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Trial record 1 of 1 for:    U3-1402 colorectal cancer
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A Study to Evaluate U3-1402 in Subjects With Advanced or Metastatic Colorectal Cancer

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ClinicalTrials.gov Identifier: NCT04479436
Recruitment Status : Recruiting
First Posted : July 21, 2020
Last Update Posted : September 17, 2020
Sponsor:
Information provided by (Responsible Party):
Daiichi Sankyo, Inc.

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.

Condition or disease Intervention/treatment Phase
Metastatic Colorectal Cancer Drug: U3-1402 Phase 2

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 80 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: 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)
Actual Study Start Date : September 14, 2020
Estimated Primary Completion Date : February 10, 2023
Estimated Study Completion Date : May 15, 2023

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Cohort 1: HER3 High (IHC 3+, 2+)
Cohort 1 participants will have high tumor expression levels of human epidermal receptor 3 (HER3) in a pre-treatment biopsy specimen.
Drug: U3-1402
U3-1402 will be dosed at 5.6 mg/kg as an intravenous (IV) infusion administered on Day 1 of each 21-day cycle.

Experimental: Cohort 2: HER3 Low/Negative (IHC 1+, 0)
Cohort 2 participants will have low or negative tumor expression levels of human epidermal receptor 3 (HER3) expression levels in a pre-treatment biopsy specimen.
Drug: U3-1402
U3-1402 will be dosed at 5.6 mg/kg as an intravenous (IV) infusion administered on Day 1 of each 21-day cycle.




Primary Outcome Measures :
  1. Objective Response Rate (ORR) As Assessed By Blinded Independent Central Review Following Administration of U3-1402 In Participants with Advanced or Metastatic Colorectal Cancer [ Time Frame: From baseline up to disease progression or other protocol-defined reasons (whichever occurs first), up to approximately 27 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.


Secondary Outcome Measures :
  1. Duration of Response (DOR) As Assessed by Blinded Independent Central Review Following Administration of U3-1402 In Participants with Advanced or Metastatic Colorectal Cancer [ Time Frame: From baseline up to disease progression or other protocol-defined reasons (whichever occurs first), up to approximately 27 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.

  2. Objective Response Rate (ORR) As Assessed by Investigator Following Administration of U3-1402 In Participants with Advanced or Metastatic Colorectal Cancer [ Time Frame: From baseline up to disease progression or other protocol-defined reasons (whichever occurs first), up to approximately 27 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.

  3. Duration of Response (DoR) As Assessed by Investigator Following Administration of U3-1402 In Participants with Advanced or Metastatic Colorectal Cancer [ Time Frame: From baseline up to disease progression or other protocol-defined reasons (whichever occurs first), up to approximately 27 months ]
    DoR defined as the time from the first documented response (complete response [CR] or partial response [PR]) to the date of disease progression or death due to any cause.

  4. Disease Control Rate (DCR) by Blinded Independent Central Review and Investigator Following Administration of U3-1402 In Participants with Advanced or Metastatic Colorectal Cancer [ Time Frame: From baseline up to disease progression or other protocol-defined reasons (whichever occurs first), up to approximately 27 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

  5. Time to Tumor Response (TTR) As Assessed by Blinded Independent Central Review and Investigator Following Administration of U3-1402 In Participants with Advanced or Metastatic Colorectal Cancer [ Time Frame: From baseline up to disease progression or other protocol-defined reasons (whichever occurs first), up to approximately 27 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

  6. Progression-free Survival (PFS) Assessed by Blinded Independent Central Review and Investigator Following Administration of U3-1402 In Participants with Advanced or Metastatic Colorectal Cancer [ Time Frame: From baseline until disease progression or other protocol defined reason (whichever occurs first), assessed up to 27 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

  7. Overall Survival (OS) Following Administration of U3-1402 In Participants with Advanced or Metastatic Colorectal Cancer [ Time Frame: From baseline up to the date of death due to any cause or 27 months, whichever is earlier. ]
    OS defined as the time from the start of study treatment to the date of death due to any cause.

  8. Summary of Reported Treatment-emergent Adverse Events (TEAEs) and other safe parameters during the study [ Time Frame: From baseline up to Day 40 post last dose, approximately 27 months ]
    Incidence of TEAEs, serious adverse events, adverse events of special interests (interstitial lung disease; and elevation of aminotransferases and total bilirubin), Eastern Cooperative Oncology Group performance status, vital sign measurements, standard clinical laboratory parameters will be assessed

  9. Pharmacokinetic (PK) of Maximum Serum Concentration (Cmax) of analytes of U3-1402 Following Administration In Participants with Advanced or Metastatic Colorectal Cancer [ 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 through Cycle 8 (each cycle is 21 days) ]
    Plasma concentrations at each time point and PK parameters Cmax of U3-1402 (ADC, total anti-HE antibody, and MAAA-1181a) will be assessed in the full PK sampling cohort

  10. Pharmacokinetic of Time to Reach Maximum Serum Concentration (Tmax) of analytes of U3-1402 Following Administration In Participants with Advanced or Metastatic Colorectal Cancer [ 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 through Cycle 8 (each cycle is 21 days) ]
    Plasma concentrations at each time point and PK parameters Tmax of U3-1402 (ADC, total anti-HE antibody, and MAAA-1181a) will be assessed in the full PK sampling cohort

  11. Pharmacokinetic of Trough Serum Concentration (Ctrough) of analytes of U3-1402 Following Administration In Participants with Advanced or Metastatic Colorectal Cancer [ 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 through Cycle 8 (each cycle is 21 days) ]
    Plasma concentrations at each time point and PK parameters Ctrough of U3-1402 (ADC, total anti-HE antibody, and MAAA-1181a) will be assessed in the full PK sampling cohort

  12. Pharmacokinetic of Area Under the Serum Concentration-Time Curve Up to Last Quantifiable Time (AUClast) and During Dosing Interval (AUCtau) of analytes of U3-1402 Following Administration In Participants with Advanced or Metastatic Colorectal Cancer [ 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 through Cycle 8 (each cycle is 21 days) ]
    Plasma concentrations at each time point and PK parameters AUClast and AUCtau of U3-1402 (ADC, total anti-HE antibody, and MAAA-1181a) will be assessed in the full PK sampling cohort



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years to 100 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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 (eg, RAS/BRAF wildtype)
    • An anti-VEGF agent, unless contraindicated (eg, bevacizumab) Note: Participants with known microsatellite instability-high (MSI-H) status must have received treatment with an immune checkpoint inhibitor unless contraindicated.
  • 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 required archival and pre-treatment tumor biopsy for 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. Archival tissue must be available and of sufficient quantity, as defined above, at the time of screening. If archival tissue is not available, a participant 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-study tumor biopsy. When at least 10 on-study 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:

The following Parameters / Laboratory values:

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 pneumonectomy.
  • Is receiving chronic systemic corticosteroids dosed at >10 mg prednisone or equivalent or any form of immunosuppressive therapy prior to Cycle 1 Day 1. Participants who require use of bronchodilators, inhaled steroids, or local steroid injections may be included in the study.
  • Evidence of leptomeningeal disease.
  • Has 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. Immune checkpoint inhibitor therapy <21 days;
    4. Major surgery (excluding placement of vascular access) <4 weeks;
    5. Radiotherapy treatment to >30% of the bone marrow or with a wide field of radiation <28 days or palliative radiation therapy <14 days;
    6. 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. Participants with chronic Grade 2 toxicities may be eligible per the discretion of the Investigator after consultation with the Sponsor (Medical Monitor or designee).
  • 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. Participants will be eligible for enrollment only if the viral load, according to local standards of detection, is documented to be low or undetectable in the absence of anti-viral therapy and during the previous 12 weeks prior to the viral load evaluation.
  • Any evidence of severe or uncontrolled systemic diseases (including active bleeding diatheses, active infection [including human immunodeficiency virus (HIV)]), 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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04479436


Contacts
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Contact: (US sites only) Daiichi Sankyo Contact for Clinical Trial Information 908-992-6400 CTRinfo@dsi.com
Contact: (Asia sites only) Daiichi Sankyo Contact for Clinical Trial Information +81-3-6225-1111(M-F 9-5 JST) dsclinicaltrial@daiichisankyo.co.jp

Locations
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Sponsors and Collaborators
Daiichi Sankyo, Inc.
Investigators
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Study Director: Global Clinical Leader Daiichi Sankyo, Inc.
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Responsible Party: Daiichi Sankyo, Inc.
ClinicalTrials.gov Identifier: NCT04479436    
Other Study ID Numbers: U31402-A-U202
2019-004418-32 ( EudraCT Number )
First Posted: July 21, 2020    Key Record Dates
Last Update Posted: September 17, 2020
Last Verified: September 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: De-identified individual participant data (IPD) and applicable supporting clinical trial documents may be available upon request at https://vivli.org/. In cases where clinical trial data and supporting documents are provided pursuant to our company policies and procedures, Daiichi Sankyo will continue to protect the privacy of our clinical trial participants. Details on data sharing criteria and the procedure for requesting access can be found at this web address: https://vivli.org/ourmember/daiichi-sankyo/
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Clinical Study Report (CSR)
Time Frame: Studies for which the medicine and indication have received European Union (EU) and United States (US), and/or Japan (JP) marketing approval on or after 01 January 2014 or by the US or EU or JP Health Authorities when regulatory submissions in all regions are not planned and after the primary study results have been accepted for publication.
Access Criteria: Formal request from qualified scientific and medical researchers on IPD and clinical study documents from clinical trials supporting products submitted and licensed in the United States, the European Union and/or Japan from 01 January 2014 and beyond for the purpose of conducting legitimate research. This must be consistent with the principle of safeguarding study participants' privacy and consistent with provision of informed consent.
URL: https://vivli.org/ourmember/daiichi-sankyo/

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Daiichi Sankyo, Inc.:
Metastatic Colorectal Cancer
U3-1402
Additional relevant MeSH terms:
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Colorectal Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Colonic Diseases
Intestinal Diseases
Rectal Diseases