Metastatic Colorectal Cancer
Conditions
Keywords
Metastatic Colorectal Cancer, U3-1402
Brief summary
This study is designed to primarily evaluate the safety and efficacy of U3-1402 in participants with advanced or metastatic colorectal cancer (CRC) who have received at least 2 prior lines of therapy and will explore clinical benefit according to human epidermal growth factor receptor 3 (HER3) tumor expression level in otherwise refractory tumors.
Detailed description
There will be 2 cohorts with enrollment in 2 parts. Participants will be treated on Day 1 of each 21-day cycle (every 3 weeks) with U3-1402 5.6 mg/kg intravenous (IV). The estimated treatment period is approximately 8 months and the follow-up period is approximately 4 months.
Interventions
U3-1402 will be dosed at 5.6 mg/kg as an intravenous (IV) infusion administered on Day 1 of each 21-day cycle.
Sponsors
Daiichi Sankyo
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 100 Years
Healthy volunteers
No
Inclusion criteria
* Participant has provided written informed consent prior to the start of any study specific procedures. * Participants ≥18 years (follow local regulatory requirements if the legal age of consent for study participation is \>18 years old). * Pathological/histological confirmation of advanced or metastatic colon or rectal adenocarcinoma. * Must be resistant, refractory, or intolerant to at least 2 prior lines of systemic therapy, that must include all of the following agents: * Fluoropyrimidine * Irinotecan * Platinum agents (e.g, oxaliplatin) * An anti-epidermal growth factor receptor (EGFR) agent, if clinically indicated * An anti-VEGF agent, if clinically indicated (eg, bevacizumab) * An immune checkpoint inhibitor (eg, microsatellite instability-high \[MSI-H\] status) * A BRAF inhibitor, if clinically indicated (eg, BRAF V600E positive) * Has at least 1 measurable lesion confirmed by blinded independent central review (BICR) as per Response Evaluation Criteria in Solid Tumors (RECIST) Version (v) 1.1. * Willing to provide a required pre-treatment tumor biopsy and an additional archival tissue sample for the assessment of HER3 expression levels by immunohistochemistry and exploratory biomarkers, defined as: 1. Pre-treatment tumor biopsy. Participants may be exempted from the requirement to provide a pre-treatment tumor biopsy if archival tumor tissue was collected within 3 months of screening during or after treatment with the last prior cancer treatment and is of sufficient quantity (2 cores or 20 slides with adequate tumor tissue content). 2. An additional archival tissue sample collected greater than 3 months prior to screening must be available and of sufficient quantity, as defined above, at the time of screening. If an archival tissue sample (collected greater than 3 months prior to screening) is not available, a subject may be included provided the pre-treatment tumor biopsy is obtained and after discussion and agreement from Sponsor (Medical Monitor or designee). 3. Consent to provide on-treatment tumor biopsy. When at least 10 treatment tumor biopsies have been collected, the Sponsor will provide written notification of a change to the requirement. * Eastern Cooperative Oncology Group performance status (ECOG PS) of 0 or 1. * Life expectancy ≥3 months. * Has adequate bone marrow reserve and organ function at baseline based on local laboratory data defined as follows within 14 days prior to Cycle 1 Day 1: * Platelet count: ≥100,000/mm\^3 or ≥100 × 10\^9/L (platelet transfusions are not allowed up to 14 days prior to Cycle 1 Day 1 to meet eligibility) * Hemoglobin: ≥9.0 g/dL (transfusion and/or growth factor support is allowed) * Absolute neutrophil count: ≥1500/mm\^3 or ≥1.5 × 10\^9/L * Serum creatinine (SCr) OR creatinine clearance (CrCl): SCr ≤ 1.5 × upper limit of normal (ULN), OR CrCl ≥ 30 mL/min as calculated using the Cockcroft- Gault equation or measured CrCl; confirmation of CrCl is only required when creatinine is \>1.5 × ULN * Alanine aminotransferase /aspartate aminotransferase: ≤3 × ULN (if liver metastases are present, ≤5 × ULN) * Total bilirubin: ≤1.5 × ULN if no liver metastases (\<3 × ULN in the presence of documented Gilbert's syndrome \[unconjugated hyperbilirubinemia\] or liver metastases) * Serum albumin: ≥2.5 g/dL * Prothrombin time (PT) or PT-international normalized ratio (INR) and activated partial thromboplastin time (aPTT) / partial thromboplastin time (PTT): ≤1.5 × ULN except for subjects on coumarin- derivative anticoagulants or other similar anticoagulant therapy, who must have PT-INR within therapeutic range as deemed appropriate by the Investigator
Exclusion criteria
* Any history of interstitial lung disease (including pulmonary fibrosis or radiation pneumonitis), has current interstitial lung disease (ILD), or is suspected to have such disease by imaging during screening. * Clinically severe pulmonary compromise (based on Investigator's assessment) resulting from intercurrent pulmonary illnesses including, but not limited to: 1. any underlying pulmonary disorder (e.g., pulmonary emboli, severe asthma, severe chronic obstructive pulmonary disease, restrictive lung disease, pleural effusion) 2. any autoimmune, connective tissue or inflammatory disorder with pulmonary involvement (eg, rheumatoid arthritis, Sjögren's syndrome, sarcoidosis) * OR prior complete pneumonectomy. * Is receiving chronic systemic corticosteroids dosed at \>10 mg prednisone or equivalent anti-inflammatory activity or any form of immunosuppressive therapy prior to Cycle 1 Day 1. Participants who require use of bronchodilators, inhaled or topical steroids, or local steroid injections may be included in the study. * Evidence of leptomeningeal disease. * Evidence of clinically active spinal cord compression or brain metastases * Inadequate washout period prior to Cycle 1 Day 1 of U3-1402: 1. Whole brain radiation therapy \<14 days or stereotactic brain radiation therapy \<7 days; 2. Any cytotoxic chemotherapy, investigational agent or other anticancer drug(s) from a previous cancer treatment regimen or clinical study \<14 days or 5 half-lives, whichever is longer; 3. Monoclonal antibodies other than immune checkpoint inhibitors, such as bevacizumab (anti-VEGF) and cetuximab (anti-EGFRs) \<28 days; 4. Immune checkpoint inhibitor therapy \<21 days; 5. Major surgery (excluding placement of vascular access) \<4 weeks; 6. Radiotherapy treatment to \>30% of the bone marrow or with a wide field of radiation \<28 days or palliative radiation therapy \<14 days; 7. Chloroquine/hydroxychloroquine ≤14 days. * Prior treatment with an anti-HER3 antibody and/or antibody drug conjugate (ADC) that consists of an exatecan derivative that is any topoisomerase I inhibitor (e.g, trastuzumab deruxtecan). * Has unresolved toxicities from previous anticancer therapy, defined as toxicities (other than alopecia) not yet resolved to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) v5.0 Grade ≤1 or baseline. * Had primary malignancies other than CRC within 3 years prior to Cycle 1 Day 1, except adequately resected non-melanoma skin cancer, curatively treated in-situ disease, or other solid tumors curatively treated. * Uncontrolled or significant cardiovascular disease prior to Cycle 1 Day 1. * Known Hepatitis B and/or Hepatitis C infection, such as those with serologic evidence of viral infection within 28 days of Cycle 1 Day 1. 1. Participants with past or resolved hepatitis B virus (HBV) infection are eligible if: * Hepatitis B surface antigen (HBsAg) negative and hepatitis B core antibody (anti-HBc) positive; OR * HBsAg positive and HBV deoxyribonucleic acid (DNA) viral load is documented to be ≤2000 IU/mL in the absence of anti-viral therapy and during the previous 12 weeks prior to the viral load evaluation with normal transaminases values (in the absence of liver metastasis); OR * HBsAg positive and HBV DNA viral load is documented to be ≤2000 IU/mL in the absence of anti-viral therapy and during the previous 12 weeks prior to the viral load evaluation for participants with liver metastasis and abnormal transaminases with a result of AST/ALT \<3 × ULN. 2. Participants with a history of hepatitis C infection will be eligible for enrollment only if the viral load according to local standards of detection is documented to be below the level of detection in the absence of anti-viral therapy during the previous 12 weeks (ie, sustained viral response according to the local product label but no less than 12 weeks, whichever is longer). * Participant with any human immunodeficiency virus (HIV) infection. * Any evidence of severe or uncontrolled systemic diseases (including active bleeding diatheses, active infection), psychiatric illness/social situations, geographical factors, substance abuse, or other factors which in the Investigator's opinion makes it undesirable for the participant to participate in the study or which would jeopardize compliance with the protocol. Screening for chronic conditions is not required.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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 | From Baseline (Day 0) to data cut off (up to approximately 16.5 months) | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Objective Response Rate (ORR) As Assessed by Investigator Following Administration of U3-1402 In Participants With Advanced or Metastatic Colorectal Cancer | From Baseline (Day 0) to data cut off (up to approximately 16.5 months) | 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. |
| 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 | From Baseline (Day 0) to data cut off (up to approximately 16.5 months) | 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. |
| 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 | From Baseline (Day 0) to data cut off (up to approximately 16.5 months) | 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. |
| 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 | From Baseline (Day 0) to data cut off (up to approximately 16.5 months) | 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. |
| Overall Survival (OS) Following Administration of U3-1402 In Participants With Advanced or Metastatic Colorectal Cancer | From Baseline (Day 0) to data cut off (up to approximately 16.5 months) | OS defined as the time from the start of study treatment to the date of death due to any cause. |
| Number of Participants Reporting Treatment-emergent Adverse Events (TEAEs) and Other Safety Parameters During the Study | From Baseline (Day 0) to data cut off (up to approximately 16.5 months) | 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. |
| Number of Participants Who Are Anti-Drug Antibody (ADA)-Positive (Baseline and Post-Baseline) | 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). | Blood samples were collected to assess the immunogenicity of U3-1402. |
| 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 | From Baseline (Day 0) to data cut off (up to approximately 16.5 months) | 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. |
| Pharmacokinetic Parameter Maximum Serum Concentration (Cmax) Following Administration of U3-1402 In Participants With Advanced or Metastatic Colorectal Cancer | 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) | 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. |
| Pharmacokinetic Parameter Maximum Serum Concentration (Cmax) of MAAA-1181a Following Administration of U3-1402 In Participants With Advanced or Metastatic Colorectal Cancer | 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) | Serum PK parameter Cmax of MAAA-1181a was assessed in the full PK sampling cohort using noncompartmental methods. |
| Pharmacokinetic Parameter Time to Reach Maximum Serum Concentration (Tmax) Following Administration of U3-1402 In Participants With Advanced or Metastatic Colorectal Cancer | 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) | 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. |
| Pharmacokinetic ParameterTrough Serum Concentration (Ctrough) Following Administration of U3-1402 In Participants With Advanced or Metastatic Colorectal Cancer | 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) | Serum PK parameter Ctrough (antibody drug conjugate \[ADC\] and total anti-HER3 antibody) were assessed in the full PK sampling cohort using noncompartmental methods. |
| Pharmacokinetic ParameterTrough Serum Concentration (Ctrough) of MAAA-1181a Following Administration of U3-1402 In Participants With Advanced or Metastatic Colorectal Cancer | 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) | Serum PK parameter Ctrough of MAAA-1181a was assessed in the full PK sampling cohort using noncompartmental methods. |
| 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 | 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) | 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. |
| 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 | 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) | Serum PK parameter AUC of MAAA-1181a was assessed in the full PK sampling cohort using noncompartmental methods. |
| Number of Participants Who Have Treatment-emergent Anti-Drug Antibody (ADA) | 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). | 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. |
Countries
Belgium, France, Italy, Japan, Poland, Spain, United Kingdom, United States
Participant flow
Recruitment details
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.
Participants by arm
| Arm | Count |
|---|---|
| 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. | 39 |
| 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. | 1 |
| Total | 40 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 6 | 0 |
| Overall Study | Clinical progression | 1 | 0 |
| Overall Study | Physician Decision | 1 | 0 |
| Overall Study | Progressive disease | 26 | 1 |
| Overall Study | Withdrawal by Subject | 5 | 0 |
Baseline characteristics
| Characteristic | Cohort 1: HER3 High (IHC 3+, 2+) | Cohort 2: HER3 Low/Negative (IHC 1+, 0) | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 9 Participants | 1 Participants | 10 Participants |
| Age, Categorical Between 18 and 65 years | 30 Participants | 0 Participants | 30 Participants |
| Age, Continuous | 57.0 years STANDARD_DEVIATION 8.64 | 67 years | 57.3 years STANDARD_DEVIATION 8.67 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 10 Participants | 0 Participants | 10 Participants |
| Race (NIH/OMB) Black or African American | 3 Participants | 0 Participants | 3 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 26 Participants | 1 Participants | 27 Participants |
| Region of Enrollment Japan | 10 participants | 0 participants | 10 participants |
| Region of Enrollment United States | 29 participants | 1 participants | 30 participants |
| Sex: Female, Male Female | 13 Participants | 1 Participants | 14 Participants |
| Sex: Female, Male Male | 26 Participants | 0 Participants | 26 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 23 / 40 |
| other Total, other adverse events | 40 / 40 |
| serious Total, serious adverse events | 17 / 40 |
Outcome results
Primary
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
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.
Time frame: 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.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Cohort 1: HER3 High (IHC 3+, 2+) | 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 |
| Cohort 2: HER3 Low/Negative (IHC 1+, 0) | 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 | 0 Participants |
Secondary
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
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.
Time frame: 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.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Cohort 1: HER3 High (IHC 3+, 2+) | 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 |
| Cohort 1: HER3 High (IHC 3+, 2+) | 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 |
Secondary
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
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.
Time frame: 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.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Cohort 1: HER3 High (IHC 3+, 2+) | 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 |
| Cohort 1: HER3 High (IHC 3+, 2+) | 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 |
Secondary
Number of Participants Reporting Treatment-emergent Adverse Events (TEAEs) and Other Safety Parameters During the Study
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.
Time frame: From Baseline (Day 0) to data cut off (up to approximately 16.5 months)
Population: Safety events were assessed in the Safety Analysis Set.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Cohort 1: HER3 High (IHC 3+, 2+) | Number of Participants Reporting Treatment-emergent Adverse Events (TEAEs) and Other Safety Parameters During the Study | Study-drug related TEAE | 37 Participants |
| Cohort 1: HER3 High (IHC 3+, 2+) | Number of Participants Reporting Treatment-emergent Adverse Events (TEAEs) and Other Safety Parameters During the Study | Adverse event of special interest (AESI) | 2 Participants |
| Cohort 1: HER3 High (IHC 3+, 2+) | Number of Participants Reporting Treatment-emergent Adverse Events (TEAEs) and Other Safety Parameters During the Study | Treatment-emergent adverse events (TEAEs) | 40 Participants |
| Cohort 1: HER3 High (IHC 3+, 2+) | Number of Participants Reporting Treatment-emergent Adverse Events (TEAEs) and Other Safety Parameters During the Study | Serious TEAE (SAE) | 17 Participants |
| Cohort 1: HER3 High (IHC 3+, 2+) | Number of Participants Reporting Treatment-emergent Adverse Events (TEAEs) and Other Safety Parameters During the Study | Study-drug related SAE | 9 Participants |
Secondary
Number of Participants Who Are Anti-Drug Antibody (ADA)-Positive (Baseline and Post-Baseline)
Blood samples were collected to assess the immunogenicity of U3-1402.
Time frame: 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.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Cohort 1: HER3 High (IHC 3+, 2+) | Number of Participants Who Are Anti-Drug Antibody (ADA)-Positive (Baseline and Post-Baseline) | Baseline: Positive | 0 Participants |
| Cohort 1: HER3 High (IHC 3+, 2+) | Number of Participants Who Are Anti-Drug Antibody (ADA)-Positive (Baseline and Post-Baseline) | Baseline: Negative | 37 Participants |
| Cohort 1: HER3 High (IHC 3+, 2+) | Number of Participants Who Are Anti-Drug Antibody (ADA)-Positive (Baseline and Post-Baseline) | Baseline: Missing | 2 Participants |
| Cohort 1: HER3 High (IHC 3+, 2+) | Number of Participants Who Are Anti-Drug Antibody (ADA)-Positive (Baseline and Post-Baseline) | Post-baseline: Positive | 0 Participants |
| Cohort 1: HER3 High (IHC 3+, 2+) | Number of Participants Who Are Anti-Drug Antibody (ADA)-Positive (Baseline and Post-Baseline) | Post-baseline: Negative | 38 Participants |
Secondary
Number of Participants Who Have Treatment-emergent Anti-Drug Antibody (ADA)
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.
Time frame: 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.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Cohort 1: HER3 High (IHC 3+, 2+) | Number of Participants Who Have Treatment-emergent Anti-Drug Antibody (ADA) | Treatment-induced ADA | 0 Participants |
| Cohort 1: HER3 High (IHC 3+, 2+) | Number of Participants Who Have Treatment-emergent Anti-Drug Antibody (ADA) | Treatment-boosted ADA | 0 Participants |
| Cohort 1: HER3 High (IHC 3+, 2+) | Number of Participants Who Have Treatment-emergent Anti-Drug Antibody (ADA) | Treatment-emergent ADA | 0 Participants |
| Cohort 1: HER3 High (IHC 3+, 2+) | Number of Participants Who Have Treatment-emergent Anti-Drug Antibody (ADA) | ADA missing at baseline but positive at post-baseline | 0 Participants |
Secondary
Objective Response Rate (ORR) As Assessed by Investigator Following Administration of U3-1402 In Participants With Advanced or Metastatic Colorectal Cancer
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.
Time frame: 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.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Cohort 1: HER3 High (IHC 3+, 2+) | Objective Response Rate (ORR) As Assessed by Investigator Following Administration of U3-1402 In Participants With Advanced or Metastatic Colorectal Cancer | 2 Participants |
Secondary
Overall Survival (OS) Following Administration of U3-1402 In Participants With Advanced or Metastatic Colorectal Cancer
OS defined as the time from the start of study treatment to the date of death due to any cause.
Time frame: From Baseline (Day 0) to data cut off (up to approximately 16.5 months)
Population: Overall survival was assessed in the Full Analysis Set.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Cohort 1: HER3 High (IHC 3+, 2+) | Overall Survival (OS) Following Administration of U3-1402 In Participants With Advanced or Metastatic Colorectal Cancer | 10.58 months |
| Cohort 2: HER3 Low/Negative (IHC 1+, 0) | Overall Survival (OS) Following Administration of U3-1402 In Participants With Advanced or Metastatic Colorectal Cancer | 8.9 months |
Secondary
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
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.
Time frame: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 1: HER3 High (IHC 3+, 2+) | 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 |
| Cohort 1: HER3 High (IHC 3+, 2+) | 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 |
| Cohort 1: HER3 High (IHC 3+, 2+) | 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 |
| Cohort 1: HER3 High (IHC 3+, 2+) | 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 |
| Cohort 1: HER3 High (IHC 3+, 2+) | 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 |
| Cohort 1: HER3 High (IHC 3+, 2+) | 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
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
Serum PK parameter AUC of MAAA-1181a was assessed in the full PK sampling cohort using noncompartmental methods.
Time frame: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 1: HER3 High (IHC 3+, 2+) | 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 34.6 |
| Cohort 1: HER3 High (IHC 3+, 2+) | 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 |
| Cohort 1: HER3 High (IHC 3+, 2+) | 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 |
Secondary
Pharmacokinetic Parameter Maximum Serum Concentration (Cmax) Following Administration of U3-1402 In Participants With Advanced or Metastatic Colorectal Cancer
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.
Time frame: 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
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 1: HER3 High (IHC 3+, 2+) | 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 |
| Cohort 1: HER3 High (IHC 3+, 2+) | 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 |
| Cohort 1: HER3 High (IHC 3+, 2+) | 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 |
| Cohort 1: HER3 High (IHC 3+, 2+) | 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
Pharmacokinetic Parameter Maximum Serum Concentration (Cmax) of MAAA-1181a Following Administration of U3-1402 In Participants With Advanced or Metastatic Colorectal Cancer
Serum PK parameter Cmax of MAAA-1181a was assessed in the full PK sampling cohort using noncompartmental methods.
Time frame: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 1: HER3 High (IHC 3+, 2+) | 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 |
| Cohort 1: HER3 High (IHC 3+, 2+) | 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 |
Secondary
Pharmacokinetic Parameter Time to Reach Maximum Serum Concentration (Tmax) Following Administration of U3-1402 In Participants With Advanced or Metastatic Colorectal Cancer
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.
Time frame: 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.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Cohort 1: HER3 High (IHC 3+, 2+) | 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 |
| Cohort 1: HER3 High (IHC 3+, 2+) | 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 |
| Cohort 1: HER3 High (IHC 3+, 2+) | 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 |
| Cohort 1: HER3 High (IHC 3+, 2+) | 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 |
| Cohort 1: HER3 High (IHC 3+, 2+) | 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 |
| Cohort 1: HER3 High (IHC 3+, 2+) | 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 |
Secondary
Pharmacokinetic ParameterTrough Serum Concentration (Ctrough) Following Administration of U3-1402 In Participants With Advanced or Metastatic Colorectal Cancer
Serum PK parameter Ctrough (antibody drug conjugate \[ADC\] and total anti-HER3 antibody) were assessed in the full PK sampling cohort using noncompartmental methods.
Time frame: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 1: HER3 High (IHC 3+, 2+) | 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 24.2 |
| Cohort 1: HER3 High (IHC 3+, 2+) | 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 |
| Cohort 1: HER3 High (IHC 3+, 2+) | 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 |
| Cohort 1: HER3 High (IHC 3+, 2+) | 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
Pharmacokinetic ParameterTrough Serum Concentration (Ctrough) of MAAA-1181a Following Administration of U3-1402 In Participants With Advanced or Metastatic Colorectal Cancer
Serum PK parameter Ctrough of MAAA-1181a was assessed in the full PK sampling cohort using noncompartmental methods.
Time frame: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 1: HER3 High (IHC 3+, 2+) | 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 |
| Cohort 1: HER3 High (IHC 3+, 2+) | 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
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
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.
Time frame: 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.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Cohort 1: HER3 High (IHC 3+, 2+) | 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 |
| Cohort 1: HER3 High (IHC 3+, 2+) | 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 |
| Cohort 2: HER3 Low/Negative (IHC 1+, 0) | 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) | 5.5 months |
Secondary
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
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.
Time frame: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 1: HER3 High (IHC 3+, 2+) | 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 |
| Cohort 1: HER3 High (IHC 3+, 2+) | 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 |