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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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04147819
Recruitment Status : Not yet recruiting
First Posted : November 1, 2019
Last Update Posted : March 23, 2020
Sponsor:
Information provided by (Responsible Party):
Bayer

Brief 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. 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.


Condition or disease Intervention/treatment Phase
Cancers With HER2 Expression Drug: BAY2701439 Drug: BAY2701438 Phase 1

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 176 participants
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Estimated Study Start Date : March 30, 2020
Estimated Primary Completion Date : October 6, 2024
Estimated Study Completion Date : September 7, 2026

Arm Intervention/treatment
Experimental: Dose escalation of BAY2701439
The target population consists of participants with advanced HER2-expressing/amplified breast, gastric or gastroesophageal cancer.
Drug: BAY2701439
Intravenous (IV) injection on Day 1 of each cycle.The duration of each cycle will be 6 weeks (42 days).

Drug: BAY2701438
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).

Experimental: HER2 overexpressing breast cancer
Dose expansion of BAY2701439
Drug: BAY2701439
Intravenous (IV) injection on Day 1 of each cycle.The duration of each cycle will be 6 weeks (42 days).

Drug: BAY2701438
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).

Experimental: HER2 low expressing breast cancer
Dose expansion of BAY2701439
Drug: BAY2701439
Intravenous (IV) injection on Day 1 of each cycle.The duration of each cycle will be 6 weeks (42 days).

Drug: BAY2701438
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).

Experimental: Other HER2 overexpressing advanced carcinomas
Dose expansion of BAY2701439
Drug: BAY2701439
Intravenous (IV) injection on Day 1 of each cycle.The duration of each cycle will be 6 weeks (42 days).

Drug: BAY2701438
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).




Primary Outcome Measures :
  1. 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 ]
    TEAE: Treatment-emergent adverse event TESAE: Treatment-emergent serious adverse event

  2. Dose escalation: Severity of TEAEs including TESAEs [ Time Frame: 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 [ Time Frame: Up to 42 days after first administration of study intervention on cycle 1 (42 days) day 1 ]
    DLT:Dose limiting toxicity

  4. Dose expansion: ORR by RECIST 1.1 [ Time Frame: Up to 12 months after End of treatment ]
    ORR: Objective response rate

  5. Dose expansion: Frequency of TEAEs [ Time Frame: After first administration of study intervention up to 42 days after the last dose of study intervention ]
  6. Dose expansion: Severity of TEAEs [ Time Frame: After first administration of study intervention up to 42 days after the last dose of study intervention ]

Secondary Outcome Measures :
  1. Dose escalation: Recommended dose level(s) of BAY2701439 for the dose expansion cohorts [ Time Frame: Maximum 6 cycles (each cycle is 42 days) ]
    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.

  2. Dose escalation: Recommended treatment schedule of BAY2701439 for the dose expansion cohorts [ Time Frame: Maximum 6 cycles (each cycle is 42 days) ]
    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.

  3. Dose expansion: Recommended dose for further clinical development of BAY2701439 [ Time Frame: Maximum 6 cycles (each cycle is 42 days) ]
    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.

  4. Cmax of thorium-227 [ Time Frame: Cycle 1 (42 days) ]
    Cmax: Maximum observed exposure

  5. Cmax of radium-223 [ Time Frame: Cycle 1 (42 days) ]
    Cmax: Maximum observed exposure

  6. Cmax of total antibody [ Time Frame: Cycle 1 (42 days) ]
    Cmax: Maximum observed exposure

  7. AUC(0-42 days) of thorium-227 [ Time Frame: Cycle 1 (42 days) ]
    AUC: Area under the curve

  8. AUC(0-42 days) of radium-223 [ Time Frame: Cycle 1 (42 days) ]
    AUC: Area under the curve

  9. AUC(0-42 days) of total antibody [ Time Frame: Cycle 1 (42 days) ]
    AUC: Area under the curve



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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 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.

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

Exclusion Criteria:

  • 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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04147819


Contacts
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Contact: Bayer Clinical Trials Contact (+)1-888-84 22937 clinical-trials-contact@bayer.com

Locations
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United States, Maryland
Johns Hopkins Hospital/Health System
Baltimore, Maryland, United States, 21287
United States, New York
Memorial Sloan-Kettering Cancer Center
New York, New York, United States, 10022
United States, Texas
University of Texas MD Anderson Cancer Center
Houston, Texas, United States, 77030
United Kingdom
Royal Marsden NHS Trust (Surrey)
Sutton, Surrey, United Kingdom, SM2 5PT
Sponsors and Collaborators
Bayer

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Responsible Party: Bayer
ClinicalTrials.gov Identifier: NCT04147819    
Other Study ID Numbers: 19829
2019-001741-40 ( EudraCT Number )
First Posted: November 1, 2019    Key Record Dates
Last Update Posted: March 23, 2020
Last Verified: March 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided
Plan Description:

Availability of this study's data will 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.clinicalstudydatarequest.com 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 Study sponsors section of the portal.


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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Bayer:
Human epidermal growth factor receptor 2(HER2)
Targeted alpha therapy
Thorium-227