General Information

Age Group

Adults

Status

Recruiting

Protocol Number

NCT06324357

Background Information

The purpose of this trial is to learn more about how zongertinib  works for people with advanced cancers. The trial drug will be given alone or in combination with other approved anti-cancer drugs, such as trastuzumab deruxtecan (T-DXd) and trastuzumab emtansine (T-DM1), and trastuzumab (with or without capecitabine).  

  • The use of zongertinib in this trial is experimental, which means that health authorities in your country have not approved the trial drug for medical use in your cancer type outside of clinical trial. Both T-DXd, T-DM1, trastuzumab and capecitabine are already approved for the treatment of breast cancer. T-DXd is also approved for use in people with stomach cancer. 

Trastuzumab is currently investigated in combination with chemotherapy and/or other targeted therapies for the trial treatment of bowel cancer. The trial drug will be given in cycles. Each cycle will last 21 days. The trial drug comes in the form of a tablet, which must be taken by mouth every day. Capecitabine is available as a tablet that will be taken by mouth, twice daily, from Days 1 to 14 of each cycle. T-DXd and T-DM1 and trastuzumab are given as a drip into your vein (an infusion), at the beginning of each cycle.  

For more information, please visit: https://clinicaltrials.gov/study/NCT06324357

Offered At

8081 Innovation Park Drive
Fairfax, VA 22031
Principal Investigator

Kathleen Harnden, MD

Eligibility Information

  • Patients ≥18 years of age or over the legal age of consent in countries where that is greater than 18 years at the time of signature of the informed consent form (ICF)
  • Cohorts A to K and Cohort O: Documented HER2+ mBC or mGEAC according to ASCO-CAP guidelines [R23-3591, R23-3707], for the respective cancer indication according to the result of local testing from the latest available biopsy.
  • Cohorts L (L-ext), M, and N (mCRC): Documented HER2 overexpression/amplification according to ASCO/CAP gastric cancer guidelines [R23-3591] and according to the result of local testing:
    • HER2 IHC 3+ by gastric algorithm, or
    • HER2 IHC 2+ and HER2 amplification by ISH, or
    • HER2 amplification in archival tissue by next generation 
      sequencing (NGS) assay (copy number ≥6), or
    • HER2 amplification in ctDNA by blood based NGS assay and investigator confirmation by IHC/ISH or tissue NGS prior to or in parallel with the screening process
  • For dose optimization and justification (Phase II): Patient must provide tumor tissue from locations not radiated prior to biopsy, if possible, collected through archival tissue
  • History of prior treatment lines in palliative setting:
    • For cohorts A, B, C, D, E, F, G, H, I, I-ext, J, J-ext, K and O documented investigator assessed progression after HER2-directed treatment for unresectable locally advanced or metastatic disease (For Cohorts D, H, I (I-ext), J (J-ext) - patients must have been pretreated with T-DXd and have progressed or have been intolerant to previous T-DXd).
    • For cohorts L, L-ext, M and N documented progression or recurrence of disease during or following their latest line of therapy. Patients must have had at least one prior line of therapy for locally advanced unresectable disease or metastatic disease (adjuvant and neoadjuvant therapy excluded) and documented disease progression or recurrence of disease during or following their latest line of therapy. In the opinion 
      of the Investigator, patients must be unlikely to tolerate or derive clinically meaningful benefit from further standard of care therapy known to prolong survival.

Ineligibility Information

  • Previous treatment with:
    • Any small molecule HER2 inhibitor in the palliative setting in Cohorts D, E, F, H, L, L-ext, M, and N. In Cohort D allowed in up to 15 patients in each DL.
    • T-DXd in Cohorts E and F. In Cohort E allowed in up to 15 patients in each DL.
    • T-DM1 in the palliative setting in Cohort D and H. In Cohort H allowed in up to 15 patients in each DL. 
    • Capecitabine in Cohort D and H. In Cohort D allowed in up to 15 patients in each DL
  • Presence of uncontrolled and/or symptomatic brain metastases, or leptomeningeal disease
  • Mean resting corrected QT interval (QTcF) >470 msec.
  • Any factors that increase the risk of QTc prolongation or risk of arrhythmic events such as heart failure, hypokalemia, congenital long QT syndrome, personal or family history of long QT syndrome or unexplained sudden death under 40 years-of-age.
  • Ejection fraction <50% or the lower limit of normal of the institutional standard within 28 days prior to randomization
  • History of (non-infectious) interstitial lung disease (ILD)/pneumonitis that required steroids, current ILD/pneumonitis, or where suspected ILD/pneumonitis cannot be ruled out by imaging at screening