Trial Outcomes & Findings for A Study to Evaluate U3-1402 in Subjects With Advanced or Metastatic Colorectal Cancer (NCT NCT04479436)

NCT ID: NCT04479436

Last Updated: 2025-05-18

Results Overview

ORR defined as the proportion of participants with a best overall response of confirmed complete response (CR) or partial response (PR) as assessed by blinded independent central review. CR was defined as a disappearance of all lesions and PR was defined as at least a 30% decrease in the sum of diameters of target lesion based on RECIST v1.1.

• Recruitment status: TERMINATED
• Study phase: PHASE2
• Target enrollment: 40 participants
• Primary outcome timeframe: From Baseline (Day 0) to data cut off (up to approximately 16.5 months)
• Results posted on: 2025-05-18

Participant Flow

A total of 40 participants who met all inclusion criteria and no exclusion criteria were enrolled in the study at 12 sites. All 40 patients received at least one dose of study drug.

Participant milestones

Measure	Cohort 1: HER3 High (IHC 3+, 2+) Participants in Cohort 1 had high tumor expression levels of human epidermal receptor 3 (HER3) and received an intravenous (IV) infusion of U3-1402 5.6 mg/kg on Day 1 of each 21-day cycle.	Cohort 2: HER3 Low/Negative (IHC 1+, 0) Participants in Cohort 2 had low or negative tumor expression levels of human epidermal receptor 3 (HER3) expression levels and received an intravenous (IV) infusion of U3-1402 5.6 mg/kg on Day 1 of each 21-day cycle.
Overall Study STARTED	39	1
Overall Study COMPLETED	0	0
Overall Study NOT COMPLETED	39	1

Reasons for withdrawal

Measure	Cohort 1: HER3 High (IHC 3+, 2+) Participants in Cohort 1 had high tumor expression levels of human epidermal receptor 3 (HER3) and received an intravenous (IV) infusion of U3-1402 5.6 mg/kg on Day 1 of each 21-day cycle.	Cohort 2: HER3 Low/Negative (IHC 1+, 0) Participants in Cohort 2 had low or negative tumor expression levels of human epidermal receptor 3 (HER3) expression levels and received an intravenous (IV) infusion of U3-1402 5.6 mg/kg on Day 1 of each 21-day cycle.
Overall Study Progressive disease	26	1
Overall Study Adverse Event	6	0
Overall Study Withdrawal by Subject	5	0
Overall Study Clinical progression	1	0
Overall Study Physician Decision	1	0

Baseline Characteristics

A Study to Evaluate U3-1402 in Subjects With Advanced or Metastatic Colorectal Cancer

Baseline characteristics by cohort

Measure	Cohort 1: HER3 High (IHC 3+, 2+) n=39 Participants Participants in Cohort 1 had high tumor expression levels of human epidermal receptor 3 (HER3) and received an intravenous (IV) infusion of U3-1402 5.6 mg/kg on Day 1 of each 21-day cycle.	Cohort 2: HER3 Low/Negative (IHC 1+, 0) n=1 Participants Participants in Cohort 2 had low or negative tumor expression levels of human epidermal receptor 3 (HER3) expression levels and received an intravenous (IV) infusion of U3-1402 5.6 mg/kg on Day 1 of each 21-day cycle.	Total n=40 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants
Age, Categorical Between 18 and 65 years	30 Participants n=93 Participants	0 Participants n=4 Participants	30 Participants n=27 Participants
Age, Categorical >=65 years	9 Participants n=93 Participants	1 Participants n=4 Participants	10 Participants n=27 Participants
Age, Continuous	57.0 years STANDARD_DEVIATION 8.64 • n=93 Participants	67 years n=4 Participants	57.3 years STANDARD_DEVIATION 8.67 • n=27 Participants
Sex: Female, Male Female	13 Participants n=93 Participants	1 Participants n=4 Participants	14 Participants n=27 Participants
Sex: Female, Male Male	26 Participants n=93 Participants	0 Participants n=4 Participants	26 Participants n=27 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants
Race (NIH/OMB) Asian	10 Participants n=93 Participants	0 Participants n=4 Participants	10 Participants n=27 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants
Race (NIH/OMB) Black or African American	3 Participants n=93 Participants	0 Participants n=4 Participants	3 Participants n=27 Participants
Race (NIH/OMB) White	26 Participants n=93 Participants	1 Participants n=4 Participants	27 Participants n=27 Participants
Race (NIH/OMB) More than one race	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants
Region of Enrollment United States	29 participants n=93 Participants	1 participants n=4 Participants	30 participants n=27 Participants
Region of Enrollment Japan	10 participants n=93 Participants	0 participants n=4 Participants	10 participants n=27 Participants

PRIMARY outcome

Timeframe: From Baseline (Day 0) to data cut off (up to approximately 16.5 months)

Population: Overall response rate was assessed in the Full Analysis Set.

ORR defined as the proportion of participants with a best overall response of confirmed complete response (CR) or partial response (PR) as assessed by blinded independent central review. CR was defined as a disappearance of all lesions and PR was defined as at least a 30% decrease in the sum of diameters of target lesion based on RECIST v1.1.

Outcome measures

Measure	Cohort 1: HER3 High (IHC 3+, 2+) n=39 Participants Participants in Cohort 1 had high tumor expression levels of human epidermal receptor 3 (HER3) and received an intravenous (IV) infusion of U3-1402 5.6 mg/kg on Day 1 of each 21-day cycle.	Cohort 2: HER3 Low/Negative (IHC 1+, 0) n=1 Participants Participants in Cohort 2 had low or negative tumor expression levels of human epidermal receptor 3 (HER3) expression levels and received an intravenous (IV) infusion of U3-1402 5.6 mg/kg on Day 1 of each 21-day cycle.
Objective Response Rate (ORR) As Assessed By Blinded Independent Central Review (BICR) Following Administration of U3-1402 In Participants With Advanced or Metastatic Colorectal Cancer	2 Participants	0 Participants

SECONDARY outcome

Timeframe: From Baseline (Day 0) to data cut off (up to approximately 16.5 months)

Population: Duration of response was only assessed in patient responders in Cohort 1 of the Full Analysis Set.

DoR defined as the time from the first documented response (CR or PR) to the date of disease progression or death due to any cause. CR was defined as a disappearance of all lesions and PR was defined as at least a 30% decrease in the sum of diameters of target lesions based on RECIST v1.1.

Outcome measures

Measure	Cohort 1: HER3 High (IHC 3+, 2+) n=2 Participants Participants in Cohort 1 had high tumor expression levels of human epidermal receptor 3 (HER3) and received an intravenous (IV) infusion of U3-1402 5.6 mg/kg on Day 1 of each 21-day cycle.	Cohort 2: HER3 Low/Negative (IHC 1+, 0) Participants in Cohort 2 had low or negative tumor expression levels of human epidermal receptor 3 (HER3) expression levels and received an intravenous (IV) infusion of U3-1402 5.6 mg/kg on Day 1 of each 21-day cycle.
Duration of Response (DoR) As Assessed by Blinded Independent Central Review (BICR) and Investigator Following Administration of U3-1402 In Participants With Advanced or Metastatic Colorectal Cancer Duration of Response: BICR	2.91 months Interval 2.79 to 3.02	—
Duration of Response (DoR) As Assessed by Blinded Independent Central Review (BICR) and Investigator Following Administration of U3-1402 In Participants With Advanced or Metastatic Colorectal Cancer Duration of Response: Investigator	4.48 months Interval 2.56 to 6.41	—

SECONDARY outcome

Timeframe: From Baseline (Day 0) to data cut off (up to approximately 16.5 months)

Population: Objective response rate was assessed only in Cohort 1 of the Full Analysis Set. Per prespecified criteria cohort 2 was not able to be assessed.

ORR defined as the proportion of participants with a best overall response (BOR) of confirmed complete response (CR) or partial response (PR) as assessed by Investigator. CR was defined as a disappearance of all lesions and PR was defined as at least a 30% decrease in the sum of diameters of target lesion based on RECIST v1.1.

Outcome measures

Measure	Cohort 1: HER3 High (IHC 3+, 2+) n=39 Participants Participants in Cohort 1 had high tumor expression levels of human epidermal receptor 3 (HER3) and received an intravenous (IV) infusion of U3-1402 5.6 mg/kg on Day 1 of each 21-day cycle.	Cohort 2: HER3 Low/Negative (IHC 1+, 0) Participants in Cohort 2 had low or negative tumor expression levels of human epidermal receptor 3 (HER3) expression levels and received an intravenous (IV) infusion of U3-1402 5.6 mg/kg on Day 1 of each 21-day cycle.
Objective Response Rate (ORR) As Assessed by Investigator Following Administration of U3-1402 In Participants With Advanced or Metastatic Colorectal Cancer	2 Participants	—

SECONDARY outcome

Timeframe: From Baseline (Day 0) to data cut off (up to approximately 16.5 months)

Population: Disease control rate was assessed only in Cohort 1 of the Full Analysis Set. Per prespecified criteria cohort 2 was not able to be assessed.

DCR is defined as the proportion of participants who achieved a confirmed best overall response (BOR) of complete response (CR), partial response (PR), or stable disease (SD) as assessed by blinded independent central review or by the Investigator. Based on RECIST v1.1, CR was defined as a disappearance of all target lesions, PR was defined as at least a 30% decrease in the sum of diameters of target lesions, and stable disease (SD) was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (PD; at least a 20% increase in the sum of diameters of target lesions.

Outcome measures

Measure	Cohort 1: HER3 High (IHC 3+, 2+) n=39 Participants Participants in Cohort 1 had high tumor expression levels of human epidermal receptor 3 (HER3) and received an intravenous (IV) infusion of U3-1402 5.6 mg/kg on Day 1 of each 21-day cycle.	Cohort 2: HER3 Low/Negative (IHC 1+, 0) Participants in Cohort 2 had low or negative tumor expression levels of human epidermal receptor 3 (HER3) expression levels and received an intravenous (IV) infusion of U3-1402 5.6 mg/kg on Day 1 of each 21-day cycle.
Disease Control Rate (DCR) by Blinded Independent Central Review (BICR) and Investigator Following Administration of U3-1402 In Participants With Advanced or Metastatic Colorectal Cancer Disease control rate (BICR)	22 Participants	—
Disease Control Rate (DCR) by Blinded Independent Central Review (BICR) and Investigator Following Administration of U3-1402 In Participants With Advanced or Metastatic Colorectal Cancer Disease control rate (Investigator)	22 Participants	—

SECONDARY outcome

Timeframe: From Baseline (Day 0) to data cut off (up to approximately 16.5 months)

Population: Time to tumor response was assessed only in Cohort 1 responders who had a documented CR or PR in the Full Analysis Set.

TTR defined as the time from the start of study treatment to the date of the first documentation of objective response (complete response [CR] or partial response [PR]) that is subsequently confirmed by Blinded Independent Central Review or by the Investigator. CR was defined as a disappearance of all lesions and PR was defined as at least a 30% decrease in the sum of diameters of target lesions based on RECIST v1.1.

Outcome measures

Measure	Cohort 1: HER3 High (IHC 3+, 2+) n=2 Participants Participants in Cohort 1 had high tumor expression levels of human epidermal receptor 3 (HER3) and received an intravenous (IV) infusion of U3-1402 5.6 mg/kg on Day 1 of each 21-day cycle.	Cohort 2: HER3 Low/Negative (IHC 1+, 0) Participants in Cohort 2 had low or negative tumor expression levels of human epidermal receptor 3 (HER3) expression levels and received an intravenous (IV) infusion of U3-1402 5.6 mg/kg on Day 1 of each 21-day cycle.
Time to Tumor Response (TTR) As Assessed by Blinded Independent Central Review (BICR) and Investigator Following Administration of U3-1402 In Participants With Advanced or Metastatic Colorectal Cancer Time to tumor response (BICR)	1.99 months Standard Deviation 0.813	—
Time to Tumor Response (TTR) As Assessed by Blinded Independent Central Review (BICR) and Investigator Following Administration of U3-1402 In Participants With Advanced or Metastatic Colorectal Cancer Time to tumor response (Investigator)	1.53 months Standard Deviation 0.163	—

SECONDARY outcome

Timeframe: From Baseline (Day 0) to data cut off (up to approximately 16.5 months)

Population: Progression-free survival was assessed in the Full Analysis Set.

PFS is defined as the time from the start of study treatment to the date of the first documentation of objective PD or death due to any cause, whichever is earlier.

Outcome measures

Measure	Cohort 1: HER3 High (IHC 3+, 2+) n=39 Participants Participants in Cohort 1 had high tumor expression levels of human epidermal receptor 3 (HER3) and received an intravenous (IV) infusion of U3-1402 5.6 mg/kg on Day 1 of each 21-day cycle.	Cohort 2: HER3 Low/Negative (IHC 1+, 0) n=1 Participants Participants in Cohort 2 had low or negative tumor expression levels of human epidermal receptor 3 (HER3) expression levels and received an intravenous (IV) infusion of U3-1402 5.6 mg/kg on Day 1 of each 21-day cycle.
Progression-free Survival (PFS) Assessed by Blinded Independent Central Review (BICR) and Investigator Following Administration of U3-1402 In Participants With Advanced or Metastatic Colorectal Cancer Progression-free survival (BICR)	2.27 months Interval 1.51 to 2.96	5.5 months
Progression-free Survival (PFS) Assessed by Blinded Independent Central Review (BICR) and Investigator Following Administration of U3-1402 In Participants With Advanced or Metastatic Colorectal Cancer Progression-free survival (Investigator)	2.53 months Interval 1.64 to 3.71	—

SECONDARY outcome

Timeframe: From Baseline (Day 0) to data cut off (up to approximately 16.5 months)

Population: Overall survival was assessed in the Full Analysis Set.

OS defined as the time from the start of study treatment to the date of death due to any cause.

Outcome measures

Measure	Cohort 1: HER3 High (IHC 3+, 2+) n=39 Participants Participants in Cohort 1 had high tumor expression levels of human epidermal receptor 3 (HER3) and received an intravenous (IV) infusion of U3-1402 5.6 mg/kg on Day 1 of each 21-day cycle.	Cohort 2: HER3 Low/Negative (IHC 1+, 0) n=1 Participants Participants in Cohort 2 had low or negative tumor expression levels of human epidermal receptor 3 (HER3) expression levels and received an intravenous (IV) infusion of U3-1402 5.6 mg/kg on Day 1 of each 21-day cycle.
Overall Survival (OS) Following Administration of U3-1402 In Participants With Advanced or Metastatic Colorectal Cancer	10.58 months Interval 5.36 to 12.09	8.9 months

SECONDARY outcome

Timeframe: From Baseline (Day 0) to data cut off (up to approximately 16.5 months)

Population: Safety events were assessed in the Safety Analysis Set.

TEAEs, study-drug related TEAE, serious adverse events (SAE), study-drug related SAE, and adverse events of special interest (eg. interstitial lung disease and elevation of aminotransferases and total bilirubin) were assessed. A TEAE was defined as an AE with a start or worsening date during the on-treatment period. An SAE was an AE that resulted in death, was life threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect, or was an important medical event.

Outcome measures

Measure	Cohort 1: HER3 High (IHC 3+, 2+) n=40 Participants Participants in Cohort 1 had high tumor expression levels of human epidermal receptor 3 (HER3) and received an intravenous (IV) infusion of U3-1402 5.6 mg/kg on Day 1 of each 21-day cycle.	Cohort 2: HER3 Low/Negative (IHC 1+, 0) Participants in Cohort 2 had low or negative tumor expression levels of human epidermal receptor 3 (HER3) expression levels and received an intravenous (IV) infusion of U3-1402 5.6 mg/kg on Day 1 of each 21-day cycle.
Number of Participants Reporting Treatment-emergent Adverse Events (TEAEs) and Other Safety Parameters During the Study Treatment-emergent adverse events (TEAEs)	40 Participants	—
Number of Participants Reporting Treatment-emergent Adverse Events (TEAEs) and Other Safety Parameters During the Study Study-drug related TEAE	37 Participants	—
Number of Participants Reporting Treatment-emergent Adverse Events (TEAEs) and Other Safety Parameters During the Study Serious TEAE (SAE)	17 Participants	—
Number of Participants Reporting Treatment-emergent Adverse Events (TEAEs) and Other Safety Parameters During the Study Study-drug related SAE	9 Participants	—
Number of Participants Reporting Treatment-emergent Adverse Events (TEAEs) and Other Safety Parameters During the Study Adverse event of special interest (AESI)	2 Participants	—

SECONDARY outcome

Timeframe: At Baseline, and post-Baseline. Post-Baseline including any of the following timepoints- Cycle 1, Days 1&8; Cycles 2&4 and every 2 cycles thereafter, Day 1 (each cycle, 21 days), and at EOT (~16.5 months).

Population: Immunogenicity was assessed in the Safety Analysis Set only in Cohort 1. Per prespecified criteria cohort 2 was not able to be assessed.

Blood samples were collected to assess the immunogenicity of U3-1402.

Outcome measures

Measure	Cohort 1: HER3 High (IHC 3+, 2+) n=39 Participants Participants in Cohort 1 had high tumor expression levels of human epidermal receptor 3 (HER3) and received an intravenous (IV) infusion of U3-1402 5.6 mg/kg on Day 1 of each 21-day cycle.	Cohort 2: HER3 Low/Negative (IHC 1+, 0) Participants in Cohort 2 had low or negative tumor expression levels of human epidermal receptor 3 (HER3) expression levels and received an intravenous (IV) infusion of U3-1402 5.6 mg/kg on Day 1 of each 21-day cycle.
Number of Participants Who Are Anti-Drug Antibody (ADA)-Positive (Baseline and Post-Baseline) Baseline: Positive	0 Participants	—
Number of Participants Who Are Anti-Drug Antibody (ADA)-Positive (Baseline and Post-Baseline) Baseline: Negative	37 Participants	—
Number of Participants Who Are Anti-Drug Antibody (ADA)-Positive (Baseline and Post-Baseline) Baseline: Missing	2 Participants	—
Number of Participants Who Are Anti-Drug Antibody (ADA)-Positive (Baseline and Post-Baseline) Post-baseline: Positive	0 Participants	—
Number of Participants Who Are Anti-Drug Antibody (ADA)-Positive (Baseline and Post-Baseline) Post-baseline: Negative	38 Participants	—

SECONDARY outcome

Timeframe: At Baseline, and post-Baseline. Post-Baseline including any of the following timepoints- Cycle 1, Days 1&8; Cycles 2&4 and every 2 cycles thereafter, Day 1 (each cycle, 21 days), and at EOT (~16.5 months).

Population: Immunogenicity was assessed in the Safety Analysis Set only in Cohort 1 participants at baseline and in participants post-baseline with at least 1 ADA sample. Per prespecified criteria cohort 2 was not able to be assessed.

Blood samples were collected to assess the immunogenicity of U3-1402. Treatment-emergent ADA was defined as participants with a negative ADA status at Baseline who had a positive ADA status post-Baseline (treatment-induced ADA), or participants with a positive ADA status at both Baseline and post-Baseline but with an increase of at least 4-fold in ADA titer from Baseline to post-Baseline (treatment-boosted ADA), or participants who had missing ADA data at Baseline and had a positive ADA status post-Baseline.

Outcome measures

Measure	Cohort 1: HER3 High (IHC 3+, 2+) n=39 Participants Participants in Cohort 1 had high tumor expression levels of human epidermal receptor 3 (HER3) and received an intravenous (IV) infusion of U3-1402 5.6 mg/kg on Day 1 of each 21-day cycle.	Cohort 2: HER3 Low/Negative (IHC 1+, 0) Participants in Cohort 2 had low or negative tumor expression levels of human epidermal receptor 3 (HER3) expression levels and received an intravenous (IV) infusion of U3-1402 5.6 mg/kg on Day 1 of each 21-day cycle.
Number of Participants Who Have Treatment-emergent Anti-Drug Antibody (ADA) Treatment-emergent ADA	0 Participants	—
Number of Participants Who Have Treatment-emergent Anti-Drug Antibody (ADA) Treatment-induced ADA	0 Participants	—
Number of Participants Who Have Treatment-emergent Anti-Drug Antibody (ADA) Treatment-boosted ADA	0 Participants	—
Number of Participants Who Have Treatment-emergent Anti-Drug Antibody (ADA) ADA missing at baseline but positive at post-baseline	0 Participants	—

SECONDARY outcome

Timeframe: At baseline (-8 hour to 0 hour), pre-infusion, and 15 minutes, 1 hour, 2 hour, 4 hour, and 8 hour post-infusion of Cycle 1 and Cycle 3 (each cycle is 21 days)

Population: Pharmacokinetic parameters were assessed in the Pharmacokinetic Analysis Set only in Cohort 1 participants with available data. Per prespecified criteria cohort 2 was not able to be assessed

Serum PK parameter Cmax (antibody drug conjugate [ADC], total anti-HER3 antibody, and MAAA-1181a) were assessed in the full PK sampling cohort using noncompartmental methods.

Outcome measures

Measure	Cohort 1: HER3 High (IHC 3+, 2+) n=39 Participants Participants in Cohort 1 had high tumor expression levels of human epidermal receptor 3 (HER3) and received an intravenous (IV) infusion of U3-1402 5.6 mg/kg on Day 1 of each 21-day cycle.	Cohort 2: HER3 Low/Negative (IHC 1+, 0) Participants in Cohort 2 had low or negative tumor expression levels of human epidermal receptor 3 (HER3) expression levels and received an intravenous (IV) infusion of U3-1402 5.6 mg/kg on Day 1 of each 21-day cycle.
Pharmacokinetic Parameter Maximum Serum Concentration (Cmax) Following Administration of U3-1402 In Participants With Advanced or Metastatic Colorectal Cancer U3-1402: Cycle 1	155.67 ug/mL Standard Deviation 43.45	—
Pharmacokinetic Parameter Maximum Serum Concentration (Cmax) Following Administration of U3-1402 In Participants With Advanced or Metastatic Colorectal Cancer U3-1402: Cycle 3	159.80 ug/mL Standard Deviation 47.94	—
Pharmacokinetic Parameter Maximum Serum Concentration (Cmax) Following Administration of U3-1402 In Participants With Advanced or Metastatic Colorectal Cancer Total anti-HER3 antibody: Cycle 1	154.08 ug/mL Standard Deviation 32.82	—
Pharmacokinetic Parameter Maximum Serum Concentration (Cmax) Following Administration of U3-1402 In Participants With Advanced or Metastatic Colorectal Cancer Total anti-HER3 antibody: Cycle 3	153.86 ug/mL Standard Deviation 39.31	—

SECONDARY outcome

Timeframe: At baseline (-8 hour to 0 hour), pre-infusion, and 15 minutes, 1 hour, 2 hour, 4 hour, and 8 hour post-infusion of Cycle 1 and Cycle 3 (each cycle is 21 days)

Population: Pharmacokinetic parameters were assessed in the Pharmacokinetic Analysis Set only in Cohort 1 participants with available data. Per prespecified criteria cohort 2 was not able to be assessed.

Serum PK parameter Cmax of MAAA-1181a was assessed in the full PK sampling cohort using noncompartmental methods.

Outcome measures

Measure	Cohort 1: HER3 High (IHC 3+, 2+) n=39 Participants Participants in Cohort 1 had high tumor expression levels of human epidermal receptor 3 (HER3) and received an intravenous (IV) infusion of U3-1402 5.6 mg/kg on Day 1 of each 21-day cycle.	Cohort 2: HER3 Low/Negative (IHC 1+, 0) Participants in Cohort 2 had low or negative tumor expression levels of human epidermal receptor 3 (HER3) expression levels and received an intravenous (IV) infusion of U3-1402 5.6 mg/kg on Day 1 of each 21-day cycle.
Pharmacokinetic Parameter Maximum Serum Concentration (Cmax) of MAAA-1181a Following Administration of U3-1402 In Participants With Advanced or Metastatic Colorectal Cancer Cycle 1	38.09 ng/mL Standard Deviation 19.68	—
Pharmacokinetic Parameter Maximum Serum Concentration (Cmax) of MAAA-1181a Following Administration of U3-1402 In Participants With Advanced or Metastatic Colorectal Cancer Cycle 3	16.13 ng/mL Standard Deviation 9.29	—

SECONDARY outcome

Timeframe: At baseline (-8 hour to 0 hour), pre-infusion, and 15 minutes, 1 hour, 2 hour, 4 hour, and 8 hour post-infusion of Cycle 1 and Cycle 3 (each cycle is 21 days)

Population: Pharmacokinetic parameters were assessed in the Pharmacokinetic Analysis Set only in Cohort 1 participants with available data. Per prespecified criteria cohort 2 was not able to be assessed.

Serum PK parameter Tmax (antibody drug conjugate [ADC], total anti-HER3 antibody, and MAAA-1181a) were assessed in the full PK sampling cohort using noncompartmental methods.

Outcome measures

Measure	Cohort 1: HER3 High (IHC 3+, 2+) n=39 Participants Participants in Cohort 1 had high tumor expression levels of human epidermal receptor 3 (HER3) and received an intravenous (IV) infusion of U3-1402 5.6 mg/kg on Day 1 of each 21-day cycle.	Cohort 2: HER3 Low/Negative (IHC 1+, 0) Participants in Cohort 2 had low or negative tumor expression levels of human epidermal receptor 3 (HER3) expression levels and received an intravenous (IV) infusion of U3-1402 5.6 mg/kg on Day 1 of each 21-day cycle.
Pharmacokinetic Parameter Time to Reach Maximum Serum Concentration (Tmax) Following Administration of U3-1402 In Participants With Advanced or Metastatic Colorectal Cancer U3-1402: Cycle 1	2.42 hours Interval 1.52 to 5.67	—
Pharmacokinetic Parameter Time to Reach Maximum Serum Concentration (Tmax) Following Administration of U3-1402 In Participants With Advanced or Metastatic Colorectal Cancer U3-1402: Cycle 3	4.39 hours Interval 0.53 to 8.78	—
Pharmacokinetic Parameter Time to Reach Maximum Serum Concentration (Tmax) Following Administration of U3-1402 In Participants With Advanced or Metastatic Colorectal Cancer Total anti-HER3 antibody: Cycle 1	1.72 hours Interval 1.45 to 505.5	—
Pharmacokinetic Parameter Time to Reach Maximum Serum Concentration (Tmax) Following Administration of U3-1402 In Participants With Advanced or Metastatic Colorectal Cancer Total anti-HER3 antibody: Cycle 3	3.86 hours Interval 0.53 to 8.78	—
Pharmacokinetic Parameter Time to Reach Maximum Serum Concentration (Tmax) Following Administration of U3-1402 In Participants With Advanced or Metastatic Colorectal Cancer MAAA-1181a: Cycle 1	5.28 hours Interval 2.57 to 9.47	—
Pharmacokinetic Parameter Time to Reach Maximum Serum Concentration (Tmax) Following Administration of U3-1402 In Participants With Advanced or Metastatic Colorectal Cancer MAAA-1181a: Cycle 3	4.45 hours Interval 0.65 to 8.33	—

SECONDARY outcome

Timeframe: At baseline (-8 hour to 0 hour), pre-infusion, and 15 minutes, 1 hour, 2 hour, 4 hour, and 8 hour post-infusion of Cycle 1 and Cycle 3 (each cycle is 21 days)

Population: Pharmacokinetic paramters were assessed in the Pharmacokinetic Analysis Set only in Cohort 1 participants with available data. Per prespecified criteria cohort 2 was not able to be assessed.

Serum PK parameter Ctrough (antibody drug conjugate [ADC] and total anti-HER3 antibody) were assessed in the full PK sampling cohort using noncompartmental methods.

Outcome measures

Measure	Cohort 1: HER3 High (IHC 3+, 2+) n=35 Participants Participants in Cohort 1 had high tumor expression levels of human epidermal receptor 3 (HER3) and received an intravenous (IV) infusion of U3-1402 5.6 mg/kg on Day 1 of each 21-day cycle.	Cohort 2: HER3 Low/Negative (IHC 1+, 0) Participants in Cohort 2 had low or negative tumor expression levels of human epidermal receptor 3 (HER3) expression levels and received an intravenous (IV) infusion of U3-1402 5.6 mg/kg on Day 1 of each 21-day cycle.
Pharmacokinetic ParameterTrough Serum Concentration (Ctrough) Following Administration of U3-1402 In Participants With Advanced or Metastatic Colorectal Cancer U3-1402: Cycle 1	7.98 ug/mL Standard Deviation 24.20	—
Pharmacokinetic ParameterTrough Serum Concentration (Ctrough) Following Administration of U3-1402 In Participants With Advanced or Metastatic Colorectal Cancer U3-1402: Cycle 3	12.76 ug/mL Standard Deviation 9.19	—
Pharmacokinetic ParameterTrough Serum Concentration (Ctrough) Following Administration of U3-1402 In Participants With Advanced or Metastatic Colorectal Cancer Total anti-HER3 antibody: Cycle 1	8.55 ug/mL Standard Deviation 29.61	—
Pharmacokinetic ParameterTrough Serum Concentration (Ctrough) Following Administration of U3-1402 In Participants With Advanced or Metastatic Colorectal Cancer Total anti-HER3 antibody: Cycle 3	11.49 ug/mL Standard Deviation 9.25	—

SECONDARY outcome

Timeframe: At baseline (-8 hour to 0 hour), pre-infusion, and 15 minutes, 1 hour, 2 hour, 4 hour, and 8 hour post-infusion of Cycle 1 and Cycle 3 (each cycle is 21 days)

Population: Pharmacokinetic parameters were assessed in the Pharmacokinetic Analysis Set only in Cohort 1 participants with available data. Per prespecified criteria cohort 2 was not able to be assessed.

Serum PK parameter Ctrough of MAAA-1181a was assessed in the full PK sampling cohort using noncompartmental methods.

Outcome measures

Measure	Cohort 1: HER3 High (IHC 3+, 2+) n=35 Participants Participants in Cohort 1 had high tumor expression levels of human epidermal receptor 3 (HER3) and received an intravenous (IV) infusion of U3-1402 5.6 mg/kg on Day 1 of each 21-day cycle.	Cohort 2: HER3 Low/Negative (IHC 1+, 0) Participants in Cohort 2 had low or negative tumor expression levels of human epidermal receptor 3 (HER3) expression levels and received an intravenous (IV) infusion of U3-1402 5.6 mg/kg on Day 1 of each 21-day cycle.
Pharmacokinetic ParameterTrough Serum Concentration (Ctrough) of MAAA-1181a Following Administration of U3-1402 In Participants With Advanced or Metastatic Colorectal Cancer MAAA-1181a: Cycle 1	0.49 ng/mL Standard Deviation 1.42	—
Pharmacokinetic ParameterTrough Serum Concentration (Ctrough) of MAAA-1181a Following Administration of U3-1402 In Participants With Advanced or Metastatic Colorectal Cancer MAAA-1181a: Cycle 3	0.68 ng/mL Standard Deviation 0.66	—

SECONDARY outcome

Timeframe: At baseline (-8 hour to 0 hour), pre-infusion, and 15 minutes, 1 hour, 2 hour, 4 hour, and 8 hour post-infusion of Cycle 1 and Cycle 3 (each cycle is 21 days)

Population: Pharmacokinetic parameters were assessed in the Pharmacokinetic Analysis Set only in Cohort 1 participants with available data. Per prespecified criteria cohort 2 was not able to be assessed.

Serum PK parameter AUC (antibody drug conjugate [ADC], total anti-HER3 antibody, and MAAA-1181a) were assessed in the full PK sampling cohort using noncompartmental methods.

Outcome measures

Measure	Cohort 1: HER3 High (IHC 3+, 2+) n=20 Participants Participants in Cohort 1 had high tumor expression levels of human epidermal receptor 3 (HER3) and received an intravenous (IV) infusion of U3-1402 5.6 mg/kg on Day 1 of each 21-day cycle.	Cohort 2: HER3 Low/Negative (IHC 1+, 0) Participants in Cohort 2 had low or negative tumor expression levels of human epidermal receptor 3 (HER3) expression levels and received an intravenous (IV) infusion of U3-1402 5.6 mg/kg on Day 1 of each 21-day cycle.
Pharmacokinetic of Area Under the Serum Concentration-Time Curve Up to Last Quantifiable Time (AUClast) and During Dosing Interval (AUCtau) Following Administration of U3-1402 In Participants With Advanced or Metastatic Colorectal Cancer U3-1402, AUClast: Cycle 1	562.05 day*ug/mL Standard Deviation 246.93	—
Pharmacokinetic of Area Under the Serum Concentration-Time Curve Up to Last Quantifiable Time (AUClast) and During Dosing Interval (AUCtau) Following Administration of U3-1402 In Participants With Advanced or Metastatic Colorectal Cancer U3-1402, AUCtau: Cycle 1	569.42 day*ug/mL Standard Deviation 191.03	—
Pharmacokinetic of Area Under the Serum Concentration-Time Curve Up to Last Quantifiable Time (AUClast) and During Dosing Interval (AUCtau) Following Administration of U3-1402 In Participants With Advanced or Metastatic Colorectal Cancer U3-1402, AUCtau: Cycle 3	1230.44 day*ug/mL Standard Deviation 257.08	—
Pharmacokinetic of Area Under the Serum Concentration-Time Curve Up to Last Quantifiable Time (AUClast) and During Dosing Interval (AUCtau) Following Administration of U3-1402 In Participants With Advanced or Metastatic Colorectal Cancer Total anti-HER3 antibody, AUClast: Cycle 1	590.11 day*ug/mL Standard Deviation 279.67	—
Pharmacokinetic of Area Under the Serum Concentration-Time Curve Up to Last Quantifiable Time (AUClast) and During Dosing Interval (AUCtau) Following Administration of U3-1402 In Participants With Advanced or Metastatic Colorectal Cancer Total anti-HER3 antibody, AUCtau: Cycle 1	596.24 day*ug/mL Standard Deviation 217.23	—
Pharmacokinetic of Area Under the Serum Concentration-Time Curve Up to Last Quantifiable Time (AUClast) and During Dosing Interval (AUCtau) Following Administration of U3-1402 In Participants With Advanced or Metastatic Colorectal Cancer Total anti-HER3 antibody, AUCtau: Cycle 3	1104.22 day*ug/mL Standard Deviation 397.93	—

SECONDARY outcome

Timeframe: At baseline (-8 hour to 0 hour), pre-infusion, and 15 minutes, 1 hour, 2 hour, 4 hour, and 8 hour post-infusion of Cycle 1 and Cycle 3 (each cycle is 21 days)

Population: Pharmacokinetic parameters were assessed in the Pharmacokinetic Analysis Set only in Cohort 1 participants with available data. Per prespecified criteria cohort 2 was not able to be assessed.

Serum PK parameter AUC of MAAA-1181a was assessed in the full PK sampling cohort using noncompartmental methods.

Outcome measures

Measure	Cohort 1: HER3 High (IHC 3+, 2+) n=20 Participants Participants in Cohort 1 had high tumor expression levels of human epidermal receptor 3 (HER3) and received an intravenous (IV) infusion of U3-1402 5.6 mg/kg on Day 1 of each 21-day cycle.	Cohort 2: HER3 Low/Negative (IHC 1+, 0) Participants in Cohort 2 had low or negative tumor expression levels of human epidermal receptor 3 (HER3) expression levels and received an intravenous (IV) infusion of U3-1402 5.6 mg/kg on Day 1 of each 21-day cycle.
Pharmacokinetic of Area Under the Serum Concentration-Time Curve Up to Last Quantifiable Time (AUClast) and During Dosing Interval (AUCtau) of MAAA-1181a Following Administration of U3-1402 In Participants With Advanced or Metastatic Colorectal Cancer AUClast: Cycle 1	89.96 day*ng/mL Standard Deviation 60.43	—
Pharmacokinetic of Area Under the Serum Concentration-Time Curve Up to Last Quantifiable Time (AUClast) and During Dosing Interval (AUCtau) of MAAA-1181a Following Administration of U3-1402 In Participants With Advanced or Metastatic Colorectal Cancer AUCtau: Cycle 1	92.81 day*ng/mL Standard Deviation 58.94	—
Pharmacokinetic of Area Under the Serum Concentration-Time Curve Up to Last Quantifiable Time (AUClast) and During Dosing Interval (AUCtau) of MAAA-1181a Following Administration of U3-1402 In Participants With Advanced or Metastatic Colorectal Cancer AUCtau: Cycle 3	78.68 day*ng/mL Standard Deviation 34.60	—

Adverse Events

Overall

Serious events: 17 serious events

Other events: 40 other events

Deaths: 23 deaths

Serious adverse events

Measure	Overall n=40 participants at risk This cohort includes all patients with human epidermal receptor 3 (HER3) tumor expression (regardless of expression level) and received an intravenous (IV) infusion of U3-1402 5.6 mg/kg on Day 1 of each 21-day cycle.
General disorders Disease progression	7.5% 3/40 • Adverse events (AEs) were collected for approximately 16.5 months. An adverse event (AE) is any untoward medical occurrence in a participant administered pharmaceutical product and that does not necessarily have to have a causal relationship with this treatment. An AE can be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. It was pre-specified that AE results would be presented for the overall subject population, rather than by cohort.
Gastrointestinal disorders Abdominal pain	5.0% 2/40 • Adverse events (AEs) were collected for approximately 16.5 months. An adverse event (AE) is any untoward medical occurrence in a participant administered pharmaceutical product and that does not necessarily have to have a causal relationship with this treatment. An AE can be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. It was pre-specified that AE results would be presented for the overall subject population, rather than by cohort.
Renal and urinary disorders Acute kidney injury	5.0% 2/40 • Adverse events (AEs) were collected for approximately 16.5 months. An adverse event (AE) is any untoward medical occurrence in a participant administered pharmaceutical product and that does not necessarily have to have a causal relationship with this treatment. An AE can be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. It was pre-specified that AE results would be presented for the overall subject population, rather than by cohort.
Blood and lymphatic system disorders Febrile neutropenia	5.0% 2/40 • Adverse events (AEs) were collected for approximately 16.5 months. An adverse event (AE) is any untoward medical occurrence in a participant administered pharmaceutical product and that does not necessarily have to have a causal relationship with this treatment. An AE can be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. It was pre-specified that AE results would be presented for the overall subject population, rather than by cohort.
General disorders Nausea	5.0% 2/40 • Adverse events (AEs) were collected for approximately 16.5 months. An adverse event (AE) is any untoward medical occurrence in a participant administered pharmaceutical product and that does not necessarily have to have a causal relationship with this treatment. An AE can be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. It was pre-specified that AE results would be presented for the overall subject population, rather than by cohort.
Respiratory, thoracic and mediastinal disorders Acute respiratory failure	2.5% 1/40 • Adverse events (AEs) were collected for approximately 16.5 months. An adverse event (AE) is any untoward medical occurrence in a participant administered pharmaceutical product and that does not necessarily have to have a causal relationship with this treatment. An AE can be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. It was pre-specified that AE results would be presented for the overall subject population, rather than by cohort.
Blood and lymphatic system disorders Anaemia	2.5% 1/40 • Adverse events (AEs) were collected for approximately 16.5 months. An adverse event (AE) is any untoward medical occurrence in a participant administered pharmaceutical product and that does not necessarily have to have a causal relationship with this treatment. An AE can be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. It was pre-specified that AE results would be presented for the overall subject population, rather than by cohort.
Hepatobiliary disorders Biliary obstruction	2.5% 1/40 • Adverse events (AEs) were collected for approximately 16.5 months. An adverse event (AE) is any untoward medical occurrence in a participant administered pharmaceutical product and that does not necessarily have to have a causal relationship with this treatment. An AE can be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. It was pre-specified that AE results would be presented for the overall subject population, rather than by cohort.
Nervous system disorders Cauda equina syndrome	2.5% 1/40 • Adverse events (AEs) were collected for approximately 16.5 months. An adverse event (AE) is any untoward medical occurrence in a participant administered pharmaceutical product and that does not necessarily have to have a causal relationship with this treatment. An AE can be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. It was pre-specified that AE results would be presented for the overall subject population, rather than by cohort.
Infections and infestations Cytomegalovirus infection	2.5% 1/40 • Adverse events (AEs) were collected for approximately 16.5 months. An adverse event (AE) is any untoward medical occurrence in a participant administered pharmaceutical product and that does not necessarily have to have a causal relationship with this treatment. An AE can be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. It was pre-specified that AE results would be presented for the overall subject population, rather than by cohort.
Respiratory, thoracic and mediastinal disorders Dyspnoea	2.5% 1/40 • Adverse events (AEs) were collected for approximately 16.5 months. An adverse event (AE) is any untoward medical occurrence in a participant administered pharmaceutical product and that does not necessarily have to have a causal relationship with this treatment. An AE can be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. It was pre-specified that AE results would be presented for the overall subject population, rather than by cohort.
Hepatobiliary disorders Hyperbilirubinaemia	2.5% 1/40 • Adverse events (AEs) were collected for approximately 16.5 months. An adverse event (AE) is any untoward medical occurrence in a participant administered pharmaceutical product and that does not necessarily have to have a causal relationship with this treatment. An AE can be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. It was pre-specified that AE results would be presented for the overall subject population, rather than by cohort.
Metabolism and nutrition disorders Hypokalaemia	2.5% 1/40 • Adverse events (AEs) were collected for approximately 16.5 months. An adverse event (AE) is any untoward medical occurrence in a participant administered pharmaceutical product and that does not necessarily have to have a causal relationship with this treatment. An AE can be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. It was pre-specified that AE results would be presented for the overall subject population, rather than by cohort.
Investigations International normalised ratio increased	2.5% 1/40 • Adverse events (AEs) were collected for approximately 16.5 months. An adverse event (AE) is any untoward medical occurrence in a participant administered pharmaceutical product and that does not necessarily have to have a causal relationship with this treatment. An AE can be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. It was pre-specified that AE results would be presented for the overall subject population, rather than by cohort.
Respiratory, thoracic and mediastinal disorders Interstitial lung disease	2.5% 1/40 • Adverse events (AEs) were collected for approximately 16.5 months. An adverse event (AE) is any untoward medical occurrence in a participant administered pharmaceutical product and that does not necessarily have to have a causal relationship with this treatment. An AE can be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. It was pre-specified that AE results would be presented for the overall subject population, rather than by cohort.
Infections and infestations Liver abscess	2.5% 1/40 • Adverse events (AEs) were collected for approximately 16.5 months. An adverse event (AE) is any untoward medical occurrence in a participant administered pharmaceutical product and that does not necessarily have to have a causal relationship with this treatment. An AE can be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. It was pre-specified that AE results would be presented for the overall subject population, rather than by cohort.
Investigations Platelet count decreased	2.5% 1/40 • Adverse events (AEs) were collected for approximately 16.5 months. An adverse event (AE) is any untoward medical occurrence in a participant administered pharmaceutical product and that does not necessarily have to have a causal relationship with this treatment. An AE can be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. It was pre-specified that AE results would be presented for the overall subject population, rather than by cohort.
Respiratory, thoracic and mediastinal disorders Pleural effusion	2.5% 1/40 • Adverse events (AEs) were collected for approximately 16.5 months. An adverse event (AE) is any untoward medical occurrence in a participant administered pharmaceutical product and that does not necessarily have to have a causal relationship with this treatment. An AE can be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. It was pre-specified that AE results would be presented for the overall subject population, rather than by cohort.
Infections and infestations Pneumonia	2.5% 1/40 • Adverse events (AEs) were collected for approximately 16.5 months. An adverse event (AE) is any untoward medical occurrence in a participant administered pharmaceutical product and that does not necessarily have to have a causal relationship with this treatment. An AE can be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. It was pre-specified that AE results would be presented for the overall subject population, rather than by cohort.
Respiratory, thoracic and mediastinal disorders Pneumonitis	2.5% 1/40 • Adverse events (AEs) were collected for approximately 16.5 months. An adverse event (AE) is any untoward medical occurrence in a participant administered pharmaceutical product and that does not necessarily have to have a causal relationship with this treatment. An AE can be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. It was pre-specified that AE results would be presented for the overall subject population, rather than by cohort.
Infections and infestations Pyelonephritis	2.5% 1/40 • Adverse events (AEs) were collected for approximately 16.5 months. An adverse event (AE) is any untoward medical occurrence in a participant administered pharmaceutical product and that does not necessarily have to have a causal relationship with this treatment. An AE can be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. It was pre-specified that AE results would be presented for the overall subject population, rather than by cohort.
Gastrointestinal disorders Rectal haemorrhage	2.5% 1/40 • Adverse events (AEs) were collected for approximately 16.5 months. An adverse event (AE) is any untoward medical occurrence in a participant administered pharmaceutical product and that does not necessarily have to have a causal relationship with this treatment. An AE can be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. It was pre-specified that AE results would be presented for the overall subject population, rather than by cohort.
Gastrointestinal disorders Rectal obstruction	2.5% 1/40 • Adverse events (AEs) were collected for approximately 16.5 months. An adverse event (AE) is any untoward medical occurrence in a participant administered pharmaceutical product and that does not necessarily have to have a causal relationship with this treatment. An AE can be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. It was pre-specified that AE results would be presented for the overall subject population, rather than by cohort.
Infections and infestations Sepsis	2.5% 1/40 • Adverse events (AEs) were collected for approximately 16.5 months. An adverse event (AE) is any untoward medical occurrence in a participant administered pharmaceutical product and that does not necessarily have to have a causal relationship with this treatment. An AE can be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. It was pre-specified that AE results would be presented for the overall subject population, rather than by cohort.
Gastrointestinal disorders Small intestinal obstruction	2.5% 1/40 • Adverse events (AEs) were collected for approximately 16.5 months. An adverse event (AE) is any untoward medical occurrence in a participant administered pharmaceutical product and that does not necessarily have to have a causal relationship with this treatment. An AE can be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. It was pre-specified that AE results would be presented for the overall subject population, rather than by cohort.
Infections and infestations Urinary tract infection	2.5% 1/40 • Adverse events (AEs) were collected for approximately 16.5 months. An adverse event (AE) is any untoward medical occurrence in a participant administered pharmaceutical product and that does not necessarily have to have a causal relationship with this treatment. An AE can be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. It was pre-specified that AE results would be presented for the overall subject population, rather than by cohort.

Other adverse events

Measure	Overall n=40 participants at risk This cohort includes all patients with human epidermal receptor 3 (HER3) tumor expression (regardless of expression level) and received an intravenous (IV) infusion of U3-1402 5.6 mg/kg on Day 1 of each 21-day cycle.
Metabolism and nutrition disorders Hyperglycaemia	5.0% 2/40 • Adverse events (AEs) were collected for approximately 16.5 months. An adverse event (AE) is any untoward medical occurrence in a participant administered pharmaceutical product and that does not necessarily have to have a causal relationship with this treatment. An AE can be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. It was pre-specified that AE results would be presented for the overall subject population, rather than by cohort.
Blood and lymphatic system disorders Anaemia	37.5% 15/40 • Adverse events (AEs) were collected for approximately 16.5 months. An adverse event (AE) is any untoward medical occurrence in a participant administered pharmaceutical product and that does not necessarily have to have a causal relationship with this treatment. An AE can be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. It was pre-specified that AE results would be presented for the overall subject population, rather than by cohort.
Blood and lymphatic system disorders Febrile neutropenia	10.0% 4/40 • Adverse events (AEs) were collected for approximately 16.5 months. An adverse event (AE) is any untoward medical occurrence in a participant administered pharmaceutical product and that does not necessarily have to have a causal relationship with this treatment. An AE can be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. It was pre-specified that AE results would be presented for the overall subject population, rather than by cohort.
Blood and lymphatic system disorders Neutropenia	7.5% 3/40 • Adverse events (AEs) were collected for approximately 16.5 months. An adverse event (AE) is any untoward medical occurrence in a participant administered pharmaceutical product and that does not necessarily have to have a causal relationship with this treatment. An AE can be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. It was pre-specified that AE results would be presented for the overall subject population, rather than by cohort.
Gastrointestinal disorders Nausea	57.5% 23/40 • Adverse events (AEs) were collected for approximately 16.5 months. An adverse event (AE) is any untoward medical occurrence in a participant administered pharmaceutical product and that does not necessarily have to have a causal relationship with this treatment. An AE can be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. It was pre-specified that AE results would be presented for the overall subject population, rather than by cohort.
Gastrointestinal disorders Diarrhoea	37.5% 15/40 • Adverse events (AEs) were collected for approximately 16.5 months. An adverse event (AE) is any untoward medical occurrence in a participant administered pharmaceutical product and that does not necessarily have to have a causal relationship with this treatment. An AE can be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. It was pre-specified that AE results would be presented for the overall subject population, rather than by cohort.
Gastrointestinal disorders Vomiting	32.5% 13/40 • Adverse events (AEs) were collected for approximately 16.5 months. An adverse event (AE) is any untoward medical occurrence in a participant administered pharmaceutical product and that does not necessarily have to have a causal relationship with this treatment. An AE can be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. It was pre-specified that AE results would be presented for the overall subject population, rather than by cohort.
Gastrointestinal disorders Constipation	27.5% 11/40 • Adverse events (AEs) were collected for approximately 16.5 months. An adverse event (AE) is any untoward medical occurrence in a participant administered pharmaceutical product and that does not necessarily have to have a causal relationship with this treatment. An AE can be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. It was pre-specified that AE results would be presented for the overall subject population, rather than by cohort.
Gastrointestinal disorders Abdominal pain	12.5% 5/40 • Adverse events (AEs) were collected for approximately 16.5 months. An adverse event (AE) is any untoward medical occurrence in a participant administered pharmaceutical product and that does not necessarily have to have a causal relationship with this treatment. An AE can be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. It was pre-specified that AE results would be presented for the overall subject population, rather than by cohort.
Gastrointestinal disorders Stomatitis	12.5% 5/40 • Adverse events (AEs) were collected for approximately 16.5 months. An adverse event (AE) is any untoward medical occurrence in a participant administered pharmaceutical product and that does not necessarily have to have a causal relationship with this treatment. An AE can be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. It was pre-specified that AE results would be presented for the overall subject population, rather than by cohort.
Gastrointestinal disorders Gastrooesophageal reflux disease	10.0% 4/40 • Adverse events (AEs) were collected for approximately 16.5 months. An adverse event (AE) is any untoward medical occurrence in a participant administered pharmaceutical product and that does not necessarily have to have a causal relationship with this treatment. An AE can be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. It was pre-specified that AE results would be presented for the overall subject population, rather than by cohort.
General disorders Fatigue	60.0% 24/40 • Adverse events (AEs) were collected for approximately 16.5 months. An adverse event (AE) is any untoward medical occurrence in a participant administered pharmaceutical product and that does not necessarily have to have a causal relationship with this treatment. An AE can be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. It was pre-specified that AE results would be presented for the overall subject population, rather than by cohort.
General disorders Oedema peripheral	17.5% 7/40 • Adverse events (AEs) were collected for approximately 16.5 months. An adverse event (AE) is any untoward medical occurrence in a participant administered pharmaceutical product and that does not necessarily have to have a causal relationship with this treatment. An AE can be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. It was pre-specified that AE results would be presented for the overall subject population, rather than by cohort.
General disorders Pyrexia	10.0% 4/40 • Adverse events (AEs) were collected for approximately 16.5 months. An adverse event (AE) is any untoward medical occurrence in a participant administered pharmaceutical product and that does not necessarily have to have a causal relationship with this treatment. An AE can be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. It was pre-specified that AE results would be presented for the overall subject population, rather than by cohort.
General disorders Disease progression	7.5% 3/40 • Adverse events (AEs) were collected for approximately 16.5 months. An adverse event (AE) is any untoward medical occurrence in a participant administered pharmaceutical product and that does not necessarily have to have a causal relationship with this treatment. An AE can be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. It was pre-specified that AE results would be presented for the overall subject population, rather than by cohort.
Hepatobiliary disorders Hyperbilirubinaemia	10.0% 4/40 • Adverse events (AEs) were collected for approximately 16.5 months. An adverse event (AE) is any untoward medical occurrence in a participant administered pharmaceutical product and that does not necessarily have to have a causal relationship with this treatment. An AE can be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. It was pre-specified that AE results would be presented for the overall subject population, rather than by cohort.
Infections and infestations Pneumonia	5.0% 2/40 • Adverse events (AEs) were collected for approximately 16.5 months. An adverse event (AE) is any untoward medical occurrence in a participant administered pharmaceutical product and that does not necessarily have to have a causal relationship with this treatment. An AE can be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. It was pre-specified that AE results would be presented for the overall subject population, rather than by cohort.
Infections and infestations Urinary tract infection	5.0% 2/40 • Adverse events (AEs) were collected for approximately 16.5 months. An adverse event (AE) is any untoward medical occurrence in a participant administered pharmaceutical product and that does not necessarily have to have a causal relationship with this treatment. An AE can be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. It was pre-specified that AE results would be presented for the overall subject population, rather than by cohort.
Investigations Neutrophil count decreased	35.0% 14/40 • Adverse events (AEs) were collected for approximately 16.5 months. An adverse event (AE) is any untoward medical occurrence in a participant administered pharmaceutical product and that does not necessarily have to have a causal relationship with this treatment. An AE can be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. It was pre-specified that AE results would be presented for the overall subject population, rather than by cohort.
Investigations Platelet count decreased	32.5% 13/40 • Adverse events (AEs) were collected for approximately 16.5 months. An adverse event (AE) is any untoward medical occurrence in a participant administered pharmaceutical product and that does not necessarily have to have a causal relationship with this treatment. An AE can be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. It was pre-specified that AE results would be presented for the overall subject population, rather than by cohort.
Investigations Lymphocyte count decreased	20.0% 8/40 • Adverse events (AEs) were collected for approximately 16.5 months. An adverse event (AE) is any untoward medical occurrence in a participant administered pharmaceutical product and that does not necessarily have to have a causal relationship with this treatment. An AE can be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. It was pre-specified that AE results would be presented for the overall subject population, rather than by cohort.
Investigations White blood cell count decreased	17.5% 7/40 • Adverse events (AEs) were collected for approximately 16.5 months. An adverse event (AE) is any untoward medical occurrence in a participant administered pharmaceutical product and that does not necessarily have to have a causal relationship with this treatment. An AE can be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. It was pre-specified that AE results would be presented for the overall subject population, rather than by cohort.
Investigations Aspartate aminotransferase increased	5.0% 2/40 • Adverse events (AEs) were collected for approximately 16.5 months. An adverse event (AE) is any untoward medical occurrence in a participant administered pharmaceutical product and that does not necessarily have to have a causal relationship with this treatment. An AE can be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. It was pre-specified that AE results would be presented for the overall subject population, rather than by cohort.
Investigations Blood bilirubin increased	5.0% 2/40 • Adverse events (AEs) were collected for approximately 16.5 months. An adverse event (AE) is any untoward medical occurrence in a participant administered pharmaceutical product and that does not necessarily have to have a causal relationship with this treatment. An AE can be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. It was pre-specified that AE results would be presented for the overall subject population, rather than by cohort.
Investigations Blood lactate dehydrogenase increased	5.0% 2/40 • Adverse events (AEs) were collected for approximately 16.5 months. An adverse event (AE) is any untoward medical occurrence in a participant administered pharmaceutical product and that does not necessarily have to have a causal relationship with this treatment. An AE can be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. It was pre-specified that AE results would be presented for the overall subject population, rather than by cohort.
Investigations Weight decreased	5.0% 2/40 • Adverse events (AEs) were collected for approximately 16.5 months. An adverse event (AE) is any untoward medical occurrence in a participant administered pharmaceutical product and that does not necessarily have to have a causal relationship with this treatment. An AE can be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. It was pre-specified that AE results would be presented for the overall subject population, rather than by cohort.
Metabolism and nutrition disorders Decreased appetite	42.5% 17/40 • Adverse events (AEs) were collected for approximately 16.5 months. An adverse event (AE) is any untoward medical occurrence in a participant administered pharmaceutical product and that does not necessarily have to have a causal relationship with this treatment. An AE can be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. It was pre-specified that AE results would be presented for the overall subject population, rather than by cohort.
Metabolism and nutrition disorders Hypokalaemia	22.5% 9/40 • Adverse events (AEs) were collected for approximately 16.5 months. An adverse event (AE) is any untoward medical occurrence in a participant administered pharmaceutical product and that does not necessarily have to have a causal relationship with this treatment. An AE can be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. It was pre-specified that AE results would be presented for the overall subject population, rather than by cohort.
Metabolism and nutrition disorders Hypomagnesaemia	7.5% 3/40 • Adverse events (AEs) were collected for approximately 16.5 months. An adverse event (AE) is any untoward medical occurrence in a participant administered pharmaceutical product and that does not necessarily have to have a causal relationship with this treatment. An AE can be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. It was pre-specified that AE results would be presented for the overall subject population, rather than by cohort.
Metabolism and nutrition disorders Hyponatraemia	7.5% 3/40 • Adverse events (AEs) were collected for approximately 16.5 months. An adverse event (AE) is any untoward medical occurrence in a participant administered pharmaceutical product and that does not necessarily have to have a causal relationship with this treatment. An AE can be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. It was pre-specified that AE results would be presented for the overall subject population, rather than by cohort.
Metabolism and nutrition disorders Dehydration	5.0% 2/40 • Adverse events (AEs) were collected for approximately 16.5 months. An adverse event (AE) is any untoward medical occurrence in a participant administered pharmaceutical product and that does not necessarily have to have a causal relationship with this treatment. An AE can be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. It was pre-specified that AE results would be presented for the overall subject population, rather than by cohort.
Musculoskeletal and connective tissue disorders Back pain	5.0% 2/40 • Adverse events (AEs) were collected for approximately 16.5 months. An adverse event (AE) is any untoward medical occurrence in a participant administered pharmaceutical product and that does not necessarily have to have a causal relationship with this treatment. An AE can be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. It was pre-specified that AE results would be presented for the overall subject population, rather than by cohort.
Musculoskeletal and connective tissue disorders Muscular weakness	5.0% 2/40 • Adverse events (AEs) were collected for approximately 16.5 months. An adverse event (AE) is any untoward medical occurrence in a participant administered pharmaceutical product and that does not necessarily have to have a causal relationship with this treatment. An AE can be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. It was pre-specified that AE results would be presented for the overall subject population, rather than by cohort.
Nervous system disorders Dizziness	12.5% 5/40 • Adverse events (AEs) were collected for approximately 16.5 months. An adverse event (AE) is any untoward medical occurrence in a participant administered pharmaceutical product and that does not necessarily have to have a causal relationship with this treatment. An AE can be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. It was pre-specified that AE results would be presented for the overall subject population, rather than by cohort.
Nervous system disorders Headache	10.0% 4/40 • Adverse events (AEs) were collected for approximately 16.5 months. An adverse event (AE) is any untoward medical occurrence in a participant administered pharmaceutical product and that does not necessarily have to have a causal relationship with this treatment. An AE can be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. It was pre-specified that AE results would be presented for the overall subject population, rather than by cohort.
Psychiatric disorders Anxiety	5.0% 2/40 • Adverse events (AEs) were collected for approximately 16.5 months. An adverse event (AE) is any untoward medical occurrence in a participant administered pharmaceutical product and that does not necessarily have to have a causal relationship with this treatment. An AE can be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. It was pre-specified that AE results would be presented for the overall subject population, rather than by cohort.
Psychiatric disorders Insomnia	5.0% 2/40 • Adverse events (AEs) were collected for approximately 16.5 months. An adverse event (AE) is any untoward medical occurrence in a participant administered pharmaceutical product and that does not necessarily have to have a causal relationship with this treatment. An AE can be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. It was pre-specified that AE results would be presented for the overall subject population, rather than by cohort.
Renal and urinary disorders Acute kidney injury	7.5% 3/40 • Adverse events (AEs) were collected for approximately 16.5 months. An adverse event (AE) is any untoward medical occurrence in a participant administered pharmaceutical product and that does not necessarily have to have a causal relationship with this treatment. An AE can be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. It was pre-specified that AE results would be presented for the overall subject population, rather than by cohort.
Respiratory, thoracic and mediastinal disorders Cough	10.0% 4/40 • Adverse events (AEs) were collected for approximately 16.5 months. An adverse event (AE) is any untoward medical occurrence in a participant administered pharmaceutical product and that does not necessarily have to have a causal relationship with this treatment. An AE can be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. It was pre-specified that AE results would be presented for the overall subject population, rather than by cohort.
Respiratory, thoracic and mediastinal disorders Dyspnoea	10.0% 4/40 • Adverse events (AEs) were collected for approximately 16.5 months. An adverse event (AE) is any untoward medical occurrence in a participant administered pharmaceutical product and that does not necessarily have to have a causal relationship with this treatment. An AE can be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. It was pre-specified that AE results would be presented for the overall subject population, rather than by cohort.
Respiratory, thoracic and mediastinal disorders Epistaxis	5.0% 2/40 • Adverse events (AEs) were collected for approximately 16.5 months. An adverse event (AE) is any untoward medical occurrence in a participant administered pharmaceutical product and that does not necessarily have to have a causal relationship with this treatment. An AE can be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. It was pre-specified that AE results would be presented for the overall subject population, rather than by cohort.
Respiratory, thoracic and mediastinal disorders Hiccups	5.0% 2/40 • Adverse events (AEs) were collected for approximately 16.5 months. An adverse event (AE) is any untoward medical occurrence in a participant administered pharmaceutical product and that does not necessarily have to have a causal relationship with this treatment. An AE can be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. It was pre-specified that AE results would be presented for the overall subject population, rather than by cohort.
Respiratory, thoracic and mediastinal disorders Pulmonary embolism	5.0% 2/40 • Adverse events (AEs) were collected for approximately 16.5 months. An adverse event (AE) is any untoward medical occurrence in a participant administered pharmaceutical product and that does not necessarily have to have a causal relationship with this treatment. An AE can be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. It was pre-specified that AE results would be presented for the overall subject population, rather than by cohort.
Skin and subcutaneous tissue disorders Rash	20.0% 8/40 • Adverse events (AEs) were collected for approximately 16.5 months. An adverse event (AE) is any untoward medical occurrence in a participant administered pharmaceutical product and that does not necessarily have to have a causal relationship with this treatment. An AE can be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. It was pre-specified that AE results would be presented for the overall subject population, rather than by cohort.
Skin and subcutaneous tissue disorders Alopecia	17.5% 7/40 • Adverse events (AEs) were collected for approximately 16.5 months. An adverse event (AE) is any untoward medical occurrence in a participant administered pharmaceutical product and that does not necessarily have to have a causal relationship with this treatment. An AE can be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. It was pre-specified that AE results would be presented for the overall subject population, rather than by cohort.
Skin and subcutaneous tissue disorders Dry skin	5.0% 2/40 • Adverse events (AEs) were collected for approximately 16.5 months. An adverse event (AE) is any untoward medical occurrence in a participant administered pharmaceutical product and that does not necessarily have to have a causal relationship with this treatment. An AE can be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. It was pre-specified that AE results would be presented for the overall subject population, rather than by cohort.
Skin and subcutaneous tissue disorders Pruritus	5.0% 2/40 • Adverse events (AEs) were collected for approximately 16.5 months. An adverse event (AE) is any untoward medical occurrence in a participant administered pharmaceutical product and that does not necessarily have to have a causal relationship with this treatment. An AE can be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. It was pre-specified that AE results would be presented for the overall subject population, rather than by cohort.
Vascular disorders Hypertension	7.5% 3/40 • Adverse events (AEs) were collected for approximately 16.5 months. An adverse event (AE) is any untoward medical occurrence in a participant administered pharmaceutical product and that does not necessarily have to have a causal relationship with this treatment. An AE can be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. It was pre-specified that AE results would be presented for the overall subject population, rather than by cohort.

Additional Information

Contact for Clinical Trial Information

Daiichi Sankyo, Inc.

Phone: 9089926400

Email: CTRinfo@dsi.com

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place