MC# 19-04 - Phase I Study of KN026 in HER2 Expressing Breast Cancer, Gastric/Gastroesophageal Junction Cancer and other Locally Advanced/Metastatic Solid Tumors

  • Agent(s): KN026
  • Disease Type(s): Solid Tumor
  • Phase(s): I
  • Drug Classification(s): Bispecific Antibodies
  • Molecular Target(s): ERBB2 (HER2)

Mechanism of Action

KN026 is an anti-HER2 Fc-based heterodimer bispecific antibody that can simultaneously bind two non-overlapping epitopes of HER2, leading to a dual HER2 signal blockade.


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

  • How much of KN026 can be given with an acceptable level of side effects
  • The effects of KN026 (good and bad)
  • How fast KN026 is removed from the body
  • How the body’s immune system reacts to KN026
  • If research tests can be used in the future to predict who will benefit from KN026
Inclusion Criteria
  • Histologically/cytologically confirmed, locally advanced unresectable or metastatic solid tumors that are refractory to or ineligible for standard therapy, or for which no standard therapy exists. In this protocol, HER2 expressing is defined as HER2 expression of ≥ 1+ determined by validated IHC and HER2 positive that is determined by IHC (3+ or 2+ with positive ISH), HER2 amplification determined by NGS, or ISH +.
    • Breast cancer patients should have progressed after 2 lines of prior treatment with HER2 targeted therapy (Herceptin or Perjeta or Kadcyla, or Lapatinib, or tyrosine kinase inhibitors)
    • Gastric cancer / gastroesophageal junction cancer patients should have progressed after Herceptin in combination with capecitabine and platinum-based treatment or fluoropyrimidine-based treatment
  • Must have adequate organ function, prior to start of KN026, including the following:
    • Bone marrow reserve: absolute neutrophil count (ANC) ≥ 1.0 ×109/L; platelet count ≥ 100 × 109/L; hemoglobin ≥ 9 g/dL or ≥ 5.6 mmol/L
    • Hepatic: total bilirubin ≤ 1.5 times the upper limit of normal (ULN), aspartate transaminase (AST) and/or alanine aminotransferase (ALT) ≤ 3 × ULN (≤5 × ULN if with liver involvement)
    • Renal: serum creatinine ≤1.5 times the ULN or estimated creatinine clearance ≥50 mL/min
    • Coagulation tests prothrombin time (PT), activated partial thromboplastin time (aPTT) ≤ 1.5 × ULN
  • Left ventricular ejection fraction (LVEF) should be within the normal limits of the institution's specific testing
  • Able to provide a fresh formalin-fixed, paraffin-embedded (FFPE) tumor sample for evaluation of HER2 status or an archived tumor biopsy sample
  • Subjects (women of child-bearing potential and males with fertile female partner) must be willing to use viable contraception method
  • According to RECIST1.1, the subject should have an assessable lesion (target lesion or non-target lesion)
  • ECOG score 0 or 1
  • Other criteria required by the protocol
Exclusion Criteria
  • Accepted any other anti-tumor drug therapies, and they are still within 5 half-lives before the first KN026 dosing
  • Any treatment with Trastuzumab, Pertuzumab, Lapatinib, Kadcyla (T-DM1) or tyrosine kinase inhibitors targeted for HER2 within 4 weeks before first KN026 dosing
  • Subject with primary central nervous system (CNS) malignancy or symptomatic CNS or leptomeningeal metastases are not allowed. Subjects with asymptomatic CNS metastases are eligible if clinically controlled, which is defined as ≥8 weeks of stable neurologic function following CNS-directed therapy, and no evidence of CNS disease progression as determined by radiographic imaging ≥ 4 weeks prior to screening. No interim progression between the completion of CNS-directed therapy 2 weeks or more from the screening tumor assessment.
  • History of ≥10% absolute point fall in left ventricular ejection fraction (LVEF) from pretreatment value after receiving HER2 inhibitor treatment in the past, and with resultant LVEF that is below the lower limit of normal for the institution
  • Acute or chroic uncontrolled renal disease, pancreatitis or liver disease (per investigator assessment)
  • Peripheral neuropathy ≥ Grade 3
  • Clinically significant interstitial lung disease or history of treatment emergent interstitial lung disease after HER2 inhibitor treatment
  • Human immunodeficiency virus (HIV) positive
  • Active hepatitis B or C. HBV carriers without active disease or cured Hepatitis C may be enrolled.
  • Subjects with any type of primary immunodeficiencies will be excluded from the study
  • Use of more than 15 mg of prednisone or equivalent dose of steroids per day within 3 months of the initial administration
  • Severe or uncontrolled cardiac disease requiring treatment, congestive heart failure NYHA III or IV, unstable angina pectoris even if medically controlled, history of myocardial infarction during the last 6 months, ECG QTcB (Bazetts) > 450 msec, serious arrhythmias requiring medication (with exception of atrial fibrillation or paroxysmal supraventricular tachycardia)
  • Hypertension
  • Current dyspnea at rest due to complications of advanced malignancy, or other diseases requiring continuous oxygen therapy
  • Other criteria required by the protocol


  • Dallas, TX - Mary Crowley Cancer Research - Medical City
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Re: MC# 19-04