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DS-1205c With Osimertinib for Metastatic or Unresectable Epidermal Growth Factor Receptor (EGFR)-Mutant Non-Small Cell Lung Cancer

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ClinicalTrials.gov Identifier: NCT03255083
Recruitment Status : Recruiting
First Posted : August 21, 2017
Last Update Posted : March 14, 2019
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 DS-1205c when combined with osimertinib in the study population and to determine the recommended dose for expansion of DS-1205c when combined with osimertinib in the study population
  • For Dose Expansion, to assess the safety and tolerability of DS-1205c when combined with osimertinib in the study population

In Dose Escalation, after a 7-day run in period (Cycle 0), there will be 21-day cycles (Cycle 1 onward). In Dose Expansion, there will be 21-day cycles.

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).


Condition or disease Intervention/treatment Phase
Non-small Cell Lung Cancer (NSCLC) Drug: DS-1205c Drug: Osimertinib Phase 1

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 118 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Multicenter, Open-Label Phase 1 Study of DS-1205c in Combination With Osimertinib in Subjects With Metastatic or Unresectable EGFR-Mutant Non-Small Cell Lung Cancer
Actual Study Start Date : December 22, 2017
Estimated Primary Completion Date : October 15, 2020
Estimated Study Completion Date : October 15, 2020

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Lung Cancer
Drug Information available for: Osimertinib

Arm Intervention/treatment
Experimental: DS-1205c with osimertinib
Participants receive DS-1205c (at planned doses given orally twice daily: 200 mg, 400 mg, 600 mg, 800 mg) in combination with daily 80 mg oral dose of osimertinib
Drug: DS-1205c
DS-1205c 200 mg capsule

Drug: Osimertinib
Osimertinib 80 mg tablet




Primary Outcome Measures :
  1. Number of participants with dose-limiting toxicities (DLTs) during the Dose Escalation period [ Time Frame: within 28 days ]
  2. Number of participants with adverse events (AEs) [ Time Frame: within 36 months ]
    An adverse event (AE) is any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product.


Secondary Outcome Measures :
  1. Plasma concentration of DS-1205a versus time [ Time Frame: during the 7 day run-in period ]
  2. Maximum observed analyte concentration (Cmax) [ Time Frame: during the 7 day run-in period ]
  3. Actual sampling time to reach Cmax (Tmax) [ Time Frame: during the 7 day run-in period ]
  4. Area under the analyte concentration versus time curve during a dosing interval (AUCtau) [ Time Frame: during the 7 day run-in period ]
  5. Minimum observed analyte concentration prior to the beginning, or at the end, of a dosing interval (Ctrough) [ Time Frame: during the 7 day run-in period ]
  6. Cmax during a dosing interval (Tau) at steady state (Cmax,ss) [ Time Frame: during the dose expansion period, within 36 months ]
    Categories: DS-1205a, osimertinib, and osimertinib active metabolites (AZ5104 and AZ7550)

  7. Plasma concentration of DS-1205a versus time [ Time Frame: during the dose expansion period, within 36 months ]
    Categories: DS-1205a, osimertinib, and osimertinib active metabolites (AZ5104 and AZ7550)

  8. Tmax [ Time Frame: during the dose expansion period, within 36 months ]
    Categories: DS-1205a, osimertinib, and osimertinib active metabolites (AZ5104 and AZ7550)

  9. Ctrough [ Time Frame: during the dose expansion period, within 36 months ]
    Categories: DS-1205a, osimertinib, and osimertinib active metabolites (AZ5104 and AZ7550)

  10. AUCtau [ Time Frame: during the dose expansion period, within 36 months ]
    Categories: DS-1205a, osimertinib, and osimertinib active metabolites

  11. Objective response rate (ORR), graded according to RECIST version 1.1 [ Time Frame: within 36 months ]
    Objective response rate is calculated as the number of participants with best objective response [complete response (CR) or partial response (PR) determined by Investigator assessment based on Response Evaluation Criteria In Solid Tumors (RECIST) version 1.1], divided by the number of participants in the analysis population.

  12. Change from baseline in size of target lesion(s) [ Time Frame: within 36 months ]
  13. Duration of response (DOR) [ Time Frame: within 36 months ]
    DOR is defined as the time from documentation of tumor response [either CR or PR] to disease progression

  14. Disease control rate (DCR) [ Time Frame: first dose to 36 months ]
    DCR is defined as the sum of CR rate, PR rate, and stable disease (SD) rate

  15. Progression-free survival (PFS) [ Time Frame: baseline to objective disease progression or death from any cause (within 36 months) ]
    PFS is defined as the time from the date of the first dose to the earlier of the dates of the first objective documentation of radiographic PD, or death due to any cause

  16. Overall survival (OS) [ Time Frame: baseline to death from any cause (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 EGFR mutation known to be associated with EGFR TKI sensitivity (including G719X, exon 19 deletion, L858R, L861Q).
    2. Has experienced clinical benefit from an EGFR TKI, followed by systemic progression (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, or afatinib.
  5. Has been receiving erlotinib, gefitinib, or afatinib for at least 6 weeks with well-controlled related toxicities less than Grade 3 in severity at the time of screening period.
  6. Has radiological documentation of disease progression while receiving continuous treatment with erlotinib, gefitinib, or afatinib.
  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, or afatinib 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.
  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 since 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. Has received treatment with any of the following:

    1. Any cytotoxic chemotherapy, immune checkpoint inhibitor therapy, 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 first dose of study treatment.
    3. Major surgery (excluding placement of vascular access) within 4 weeks of the first dose of study treatment.
    4. Radiotherapy treatment to more than 30% of the bone marrow or with a wide field of radiation within 4 weeks, 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 brain metastases, defined as untreated and symptomatic, or requiring therapy with corticosteroids or anticonvulsants to control associated symptoms. Subjects with clinically inactive brain metastases may be included in the study. Subjects 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. Presence of retinal disease in the eye that is not due to neovascular age-related macular degeneration (nAMD; eg, significant diabetic retinopathy, glaucomatous retinal atrophy, retinal detachment).
  7. Has history of myocardial infarction within the past 6 months.
  8. Has symptomatic congestive heart failure (New York Heart Association [NYHA] Classes II-IV), unstable angina, or cardiac arrhythmia requiring antiarrhythmic treatment.
  9. Has left ventricular ejection fraction (LVEF) < 45% by either echocardiogram (ECHO) or multigated acquisition (MUGA) scan.
  10. Has any clinically important abnormalities in rhythm, conduction or morphology of resting ECG, eg, complete left bundle branch block, third-degree heart block, second-degree heart block, or PR interval > 250 milliseconds (ms).
  11. Has a mean QTcF prolongation >470 ms for females and >450 ms for males in three successive Screening measurements.
  12. Unable or unwilling to discontinue concomitant use of drugs that are known to prolong the QT interval.
  13. Has any factors that increase the risk of QTc 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.
  14. Has any history of interstitial lung disease (pulmonary fibrosis or severe radiation pneumonitis) or is suspected to have such disease by imaging during screening.

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): NCT03255083


Locations
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United States, Massachusetts
Dana-Farber Cancer Institute Withdrawn
Boston, Massachusetts, United States, 02215
United States, New York
Memorial Sloan Kettering Cancer Center Withdrawn
New York, New York, United States, 10065
France
CHU de Grenoble - Hôpital Albert Michallon Withdrawn
Grenoble, France, 38043
Hôpital de la Timone Withdrawn
Marseille, France, 13005
Institut Gustave Roussy Withdrawn
Villejuif, France, 94800
Taiwan
Taipei Medical University, Shuang Ho Hospital Not yet recruiting
New Taipei City, Taiwan, 235
China Medical University Hospital Not yet recruiting
Taichung, Taiwan, 404
Taichung Veterans General Hospital Recruiting
Taichung, Taiwan, 40705
Contact: Principal Investigator    +886 423592525 ext 3259    august@vghtc.gov.tw   
National Cheng-Kung University Hospital Not yet recruiting
Tainan, Taiwan, 704
National Taiwan University Hospital Not yet recruiting
Taipei, Taiwan, 100
Taipei Medical University Hospital Not yet recruiting
Taipei, Taiwan, 110
Taipei Veterans General Hospital Recruiting
Taipei, Taiwan, 11217
Contact: Principal Investigator    +886 228757496    chaohuachiu@gmail.com   
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: NCT03255083     History of Changes
Other Study ID Numbers: DS1205-A-U101
2017-000542-21 ( EudraCT Number )
First Posted: August 21, 2017    Key Record Dates
Last Update Posted: March 14, 2019
Last Verified: March 2019
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)
Informed Consent Form (ICF)
Clinical Study Report (CSR)
Analytic Code
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
Non-resectable
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
Osimertinib
Antineoplastic Agents
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action