Clinical Trial Results:
A MULTI-CENTER, OPEN-LABEL, PHASE 2 STUDY TO EVALUATE SAFETY AND EFFICACY OF U3-1402 IN SUBJECTS WITH ADVANCED OR METASTATIC COLORECTAL CANCER (CRC)
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Summary
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EudraCT number |
2019-004418-32 |
Trial protocol |
GB PL BE IT |
Global end of trial date |
03 Feb 2022
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Results information
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Results version number |
v1(current) |
This version publication date |
20 Feb 2023
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First version publication date |
20 Feb 2023
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Other versions |
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Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
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Trial identification
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Sponsor protocol code |
U31402-A-U202
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT04479436 | ||
WHO universal trial number (UTN) |
- | ||
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Sponsors
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Sponsor organisation name |
Daiichi Sankyo, Inc.
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Sponsor organisation address |
211 Mt. Airy Rd., Basking Ridge, United States, 07920
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Public contact |
Global Clinical Director, Daiichi Sankyo, Inc., +1 908-992- 6400, CTRinfo@dsi.com
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Scientific contact |
Global Clinical Director, Daiichi Sankyo, Inc., +1 908-992- 6400, CTRinfo@dsi.com
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
No
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Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
03 Feb 2022
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Is this the analysis of the primary completion data? |
No
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Global end of trial reached? |
Yes
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Global end of trial date |
03 Feb 2022
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Was the trial ended prematurely? |
Yes
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General information about the trial
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Main objective of the trial |
To assess the tolerability and antitumor activity of U3-1402 in subjects with advanced or metastatic CRC who are resistant, refractory, or intolerant to at least 2 prior lines of therapy
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Protection of trial subjects |
The study protocol, amendments, the informed consent form(s) (ICF[s]), and information sheets were approved by the appropriate and applicable Independent Ethics Committees (IECs) or Institutional Review Boards (IRBs). The study was conducted in compliance with the protocol, the ethical principles that have their origin in the Declaration of Helsinki, the International Council for Harmonisation (ICH) consolidated Guideline E6 for Good Clinical Practice (GCP) (CPMP/ICH/135/95), and applicable regulatory requirement(s).
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
14 Aug 2020
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
No
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Population of trial subjects
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Number of subjects enrolled per country |
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Country: Number of subjects enrolled |
United States: 30
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Country: Number of subjects enrolled |
Japan: 10
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Worldwide total number of subjects |
40
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EEA total number of subjects |
0
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Number of subjects enrolled per age group |
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In utero |
0
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Preterm newborn - gestational age < 37 wk |
0
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Newborns (0-27 days) |
0
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Infants and toddlers (28 days-23 months) |
0
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Children (2-11 years) |
0
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Adolescents (12-17 years) |
0
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Adults (18-64 years) |
30
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From 65 to 84 years |
10
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85 years and over |
0
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Recruitment
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Recruitment details |
A total of 40 participants were enrolled and treated at 12 sites in the United States and Japan. | |||||||||||||||||||||||||||
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Pre-assignment
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Screening details |
60 participants were screened and 20 participants were screen failures. A total of 39 participants with high HER3 expression CRC were enrolled in Cohort 1 and 1 participant with low HER3 expression CRC was enrolled in Cohort 2. | |||||||||||||||||||||||||||
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Period 1
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Period 1 title |
Overall (overall period)
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Is this the baseline period? |
Yes | |||||||||||||||||||||||||||
Allocation method |
Non-randomised - controlled
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Blinding used |
Not blinded | |||||||||||||||||||||||||||
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Arms
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Are arms mutually exclusive |
Yes
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Arm title
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Cohort 1: HER3 High (IHC 3+, 2+) | |||||||||||||||||||||||||||
Arm description |
Participants with high tumor expression levels of human epidermal receptor 3 (HER3) in a pre-treatment biopsy specimen who received 5.6 mg/Kg of U3-1402 intravenously (IV) on Day 1 of each 21-day cycle. | |||||||||||||||||||||||||||
Arm type |
Experimental | |||||||||||||||||||||||||||
Investigational medicinal product name |
U3-1402
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Powder for solution for infusion
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Routes of administration |
Intravenous use
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Dosage and administration details |
U3-1402 will be dosed at 5.6 mg/kg as an intravenous (IV) infusion administered on Day 1 of each 21-day cycle.
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Arm title
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Cohort 2: HER3 Low/Negative (IHC 1+, 0) | |||||||||||||||||||||||||||
Arm description |
Participants with low or negative tumor expression levels of human epidermal receptor 3 (HER3) in a pre-treatment biopsy specimen who received 5.6 mg/Kg of U3-1402 intravenously (IV) on Day 1 of each 21-day cycle. | |||||||||||||||||||||||||||
Arm type |
Experimental | |||||||||||||||||||||||||||
Investigational medicinal product name |
U3-1402
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Powder for solution for infusion
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Routes of administration |
Intravenous use
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Dosage and administration details |
U3-1402 will be dosed at 5.6 mg/kg as an intravenous (IV) infusion administered on Day 1 of each 21-day cycle.
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Baseline characteristics reporting groups
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Reporting group title |
Cohort 1: HER3 High (IHC 3+, 2+)
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Reporting group description |
Participants with high tumor expression levels of human epidermal receptor 3 (HER3) in a pre-treatment biopsy specimen who received 5.6 mg/Kg of U3-1402 intravenously (IV) on Day 1 of each 21-day cycle. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Cohort 2: HER3 Low/Negative (IHC 1+, 0)
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Reporting group description |
Participants with low or negative tumor expression levels of human epidermal receptor 3 (HER3) in a pre-treatment biopsy specimen who received 5.6 mg/Kg of U3-1402 intravenously (IV) on Day 1 of each 21-day cycle. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Cohort 1: HER3 High (IHC 3+, 2+)
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Reporting group description |
Participants with high tumor expression levels of human epidermal receptor 3 (HER3) in a pre-treatment biopsy specimen who received 5.6 mg/Kg of U3-1402 intravenously (IV) on Day 1 of each 21-day cycle. | ||
Reporting group title |
Cohort 2: HER3 Low/Negative (IHC 1+, 0)
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Reporting group description |
Participants with low or negative tumor expression levels of human epidermal receptor 3 (HER3) in a pre-treatment biopsy specimen who received 5.6 mg/Kg of U3-1402 intravenously (IV) on Day 1 of each 21-day cycle. | ||
Subject analysis set title |
Cohort 1 & 2: HER3 High (IHC 3+, 2+) & HER3 Low/Negative (IHC)
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Subject analysis set type |
Safety analysis | ||
Subject analysis set description |
Participants with high tumor expression & low or negative levels of human epidermal receptor 3 (HER3) low or negative and who received 5.6 mg/Kg of U3-1402 intravenously (IV) on Day 1 of each 21-day cycle (Safety Analysis Set).
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End point title |
Objective Response Rate (ORR) Based on Blinded Independent Central Review (BICR) Following Administration of U3-1402 in Participants with Advanced or Metastatic Colorectal Cancer [1] [2] | ||||||||
End point description |
The Objective Response Rate (ORR) was defined as the percentage of participants who achieved a best overall response of confirmed Complete Response (CR) or Partial Response (PR), assessed by blinded independent central review (BICR) based on RECIST version 1.1. CR was defined as a reduction of target lesions to non-measurable dimensions and PR was defined as at least a 30% decrease in the sum of diameters of target lesions. Confirmed ORR based on BICR is reported and was assessed in the Full Analysis Set.
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End point type |
Primary
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End point timeframe |
From baseline up to disease progression by BICR, death, lost to follow up, or withdrawal of consent by subject (whichever occurs first), up to approximately 16.9 months
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| Notes [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: No further statistical analysis performed as this is a single arm study with no comparators. [2] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: Only 1 participant was enrolled into cohort 2, data for this one participant was presented descriptively and was not summarized in aggregated form. |
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| No statistical analyses for this end point | |||||||||
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End point title |
Duration of Response (DOR) Based on Blinded Independent Central Review (BICR) and Investigator Following Administration of U3-1402 in Participants with Advanced or Metastatic Colorectal Cancer [3] | ||||||||||||
End point description |
Duration of Response (DOR) was defined as the time from the date of the first documentation of objective response (complete response [CR] or partial response [PR]) to the date of the first objective documentation of progressive disease (PD) or death due to any cause. DOR based on BICR and Investigator assessment and was calculated for responders (participants with CR/PR) only.
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End point type |
Secondary
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End point timeframe |
From baseline up to disease progression by BICR, death, lost to follow up, or withdrawal of consent by subject (whichever occurs first), up to approximately 16.9 months
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| Notes [3] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: Only 1 participant was enrolled into cohort 2, data for this one participant was presented descriptively and was not summarized in aggregated form. |
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Objective Response Rate (ORR) Based on Investigator Following Administration of U3-1402 in Participants with Advanced or Metastatic Colorectal Cancer [4] | ||||||||
End point description |
The Objective Response Rate (ORR) was defined as the percentage of participants who achieved a best overall response of confirmed Complete Response (CR) or Partial Response (PR), assessed by investigator assessment based on RECIST version 1.1.CR was defined as a reduction of target lesions to non-measurable dimensions and PR was defined as at least a 30% decrease in the sum of diameters of target lesions. Confirmed ORR based on investigator assessment is reported and was assessed in the Full Analysis Set.
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End point type |
Secondary
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End point timeframe |
From baseline up to disease progression, death, lost to follow up, or withdrawal of consent by subject (whichever occurs first), up to approximately 16.9 months
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| Notes [4] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: Only 1 participant was enrolled into cohort 2, data for this one participant was presented descriptively and was not summarized in aggregated form. |
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| No statistical analyses for this end point | |||||||||
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End point title |
Disease Control Rate (DCR) Based on Blinded Independent Central Review (BICR) and Investigator Following Administration of U3-1402 in Participants with Advanced or Metastatic Colorectal Cancer [5] | ||||||||||||
End point description |
Disease Control Rate (DCR) was 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 BICR or Investigator assessment. DCR was assessed in the Full Analysis Set.
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End point type |
Secondary
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End point timeframe |
From baseline up to disease progression by BICR, death, lost to follow up, or withdrawal of consent by subject (whichever occurs first), up to approximately 16.9 months
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| Notes [5] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: Only 1 participant was enrolled into cohort 2, data for this one participant was presented descriptively and was not summarized in aggregated form. |
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Time to Tumor Response (TTR) Based on Blinded Independent Central Review (BICR) and Investigator Following Administration of U3-1402 in Participants with Advanced or Metastatic Colorectal Cancer [6] | ||||||||||||
End point description |
Time to Tumor Response (TTR) was defined as the time from the start of study treatment to the date of the first documentation of objective response (CR or PR) that is subsequently confirmed. TTR based on BICR and Investigator assessment is reported and was calculated for responders only.
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End point type |
Secondary
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End point timeframe |
From baseline up to disease progression by BICR, death, lost to follow up, or withdrawal of consent by subject (whichever occurs first), up to approximately 16.9 months
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| Notes [6] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: Only 1 participant was enrolled into cohort 2, data for this one participant was presented descriptively and was not summarized in aggregated form. |
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Progression-free Survival (PFS) Based on Blinded Independent Central Review (BICR) and Investigator Following Administration of U3-1402 in Participants with Advanced or Metastatic Colorectal Cancer [7] | ||||||||||||
End point description |
Progression-free survival (PFS) was defined as the time from the date of enrollment to the earlier of the dates of the first objective documentation of disease progression (as per RECIST v1.1) or death due to any cause. Progressive disease was defined as at least a 20% increase in the sum of diameters of target lesions. PFS was assessed in the Full Analysis Set.
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End point type |
Secondary
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End point timeframe |
From baseline until disease progression by BICR, death, lost to follow up, or withdrawal of consent by subject (whichever occurs first), up to approximately 16.9 months
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| Notes [7] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: Only 1 participant was enrolled into cohort 2, data for this one participant was presented descriptively and was not summarized in aggregated form. |
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Overall Survival (OS) Following Administration of U3-1402 in Participants with Advanced or Metastatic Colorectal Cancer [8] | ||||||||
End point description |
Overall survival (OS) was defined as the time from the date of first dose of study drug to the date of death due to any cause. OS was assessed in the Full Analysis Set.
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End point type |
Secondary
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End point timeframe |
From baseline up to the date of death due to any cause, up to 16.9 months
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| Notes [8] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: Only 1 participant was enrolled into cohort 2, data for this one participant was presented descriptively and was not summarized in aggregated form. |
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| No statistical analyses for this end point | |||||||||
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End point title |
Summary of Treatment Emergent Adverse Events (TEAEs) Following Administration of U3-1402 in Participants with Advanced or Metastatic Colorectal Cancer | ||||||||||||||||||||||
End point description |
A Treatment Emergent Adverse Events (TEAEs) was defined as an adverse event with start or worsening date from the first dose date of the study drug to 47 days after the last dose date of the study drug. TEAEs, study drug-related TEAEs, serious TEAEs, study drug-related TEAEs, and any Adverse Events of Special Interests (AESIs) are presented and were assessed in the Safety Analysis Set.
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End point type |
Secondary
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End point timeframe |
From the signing of the main ICF to 47 days after the last dose of study drug, up to approximately 16.9 months
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| No statistical analyses for this end point | |||||||||||||||||||||||
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End point title |
Number of Participants With HER3 Protein Expression Based on Immunohistochemistry (IHC) Assay [9] | ||||||||||||||||||||||||||||||||
End point description |
(HER3) protein expression will be measured by an investigational device (HER3 immunohistochemistry [IHC] assay). There is no scoring algorithm developed for the HER3 IHC assay in colon cancer; therefore, the American Society of Clinical Oncology guidelines for HER2 gastric cancer scoring were adopted for use in this study.
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End point type |
Secondary
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End point timeframe |
At Baseline (archival and pre-treatment tumor biopsy) and at Cycle 2
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| Notes [9] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: Only 1 participant was enrolled into cohort 2, data for this one participant was presented descriptively and was not summarized in aggregated form. |
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| No statistical analyses for this end point | |||||||||||||||||||||||||||||||||
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End point title |
Percentage of Participants Who Are Anti-Drug Antibody (ADA)-Positive [10] | ||||||||
End point description |
Participants who are Anti-Drug Antibody (ADA)-Positive were defined as any participant having a confirmed positive ADA sample at any point in time. ADA titer will be determined for confirmed ADA-positive samples and assessed in the Full Analysis Set.
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End point type |
Secondary
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End point timeframe |
From the start of study treatment to the end of treatment, up to approximately 16.9 months
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| Notes [10] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: Only 1 participant was enrolled into cohort 2, data for this one participant was presented descriptively and was not summarized in aggregated form. |
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| No statistical analyses for this end point | |||||||||
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End point title |
Percentage of Participants Who Have Treatment Emergent Anti-Drug Antibody (ADA) [11] | ||||||||
End point description |
Participants who are Treatment Emergent Anti-Drug Antibody (ADA) positive will be assessed in the Full Analysis Set.
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End point type |
Secondary
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End point timeframe |
From the start of study treatment to the end of treatment, up to approximately 16.9 months
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| Notes [11] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: Only 1 participant was enrolled into cohort 2, data for this one participant was presented descriptively and was not summarized in aggregated form. |
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| No statistical analyses for this end point | |||||||||
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End point title |
Maximum Serum Concentration (Cmax) of U3-1402 and Total Anti-HER3 Following Administration of U3-1402 in Participants with Advanced or Metastatic Colorectal Cancer [12] | ||||||||||||||||
End point description |
Maximum Plasma Concentration (Cmax) was defined as the maximum observed plasma concentration and was calculated using non-compartmental analysis. Cmax for U3-1402 and Total Anti-HER3 are presented and was assessed in the Pharmacokinetic Analysis Set. Cmax was evaluated at select time points.
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End point type |
Secondary
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End point timeframe |
Cycle 1 & 3: Day(D)1 (Before Infusion [BI] & End of Infusion [EOI]), D8, D15; Cycle 2: D1 (BI & EOI), D3, D15; Cycle 4 and thereafter: BI & EOI; End of Treatment; 3 month Follow-up
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| Notes [12] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: Only 1 participant was enrolled into cohort 2, data for this one participant was presented descriptively and was not summarized in aggregated form. |
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| Notes [13] - Cycle 3: U3-1402, n=24; Cycle 3: Total Anti-HER3, n=24 |
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| No statistical analyses for this end point | |||||||||||||||||
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End point title |
Maximum Serum Concentration (Cmax) of MAAA-1181 Following Administration of U3-1402 in Participants with Advanced or Metastatic Colorectal Cancer [14] | ||||||||||||
End point description |
Maximum Serum Concentration (Cmax) was defined as the maximum observed serum concentration and was calculated using non-compartmental analysis. Cmax was assessed in the Pharmacokinetic Analysis Set. Cmax was evaluated at select time points.
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End point type |
Secondary
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End point timeframe |
Cycle 1 & 3: Day(D)1 (Before Infusion [BI] & End of Infusion [EOI]), D8, D15; Cycle 2: D1 (BI & EOI), D3, D15; Cycle 4 and thereafter: BI & EOI; End of Treatment; 3 month Follow-up
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| Notes [14] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: Only 1 participant was enrolled into cohort 2, data for this one participant was presented descriptively and was not summarized in aggregated form. |
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| Notes [15] - Cycle 3, n=24 |
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Time to Reach Maximum Serum Concentration (Tmax) of U31402, Total Anti-HER3, and MAAA-1181 Following Administration of U3-1402 in Participants with Advanced or Metastatic Colorectal Cancer [16] | ||||||||||||||||||||
End point description |
Time of Maximum Serum Concentration (Tmax) was defined as the time of maximum observed serum concentration and was calculated using non-compartmental analysis. Tmax for U3-1402, Total Anti-HER3, and MAAA-1181 are presented and was assessed in the Pharmacokinetic Analysis Set. Tmax was evaluated at select time points.
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End point type |
Secondary
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End point timeframe |
Cycle 1 & 3: Day(D)1 (Before Infusion [BI] & End of Infusion [EOI]), D8, D15; Cycle 2: D1 (BI & EOI), D3, D15; Cycle 4 and thereafter: BI & EOI; End of Treatment; 3 month Follow-up
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| Notes [16] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: Only 1 participant was enrolled into cohort 2, data for this one participant was presented descriptively and was not summarized in aggregated form. |
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|
|||||||||||||||||||||
| Notes [17] - Cycle 3: U3-1402, Total-Anti-HER3, and MAAA-1181, n=24 |
|||||||||||||||||||||
| No statistical analyses for this end point | |||||||||||||||||||||
|
|||||||||||||||||
End point title |
Trough Serum Concentration (Ctrough) of U3-1402 and Total Anti-HER3 Following Administration of U3-1402 in Participants with Advanced or Metastatic Colorectal Cancer [18] | ||||||||||||||||
End point description |
Trough Serum Concentration (Ctrough) was calculated using non-compartmental analysis. Ctrough for U3-1402 and Total Anti-HER3 are presented and was assessed in the Pharmacokinetic Analysis Set. Ctrough was evaluated at select time points.
|
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End point type |
Secondary
|
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End point timeframe |
Cycle 1 & 3: Day(D)1 (Before Infusion [BI] & End of Infusion [EOI]), D8, D15; Cycle 2: D1 (BI & EOI), D3, D15; Cycle 4 and thereafter: BI & EOI; End of Treatment; 3 month Follow-up
|
||||||||||||||||
| Notes [18] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: Only 1 participant was enrolled into cohort 2, data for this one participant was presented descriptively and was not summarized in aggregated form. |
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|
|||||||||||||||||
| Notes [19] - Cycle 1: U3-1402 & Total Anti-HER3, n=35; Cycle 3: U3-1402 & Total Anti-HER3, n=15 |
|||||||||||||||||
| No statistical analyses for this end point | |||||||||||||||||
|
|||||||||||||
End point title |
Trough Serum Concentration (Ctrough) of MAAA-1181 Following Administration in Participants with Advanced or Metastatic Colorectal Cancer [20] | ||||||||||||
End point description |
Trough Serum Concentration (Ctrough) was calculated using non-compartmental analysis. Ctrough is presented and was assessed in the Pharmacokinetic Analysis Set. Ctrough was evaluated at select time points.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Cycle 1 & 3: Day(D)1 (Before Infusion [BI] & End of Infusion [EOI]), D8, D15; Cycle 2: D1 (BI & EOI), D3, D15; Cycle 4 and thereafter: BI & EOI; End of Treatment; 3 month Follow-up
|
||||||||||||
| Notes [20] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: Only 1 participant was enrolled into cohort 2, data for this one participant was presented descriptively and was not summarized in aggregated form. |
|||||||||||||
|
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| Notes [21] - Cycle 1, n=35; Cycle 3, n=16 |
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| No statistical analyses for this end point | |||||||||||||
|
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End point title |
Area Under the Serum Concentration-Time Curve up to Last Quantifiable Time (AUClast) and During Dosing Interval (AUCtau) of U3-1402 and Total Anti-HER3 Following Administration in Participants with Advanced or Metastatic Colorectal Cancer [22] | ||||||||||||||||||||
End point description |
Area under the concentration versus-time curve from time 0 to the last quantifiable concentration (AUClast) and during the dosing interval (AUCtau) was calculated using non-compartmental analysis. AUClast and AUCtau for U3-1402 and Total Anti-HER3 are presented and was assessed in the Pharmacokinetic Analysis Set at select time points.
|
||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||
End point timeframe |
Cycle 1 & 3: Day(D)1 (Before Infusion [BI] & End of Infusion [EOI]), D8, D15; Cycle 2: D1 (BI & EOI), D3, D15; Cycle 4 and thereafter: BI & EOI; End of Treatment; 3 month Follow-up
|
||||||||||||||||||||
| Notes [22] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: Only 1 participant was enrolled into cohort 2, data for this one participant was presented descriptively and was not summarized in aggregated form. |
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|
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| Notes [23] - C1:U3-1402 & Anti-HER3 (AUClast n=20)&(AUCtau n=18);C3:U3-1402 (AUCtau n=7)&Anti-HER3 (AUCtau n=9) |
|||||||||||||||||||||
| No statistical analyses for this end point | |||||||||||||||||||||
|
|||||||||||||||
End point title |
Area Under the Serum Concentration-Time Curve up to Last Quantifiable Time (AUClast) and During Dosing Interval (AUCtau) of MAAA-1181 Following Administration in Participants with Advanced or Metastatic Colorectal Cancer [24] | ||||||||||||||
End point description |
Area under the concentration versus-time curve from time 0 to the last quantifiable concentration (AUClast) and during the dosing interval (AUCtau) was calculated using non-compartmental analysis. AUClast and AUCtau for MAAA-1181 is presented and was assessed in the Pharmacokinetic Analysis Set at select time points.
|
||||||||||||||
End point type |
Secondary
|
||||||||||||||
End point timeframe |
Cycle 1 & 3: Day(D)1 (Before Infusion [BI] & End of Infusion [EOI]), D8, D15; Cycle 2: D1 (BI & EOI), D3, D15; Cycle 4 and thereafter: BI & EOI; End of Treatment; 3 month Follow-up
|
||||||||||||||
| Notes [24] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: Only 1 participant was enrolled into cohort 2, data for this one participant was presented descriptively and was not summarized in aggregated form. |
|||||||||||||||
|
|||||||||||||||
| Notes [25] - Cycle 1: AUClast n=20; Cycle 1: AUCtau n=17; Cycle 3 AUCtau n=5 |
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| No statistical analyses for this end point | |||||||||||||||
|
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Adverse events information
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Timeframe for reporting adverse events |
Adverse events (AE) were collected from the date of signing the informed consent form up to 47 days after last dose of the study drug, up 16.9 months.
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Adverse event reporting additional description |
An AE is any untoward medical occurrence in a subject administered a pharmaceutical product and that does not necessarily have to have a causal relationship with this treatment.
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Assessment type |
Systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
24.1
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Reporting groups
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Reporting group title |
Overall
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Reporting group description |
Participants with high tumor expression & low or negative levels of human epidermal receptor 3 (HER3) low or negative and who received 5.6 mg/Kg of U3-1402 intravenously (IV) on Day 1 of each 21-day cycle (Safety Analysis Set). | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Frequency threshold for reporting non-serious adverse events: 5% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Substantial protocol amendments (globally) |
|||||||
| Were there any global substantial amendments to the protocol? Yes | |||||||
Date |
Amendment |
||||||
06 Jun 2020 |
This amendment provided revisions to the protocol design to enhance subject safety by implementing further guidance related to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and also to ensure that subjects with a history of microsatellite instability-high (MSI-H) colorectal cancer have received immune checkpoint inhibitor therapy (if there were no contraindications) prior to enrollment into this study. Other minor editorial changes were provided to enhance clarity. |
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24 Aug 2020 |
This amendment provided revisions to the protocol design to enhance subject safety by clarifying that membrane transport inhibitors are permitted, and their use will be closely monitored. Other minor editorial changes were provided to enhance clarity. |
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24 Nov 2020 |
This amendment provided greater uniformity in the enrolled population by ensuring the prior use of a BRAF inhibitor in patients whose tumors expressed a BRAF V600E mutation. It also provided further specification regarding the required antibody washout period, conditions under which tumor assessments should be conducted, screening, rescreening, and study closure procedures. Other minor editorial changes were provided to enhance clarity. |
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Interruptions (globally) |
|||||||
| Were there any global interruptions to the trial? Yes | |||||||
|
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Limitations and caveats |
|||||||
| Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||||||
| None reported | |||||||
