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Closed (no longer recruiting)Last updated: 2 February 2024

This phase I trial is trying to understand how safe and well tolerated a new targeted therapy drug is in patients with non-small cell lung cancer that has spread to other parts of the bodyA Multicenter, Open-Label Phase 1 Study of U3-1402 in Subjects With Metastatic or Unresectable Non-small Cell Lung Cancer

Clinical summary

Summary

This trial will be conducted over two parts: dose escalation and dose expansion. Eligible patients will be assigned based on their disease and treatment characteristics. Dose escalation will commence with patients receiving U3-1402 intravenously (IV) once every three weeks at 3.2 mg/kg. This will be increased to 6.4mg/kg, 9.6mg/kg and 12.8mg/kg across four cohorts. In the dose expansion phase, patients with non-small cell lung cancer will receive U3-1402 IV once every three weeks at the established recommended dose for expansion (RDE).

Conditions

This trial is treating patients with non-small cell lung cancer.

Cancer

Lung Cancers Lung cancer

Age

People18+

Phase

I

More information

Trial Identifiers

Use the hyperlinks, where available to access additional clinical trial information.

Trial sponsor

Daiichi Sankyo Ltd.

Scientific Title

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

Eligibility

Inclusion

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. For Cohorts 1, 2, 3a, and 3b: 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. Tumor tissue must be of sufficient quantity as defined in the laboratory manual and contain adequate tumor tissue content as confirmed by haematoxylin and eosin (H&S) staining at central laboratory.

    • For Cohort 4: Neither archival tumor tissue nor core tumor biopsy will be collected

Inclusion Criteria specific to Cohorts 1, 3a, 3b, and 4 of Dose Expansion:

  1. Has histologically or cytologically documented:

    1. Cohort 1: Adenocarcinoma NSCLC
    2. Cohorts 3a, 3b, and 4: NSCLC (including any histology other than small-cell or 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

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 Cohorts 1, 3a, 3b, and 4 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

Additional Exclusion Criteria for Dose Expansion Cohort 4:

  1. Evidence of any leptomeningeal disease

  2. Clinically severe respiratory compromise (based on Investigator's assessment) resulting from intercurrent pulmonary illnesses including, but not limited to:

    1. Any underlying pulmonary disorder
    2. Any autoimmune, connective tissue or inflammatory disorders with pulmonary involvement OR prior complete pneumonectomy
  3. Is receiving chronic systemic corticosteroids dosed at >10 mg/day prednisone or equivalent anti-inflammatory activity or any form of immunosuppressive therapy prior to enrollment
  4. Resting systolic blood pressure >180 mmHg or diastolic blood pressure >110 mmHg
  5. Prior or ongoing clinically relevant illness, medical condition, surgical history, physical finding, or laboratory abnormality that could affect the safety of the subject; alter the absorption, distribution, metabolism or excretion of the study drug; or confound the assessment of study results.

Inclusion

  • Your cancer has spread to other parts of the body.

Exclusion

  • You have been diagnosed with a prior or secondary type of cancer.
  • You have certain types of non-cancer medical conditions.
  • You have had certain treatments, surgical procedures or drugs.
  • You have previously been treated (or are currently being treated) on a clinical trial.
Message

Clinical trials have complex eligibility criteria.

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