the first six participants and decided whether dose would be switched to Regimen B (trastuzumab emtansine at a dose of 3.6 mg/kg q3w).	Cohort 2 (Pancreatic Cancer/Cholangiocarcinoma) n=7 Participants First six participants with metastatic pancreatic cancer/cholangiocarcinoma received Regimen A (trastuzumab emtansine at a dose of 2.4 mg/kg qw). An iDMC assessed the safety among the first six participants and decided whether dose would be switched to Regimen B (trastuzumab emtansine at a dose of 3.6 mg/kg q3w).
Overall Survival (OS)	7.03 Months Interval 3.75 to NA = NE= Not estimable. Upper limit of the 95 percent (%) confidence interval (CI) could not be calculated, as the study was terminated before a sufficient amount of data could be collected for accurate calculation.	NA Months Interval 1.45 to NA = NE= Not estimable. Median and upper limit of the 95 percent (%) confidence interval (CI) could not be calculated, as the study was terminated before a sufficient amount of data could be collected for accurate calculation.

SECONDARY outcome

Timeframe: Baseline up to approximately 18 months

Population: Urothelial bladder cancer (UBC) and Pancreatic Cancer/Cholangiocarcinoma cohorts

Incidence, type and severity of all adverse events (AEs) and serious adverse events (SAEs), based on National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE v4.03).

Outcome measures

Measure	Cohort 1 (UBC) n=13 Participants First six participants with locally advanced (unresectable and not treatable with curative intent) or metastatic UBC initially received Regimen A (trastuzumab emtansine at a dose of 2.4 mg/kg qw). An iDMC assessed the safety among the first six participants and decided whether dose would be switched to Regimen B (trastuzumab emtansine at a dose of 3.6 mg/kg q3w).	Cohort 2 (Pancreatic Cancer/Cholangiocarcinoma) n=7 Participants First six participants with metastatic pancreatic cancer/cholangiocarcinoma received Regimen A (trastuzumab emtansine at a dose of 2.4 mg/kg qw). An iDMC assessed the safety among the first six participants and decided whether dose would be switched to Regimen B (trastuzumab emtansine at a dose of 3.6 mg/kg q3w).
Percentage of Participants With Adverse Events (AEs) and Serious AEs (SAEs) SAE of special interest	0 Percentage of Participants	0 Percentage of Participants
Percentage of Participants With Adverse Events (AEs) and Serious AEs (SAEs) AEs	84.6 Percentage of Participants	100 Percentage of Participants
Percentage of Participants With Adverse Events (AEs) and Serious AEs (SAEs) Grade 1 AE	7.7 Percentage of Participants	14.3 Percentage of Participants
Percentage of Participants With Adverse Events (AEs) and Serious AEs (SAEs) Grade 2 AE	23.1 Percentage of Participants	57.1 Percentage of Participants
Percentage of Participants With Adverse Events (AEs) and Serious AEs (SAEs) Grade 3 AE	30.8 Percentage of Participants	28.1 Percentage of Participants
Percentage of Participants With Adverse Events (AEs) and Serious AEs (SAEs) Grade 4 AE	0 Percentage of Participants	0 Percentage of Participants
Percentage of Participants With Adverse Events (AEs) and Serious AEs (SAEs) Grade 5 AE	23.1 Percentage of Participants	0 Percentage of Participants
Percentage of Participants With Adverse Events (AEs) and Serious AEs (SAEs) AE greater than Grade 3	53.8 Percentage of Participants	28.6 Percentage of Participants
Percentage of Participants With Adverse Events (AEs) and Serious AEs (SAEs) AE related to Trastuzumab Emtansine (TE)	84.6 Percentage of Participants	85.7 Percentage of Participants
Percentage of Participants With Adverse Events (AEs) and Serious AEs (SAEs) SAEs	46.2 Percentage of Participants	28.6 Percentage of Participants
Percentage of Participants With Adverse Events (AEs) and Serious AEs (SAEs) SAE related to TE	0 Percentage of Participants	0 Percentage of Participants
Percentage of Participants With Adverse Events (AEs) and Serious AEs (SAEs) AE with fatal outcome	23.1 Percentage of Participants	0 Percentage of Participants
Percentage of Participants With Adverse Events (AEs) and Serious AEs (SAEs) AE leading to discontinuation of TE	23.1 Percentage of Participants	0 Percentage of Participants
Percentage of Participants With Adverse Events (AEs) and Serious AEs (SAEs) AE leading to modification of TE	61.5 Percentage of Participants	57.1 Percentage of Participants
Percentage of Participants With Adverse Events (AEs) and Serious AEs (SAEs) AE of special interest	0 Percentage of Participants	0 Percentage of Participants

SECONDARY outcome

Timeframe: Baseline up to approximately 18 months

Population: Urothelial bladder cancer (UBC) and Pancreatic Cancer/Cholangiocarcinoma cohorts

Participants from both cohorts (UBC and Pancreatic cancer/cholangiocarcinoma) were analyzed for drug-induced liver injury following Hy's Law. Hy's Law criteria for potential drug-induced liver injury includes an elevated ALT (alanine aminotransferase) or AST (aspartate aminotransferase) in combination with either elevated bilirubin or clinical jaundice.

Outcome measures

Measure	Cohort 1 (UBC) n=13 Participants First six participants with locally advanced (unresectable and not treatable with curative intent) or metastatic UBC initially received Regimen A (trastuzumab emtansine at a dose of 2.4 mg/kg qw). An iDMC assessed the safety among the first six participants and decided whether dose would be switched to Regimen B (trastuzumab emtansine at a dose of 3.6 mg/kg q3w).	Cohort 2 (Pancreatic Cancer/Cholangiocarcinoma) n=7 Participants First six participants with metastatic pancreatic cancer/cholangiocarcinoma received Regimen A (trastuzumab emtansine at a dose of 2.4 mg/kg qw). An iDMC assessed the safety among the first six participants and decided whether dose would be switched to Regimen B (trastuzumab emtansine at a dose of 3.6 mg/kg q3w).
Percentage of Participants With Drug-induced Liver Injury Meeting Hy's Law Criteria	0 Percentage of Participants	0 Percentage of Participants

SECONDARY outcome

Timeframe: Regimen A: predose (0 minutes [min]) and 15-30 min postinfusion on Days (D) 1, 8, 15 of Cycle (C) 1 and D1C4; predose on D1C2. Regimen B: predose and 15-30 min postinfusion on D1C1 and D1C4; predose on D1C2. 1 Cycle=21 days

Population: Urothelial bladder cancer (UBC) and Pancreatic Cancer/Cholangiocarcinoma cohorts.

Samples for evaluation of trastuzumab emtansine, DM1, and total trastuzumab were obtained from all participants from both cohorts at specified time points.

Outcome measures

Measure	Cohort 1 (UBC) n=13 Participants First six participants with locally advanced (unresectable and not treatable with curative intent) or metastatic UBC initially received Regimen A (trastuzumab emtansine at a dose of 2.4 mg/kg qw). An iDMC assessed the safety among the first six participants and decided whether dose would be switched to Regimen B (trastuzumab emtansine at a dose of 3.6 mg/kg q3w).	Cohort 2 (Pancreatic Cancer/Cholangiocarcinoma) n=7 Participants First six participants with metastatic pancreatic cancer/cholangiocarcinoma received Regimen A (trastuzumab emtansine at a dose of 2.4 mg/kg qw). An iDMC assessed the safety among the first six participants and decided whether dose would be switched to Regimen B (trastuzumab emtansine at a dose of 3.6 mg/kg q3w).
Plasma/Serum Concentrations of Trastuzumab Emtansine Predose, D1C1	NA ng/mL Standard Deviation NA Mean and Standard Deviation was not calculated due to below detection level.	NA ng/mL Standard Deviation NA Due to low number of participants, standard deviation can not be calculated.
Plasma/Serum Concentrations of Trastuzumab Emtansine 15-30 min post-infusion, D1C1	57.9 ng/mL Standard Deviation 16.1	52.3 ng/mL Standard Deviation 16.5
Plasma/Serum Concentrations of Trastuzumab Emtansine Predose, D8C1	8.27 ng/mL Standard Deviation 2.59	5.82 ng/mL Standard Deviation 1.96
Plasma/Serum Concentrations of Trastuzumab Emtansine 15-30 min post-infusion, D8C1	57.4 ng/mL Standard Deviation 12.0	50.3 ng/mL Standard Deviation 8.87
Plasma/Serum Concentrations of Trastuzumab Emtansine Predose, D15C1	14.8 ng/mL Standard Deviation 3.78	9.96 ng/mL Standard Deviation NA Due to low number of participants, standard deviation can not be calculated.
Plasma/Serum Concentrations of Trastuzumab Emtansine 15-30 min post-infusion, D15C8	59.3 ng/mL Standard Deviation 8.75	49.2 ng/mL Standard Deviation NA Due to low number of participants, standard deviation can not be calculated.
Plasma/Serum Concentrations of Trastuzumab Emtansine Predose, D1C2	10.5 ng/mL Standard Deviation 9.38	2.02 ng/mL Standard Deviation 2.08
Plasma/Serum Concentrations of Trastuzumab Emtansine Predose, D1C4	12.5 ng/mL Standard Deviation 8.63	11.7 ng/mL Standard Deviation 8.99
Plasma/Serum Concentrations of Trastuzumab Emtansine 15-30 min post-infusion, D1C4	62.5 ng/mL Standard Deviation 13.6	65.7 ng/mL Standard Deviation 10.5

Adverse Events

Cohort 1 (UBC)

Serious events: 6 serious events

Other events: 11 other events

Deaths: 7 deaths

Cohort 2 (Pancreatic Cancer/Cholangiocarcinoma)

Serious events: 2 serious events

Other events: 7 other events

Deaths: 1 deaths

Serious adverse events

Measure	Cohort 1 (UBC) n=13 participants at risk First six participants with locally advanced (unresectable and not treatable with curative intent) or metastatic UBC initially received Regimen A (trastuzumab emtansine at a dose of 2.4 mg/kg qw). An iDMC assessed the safety among the first six participants and decided whether dose would be switched to Regimen B (trastuzumab emtansine at a dose of 3.6 mg/kg q3w).	Cohort 2 (Pancreatic Cancer/Cholangiocarcinoma) n=7 participants at risk First six participants with metastatic pancreatic cancer/cholangiocarcinoma received Regimen A (trastuzumab emtansine at a dose of 2.4 mg/kg qw). An iDMC assessed the safety among the first six participants and decided whether dose would be switched to Regimen B (trastuzumab emtansine at a dose of 3.6 mg/kg q3w).
Gastrointestinal disorders Diarrhoea	7.7% 1/13 • Number of events 1 • Baseline up to approximately 18 months An Adverse Event (AE) is any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medical treatment or procedure that may or may not be considered related to the medical treatment or procedure.	0.00% 0/7 • Baseline up to approximately 18 months An Adverse Event (AE) is any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medical treatment or procedure that may or may not be considered related to the medical treatment or procedure.
Gastrointestinal disorders Vomiting	7.7% 1/13 • Number of events 1 • Baseline up to approximately 18 months An Adverse Event (AE) is any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medical treatment or procedure that may or may not be considered related to the medical treatment or procedure.	0.00% 0/7 • Baseline up to approximately 18 months An Adverse Event (AE) is any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medical treatment or procedure that may or may not be considered related to the medical treatment or procedure.
Infections and infestations Pulmonary sepsis	7.7% 1/13 • Number of events 1 • Baseline up to approximately 18 months An Adverse Event (AE) is any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medical treatment or procedure that may or may not be considered related to the medical treatment or procedure.	0.00% 0/7 • Baseline up to approximately 18 months An Adverse Event (AE) is any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medical treatment or procedure that may or may not be considered related to the medical treatment or procedure.
Infections and infestations Sepsis	7.7% 1/13 • Number of events 1 • Baseline up to approximately 18 months An Adverse Event (AE) is any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medical treatment or procedure that may or may not be considered related to the medical treatment or procedure.	0.00% 0/7 • Baseline up to approximately 18 months An Adverse Event (AE) is any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medical treatment or procedure that may or may not be considered related to the medical treatment or procedure.
Infections and infestations Urinary tract infection	15.4% 2/13 • Number of events 4 • Baseline up to approximately 18 months An Adverse Event (AE) is any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medical treatment or procedure that may or may not be considered related to the medical treatment or procedure.	0.00% 0/7 • Baseline up to approximately 18 months An Adverse Event (AE) is any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medical treatment or procedure that may or may not be considered related to the medical treatment or procedure.
Injury, poisoning and procedural complications Craniocerebral injury	7.7% 1/13 • Number of events 1 • Baseline up to approximately 18 months An Adverse Event (AE) is any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medical treatment or procedure that may or may not be considered related to the medical treatment or procedure.	0.00% 0/7 • Baseline up to approximately 18 months An Adverse Event (AE) is any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medical treatment or procedure that may or may not be considered related to the medical treatment or procedure.
Psychiatric disorders Confusional state	7.7% 1/13 • Number of events 1 • Baseline up to approximately 18 months An Adverse Event (AE) is any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medical treatment or procedure that may or may not be considered related to the medical treatment or procedure.	0.00% 0/7 • Baseline up to approximately 18 months An Adverse Event (AE) is any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medical treatment or procedure that may or may not be considered related to the medical treatment or procedure.
Renal and urinary disorders Haematuria	7.7% 1/13 • Number of events 1 • Baseline up to approximately 18 months An Adverse Event (AE) is any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medical treatment or procedure that may or may not be considered related to the medical treatment or procedure.	0.00% 0/7 • Baseline up to approximately 18 months An Adverse Event (AE) is any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medical treatment or procedure that may or may not be considered related to the medical treatment or procedure.
Gastrointestinal disorders Pancreatitis	0.00% 0/13 • Baseline up to approximately 18 months An Adverse Event (AE) is any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medical treatment or procedure that may or may not be considered related to the medical treatment or procedure.	14.3% 1/7 • Number of events 1 • Baseline up to approximately 18 months An Adverse Event (AE) is any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medical treatment or procedure that may or may not be considered related to the medical treatment or procedure.
General disorders Pyrexia	0.00% 0/13 • Baseline up to approximately 18 months An Adverse Event (AE) is any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medical treatment or procedure that may or may not be considered related to the medical treatment or procedure.	14.3% 1/7 • Number of events 1 • Baseline up to approximately 18 months An Adverse Event (AE) is any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medical treatment or procedure that may or may not be considered related to the medical treatment or procedure.
Infections and infestations Device-related sepsis	0.00% 0/13 • Baseline up to approximately 18 months An Adverse Event (AE) is any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medical treatment or procedure that may or may not be considered related to the medical treatment or procedure.	14.3% 1/7 • Number of events 1 • Baseline up to approximately 18 months An Adverse Event (AE) is any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medical treatment or procedure that may or may not be considered related to the medical treatment or procedure.

Other adverse events

Measure	Cohort 1 (UBC) n=13 participants at risk First six participants with locally advanced (unresectable and not treatable with curative intent) or metastatic UBC initially received Regimen A (trastuzumab emtansine at a dose of 2.4 mg/kg qw). An iDMC assessed the safety among the first six participants and decided whether dose would be switched to Regimen B (trastuzumab emtansine at a dose of 3.6 mg/kg q3w).	Cohort 2 (Pancreatic Cancer/Cholangiocarcinoma) n=7 participants at risk First six participants with metastatic pancreatic cancer/cholangiocarcinoma received Regimen A (trastuzumab emtansine at a dose of 2.4 mg/kg qw). An iDMC assessed the safety among the first six participants and decided whether dose would be switched to Regimen B (trastuzumab emtansine at a dose of 3.6 mg/kg q3w).
Investigations Alanine aminotransferase increased	15.4% 2/13 • Number of events 2 • Baseline up to approximately 18 months An Adverse Event (AE) is any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medical treatment or procedure that may or may not be considered related to the medical treatment or procedure.	14.3% 1/7 • Number of events 1 • Baseline up to approximately 18 months An Adverse Event (AE) is any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medical treatment or procedure that may or may not be considered related to the medical treatment or procedure.
Investigations Aspartate aminotransferase increased	23.1% 3/13 • Number of events 3 • Baseline up to approximately 18 months An Adverse Event (AE) is any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medical treatment or procedure that may or may not be considered related to the medical treatment or procedure.	14.3% 1/7 • Number of events 1 • Baseline up to approximately 18 months An Adverse Event (AE) is any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medical treatment or procedure that may or may not be considered related to the medical treatment or procedure.
Injury, poisoning and procedural complications Infusion related reaction	7.7% 1/13 • Number of events 1 • Baseline up to approximately 18 months An Adverse Event (AE) is any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medical treatment or procedure that may or may not be considered related to the medical treatment or procedure.	0.00% 0/7 • Baseline up to approximately 18 months An Adverse Event (AE) is any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medical treatment or procedure that may or may not be considered related to the medical treatment or procedure.
Investigations Blood alkaline phosphatase increased	7.7% 1/13 • Number of events 1 • Baseline up to approximately 18 months An Adverse Event (AE) is any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medical treatment or procedure that may or may not be considered related to the medical treatment or procedure.	14.3% 1/7 • Number of events 1 • Baseline up to approximately 18 months An Adverse Event (AE) is any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medical treatment or procedure that may or may not be considered related to the medical treatment or procedure.
Investigations Blood phosphorus decreased	7.7% 1/13 • Number of events 1 • Baseline up to approximately 18 months An Adverse Event (AE) is any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medical treatment or procedure that may or may not be considered related to the medical treatment or procedure.	0.00% 0/7 • Baseline up to approximately 18 months An Adverse Event (AE) is any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medical treatment or procedure that may or may not be considered related to the medical treatment or procedure.
Investigations Neutrophil count decreased	7.7% 1/13 • Number of events 1 • Baseline up to approximately 18 months An Adverse Event (AE) is any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medical treatment or procedure that may or may not be considered related to the medical treatment or procedure.	14.3% 1/7 • Number of events 1 • Baseline up to approximately 18 months An Adverse Event (AE) is any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medical treatment or procedure that may or may not be considered related to the medical treatment or procedure.
Investigations Platelet count decreased	15.4% 2/13 • Number of events 2 • Baseline up to approximately 18 months An Adverse Event (AE) is any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medical treatment or procedure that may or may not be considered related to the medical treatment or procedure.	28.6% 2/7 • Number of events 3 • Baseline up to approximately 18 months An Adverse Event (AE) is any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medical treatment or procedure that may or may not be considered related to the medical treatment or procedure.
Investigations Transaminases increased	7.7% 1/13 • Number of events 1 • Baseline up to approximately 18 months An Adverse Event (AE) is any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medical treatment or procedure that may or may not be considered related to the medical treatment or procedure.	0.00% 0/7 • Baseline up to approximately 18 months An Adverse Event (AE) is any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medical treatment or procedure that may or may not be considered related to the medical treatment or procedure.
Metabolism and nutrition disorders Decreased appetite	7.7% 1/13 • Number of events 1 • Baseline up to approximately 18 months An Adverse Event (AE) is any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medical treatment or procedure that may or may not be considered related to the medical treatment or procedure.	42.9% 3/7 • Number of events 4 • Baseline up to approximately 18 months An Adverse Event (AE) is any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medical treatment or procedure that may or may not be considered related to the medical treatment or procedure.
Musculoskeletal and connective tissue disorders Arthralgia	15.4% 2/13 • Number of events 2 • Baseline up to approximately 18 months An Adverse Event (AE) is any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medical treatment or procedure that may or may not be considered related to the medical treatment or procedure.	0.00% 0/7 • Baseline up to approximately 18 months An Adverse Event (AE) is any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medical treatment or procedure that may or may not be considered related to the medical treatment or procedure.
Musculoskeletal and connective tissue disorders Back pain	7.7% 1/13 • Number of events 1 • Baseline up to approximately 18 months An Adverse Event (AE) is any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medical treatment or procedure that may or may not be considered related to the medical treatment or procedure.	14.3% 1/7 • Number of events 1 • Baseline up to approximately 18 months An Adverse Event (AE) is any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medical treatment or procedure that may or may not be considered related to the medical treatment or procedure.
Musculoskeletal and connective tissue disorders Bone pain	7.7% 1/13 • Number of events 1 • Baseline up to approximately 18 months An Adverse Event (AE) is any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medical treatment or procedure that may or may not be considered related to the medical treatment or procedure.	0.00% 0/7 • Baseline up to approximately 18 months An Adverse Event (AE) is any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medical treatment or procedure that may or may not be considered related to the medical treatment or procedure.
Musculoskeletal and connective tissue disorders Myalgia	7.7% 1/13 • Number of events 1 • Baseline up to approximately 18 months An Adverse Event (AE) is any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medical treatment or procedure that may or may not be considered related to the medical treatment or procedure.	0.00% 0/7 • Baseline up to approximately 18 months An Adverse Event (AE) is any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medical treatment or procedure that may or may not be considered related to the medical treatment or procedure.
Musculoskeletal and connective tissue disorders Neck pain	7.7% 1/13 • Number of events 1 • Baseline up to approximately 18 months An Adverse Event (AE) is any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medical treatment or procedure that may or may not be considered related to the medical treatment or procedure.	0.00% 0/7 • Baseline up to approximately 18 months An Adverse Event (AE) is any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medical treatment or procedure that may or may not be considered related to the medical treatment or procedure.
Musculoskeletal and connective tissue disorders Pain in extremity	7.7% 1/13 • Number of events 1 • Baseline up to approximately 18 months An Adverse Event (AE) is any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medical treatment or procedure that may or may not be considered related to the medical treatment or procedure.	0.00% 0/7 • Baseline up to approximately 18 months An Adverse Event (AE) is any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medical treatment or procedure that may or may not be considered related to the medical treatment or procedure.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Cancer pain	7.7% 1/13 • Number of events 1 • Baseline up to approximately 18 months An Adverse Event (AE) is any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medical treatment or procedure that may or may not be considered related to the medical treatment or procedure.	0.00% 0/7 • Baseline up to approximately 18 months An Adverse Event (AE) is any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medical treatment or procedure that may or may not be considered related to the medical treatment or procedure.
Nervous system disorders Dizziness	7.7% 1/13 • Number of events 1 • Baseline up to approximately 18 months An Adverse Event (AE) is any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medical treatment or procedure that may or may not be considered related to the medical treatment or procedure.	0.00% 0/7 • Baseline up to approximately 18 months An Adverse Event (AE) is any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medical treatment or procedure that may or may not be considered related to the medical treatment or procedure.
Blood and lymphatic system disorders Anaemia	23.1% 3/13 • Number of events 3 • Baseline up to approximately 18 months An Adverse Event (AE) is any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medical treatment or procedure that may or may not be considered related to the medical treatment or procedure.	14.3% 1/7 • Number of events 1 • Baseline up to approximately 18 months An Adverse Event (AE) is any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medical treatment or procedure that may or may not be considered related to the medical treatment or procedure.
Blood and lymphatic system disorders Lymphopenia	7.7% 1/13 • Number of events 1 • Baseline up to approximately 18 months An Adverse Event (AE) is any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medical treatment or procedure that may or may not be considered related to the medical treatment or procedure.	14.3% 1/7 • Number of events 1 • Baseline up to approximately 18 months An Adverse Event (AE) is any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medical treatment or procedure that may or may not be considered related to the medical treatment or procedure.
Cardiac disorders Ventricular dysfunction	7.7% 1/13 • Number of events 1 • Baseline up to approximately 18 months An Adverse Event (AE) is any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medical treatment or procedure that may or may not be considered related to the medical treatment or procedure.	0.00% 0/7 • Baseline up to approximately 18 months An Adverse Event (AE) is any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medical treatment or procedure that may or may not be considered related to the medical treatment or procedure.
Gastrointestinal disorders Ascites	7.7% 1/13 • Number of events 1 • Baseline up to approximately 18 months An Adverse Event (AE) is any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medical treatment or procedure that may or may not be considered related to the medical treatment or procedure.	0.00% 0/7 • Baseline up to approximately 18 months An Adverse Event (AE) is any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medical treatment or procedure that may or may not be considered related to the medical treatment or procedure.
Gastrointestinal disorders Constipation	15.4% 2/13 • Number of events 2 • Baseline up to approximately 18 months An Adverse Event (AE) is any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medical treatment or procedure that may or may not be considered related to the medical treatment or procedure.	14.3% 1/7 • Number of events 1 • Baseline up to approximately 18 months An Adverse Event (AE) is any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medical treatment or procedure that may or may not be considered related to the medical treatment or procedure.
Gastrointestinal disorders Diarrhoea	7.7% 1/13 • Number of events 1 • Baseline up to approximately 18 months An Adverse Event (AE) is any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medical treatment or procedure that may or may not be considered related to the medical treatment or procedure.	0.00% 0/7 • Baseline up to approximately 18 months An Adverse Event (AE) is any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medical treatment or procedure that may or may not be considered related to the medical treatment or procedure.
Gastrointestinal disorders Dry mouth	7.7% 1/13 • Number of events 1 • Baseline up to approximately 18 months An Adverse Event (AE) is any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medical treatment or procedure that may or may not be considered related to the medical treatment or procedure.	14.3% 1/7 • Number of events 1 • Baseline up to approximately 18 months An Adverse Event (AE) is any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medical treatment or procedure that may or may not be considered related to the medical treatment or procedure.
Gastrointestinal disorders Intestinal obstruction	7.7% 1/13 • Number of events 1 • Baseline up to approximately 18 months An Adverse Event (AE) is any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medical treatment or procedure that may or may not be considered related to the medical treatment or procedure.	0.00% 0/7 • Baseline up to approximately 18 months An Adverse Event (AE) is any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medical treatment or procedure that may or may not be considered related to the medical treatment or procedure.
Gastrointestinal disorders Vomiting	15.4% 2/13 • Number of events 2 • Baseline up to approximately 18 months An Adverse Event (AE) is any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medical treatment or procedure that may or may not be considered related to the medical treatment or procedure.	14.3% 1/7 • Number of events 1 • Baseline up to approximately 18 months An Adverse Event (AE) is any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medical treatment or procedure that may or may not be considered related to the medical treatment or procedure.
General disorders Asthenia	30.8% 4/13 • Number of events 5 • Baseline up to approximately 18 months An Adverse Event (AE) is any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medical treatment or procedure that may or may not be considered related to the medical treatment or procedure.	28.6% 2/7 • Number of events 5 • Baseline up to approximately 18 months An Adverse Event (AE) is any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medical treatment or procedure that may or may not be considered related to the medical treatment or procedure.
General disorders Influenza like Illness	15.4% 2/13 • Number of events 2 • Baseline up to approximately 18 months An Adverse Event (AE) is any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medical treatment or procedure that may or may not be considered related to the medical treatment or procedure.	14.3% 1/7 • Number of events 1 • Baseline up to approximately 18 months An Adverse Event (AE) is any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medical treatment or procedure that may or may not be considered related to the medical treatment or procedure.
General disorders Oedema peripheral	7.7% 1/13 • Number of events 1 • Baseline up to approximately 18 months An Adverse Event (AE) is any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medical treatment or procedure that may or may not be considered related to the medical treatment or procedure.	14.3% 1/7 • Number of events 2 • Baseline up to approximately 18 months An Adverse Event (AE) is any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medical treatment or procedure that may or may not be considered related to the medical treatment or procedure.
General disorders Pyrexia	38.5% 5/13 • Number of events 6 • Baseline up to approximately 18 months An Adverse Event (AE) is any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medical treatment or procedure that may or may not be considered related to the medical treatment or procedure.	42.9% 3/7 • Number of events 6 • Baseline up to approximately 18 months An Adverse Event (AE) is any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medical treatment or procedure that may or may not be considered related to the medical treatment or procedure.
Blood and lymphatic system disorders Thrombocytopenia	23.1% 3/13 • Number of events 3 • Baseline up to approximately 18 months An Adverse Event (AE) is any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medical treatment or procedure that may or may not be considered related to the medical treatment or procedure.	0.00% 0/7 • Baseline up to approximately 18 months An Adverse Event (AE) is any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medical treatment or procedure that may or may not be considered related to the medical treatment or procedure.
Blood and lymphatic system disorders Leukocytosis	0.00% 0/13 • Baseline up to approximately 18 months An Adverse Event (AE) is any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medical treatment or procedure that may or may not be considered related to the medical treatment or procedure.	14.3% 1/7 • Number of events 1 • Baseline up to approximately 18 months An Adverse Event (AE) is any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medical treatment or procedure that may or may not be considered related to the medical treatment or procedure.
Blood and lymphatic system disorders Neutropenia	0.00% 0/13 • Baseline up to approximately 18 months An Adverse Event (AE) is any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medical treatment or procedure that may or may not be considered related to the medical treatment or procedure.	14.3% 1/7 • Number of events 1 • Baseline up to approximately 18 months An Adverse Event (AE) is any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medical treatment or procedure that may or may not be considered related to the medical treatment or procedure.
Blood and lymphatic system disorders Neutrophilia	0.00% 0/13 • Baseline up to approximately 18 months An Adverse Event (AE) is any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medical treatment or procedure that may or may not be considered related to the medical treatment or procedure.	14.3% 1/7 • Number of events 1 • Baseline up to approximately 18 months An Adverse Event (AE) is any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medical treatment or procedure that may or may not be considered related to the medical treatment or procedure.
Eye disorders Lacrimation increased	0.00% 0/13 • Baseline up to approximately 18 months An Adverse Event (AE) is any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medical treatment or procedure that may or may not be considered related to the medical treatment or procedure.	14.3% 1/7 • Number of events 1 • Baseline up to approximately 18 months An Adverse Event (AE) is any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medical treatment or procedure that may or may not be considered related to the medical treatment or procedure.
Eye disorders Photophobia	0.00% 0/13 • Baseline up to approximately 18 months An Adverse Event (AE) is any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medical treatment or procedure that may or may not be considered related to the medical treatment or procedure.	14.3% 1/7 • Number of events 1 • Baseline up to approximately 18 months An Adverse Event (AE) is any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medical treatment or procedure that may or may not be considered related to the medical treatment or procedure.
Gastrointestinal disorders Abdominal discomfort	0.00% 0/13 • Baseline up to approximately 18 months An Adverse Event (AE) is any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medical treatment or procedure that may or may not be considered related to the medical treatment or procedure.	14.3% 1/7 • Number of events 1 • Baseline up to approximately 18 months An Adverse Event (AE) is any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medical treatment or procedure that may or may not be considered related to the medical treatment or procedure.
Gastrointestinal disorders Abdominal pain	0.00% 0/13 • Baseline up to approximately 18 months An Adverse Event (AE) is any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medical treatment or procedure that may or may not be considered related to the medical treatment or procedure.	57.1% 4/7 • Number of events 5 • Baseline up to approximately 18 months An Adverse Event (AE) is any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medical treatment or procedure that may or may not be considered related to the medical treatment or procedure.
Gastrointestinal disorders Abdominal pain, upper	0.00% 0/13 • Baseline up to approximately 18 months An Adverse Event (AE) is any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medical treatment or procedure that may or may not be considered related to the medical treatment or procedure.	14.3% 1/7 • Number of events 1 • Baseline up to approximately 18 months An Adverse Event (AE) is any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medical treatment or procedure that may or may not be considered related to the medical treatment or procedure.
Gastrointestinal disorders Dyspepsia	0.00% 0/13 • Baseline up to approximately 18 months An Adverse Event (AE) is any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medical treatment or procedure that may or may not be considered related to the medical treatment or procedure.	14.3% 1/7 • Number of events 1 • Baseline up to approximately 18 months An Adverse Event (AE) is any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medical treatment or procedure that may or may not be considered related to the medical treatment or procedure.
Gastrointestinal disorders Gastric ulcer	0.00% 0/13 • Baseline up to approximately 18 months An Adverse Event (AE) is any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medical treatment or procedure that may or may not be considered related to the medical treatment or procedure.	14.3% 1/7 • Number of events 1 • Baseline up to approximately 18 months An Adverse Event (AE) is any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medical treatment or procedure that may or may not be considered related to the medical treatment or procedure.
Gastrointestinal disorders Nausea	0.00% 0/13 • Baseline up to approximately 18 months An Adverse Event (AE) is any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medical treatment or procedure that may or may not be considered related to the medical treatment or procedure.	42.9% 3/7 • Number of events 4 • Baseline up to approximately 18 months An Adverse Event (AE) is any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medical treatment or procedure that may or may not be considered related to the medical treatment or procedure.
Injury, poisoning and procedural complications Fall	7.7% 1/13 • Number of events 1 • Baseline up to approximately 18 months An Adverse Event (AE) is any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medical treatment or procedure that may or may not be considered related to the medical treatment or procedure.	0.00% 0/7 • Baseline up to approximately 18 months An Adverse Event (AE) is any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medical treatment or procedure that may or may not be considered related to the medical treatment or procedure.
Nervous system disorders Headache	7.7% 1/13 • Number of events 1 • Baseline up to approximately 18 months An Adverse Event (AE) is any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medical treatment or procedure that may or may not be considered related to the medical treatment or procedure.	14.3% 1/7 • Number of events 1 • Baseline up to approximately 18 months An Adverse Event (AE) is any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medical treatment or procedure that may or may not be considered related to the medical treatment or procedure.
Nervous system disorders Meralgia paraesthetica	7.7% 1/13 • Number of events 1 • Baseline up to approximately 18 months An Adverse Event (AE) is any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medical treatment or procedure that may or may not be considered related to the medical treatment or procedure.	0.00% 0/7 • Baseline up to approximately 18 months An Adverse Event (AE) is any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medical treatment or procedure that may or may not be considered related to the medical treatment or procedure.
Nervous system disorders Peripheral sensory neuropathy	7.7% 1/13 • Number of events 1 • Baseline up to approximately 18 months An Adverse Event (AE) is any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medical treatment or procedure that may or may not be considered related to the medical treatment or procedure.	14.3% 1/7 • Number of events 1 • Baseline up to approximately 18 months An Adverse Event (AE) is any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medical treatment or procedure that may or may not be considered related to the medical treatment or procedure.
Psychiatric disorders Restlessness	7.7% 1/13 • Number of events 1 • Baseline up to approximately 18 months An Adverse Event (AE) is any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medical treatment or procedure that may or may not be considered related to the medical treatment or procedure.	0.00% 0/7 • Baseline up to approximately 18 months An Adverse Event (AE) is any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medical treatment or procedure that may or may not be considered related to the medical treatment or procedure.
Renal and urinary disorders Cystitis noninfective	7.7% 1/13 • Number of events 1 • Baseline up to approximately 18 months An Adverse Event (AE) is any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medical treatment or procedure that may or may not be considered related to the medical treatment or procedure.	0.00% 0/7 • Baseline up to approximately 18 months An Adverse Event (AE) is any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medical treatment or procedure that may or may not be considered related to the medical treatment or procedure.
Renal and urinary disorders Haematuria	23.1% 3/13 • Number of events 4 • Baseline up to approximately 18 months An Adverse Event (AE) is any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medical treatment or procedure that may or may not be considered related to the medical treatment or procedure.	0.00% 0/7 • Baseline up to approximately 18 months An Adverse Event (AE) is any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medical treatment or procedure that may or may not be considered related to the medical treatment or procedure.
Renal and urinary disorders Pollakiuria	7.7% 1/13 • Number of events 1 • Baseline up to approximately 18 months An Adverse Event (AE) is any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medical treatment or procedure that may or may not be considered related to the medical treatment or procedure.	0.00% 0/7 • Baseline up to approximately 18 months An Adverse Event (AE) is any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medical treatment or procedure that may or may not be considered related to the medical treatment or procedure.
Renal and urinary disorders Renal failure	7.7% 1/13 • Number of events 1 • Baseline up to approximately 18 months An Adverse Event (AE) is any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medical treatment or procedure that may or may not be considered related to the medical treatment or procedure.	0.00% 0/7 • Baseline up to approximately 18 months An Adverse Event (AE) is any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medical treatment or procedure that may or may not be considered related to the medical treatment or procedure.
Respiratory, thoracic and mediastinal disorders Cough	7.7% 1/13 • Number of events 1 • Baseline up to approximately 18 months An Adverse Event (AE) is any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medical treatment or procedure that may or may not be considered related to the medical treatment or procedure.	28.6% 2/7 • Number of events 4 • Baseline up to approximately 18 months An Adverse Event (AE) is any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medical treatment or procedure that may or may not be considered related to the medical treatment or procedure.
Respiratory, thoracic and mediastinal disorders Dyspnoea	7.7% 1/13 • Number of events 1 • Baseline up to approximately 18 months An Adverse Event (AE) is any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medical treatment or procedure that may or may not be considered related to the medical treatment or procedure.	0.00% 0/7 • Baseline up to approximately 18 months An Adverse Event (AE) is any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medical treatment or procedure that may or may not be considered related to the medical treatment or procedure.
Respiratory, thoracic and mediastinal disorders Epistaxis	7.7% 1/13 • Number of events 2 • Baseline up to approximately 18 months An Adverse Event (AE) is any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medical treatment or procedure that may or may not be considered related to the medical treatment or procedure.	0.00% 0/7 • Baseline up to approximately 18 months An Adverse Event (AE) is any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medical treatment or procedure that may or may not be considered related to the medical treatment or procedure.
General disorders Chills	0.00% 0/13 • Baseline up to approximately 18 months An Adverse Event (AE) is any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medical treatment or procedure that may or may not be considered related to the medical treatment or procedure.	14.3% 1/7 • Number of events 1 • Baseline up to approximately 18 months An Adverse Event (AE) is any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medical treatment or procedure that may or may not be considered related to the medical treatment or procedure.
General disorders Fatigue	0.00% 0/13 • Baseline up to approximately 18 months An Adverse Event (AE) is any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medical treatment or procedure that may or may not be considered related to the medical treatment or procedure.	14.3% 1/7 • Number of events 2 • Baseline up to approximately 18 months An Adverse Event (AE) is any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medical treatment or procedure that may or may not be considered related to the medical treatment or procedure.
General disorders Malaise	0.00% 0/13 • Baseline up to approximately 18 months An Adverse Event (AE) is any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medical treatment or procedure that may or may not be considered related to the medical treatment or procedure.	14.3% 1/7 • Number of events 1 • Baseline up to approximately 18 months An Adverse Event (AE) is any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medical treatment or procedure that may or may not be considered related to the medical treatment or procedure.
Infections and infestations Urinary tract infection	0.00% 0/13 • Baseline up to approximately 18 months An Adverse Event (AE) is any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medical treatment or procedure that may or may not be considered related to the medical treatment or procedure.	14.3% 1/7 • Number of events 1 • Baseline up to approximately 18 months An Adverse Event (AE) is any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medical treatment or procedure that may or may not be considered related to the medical treatment or procedure.
Investigations Blood bilirubin increased	0.00% 0/13 • Baseline up to approximately 18 months An Adverse Event (AE) is any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medical treatment or procedure that may or may not be considered related to the medical treatment or procedure.	14.3% 1/7 • Number of events 2 • Baseline up to approximately 18 months An Adverse Event (AE) is any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medical treatment or procedure that may or may not be considered related to the medical treatment or procedure.
Investigations Gamma-glutamyltransferase increased	0.00% 0/13 • Baseline up to approximately 18 months An Adverse Event (AE) is any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medical treatment or procedure that may or may not be considered related to the medical treatment or procedure.	14.3% 1/7 • Number of events 1 • Baseline up to approximately 18 months An Adverse Event (AE) is any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medical treatment or procedure that may or may not be considered related to the medical treatment or procedure.
Investigations Lymphocyte count decreased	0.00% 0/13 • Baseline up to approximately 18 months An Adverse Event (AE) is any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medical treatment or procedure that may or may not be considered related to the medical treatment or procedure.	14.3% 1/7 • Number of events 1 • Baseline up to approximately 18 months An Adverse Event (AE) is any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medical treatment or procedure that may or may not be considered related to the medical treatment or procedure.
Investigations Weight decreased	0.00% 0/13 • Baseline up to approximately 18 months An Adverse Event (AE) is any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medical treatment or procedure that may or may not be considered related to the medical treatment or procedure.	14.3% 1/7 • Number of events 1 • Baseline up to approximately 18 months An Adverse Event (AE) is any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medical treatment or procedure that may or may not be considered related to the medical treatment or procedure.
Investigations White blood cell count decreased	0.00% 0/13 • Baseline up to approximately 18 months An Adverse Event (AE) is any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medical treatment or procedure that may or may not be considered related to the medical treatment or procedure.	14.3% 1/7 • Number of events 1 • Baseline up to approximately 18 months An Adverse Event (AE) is any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medical treatment or procedure that may or may not be considered related to the medical treatment or procedure.
Metabolism and nutrition disorders Diabetes mellitus	0.00% 0/13 • Baseline up to approximately 18 months An Adverse Event (AE) is any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medical treatment or procedure that may or may not be considered related to the medical treatment or procedure.	14.3% 1/7 • Number of events 1 • Baseline up to approximately 18 months An Adverse Event (AE) is any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medical treatment or procedure that may or may not be considered related to the medical treatment or procedure.
Metabolism and nutrition disorders Hypoalbuminaemia	0.00% 0/13 • Baseline up to approximately 18 months An Adverse Event (AE) is any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medical treatment or procedure that may or may not be considered related to the medical treatment or procedure.	14.3% 1/7 • Number of events 1 • Baseline up to approximately 18 months An Adverse Event (AE) is any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medical treatment or procedure that may or may not be considered related to the medical treatment or procedure.
Nervous system disorders Dysgeusia	0.00% 0/13 • Baseline up to approximately 18 months An Adverse Event (AE) is any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medical treatment or procedure that may or may not be considered related to the medical treatment or procedure.	28.6% 2/7 • Number of events 3 • Baseline up to approximately 18 months An Adverse Event (AE) is any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medical treatment or procedure that may or may not be considered related to the medical treatment or procedure.
Nervous system disorders Paraesthesia	0.00% 0/13 • Baseline up to approximately 18 months An Adverse Event (AE) is any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medical treatment or procedure that may or may not be considered related to the medical treatment or procedure.	42.9% 3/7 • Number of events 5 • Baseline up to approximately 18 months An Adverse Event (AE) is any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medical treatment or procedure that may or may not be considered related to the medical treatment or procedure.
Psychiatric disorders Affective disorder	0.00% 0/13 • Baseline up to approximately 18 months An Adverse Event (AE) is any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medical treatment or procedure that may or may not be considered related to the medical treatment or procedure.	14.3% 1/7 • Number of events 1 • Baseline up to approximately 18 months An Adverse Event (AE) is any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medical treatment or procedure that may or may not be considered related to the medical treatment or procedure.
Psychiatric disorders Depression	0.00% 0/13 • Baseline up to approximately 18 months An Adverse Event (AE) is any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medical treatment or procedure that may or may not be considered related to the medical treatment or procedure.	14.3% 1/7 • Number of events 1 • Baseline up to approximately 18 months An Adverse Event (AE) is any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medical treatment or procedure that may or may not be considered related to the medical treatment or procedure.
Psychiatric disorders Insomnia	0.00% 0/13 • Baseline up to approximately 18 months An Adverse Event (AE) is any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medical treatment or procedure that may or may not be considered related to the medical treatment or procedure.	14.3% 1/7 • Number of events 1 • Baseline up to approximately 18 months An Adverse Event (AE) is any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medical treatment or procedure that may or may not be considered related to the medical treatment or procedure.
Respiratory, thoracic and mediastinal disorders Dysphonia	0.00% 0/13 • Baseline up to approximately 18 months An Adverse Event (AE) is any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medical treatment or procedure that may or may not be considered related to the medical treatment or procedure.	14.3% 1/7 • Number of events 1 • Baseline up to approximately 18 months An Adverse Event (AE) is any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medical treatment or procedure that may or may not be considered related to the medical treatment or procedure.
Skin and subcutaneous tissue disorders Dermatitis	0.00% 0/13 • Baseline up to approximately 18 months An Adverse Event (AE) is any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medical treatment or procedure that may or may not be considered related to the medical treatment or procedure.	14.3% 1/7 • Number of events 1 • Baseline up to approximately 18 months An Adverse Event (AE) is any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medical treatment or procedure that may or may not be considered related to the medical treatment or procedure.
Skin and subcutaneous tissue disorders Dermatitis acneiform	0.00% 0/13 • Baseline up to approximately 18 months An Adverse Event (AE) is any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medical treatment or procedure that may or may not be considered related to the medical treatment or procedure.	14.3% 1/7 • Number of events 1 • Baseline up to approximately 18 months An Adverse Event (AE) is any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medical treatment or procedure that may or may not be considered related to the medical treatment or procedure.

Additional Information

Medical Communications

Hoffmann-La Roche

Phone: 1-800-821-8590

Email: genentech@druginfo.com

Results disclosure agreements

• Principal investigator is a sponsor employee The Study being conducted under this Agreement is part of the Overall Study. Investigator is free to publish in reputable journals or to present at professional conferences the results of the Study, but only after the first publication or presentation that involves the Overall Study. The Sponsor may request that Confidential Information be deleted and/or the publication be postponed in order to protect the Sponsor's intellectual property rights.
• Publication restrictions are in place

Restriction type: OTHER