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Cancers With HER2 ExpressionPhase 1NCT04147819

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

A Phase 1 study testing BAY2701439 in people with Cancers With HER2 Expression, run by Bayer at 6 sites in 2 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Cancers With HER2 Expression
What is being tested?
BAY2701439
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
14 participants
Where
6 sitesin 2 countries
Study dates
2 Jul 2020to 26 Sep 2023
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Male or female participants at least 18 years of age on the day of signing informed consent.
  • Participants must meet the study phase-specific disease requirements:
  • Dose escalation:
  • Pathologically documented, HER2-expressing (IHC3+, 2+, or 1+ and/or ISH+), unresectable locally advanced or metastatic gastric, gastroesophageal, or breast cancer that has relapsed after standard treatment options, or for which no standard treatment is available. Participants with gastric or gastroesophageal cancer must not have had prior definitive radiotherapy. Participants in the dose escalation cohorts must have evaluable disease by RECIST 1.1, assessed by local imaging.
  • Dose expansion: Group A: Pathologically documented unresectable, locally advanced or metastatic breast cancer with HER2 overexpression or amplification (IHC3+ or IHC2+/ISH+) that has relapsed that has relapsed after standard treatment options, or for which no standard treatment is available.
  • Group B: Pathologically documented unresectable locally advanced or metastatic breast cancer with HER2 low expression (IHC2+/ISH-, IHC1+/ISH-, or IHC1+/ISH untested) that has relapsed after standard treatment options, or for which no standard treatment is available.
Show all 26Show fewer
  • Group C: Pathologically documented, unresectable locally advanced or metastatic carcinomas other than breast cancer with HER2 overexpression or amplification/mutation (IHC3+ or IHC2+/ISH+), that has relapsed after standard treatment options or for which no standard treatment is available.
  • Participants in the dose expansion cohorts must have measurable disease by RECIST 1.1, assessed by local imaging.
  • Availability of fresh or archival tumor samples - archival tumor samples obtained after disease progression on the most recent anti-cancer treatment may be accepted; those obtained prior to the last anti-cancer treatment may be accepted, upon agreement between the Sponsor and the Investigator.
  • Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0 or 1.
  • Life expectancy of at least 6 months, as estimated by the Investigator.
  • Adequate bone marrow, hepatic, and renal function, as assessed by the following laboratory requirements, to be conducted within 28 days before start of BAY2701439 administration:
  • Hemoglobin ≥ 9.0 g/dL
  • Absolute neutrophil count (ANC) ≥ 1500/mm*3
  • Platelet count ≥ 100,000/mm*3
  • Total bilirubin ≤ 1.5 X the upper limit of normal (ULN), except if confirmed history of Gilbert's disease
  • Alanine aminotransferase (ALT) and Aspartate aminotransferase (AST) ˂ 2.5 x ULN (≤ 5 x ULN for participants with liver involvement)
  • Participants on a stable dose of anti-coagulation therapy will be allowed to participate if they have no sign of bleeding or clotting, and Prothrombin time/International normalized ratio (PT/INR) and aPTT test results are compatible with the acceptable benefit-risk ratio at the Investigator's discretion
  • Serum creatinine ≤ 1.5 x ULN and glomerular filtration rate (GFR)≥ 45 mL/min/1.73 m*2, according to the Modified Diet in Renal Disease (MDRD)abbreviated formula.
  • A negative serum pregnancy test in women of childbearing potential (WOCBP) performed within 7 days before the start of BAY2701439 administration. Women and men of reproductive potential must agree to use highly effective methods of contraception, when sexually active, during the time period between signing the informed consent form until at least 6 months after the last administration of BAY2701439.
  • Male and/or female who meet the requirements for contraception and breastfeeding as follows:
  • Male participants: A male participant must agree to use highly effective contraception during the intervention period and for at least 6 months after intervention and refrain from donating sperm during this period.
  • Female participants: A female participant is eligible to participate if she is not pregnant (confirmed by a negative serum pregnancy test within 7 days of first study treatment), not breastfeeding, or is not a woman of childbearing potential.
  • Women of childbearing potential (WOCBP) must agree to use highly effective contraception during the intervention period and for at least 6 months after the last dose of study treatment.
  • Contraceptive use by men or women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.
  • Capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol

Who cannot join

  • Impaired cardiac function or clinically significant cardiac disease (i.e. congestive heart failure (CHF) New York Heart Association (NYHA) Class II, III or IV).
  • Left ventricular ejection fraction (LVEF) < 50% (as measured at screening by echocardiogram).
  • History or concurrent condition of interstitial lung disease/pneumonitis or severely impaired pulmonary function.
  • Participants known to be affected by genetic defects linked to radiation hypersensitivity, such as ataxia-telangiectasia (A-T; Online Mendelian Inheritance in Man [OMIM] #208900) and A-T-like disorder (meiotic recombination 11 homolog [MRE11]), Nijmegen breakage syndrome (OMIM #251260) and Nijmegen breakage Syndrome-like disorder (RAD50), Fanconi anemia (OMIM #227650), DNA ligase IV deficiency (OMIM #606593), RIDDLE syndrome (RNF168), radiosensitive severe combined immunodeficiency (RS-SCID), DNA-PK radiosensitive combined immunodeficiency (DNA-PK-RS-SCID), Cornelia de Lange syndrome.
  • History of Myelodysplastic syndrome (MDS)/treatment-related acute myeloid leukemia (t-AML) or with features suggestive of MDS/AML.
  • Infections of Common terminology criteria for adverse events (CTCAE) version 5.0 Grade 2 not responding to therapy or active clinically serious infections of CTCAE Grade >2.
  • History of hypersensitivity or severe infusion related reaction to any Trastuzumab-containing drug (e.g. trastuzumab, T-DM1) or any other ingredients contained in BAY2701439.
  • Chemotherapy, experimental cancer therapy, biologic therapy or immunotherapy within 4 weeks before start of BAY2701439 administration. Start of study treatment is allowed in shorter timeframes provided 5 half-lives of the prior drug(s) have elapsed before the start of BAY2701439 administration. Previous high-dose chemotherapy needing hematopoietic-stem-cell-rescue is prohibited.

Trial locations and contacts

6 sites in 2 countries.

6 sites in 2 countries

United States4 sites

  • Johns Hopkins Hospital/Health System

    Baltimore, Maryland, 21287

  • University of Texas MD Anderson Cancer Center

    Houston, Texas, 77030

  • Memorial Sloan-Kettering Cancer Center

    New York, New York, 10022

  • Washington University School of Medicine

    St Louis, Missouri, 63110

Other trials in United States

United Kingdom2 sites

  • Southampton General Hospital

    Southampton, Hampshire, SO16 6YD

  • Royal Marsden NHS Trust (Surrey)

    Sutton, Surrey, SM2 5PT

Other trials in United Kingdom

About this study

Official title: 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

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.

Being tested
BAY2701439
Keywords
Human epidermal growth factor receptor 2(HER2), Targeted alpha therapy, Thorium-227, HER2 low, HER2-low, HER2 positive, HER2-positive, HER2 expressing, HER2-expressing, Breast cancer, Gastric cancer
Medical subject headings
Breast Neoplasms, Stomach Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • BAY2701439Drug

    Intravenous (IV) injection on Day 1 of each cycle.The duration of each cycle will be 6 weeks (42 days).

  • BAY2701439Drug

    Intravenous (IV) injection on Day 1 of each cycle and 1 hour before the start of administration of BAY2701439. The duration of each cycle will be 6 weeks (42 days).

Study groups in NCT04147819
Study groupRoleWhat they receive
Dose escalation of BAY2701439ExperimentalThe target population consists of participants with advanced HER2-expressing/amplified breast, gastric or gastroesophageal cancer.
Receives: Drug: BAY2701439
HER2 overexpressing breast cancerExperimentalDose expansion of BAY2701439
Receives: Drug: BAY2701439
HER2 low expressing breast cancerExperimentalDose expansion of BAY2701439
Receives: Drug: BAY2701439
Other HER2 overexpressing advanced carcinomasExperimentalDose expansion of BAY2701439
Receives: Drug: BAY2701439

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Dose escalation: Incidence of TEAEs including TESAEs

    TEAE: Treatment-emergent adverse event TESAE: Treatment-emergent serious adverse event

    Measured: After first administration of study intervention up to 42 days after the last dose of study intervention

  2. Dose escalation: Severity of TEAEs including TESAEs

    Measured: After first administration of study intervention up to 42 days after the last dose of study intervention

  3. Dose escalation: Frequency of DLTs at each dose level

    DLT:Dose limiting toxicity

    Measured: Up to 42 days after first administration of study intervention on cycle 1 (42 days) day 1

  4. Dose expansion: ORR by RECIST 1.1 based on Investigator review

    ORR: Objective response rate

    Measured: Up to 12 months after End of treatment

  5. Dose expansion: Frequency of TEAEs

    Measured: After first administration of study intervention up to 42 days after the last dose of study intervention

  6. Dose expansion: Severity of TEAEs

    Measured: After first administration of study intervention up to 42 days after the last dose of study intervention

Secondary outcomes (9)

  1. 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.

    Measured: Maximum 6 cycles (each cycle is 42 days)

  2. 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.

    Measured: Maximum 6 cycles (each cycle is 42 days)

  3. 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.

    Measured: Maximum 6 cycles (each cycle is 42 days)

  4. Cmax of thorium-227

    Cmax: Maximum observed exposure

    Measured: Cycle 1 (42 days)

  5. Cmax of radium-223

    Cmax: Maximum observed exposure

    Measured: Cycle 1 (42 days)

  6. Cmax of total antibody

    Cmax: Maximum observed exposure

    Measured: Cycle 1 (42 days)

  7. AUC(0-42 days) of thorium-227

    AUC: Area under the curve

    Measured: Cycle 1 (42 days)

  8. AUC(0-42 days) of radium-223

    AUC: Area under the curve

    Measured: Cycle 1 (42 days)

  9. AUC(0-42 days) of total antibody

    AUC: Area under the curve

    Measured: Cycle 1 (42 days)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted1 Nov 2019
  2. Study start2 Jul 2020
  3. Primary completion21 Aug 2023
  4. Study completion26 Sep 2023

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Sequential
Masking
None (open label)
Enrolment
14 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04147819
Sponsor's protocol ID
19829
Other IDs
2019-001741-40, 2019
Status last verified
Sep 2024
First submitted
25 Oct 2019
Last updated
27 Sep 2024
Results posted
No
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No: Availability of this study's data will later be determined according to Bayer's commitment to the EFPIA/PhRMA "Principles for responsible clinical trial data sharing". This pertains to scope, timepoint and process of data access. As such, Bayer commits to sharing upon request from qualified researchers patient-level clinical trial data, study-level clinical trial data, and protocols from clinical trials in patients for medicines and indications approved in the US and EU as necessary for conducting legitimate research. This applies to data on new medicines and indications that have been approved by the EU and US regulatory agencies on or after January 01, 2014. Interested researchers can use www.vivli.org to request access to anonymized patient-level data and supporting documents from clinical studies to conduct research. Information on the Bayer criteria for listing studies and other relevant information is provided in the member section of the portal.

Publications

  • Anderson PM, Subbiah V, Trucco MM. Current and future targeted alpha particle therapies for osteosarcoma: Radium-223, actinium-225, and thorium-227. Front Med (Lausanne). 2022 Nov 15;9:1030094. doi: 10.3389/fmed.2022.1030094. eCollection 2022.

    PubMed 36457575

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing BAY2701439 in people with Cancers With HER2 Expression, run by Bayer at 6 sites in 2 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 26 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 27 Sep 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 6 sites in United States, United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Dose escalation: Incidence of TEAEs including TESAEs (time frame: After first administration of study intervention up to 42 days after the last dose of study intervention). The study lists 6 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04147819, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Sep 2024.

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