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

Conditions:Lung Cancer, Lung Cancer, Cancer
Therapuetic Areas:Oncology
Age Range:18 - Any
Start Date:October 30, 2017
End Date:February 28, 2020

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A Multicenter, Open-Label Phase 1 Study of U3-1402 in Subjects With Metastatic or Unresectable EGFR-mutant Non-small Cell Lung Cancer

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

- For Dose Expansion, to assess the safety and tolerability of U3-1402 in the study

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.

Inclusion Criteria:

1. Has histologically or cytologically documented adenocarcinoma NSCLC

2. Has locally advanced or metastatic NSCLC, not amenable to curative surgery or

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

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

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

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

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

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

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
We found this trial at
1365 Clifton Rd NE
Atlanta, Georgia 30322
(404) 778-1900
Phone: 404-727-6123
Winship Cancer Institute at Emory University Winship Cancer Institute of Emory University is Georgia
Atlanta, GA
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Nashville, TN
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Memorial Sloan Kettering Cancer Center Memorial Sloan Kettering Cancer Center — the world's oldest and...
New York, NY
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