MC# 20-37 - Phase II, Single-arm, Open-label Study of DS-1062a in Advanced or Metastatic Non-small Cell Lung Cancer with Actionable Genomic Alterations and Progressed On or After Kinase Inhibitor Therapy and Platinum-based Chemotherapy

  • Agent(s): DS-1062a
  • Disease Type(s): Lung-NSCLC
  • Phase(s): II
  • Drug Classification(s): Antibody Drug Conjugate
  • Molecular Target(s): TROP2

Mechanism of Action

DS-1062a targets and binds to TROP2 expressed on tumor cells. Upon cellular uptake and lysosomal degradation of the linker, DXd targets and binds to DNA topoisomerase I, thereby stabilizing the cleavable complex between topoisomerase I and DNA, resulting in DNA breaks, inhibition of DNA replication and apoptosis.  This inhibits tumor cell proliferation of TROP2-expressing tumor cells.

Purpose

In this study, the sponsor and investigators want to learn:

  • If DS-1062a prevents or delays tumor growth or shrinks existing tumors
  • About the safety and tolerability of DS-1062a
  • How proteins that indicate the status of your disease are affected with use of DS-1062a
  • How quickly DS-1062a is removed from your bloodstream
  • If research tests can be used in the future to predict who will benefit from DS-1062a
Inclusion Criteria
  1. Sign and date the inform consent form (ICF) prior to the start of any study-specific qualification procedures
  2. Adults ≥18 years (if the legal age of consent is >18 years old, then follow local regulatory requirements)
  3. Has pathologically documented NSCLC that:
    1. Has stage IIIB or stage IV NSCLC disease at the time of enrollment (based on the American Joint Committee on Cancer, Eighth Edition)
    2. Has one or more of the following documented activating genomic alterations: EGFR, ALK, ROS1, NTRK, BRAF, MET exon 14 skipping, or RET
  4. Overexpression of any of the above, in the absence of activating mutations, is NOT sufficient for enrollment
  5. Participants with EGFR genomic alterations should be evaluated for the presence of EGFR T790M mutation after relapse/progression on/after the most recent anti-EGFR TKI, unless already known to carry this mutation.  Participants with EGFR mutations (regardless of T790M status) should comprise no less than 40% and no more than 50% of participants by the conclusion of study enrollment.
  6. Has documentation of radiographic disease progression while on or after receiving the most recent treatment regimen for advanced or metastatic NSCLC
  7. Participant must meet at least the following for advanced or metastatic NSCLC:
    1. Has progressed on or after at least one kinase inhibitor as specified in the study protocol
    2. Has progressed on or after at least 1 regimen of platinum-based chemotherapy
  8. Up to 4 prior lines of therapy are allowed to be eligible for this study
  9. Willing and able to undergo a mandatory pre-treatment tumor biopsy
  10. Measurable disease based on local imaging assessment using RECIST v1.1
  11. Eastern Cooperative Oncology Group performance status (ECOG PS) of 0 – 1 at screening
Exclusion Criteria
  1. 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.
  2. Has leptomeningeal carcinomatosis
  3. Has prior treatment with:
    1. Any agent including antibody drug conjugate (ADC) containing a chemotherapeutic agent targeting topoisomerase I
    2. TROP2-targeted therapy
  4. Uncontrolled or significant cardiovascular disease:
    1. History of myocardial infarction within 6 months prior to Cycle 1 Day 1
    2. History of uncontrolled angina pectoris within 6 months prior to Cycle 1 Day 1
    3. Symptomatic congestive heart failure (CHF) (New York Heart Association Class II to IV) at screening.  Participants with a history of Class II to IV CHF prior to screening must have returned to Class I CHF and have LVEF ≥50% (by either an ECHO or MUGA scan within 28 days of Cycle 1 Day 1) in order to be eligible.
    4. History of serious cardiac arrhythmia requiring treatment
    5. LVEF <50% or institutional lower limit of normal by ECHO or MUGA scan
    6. Uncontrolled hypertension (resting systolic blood pressure >180 mmHg or diastolic blood pressure >110 mmHg)
  5. Has a history of (non-infectious) interstitial lung disease (ILD)/pneumonitis that required steroids, has current ILD/pneumonitis, or where suspected ILD/pneumonitis cannot be ruled out by imaging at screening
  6. Clinically severe pulmonary compromise resulting from intercurrent pulmonary illnesses
  7. Clinically significant corneal disease
  8. Has other primary malignancies, except adequately resected nonmelanoma skin cancer, curatively treated in situ disease, or other solid tumors curatively treated, with no evidence of disease for ≥3 years
  9. Has a history of severe hypersensitivity reactions to either the drug substances or inactive ingredients (including but not limited to polysorbate 80) of DS-1062a
  10. Has a history of severe hypersensitivity reactions to other monoclonal antibodies

Location

  • Dallas, TX - Mary Crowley Cancer Research - Medical City
More Info: https://clinicaltrials.gov/ct2/show/NCT04484142

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Re: MC# 20-37