HER2CLIMB-02/SGNTUC-016: Randomized, double-blind, phase 3 study of tucatinib or placebo in combination with ado-trastuzumab emtansine (T-DM1) for subjects with unresectable locally-advanced or metastatic HER2+ breast cancer
Indication :

Cancer du sein HER2-positif localement avancé ou métastatique non résécable


Sponsor :

Seattle Genetics


Phase :

III


Ligne :

première ou plus


Traitement :

tucatinib ou placebo en combinaison avec le T-DM1


Spécificités :
  • cancer du sein HER2-positif localement avancé ou métastatique histologiquement confirmé
  • non résécable

Site :

CHUV


Contact(s) :
Khalil Zaman
Investigateur Principal

CHUV
Département d'Oncologie

Rue du Bugon 46
Lausanne
1011

0213147905
khalil.zaman@chuv.ch

Primary objective :

Évaluation de l'efficacité et de la sécurité du tacatinib versus placebo en combinaison avec le T-DM1 chez des patients atteints d'un cancer du sein HER2-positif localement avancé ou métastatique non résécable.


Inclusion criteria :
  1. Histologically confirmed HER2+ metastatic breast carcinoma, as determined by sponsor-designated central laboratory testing on tumor tissue submitted prior to randomization
  2. History of prior treatment with a taxane and trastuzumab in any setting, separately or in combination. Prior pertuzumab therapy is allowed, but not required.
  3. Have progression of unresectable LA/M breast cancer after last systemic therapy (as confirmed by investigator), or be intolerant of last systemic therapy
  4. Measureable or non-measurable disease assessable by RECIST v1.1
  5. HR (estrogen receptor [ER]/ progesterone receptor [PR]) status must be known prior to randomization
  6. Age ≥18 years at time of consent
  7. ECOG performance status score of 0 or 1
  8. Life expectancy ≥6 months, in the opinion of the investigator
  9. Adequate hepatic function
  10. Adequate baseline hematologic parameters
  11. Estimated glomerular filtration rate (GFR) ≥50 mL/min/1.73 m2 using the Modification of Diet in Renal Disease (MDRD) study equation as applicable
  12. International normalized ratio (INR) and partial thromboplastin time (PTT)/activated partial thromboplastin time (aPTT) ≤ 1.5 X ULN, unless on medication known to alter INR and PTT/aPTT.
  13. Left ventricular ejection fraction (LVEF) ≥50% as assessed by echocardiogram (ECHO) or multi-gated acquisition scan (MUGA) documented within 4 weeks prior to first dose of study treatment

Exclusion criteria :
  1. Prior treatment with tucatinib, neratinib, afatinib, trastuzumab deruxtecan (DS-8201a), or any other investigational anti-HER2, anti-EGFR, or HER2 TKI agent. Prior treatment with lapatinib within 12 months of starting study treatment (except in cases where lapatinib was given for ≤21 days and was discontinued for reasons other than disease progression or severe toxicity)
  2. Prior treatment with T-DM1
  3. History of allergic reactions to trastuzumab or compounds chemically or biologically similar to tucatinib, except for Grade 1 or 2 infusion related reactions to trastuzumab that were successfully managed, or known allergy to any of the excipients in the study drugs
  4. Treatment with any systemic anti-cancer therapy (including hormonal therapy), non-CNS radiation, experimental agent or participation in another interventional clinical trial ≤3 weeks prior to first dose of study treatment. An exception for the washout of hormonal therapies is gonadotropin releasing hormone agonists used for ovarian suppression in premenopausal women, which are permitted concomitant medications.
  5. Any toxicity related to prior cancer therapies that has not resolved to ≤ Grade 1
  6. Clinically significant cardiopulmonary disease
  7. Known myocardial infarction or unstable angina within 6 months prior to first dose of study treatment
  8. Known carrier of Hepatitis B or Hepatitis C or has other known chronic liver disease
  9. Known to be positive for human immunodeficiency virus.
  10. Subjects who are pregnant, breastfeeding, or planning to become pregnant from time of informed consent until 7 months following the last dose of study drug
  11. Unable to swallow pills or has significant gastrointestinal disease which would preclude the adequate oral absorption of medications
  12. Use of a strong CYP3A4 or CYP2C8 inhibitor within 2 weeks, or use of a strong CYP3A4 or CYP2C8 inducer within 5 days prior to the first dose of study treatment. CYP3A4 or CYP2C8 inducers and inhibitors are also prohibited as concomitant medications within two weeks of discontinuation of tucatinib treatment. Use of sensitive CYP3A substrates should be avoided two weeks before enrollment and during study treatment.
  13. Unable to undergo contrast MRI of the brain
  14. Other medical, social, or psychosocial factors that, in the opinion of the investigator, could impact safety or compliance with study procedures
  15. Evidence within 2 years of the start of study treatment of another malignancy that required systemic treatment