Clinical Trials /

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

NCT03260491

Description:

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.

Related Conditions:
  • Non-Small Cell Lung Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: U3-1402 in Metastatic or Unresectable EGFR-mutant Non-Small Cell Lung Cancer
  • 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

Clinical Trial IDs

  • ORG STUDY ID: U31402-A-U102
  • SECONDARY ID: 2017-000543-41
  • NCT ID: NCT03260491

Conditions

  • Non-Small Cell Lung Cancer (NSCLC)

Interventions

DrugSynonymsArms
U3-1402U3-1402

Purpose

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.

Trial Arms

NameTypeDescriptionInterventions
U3-1402ExperimentalParticipants receive U3-1402 intravenously (IV) once every three weeks at planned doses (3.2, 6.4, 9.6, 12.8 mg/kg)
  • U3-1402

Eligibility 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
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Dose Limiting Toxicities (DLTs) in the Dose Escalation Period
Time Frame:21 days of Cycle 1
Safety Issue:
Description:

Secondary Outcome Measures

Measure:Serum concentration of U3-1402
Time Frame:during the dose expansion period, within 36 months
Safety Issue:
Description:Anti-HER3 antibody, and free payload MAAA-1181a vs. time will be utilized
Measure:Maximum (peak) observed concentration in serum (Cmax)
Time Frame:during the dose expansion period, within 36 months
Safety Issue:
Description:
Measure:Time of maximum observed concentration (Tmax)
Time Frame:during the dose expansion period, within 36 months
Safety Issue:
Description:
Measure:Area under the serum concentration-time curve (AUC)
Time Frame:during the dose expansion period, within 36 months
Safety Issue:
Description:Categories: time 0 to 8 hours (AUC0-8), to the last quantifiable time (AUClast)
Measure:Overall Response Rate
Time Frame:during the dose expansion period, within 36 months
Safety Issue:
Description:evaluated using RECIST 1.1
Measure:Disease control rate (DCR)
Time Frame:during the dose expansion period, within 36 months
Safety Issue:
Description:
Measure:Duration of response (DOR)
Time Frame:during the dose expansion period, within 36 months
Safety Issue:
Description:
Measure:Time to response (TTR)
Time Frame:during the dose expansion period, within 36 months
Safety Issue:
Description:
Measure:Progression free survival (PFS)
Time Frame:during the dose expansion period, within 36 months
Safety Issue:
Description:
Measure:Overall Survival (OS)
Time Frame:during the dose expansion period, within 36 months
Safety Issue:
Description:

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Daiichi Sankyo, Inc.

Trial Keywords

  • Oncology
  • Advanced Non-small Cell Lung Cancer
  • Inoperable Non-small Cell Lung Cancer
  • Metastatic
  • Unresectable
  • Epidermal growth factor receptor
  • EGFR

Last Updated

November 17, 2017