check_circleStudy Completed

Cancers with HER2 expression

A first in human study of BAY2701439 to look at safety, how the body absorbs, distributes and excretes the drug, and how well the drug works in participants with advanced cancer expressing the HER2 protein

Trial purpose

In this study, researchers want to learn about the safety of drug BAY2701439 and how well the drug works in patients with advanced cancer that has the protein HER2 (Human Epidermal growth factor Receptor 2) and cannot be cured by currently available treatment options. The study will include patients with HER2 expressing breast, gastric (stomach) or gastroesophageal (stomach and esophagus) cancer, as well as other cancers that have HER2. Researchers want to find the best dose of BAY2701439 for patients and look at the way the body absorbs, distributes and excretes the drug.
The study drug is a type of therapy called a ‘targeted alpha therapy’ which uses an antibody to deliver a radioactive particle to cancer cells. BAY2701439 contains thorium-227 which emits radiation (a lot of energy that moves from one place to another with damaging effects). The thorium-227 in the drug is attached to an ‘antibody’ (large protein) that specifically binds to HER2 on the cancer cells and will emit its radiation in the form of alpha particles. The alpha particles are expected to damage the tumor cells and cause them to die, but spare surrounding tissue as alpha particles travel only very short distances in the body. This is the first study in humans for drug BAY2701439. Patients participating in this study will receive the drug by injection every 6 weeks a maximum 6 times. Observation after treatment last up to 3 years.

Key Participants Requirements

Sex

All

Age

18 - N/A

Trial summary

Enrollment Goal
14
Trial Dates
July 2020 - September 2023
Phase
Phase 1
Could I Receive a placebo
No
Products
Trastuzumab Corixetan (BAY2701439)
Accepts Healthy Volunteer
No

Where to participate

StatusInstitutionLocation
Recruiting
University of Texas MD Anderson Cancer CenterHouston, 77030, United States
Recruiting
Memorial Sloan-Kettering Cancer CenterNew York, 10022, United States
Recruiting
Johns Hopkins Hospital/Health SystemBaltimore, 21287, United States
Completed
Royal Marsden NHS Trust (Surrey)Sutton, SM2 5PT, United Kingdom
Recruiting
Washington University School of MedicineSt. Louis, 63110, United States
Completed
Southampton General HospitalSouthampton, SO16 6YD, United Kingdom

Primary Outcome

  • Dose escalation: Incidence of TEAEs including TESAEs
    TEAE: Treatment-emergent adverse event TESAE: Treatment-emergent serious adverse event
    date_rangeTime Frame:
    After first administration of study intervention up to 42 days after the last dose of study intervention
  • Dose escalation: Severity of TEAEs including TESAEs
    date_rangeTime Frame:
    After first administration of study intervention up to 42 days after the last dose of study intervention
  • Dose escalation: Frequency of DLTs at each dose level
    DLT:Dose limiting toxicity
    date_rangeTime Frame:
    Up to 42 days after first administration of study intervention on cycle 1 (42 days) day 1
  • Dose expansion: ORR by RECIST 1.1 based on Investigator review
    ORR: Objective response rate
    date_rangeTime Frame:
    Up to 12 months after End of treatment
  • Dose expansion: Frequency of TEAEs
    date_rangeTime Frame:
    After first administration of study intervention up to 42 days after the last dose of study intervention
  • Dose expansion: Severity of TEAEs
    date_rangeTime Frame:
    After first administration of study intervention up to 42 days after the last dose of study intervention

Secondary Outcome

  • Dose escalation: Recommended dose level(s) of BAY2701439 for the dose expansion cohorts
    The dose level(s) recommended for the dose expansion cohorts will be defined after evaluation of incidence and severity of TEAEs, PK, and ORR by RECIST 1.1, collected in the cycles of treatment during the dose escalation part of the study.
    date_rangeTime Frame:
    Maximum 6 cycles (each cycle is 42 days)
  • Dose escalation: Recommended treatment schedule of BAY2701439 for the dose expansion cohorts
    The treatment schedule recommended for the dose expansion cohorts will be defined after evaluation of incidence and severity of TEAEs, PK, and ORR by RECIST 1.1, collected in the cycles of treatment during the dose escalation part of the study.
    date_rangeTime Frame:
    Maximum 6 cycles (each cycle is 42 days)
  • Dose expansion: Recommended dose for further clinical development of BAY2701439
    The dose recommended for further clinical development will be defined after evaluation of incidence and severity of TEAEs, PK, and ORR by RECIST 1.1, collected in the cycles of treatment during the dose escalation and expansion parts of the study.
    date_rangeTime Frame:
    Maximum 6 cycles (each cycle is 42 days)
  • Cmax of thorium-227
    Cmax: Maximum observed exposure
    date_rangeTime Frame:
    Cycle 1 (42 days)
  • Cmax of radium-223
    Cmax: Maximum observed exposure
    date_rangeTime Frame:
    Cycle 1 (42 days)
  • Cmax of total antibody
    Cmax: Maximum observed exposure
    date_rangeTime Frame:
    Cycle 1 (42 days)
  • AUC(0-42 days) of thorium-227
    AUC: Area under the curve
    date_rangeTime Frame:
    Cycle 1 (42 days)
  • AUC(0-42 days) of radium-223
    AUC: Area under the curve
    date_rangeTime Frame:
    Cycle 1 (42 days)
  • AUC(0-42 days) of total antibody
    AUC: Area under the curve
    date_rangeTime Frame:
    Cycle 1 (42 days)

Trial design

A Phase 1 open-label, first-in-human, multi-center study to evaluate the safety, tolerability, pharmacokinetics and anti-tumor activity of thorium-227 labeled antibody-chelator conjugate BAY2701439, in participants with advanced HER2-expressing tumors
Trial Type
Interventional
Intervention Type
Drug
Trial Purpose
Treatment
Allocation
Non-randomized
Blinding
N/A
Assignment
Sequential Assignment
Trial Arms
4