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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03260491
Recruitment Status : Recruiting
First Posted : August 24, 2017
Last Update Posted : April 16, 2020
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 investigate the antitumor activity of U3-1402

The number of treatment cycles is not fixed in this study. Participants will continue study treatment (for approximately 36 months) until 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

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 198 participants
Allocation: Non-Randomized
Intervention Model: Sequential 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 Non-small Cell Lung Cancer
Actual Study Start Date : October 30, 2017
Estimated Primary Completion Date : October 31, 2021
Estimated Study Completion Date : October 31, 2023

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Dose Escalation: Cohort 1, 3.2 mg/kg
Participants in the Dose Escalation Cohort 1 will receive U3-1402 intravenously (IV) once every three weeks at 3.2 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)

Experimental: Dose Escalation: Cohort 2, 6.4 mg/kg
Participants in Dose Escalation Cohort 2 will receive U3-1402 intravenously (IV) once every three weeks at 6.4 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)

Experimental: Dose Escalation: Cohort 3, 9.6 mg/kg
Participants in Dose Escalation Cohort 3 will receive U3-1402 intravenously (IV) once every three weeks at 9.6 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)

Experimental: Dose Escalation: Cohort 4, 12.8 mg/kg
Participants in Dose Escalation Cohort 3 will receive U3-1402 intravenously (IV) once every three weeks at 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)

Experimental: Dose Expansion: Cohort 1, EGFR mutant
Participants with adenocarcinoma NSCLC with EGFR mutations in the Dose Expansion Cohort 1 will receive U3-1402 IV once every three weeks at the established recommended dose for expansion (RDE).
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)

Experimental: Dose Expansion: Cohort 2, EGFR wild-type
Participants with squamous or non-squamous NSCLC without EGFR-activating mutations in the Dose Expansion Cohort 2 will receive U3-1402 IV once every three weeks at the established recommended dose for expansion (RDE).
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)

Experimental: Dose Expansion: Cohort 3a, EGFR mutant
Randomized participants with NSCLC and EGFR mutations in the Dose Expansion Cohort 3a will receive U3-1402 IV once every three weeks at the established recommended dose for expansion (RDE) or, if applicable, adjusted RDE (aRDE).
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)

Experimental: Dose Expansion: Cohort 3b, EGFR mutant
Randomized participants with NSCLC and EGFR mutations in the Dose Expansion Cohort 3b will receive U3-1402 IV once every three weeks following an up-titration regimen (Cycle 1, Day 1: 57% of RDE or aRDE; Cycle 2, Day 1: 86% of RDE or, if applicable aRDE; Cycle 3 and subsequent cycles, Day 1: 114% of RDE or aRDE).
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 in the dose escalation period [ Time Frame: By the global end of trial date, approximately within 36 months ]
  3. Overall response rate (ORR) assessed by Independent Central Review (ICR) Committee in the dose expansion period [ Time Frame: Approximately within 36 months ]
    Evaluated using RECIST 1.1


Secondary Outcome Measures :
  1. Maximum plasma concentration (Cmax) of U3-1402, total anti-HER3 antibody, and MAAA 1181a in the dose escalation period [ Time Frame: During approximately the first 84 days after dosing ]
  2. Time of maximum concentration (Tmax) of U3-1402, total anti-HER3 antibody, and MAAA 1181a in the dose escalation period [ Time Frame: During approximately the first 84 days after dosing ]
  3. Area under the serum concentration-time curve from time 0 to 8 hours (AUC[0-8]) of U3-1402, total anti-HER3 antibody, and MAAA 1181a in the dose escalation period [ Time Frame: During approximately the first 84 days after dosing ]
  4. Area under the serum concentration-time curve up to the last quantifiable time (AUC[last]) of U3-1402, total anti-HER3 antibody, and MAAA 1181a in the dose escalation period [ Time Frame: During approximately the first 84 days after dosing ]
  5. Terminal elimination rate constant (Kel) of U3-1402, total anti-HER3 antibody, and MAAA 1181a in the dose escalation period [ Time Frame: During approximately the first 84 days after dosing ]
  6. Elimination half-life (t1/2) of U3-1402, total anti-HER3 antibody, and MAAA 1181a in the dose escalation period [ Time Frame: During approximately the first 84 days after dosing ]
  7. Total body clearance (CL) of U3-1402, total anti-HER3 antibody, and MAAA 1181a in the dose escalation period [ Time Frame: During approximately the first 84 days after dosing ]
  8. Volume of distribution after a single-dose (Vz) of U3-1402, total anti-HER3 antibody, and MAAA 1181a in the dose escalation period [ Time Frame: During approximately the first 84 days after dosing ]
  9. Volume of distribution at steady-state after multiple doses (Vss) of U3-1402, total anti-HER3 antibody, and MAAA 1181a in the dose escalation period [ Time Frame: During approximately the first 84 days after dosing ]
  10. Overall response rate (ORR) in the dose escalation period [ Time Frame: Approximately within 36 months ]
    Evaluated using RECIST 1.1

  11. Disease control rate (DCR) in the dose escalation period [ Time Frame: Approximately within 36 months ]
  12. Duration of response (DOR) in the dose escalation period [ Time Frame: Approximately within 36 months ]
  13. Time to response (TTR) in the dose escalation period [ Time Frame: Approximately within 36 months ]
  14. Progression free survival (PFS) in the dose escalation period [ Time Frame: Approximately within 36 months ]
  15. Overall Survival (OS) in the dose escalation period [ Time Frame: Approximately within 36 months ]
  16. Summary of adverse events in the dose expansion period [ Time Frame: By the global end of trial date, approximately within 36 months ]
  17. Maximum plasma concentration (Cmax) of U3-1402, total anti-HER3 antibody, and MAAA 1181a in the dose expansion period [ Time Frame: During approximately the first 84 days after dosing ]
  18. Time of maximum concentration (Tmax) of U3-1402, total anti-HER3 antibody, and MAAA 1181a in the dose expansion period [ Time Frame: During approximately the first 84 days after dosing ]
  19. Area under the serum concentration-time curve from time 0 to 8 hours (AUC[0-8]) of U3-1402, total anti-HER3 antibody, and MAAA 1181a in the dose expansion period [ Time Frame: During approximately the first 84 days after dosing ]
  20. Area under the serum concentration-time curve up to the last quantifiable time (AUC[last]) of U3-1402, total anti-HER3 antibody, and MAAA 1181a in the dose expansion period [ Time Frame: During approximately the first 84 days after dosing ]
  21. Terminal elimination rate constant (Kel) of U3-1402, total anti-HER3 antibody, and MAAA 1181a in the dose expansion period [ Time Frame: During approximately the first 84 days after dosing ]
  22. Elimination half-life (t1/2) of U3-1402, total anti-HER3 antibody, and MAAA 1181a in the dose expansion period [ Time Frame: During approximately the first 84 days after dosing ]
  23. Total body clearance (CL) of U3-1402, total anti-HER3 antibody, and MAAA 1181a in the dose expansion period [ Time Frame: During approximately the first 84 days after dosing ]
  24. Volume of distribution after a single-dose (Vz) of U3-1402, total anti-HER3 antibody, and MAAA 1181a in the dose expansion period [ Time Frame: During approximately the first 84 days after dosing ]
  25. Volume of distribution at steady-state after multiple doses (Vss) of U3-1402, total anti-HER3 antibody, and MAAA 1181a in the dose expansion period [ Time Frame: During approximately the first 84 days after dosing ]
  26. Overall response rate (ORR) in the dose expansion period [ Time Frame: Approximately within 36 months ]
    Evaluated using RECIST 1.1

  27. Disease control rate (DCR) in the dose expansion period [ Time Frame: Approximately within 36 months ]
  28. Duration of response (DOR) in the dose expansion period [ Time Frame: Approximately within 36 months ]
  29. Time to response (TTR) in the dose expansion period [ Time Frame: Approximately within 36 months ]
  30. Progression free survival (PFS) in the dose expansion period [ Time Frame: Approximately within 36 months ]
  31. Overall Survival (OS) in the dose expansion period [ Time Frame: Approximately within 36 months ]


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

Inclusion Criteria for both Dose Escalation and Dose Expansion:

  1. Has locally advanced or metastatic NSCLC, not amenable to curative surgery or radiation
  2. Has at least one measurable lesion per RECIST version 1.1
  3. Has Eastern Cooperative Oncology Group performance status of 0 or 1 at Screening

Inclusion Criteria for Dose Escalation only:

  1. Has histologically or cytologically documented adenocarcinoma NSCLC
  2. 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
  3. Is currently receiving and able to discontinue erlotinib, gefinitib, afatinib, or osimertinib
  4. 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
  5. Has radiological documentation of disease progression while receiving continuous treatment with erlotinib, gefitinib, afatinib, or osimertinib
  6. 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
  7. Demonstrates absence of EGFR T790M mutation if treated with erlotinib, gefitinib, or afatinib. No EGFR mutation testing is required if treated with osimertinib.

Inclusion Criteria for all cohorts of Dose Expansion only:

  1. Has received systemic therapy for locally advanced or metastatic disease including at least 1 platinum-based chemotherapy regimen
  2. Has documented radiological disease progression during/after most recent treatment regimen for locally-advanced or metastatic disease
  3. Is willing to provide archival tumor tissue from a biopsy performed within 6 months of consent and performed after progression during/after treatment with most recent cancer therapy regimen OR has at least 1 lesion, not previously irradiated, amenable to core biopsy and is willing to undergo tumor biopsy

Inclusion Criteria specific to Cohort 1, Cohort 3a, and Cohort 3b of Dose Expansion:

  1. Has histologically or cytologically documented:

    1. Cohort 1: Adenocarcinoma NSCLC
    2. Cohort 3a and 3b: NSCLC (including any histology other than combined small cell and non-small cell)
  2. Has documentation of radiological disease progression following one or more lines of EGFR TKI treatment. Participants with EGFR T790M mutation following treatment with erlotinib, gefitinib afatinib, or dacomitinib must have received and have documentation of radiological disease progression following treatment with osimertinib unless unable or unwilling.
  3. Has documentation of EGFR-activating mutation(s) detected from tumor tissue: G719X, exon deletion 19, L858R, or L861Q. Participants with other EGFR-activating mutations may be eligible following discussion with the Sponsor.

Inclusion Criteria specific to Cohort 2 of Dose Expansion:

  1. Has histologically or cytologically documented squamous or non-squamous NSCLC (ie, without EGFR-activating mutations).
  2. Has received prior treatment with anti-PD-1 or anti-PD-L1 antibody-based regimen in the locally advanced or metastatic setting unless unable or unwilling. Participants with NSCLC known to harbor a genomic alteration(s) other than EGFR mutation(s) (eg, ALK or ROS1 fusion) for which treatment is available must have also received prior treatment with at least 1 genotype-directed therapy.

Exclusion Criteria for Dose Escalation and Dose Expansion:

  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. 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 in Cohort 1 only), within 14 days of the first dose of study treatment
    2. Immune checkpoint inhibitor therapy within 21 days of the first dose of study treatment
    3. Prior treatment with an anti-HER3 antibody (dose escalation only)
    4. Prior treatment with a topoisomerase I inhibitor (dose escalation only)
    5. Prior treatment with an antibody-drug conjugate (ADC) that consists of an exatecan derivative that is a topoisomerase I inhibitor (eg, DS-8201a) (dose escalation only)
    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, or stereotactic radiotherapy within 1 week prior to the first dose of U3-1402
  3. 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
  4. 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)
  5. Has history of myocardial infarction within the past 6 months
  6. Has symptomatic congestive heart failure[New York Heart Association (NYHA) Classes II-IV], unstable angina within the past 6 months, or cardiac arrhythmia requiring antiarrhythmic treatment
  7. Has left ventricular ejection fraction (LVEF) < 50% by either echocardiogram (ECHO) or multigated acquisition scan (MUGA)
  8. 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)
  9. 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
  10. Unable or unwilling to discontinue concomitant drugs that are known to prolong the QT interval
  11. 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.
  12. Has any history of interstitial lung disease (ILD) (including pulmonary fibrosis or severe radiation pneumonitis), has current ILD/pneumonitis, or is suspected to have such disease by imaging during screening
  13. Has clinically significant corneal disease

Additional Exclusion Criteria for Dose Expansion Cohort 2:

1. Has documentation of one or more of the following EGFR-activating mutations: G719X, exon 19 deletion, L858R, or L861Q


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


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

Locations
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United States, California
City of Hope Recruiting
Duarte, California, United States, 91010
Contact: Principal Investigator         
University of California San Diego Recruiting
La Jolla, California, United States, 92093
Contact: Principal Investigator         
United States, Georgia
Winship Cancer Institute of Emory University Recruiting
Atlanta, Georgia, United States, 30322
Contact: Principal Investigator         
United States, Massachusetts
Dana-Farber Cancer Institute Recruiting
Boston, Massachusetts, United States, 02215
Contact: Principal Investigator         
United States, New York
Memorial Sloan-Kettering Cancer Center Recruiting
New York, New York, United States, 10065
Contact: Principal Investigator         
United States, Tennessee
Sarah Cannon Research Institute/Tennesse Oncology Recruiting
Nashville, Tennessee, United States, 37203
Contact: Principal Investigator         
United States, Washington
Seattle Cancer Care Alliance Recruiting
Seattle, Washington, United States, 98109
Contact: Principal Investigator         
Japan
Kindai University Hospital Recruiting
Osaka, Japan, 5898511
Contact: See Central Contact         
Shizuoka Cancer Center Recruiting
Shizuoka, Japan, 4118777
Contact: See Central Contact         
The Cancer Institute Hospital of Japanese Foundation for Cancer Research (JFCR) Recruiting
Tokyo, Japan, 1358550
Contact: See Central Contact         
Taiwan
National Cheng Kung University Hospital Recruiting
Tainan, Taiwan, 00704
Contact: See Central Contact         
National Taiwan University Hospital Recruiting
Taipei, Taiwan, 00100
Contact: Principal Investigator         
Sponsors and Collaborators
Daiichi Sankyo, Inc.
Investigators
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Study Director: Global Clinical Leader Daiichi Sankyo, Inc.
Publications:
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Responsible Party: Daiichi Sankyo, Inc.
ClinicalTrials.gov Identifier: NCT03260491    
Other Study ID Numbers: U31402-A-U102
2017-000543-41 ( EudraCT Number )
194868 ( Other Identifier: JapicCTI )
First Posted: August 24, 2017    Key Record Dates
Last Update Posted: April 16, 2020
Last Verified: April 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.:
Oncology
Advanced Non-small Cell Lung Cancer
Inoperable Non-small Cell Lung Cancer
Metastatic
Unresectable
Epidermal growth factor receptor
EGFR
Additional relevant MeSH terms:
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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