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U3-1402 in Metastatic or Unresectable EGFR-mutant Non-Small Cell Lung Cancer

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ClinicalTrials.gov Identifier: NCT03260491
Recruitment Status : Recruiting
First Posted : August 24, 2017
Last Update Posted : July 12, 2018
Sponsor:
Information provided by (Responsible Party):
Daiichi Sankyo, Inc.

Brief Summary:

This study has two parts: dose escalation and dose expansion.

The primary objectives are:

  • For Dose Escalation, to assess the safety and tolerability of U3-1402 in the study population and to determine the recommended dose for expansion of U3-1402 in the study population
  • For Dose Expansion, to assess the safety and tolerability of U3-1402 in the study population

The number of treatment cycles is not fixed in this study. Participants will continue study treatment for 36 months unless they decide not to (withdraw consent), their disease gets worse [progressive disease (PD)], or side effects become unacceptable (unacceptable toxicity) or other stopping reasons have been met.


Condition or disease Intervention/treatment Phase
Non-Small Cell Lung Cancer (NSCLC) Drug: U3-1402 Phase 1

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 63 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Multicenter, Open-Label Phase 1 Study of U3-1402 in Subjects With Metastatic or Unresectable EGFR-mutant Non-small Cell Lung Cancer
Actual Study Start Date : October 30, 2017
Estimated Primary Completion Date : February 28, 2020
Estimated Study Completion Date : February 28, 2020

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Lung Cancer

Arm Intervention/treatment
Experimental: U3-1402
Participants receive U3-1402 intravenously (IV) once every three weeks at planned doses (3.2, 6.4, 9.6, 12.8 mg/kg)
Drug: U3-1402
U3-1402 consists of an antibody component (patritumab, U3-1287) covalently conjugated to a drug-linker (MAAA-1162a) containing a drug component (MAAA-1181a)




Primary Outcome Measures :
  1. Dose Limiting Toxicities (DLTs) in the Dose Escalation Period [ Time Frame: 21 days of Cycle 1 ]
  2. Summary of Adverse Events [ Time Frame: by the global end of trial date, within 36 months ]

Secondary Outcome Measures :
  1. Serum concentration of U3-1402 [ Time Frame: during the dose expansion period, within 36 months ]
    Anti-HER3 antibody, and free payload MAAA-1181a vs. time will be utilized

  2. Maximum (peak) observed concentration in serum (Cmax) [ Time Frame: during the dose expansion period, within 36 months ]
  3. Time of maximum observed concentration (Tmax) [ Time Frame: during the dose expansion period, within 36 months ]
  4. Area under the serum concentration-time curve (AUC) [ Time Frame: during the dose expansion period, within 36 months ]
    Categories: time 0 to 8 hours (AUC0-8), to the last quantifiable time (AUClast)

  5. Overall Response Rate [ Time Frame: during the dose expansion period, within 36 months ]
    evaluated using RECIST 1.1

  6. Disease control rate (DCR) [ Time Frame: during the dose expansion period, within 36 months ]
  7. Duration of response (DOR) [ Time Frame: during the dose expansion period, within 36 months ]
  8. Time to response (TTR) [ Time Frame: during the dose expansion period, within 36 months ]
  9. Progression free survival (PFS) [ Time Frame: during the dose expansion period, within 36 months ]
  10. Overall Survival (OS) [ Time Frame: during the dose expansion period, within 36 months ]


Information from the National Library of Medicine

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

Inclusion Criteria:

  1. Has histologically or cytologically documented adenocarcinoma NSCLC
  2. Has locally advanced or metastatic NSCLC, not amenable to curative surgery or radiation
  3. Has acquired resistance to EGFR TKI according to the Jackman criteria (PMID: 19949011)

    1. Historical confirmation that the tumor harbors an epidermal growth factor receptor (EGFR) mutation known to be associated with EGFR tyrosine kinase inhibitor (TKI) sensitivity (including G719X, exon 19 deletion, L858R, L861Q)
    2. Has experienced clinical benefit from an EGFR TKI, followed by systemic progression of disease [Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1] or World Health Organization (WHO)] while on continuous treatment with an EGFR TKI
  4. Is currently receiving and able to discontinue erlotinib, gefinitib, afatinib, or osimertinib
  5. Has been receiving erlotinib, gefitinib, afatinib, or osimertinib for at least 6 weeks with well-controlled related toxicities less than Grade 3 in severity at the time of Screening
  6. Has radiological documentation of disease progression while receiving continuous treatment with erlotinib, gefitinib, afatinib, or osimertinib
  7. Has at least one measurable lesion per RECIST version 1.1
  8. Is willing to provide archival tumor tissue from a biopsy performed within 6 months of progression during treatment with erlotinib, gefitinib, afatinib, or osimertinib OR has at least one lesion, not previously irradiated, amenable to core biopsy and is willing to undergo screening tumor biopsy
  9. Demonstrates absence of EGFR T790M mutation if treated with erlotinib, gefitinib, or afatinib. No EGFR mutation testing is required if treated with osimertinib.
  10. Has Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1, with no deterioration over the previous 2 weeks

Exclusion Criteria:

  1. Has any evidence of small cell histology, or combined small cell and non-small cell histology, in original tumor biopsy or in Screening biopsy performed after progression
  2. Has previously documented evidence of ALK fusion, ROS1 fusion, BRAF V600E mutation, RET rearrangement, HER2 mutation, MET amplification, or MET exon 14 skipping mutation. No new testing for these genomic alterations is required for Screening.
  3. Treatment with any of the following:

    1. Any cytotoxic chemotherapy, investigational agent or other anticancer drug(s) from a previous cancer treatment regimen or clinical study (other than EGFR TKI), within 14 days of the first dose of study treatment
    2. Immune checkpoint inhibitor therapy within 30 days of the first dose of study treatment
    3. Prior treatment with an anti-HER3 antibody
    4. Prior treatment with a topoisomerase I inhibitor
    5. Prior treatment with an antibody-drug conjugate (ADC) that consists of an exatecan derivative that is a topoisomerase I inhibitor (eg, DS-8201a)
    6. Major surgery (excluding placement of vascular access) within 4 weeks of the first dose of study drug treatment
    7. Radiotherapy treatment to more than 30% of the bone marrow or with a wide field of radiation within 4 weeks of the first dose of study drug treatment, or palliative radiation therapy within 2 weeks of the first dose of study drug treatment
  4. Has history of other active malignancy within 3 years prior to enrollment, except:

    1. Adequately treated non-melanoma skin cancer OR
    2. Superficial bladder tumors (Ta, Tis, T1) OR
    3. Curatively treated in situ disease
  5. Has spinal cord compression or clinically active central nervous system metastases, defined as untreated and symptomatic, or requiring therapy with corticosteroids or anticonvulsants to control associated symptoms. Participants with clinically inactive brain metastases may be included in the study. Participants with treated brain metastases that are no longer symptomatic and who require no treatment with corticosteroids or anticonvulsants may be included in the study if they have recovered from the acute toxic effect of radiotherapy. A minimum of 2 weeks must have elapsed between the end of whole brain radiotherapy and study enrollment (1 week for stereotactic radiotherapy)
  6. Has history of myocardial infarction within the past 6 months
  7. Has symptomatic congestive heart failure[New York Heart Association (NYHA) Classes III-IV], unstable angina, or cardiac arrhythmia requiring antiarrhythmic treatment
  8. Has left ventricular ejection fraction (LVEF) < 45% by either echocardiogram (ECHO) or multigated acquisition scan (MUGA)
  9. Has any clinically important abnormalities in rhythm, conduction or morphology of resting electrocardiogram (ECG), eg, complete left bundle branch block, third-degree heart block, second-degree heart block, or PR interval > 250 milliseconds (ms)
  10. Has a mean corrected QT interval using Fridericia's Correction Formula (QTcF) prolongation to > 470 ms for females and > 450 ms for males in three successive Screening measurements
  11. Unable or unwilling to discontinue concomitant drugs that are known to prolong the QT interval
  12. Has any factors that increase the risk of corrected QT (QTc) interval prolongation or risk of arrhythmic events, such as congenital long QT syndrome, family history of long QT syndrome, or unexplained sudden death under 40 years of age in first-degree relatives.
  13. Has any history of interstitial lung disease (pulmonary fibrosis or severe radiation pneumonitis) or is suspected to have such disease by imaging during screening
  14. Has clinically significant corneal disease

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): NCT03260491


Locations
United States, Georgia
Winship Cancer Institute of Emory University Recruiting
Atlanta, Georgia, United States, 30322
Contact: Principal Investigator    404-727-6123    csteuer@emory.edu   
United States, Massachusetts
Dana-Farber Cancer Institute Recruiting
Boston, Massachusetts, United States, 02215
Contact: Principal Investigator    617-632-3000    Pasi_Janne@dfci.harvard.edu   
United States, New York
Memorial Sloan-Kettering Cancer Center Recruiting
New York, New York, United States, 10065
Contact: Principal Investigator    212-639-2000    YuH@mskcc.org   
United States, Tennessee
Sarah Cannon Research Institute/Tennesse Oncology Recruiting
Nashville, Tennessee, United States, 37203
Contact: Principal Investigator    615-329-7274    mjohnson@tnonc.com   
Sponsors and Collaborators
Daiichi Sankyo, Inc.
Investigators
Study Director: Global Clinical Leader Daiichi Sankyo, Inc.

Publications:
Responsible Party: Daiichi Sankyo, Inc.
ClinicalTrials.gov Identifier: NCT03260491     History of Changes
Other Study ID Numbers: U31402-A-U102
2017-000543-41 ( EudraCT Number )
First Posted: August 24, 2017    Key Record Dates
Last Update Posted: July 12, 2018
Last Verified: July 2018
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 http://www.clinicalstudydatarequest.com. 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://www.clinicalstudydatarequest.com/Study-Sponsors-DS-Details.aspx
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Clinical Study Report (CSR)
Analytic Code
Time Frame: Studies for which the medicine and indication have received EU and US marketing approval on or after 01 January 2014 or by the US or EU Health Authorities when regulatory submissions in both 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 and the European Union 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://www.clinicalstudydatarequest.com/Study-Sponsors-DS-Details.aspx

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Daiichi Sankyo, Inc.:
Oncology
Advanced Non-small Cell Lung Cancer
Inoperable Non-small Cell Lung Cancer
Metastatic
Unresectable
Epidermal growth factor receptor
EGFR

Additional relevant MeSH terms:
Lung Neoplasms
Carcinoma, Non-Small-Cell Lung
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Neoplasms
Lung Diseases
Respiratory Tract Diseases
Carcinoma, Bronchogenic
Bronchial Neoplasms