A First-in-human Study to Learn How Safe the Study Drug BAY3375968, an Anti-CCR8 Antibody, is, When Given Alone or in Combination With Pembrolizumab, How it Affects the Body, How it Moves Into, Through, and Out of the Body, and to Find the Best Dose in Participants With Advanced Solid Tumors

Last updated: June 26, 2025
Sponsor: Bayer
Overall Status: Active - Recruiting

Phase

1

Condition

Neoplasms

Treatment

Pembrolizumab

BAY3375968

Clinical Study ID

NCT05537740
21820
  • Ages > 18
  • All Genders

Study Summary

Researchers are looking for a better way to treat people who have advanced solid tumors. Advanced solid tumors are solid cancers that may have spread to nearby tissue, lymph nodes and/or to distant parts of the body and that are unlikely to be cured or controlled with currently available treatments.

A new therapy available for advanced solid cancers is immunotherapy with PD-1/PD-L1 inhibitors. This drug class stimulates immune cells to kill cancer cells by blocking a protein called PD-1. Although PD-1/PD-L1 inhibitors have shown benefits in treatment of cancer, only a subset of patients benefit from the initial therapy, while in others the cancer comes back. One reason could be that the ability of the patients' immune systems to kill cancer cells is weakened by so-called regulatory T cells which have a suppressive effect on the immune system.

The study treatment BAY3375968 is an antibody that binds to a protein called CCR8 which is located on the surface of regulatory T cells. This leads to a reduction in regulatory T cells and further inhibits their immune suppressive activity, so that the immune response against cancer can be strengthened as observed in animal models. Animal studies also showed that BAY3375968 may add more anti-cancer effect to immunotherapy with PD-1/PD-L1 inhibitors when used in combination. All of these previous observations need to be confirmed in humans.

The main aims of this study are to find for BAY3375968 alone and in combination with pembrolizumab (a PD-1 inhibitor):

  • how safe it is

  • the degree to which overt medical problems caused by the treatment(s) can be tolerated

  • the highest amount of BAY3375968 that can be given alone or in combination with pembrolizumab.

  • how it moves into, through, and out of the body.

To do this, researchers will collect and analyze data about:

  • the number and severity of participants' medical problems after taking their treatments

  • the best dose of BAY3375968 that can be given

  • the highest level in the blood (Cmax) and the total level (AUC) of BAY3375968.

Doctors keep track of all medical problems (also called adverse events) that participants have during the study, even if they do not think that they might be related to the study treatment.

The researchers will also study the activity of BAY3375968 alone and in combination with pembrolizumab against the cancer.

The study will have 2 parts. Part 1 (dose escalation) focuses on tumor types that respond to immunotherapy. It will help to find the best dose for BAY3375968 alone and in combination with pembrolizumab that can be given in part 2. For this, the participants will receive one specific dose of several increasing BAY3375968 doses tested in part 1. Dose escalation of BAY3375968 alone will be done prior to the dose escalation of the combination with a fixed dose of pembrolizumab.

The participants of part 2 (dose expansion), will receive the best dose of BAY3375968 alone or in combination with pembrolizumab found in part 1. This part of the study focuses on certain cancer types of the lung, breast, head and neck cancer, gastric cancer and melanoma.

The total duration of the study will be approximately 4 years and 7 months. Each participant in the study will visit the study site twice before starting their treatment. Once the treatment starts, the frequency of visits is 5 times per week in the first treatment week and 1 to 3 times per month in later treatment periods. Another visit will be scheduled for the participants within 30 days after the last treatment in the study.

During the study, the study team will:

  • take blood and urine samples

  • do physical and vital signs examinations

  • examine heart health using ECG and Echocardiogram

  • check the tumor status and if the participants' cancer has grown and/or spread using imaging techniques

  • take tumor samples

  • ask questions about the impact of the disease on the participants' general well-being and activities of daily life.

About 90 days after the participants receive their last treatment and discontinued the study, the doctors will check the participants' health. In case a new anticancer therapy has been started, medical problems will be recorded via a phone call.

The study team will continue to check the participants' cancer status about every 12 weeks until their cancer gets worse, the start of a new anti-cancer therapy, or withdrawal of consent. In addition, every 6 months for up to 24 months after the last participant left the study the study team will check the participants' survival and subsequent anticancer treatment by phone until the end of this study.

Eligibility Criteria

Inclusion

Inclusion Criteria:

  • Capable of giving signed informed consent.

  • Has received, been intolerant to, or been ineligible for all treatment optionsproven to confer clinical benefit.

  • Measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1.

  • Eastern Cooperative Oncology Group (ECOG) Performance status (PS) of 0 or 1.

  • Adequate renal and liver function.

  • Male individuals and female individuals of childbearing potential who engage inheterosexual intercourse must agree to use methods of contraception.

  • Female participants are eligible if they are not pregnant, not breastfeeding or nota Woman of childbearing potential (WOCBP).

  • Inclusion criterion for the dose-escalation: Individuals with histologically orcytologically confirmed, advanced or metastatic solid tumors.

  • Inclusion criteria for disease-specific combination expansion: Individuals withhistologically or cytologically confirmed triple-negative breast cancer (TNBC),non-small cell lung cancer (NSCLC), gastric cancer, melanoma, or head and necksquamous cell carcinoma (HNSCC).

  • Inclusion criterion for the monotherapy-MoA expansion: Individuals withhistologically or cytologically confirmed NSCLC, TNBC, HNSCC, or melanoma.

  • Willingness and medical feasibility (as per Investigator assessment) to undergopaired tumor biopsies with a non-significant risk.

Exclusion

Exclusion Criteria:

  • A known additional malignancy that is progressing or has required active treatmentwithin the past 3 years.

  • Primary central nervous system malignancy.

  • Major surgery ≤ 28 days before start of study treatment.

  • Any unresolved toxicity of Grade ≥ 2, not otherwise specified in other eligibilitycriteria, from previous anticancer treatment, except for alopecia and skinpigmentation.

  • Uncontrolled intercurrent illness requiring systemic treatment or solid organtransplant.

  • Known hypersensitivity to study treatment or any drugs similar in structure orclass, including severe hypersensitivity (≥ Grade 3) to pembrolizumab and/or any ofits excipients.

  • Any prior immune-related toxicity (Grade 3 or 4) leading to discontinuation ofimmunotherapy.

  • History of congestive heart failure New York Heart Association (NYHA) >II.

  • Medical history of (non-infectious) pneumonitis/interstitial lung disease (ILD),drug-induced ILD, radiation pneumonitis which required steroid treatment, or anyevidence of clinically-active pneumonitis/ILD.

  • HIV-infection with a history of Kaposi sarcoma and/or Multicentric CastlemanDisease.

  • Known psychiatric or substance abuse disorder that would interfere with theparticipant's ability to cooperate with the requirements of the study.

  • History or current evidence of any condition, therapy, laboratory abnormality, orother circumstance that might confound the results of the study or interfere withthe participant's participation for the full duration of the study, such that it isnot in the best interest of the participant to participate, in the opinion of thetreating Investigator.

  • Any other history, condition, therapy, or uncontrolled intercurrent illness whichcould in the opinion of the Investigator affect compliance with study requirements.

  • New brain metastases on screening brain MRI/CT; previously treated brain metastasesthat are progressive at screening or leptomeningeal disease.

  • Prior therapy with a C-C motif chemokine receptor 8 (CCR8) depleting antibody.

  • Prior allogeneic tissue/solid organ transplant.

  • Radiation therapy to the lung that is > 30 Gy within 6 months before the start ofstudy treatment.

  • Diagnosis of immunodeficiency or current chronic systemic steroid therapy (in dosingexceeding 10 mg daily of prednisone equivalent).

  • Active autoimmune disease that has required systemic treatment in the past 2 years.

Study Design

Total Participants: 354
Treatment Group(s): 2
Primary Treatment: Pembrolizumab
Phase: 1
Study Start date:
October 11, 2022
Estimated Completion Date:
May 04, 2027

Connect with a study center

  • Antwerp University Hospital | Oncology Department

    Antwerpen, 2650
    Belgium

    Active - Recruiting

  • UZ Antwerpen

    Edegem, 2650
    Belgium

    Site Not Available

  • Ghent University Hospital | Drug Research Unit Department

    Gent, 9000
    Belgium

    Active - Recruiting

  • UZ Gent

    Gent, 9000
    Belgium

    Site Not Available

  • UZ Leuven - Neurology department

    Leuven, 3000
    Belgium

    Site Not Available

  • UZ Leuven Gasthuisberg

    Leuven, 3000
    Belgium

    Site Not Available

  • Universitair Ziekenhuis Leuven | Gasthuisberg Campus - General Medical Oncology

    Leuven, 3000
    Belgium

    Active - Recruiting

  • CHU de Liège

    Liege, 4000
    Belgium

    Site Not Available

  • Cross Cancer Institute

    Edmonton, Alberta T6G 1Z2
    Canada

    Site Not Available

  • Cross Cancer Institute, Clinical Trials Unit

    Edmonton, Alberta T6G 1Z2
    Canada

    Site Not Available

  • Princess Margaret Cancer Centre

    Toronto, Ontario M5G 2M9
    Canada

    Active - Recruiting

  • Guangdong Provincial People's Hospital

    Guangzhou, Guangdong 510000
    China

    Active - Recruiting

  • The Sixth Affiliated Hospital, Sun Yat-sen University

    Guangzhou, Guangdong 510655
    China

    Site Not Available

  • The Sixth Affiliated Hospital, Sun Yat-sen University

    Guangzhou City, Guangdong 510655
    China

    Site Not Available

  • Jilin Cancer Hospital

    Changchun, Jilin 130000
    China

    Active - Recruiting

  • Zhejiang Cancer Hospital

    Hangzhou, Zhejiang 310022
    China

    Site Not Available

  • LinYi Cancer Hospital (Linyi Tumor Hospital)

    Linyi, 276001
    China

    Active - Recruiting

  • Institut Bergonie - Unicancer Nouvelle Aquitaine - Service Oncologie medicale

    Bordeaux, 33000
    France

    Active - Recruiting

  • Institut Bergonié - Unicancer Nouvelle Aquitaine

    Bordeaux, 33076
    France

    Site Not Available

  • Centre Oscar Lambret - Service Oncologie

    Lille, 59000
    France

    Active - Recruiting

  • Centre Oscar Lambret - Lille

    Lille Cedex, 59020
    France

    Site Not Available

  • Institut de Cancerologie Ouest - Saint Herblain - Oncologie medicale

    Saint Herblain, 44800
    France

    Active - Recruiting

  • Institut de Cancerologie Ouest - Saint-Herblain

    Saint-Herblain, 44800
    France

    Site Not Available

  • Institut de Cancérologie de l'Ouest - Saint Herblain

    Saint-Herblain, 44800
    France

    Site Not Available

  • Institut Gustave Roussy - Departement d'Innovation Therapeutique et d'Essais Precoces (DITEP)

    Villejuif Cedex, 94805
    France

    Active - Recruiting

  • Institut Gustave Roussy - Hematologie

    Villejuif cedex, 94805
    France

    Active - Recruiting

  • National Cancer Center Singapore

    Singapore, 168583
    Singapore

    Active - Recruiting

  • National University Hospital

    Singapore, 119074
    Singapore

    Active - Recruiting

  • National University Hospital Medical Centre

    Singapore, 119074
    Singapore

    Active - Recruiting

  • OncoCare Cancer Centre

    Singapore, 258499
    Singapore

    Site Not Available

  • OncoCare Cancer Centre | Gleneagles Medical Centre

    Singapore, 258499
    Singapore

    Site Not Available

  • Universidad de Navarra - Clinica Universidad de Navarra (CUN) - Pamplona

    Pamplona, Navarra 31008
    Spain

    Active - Recruiting

  • Hospital Universitari Vall d'Hebron - Vall d'Hebron Institut d'Oncologia (VHIO)

    Barcelona, 8035
    Spain

    Active - Recruiting

  • Hospital San Pedro

    Logrono, 26006
    Spain

    Site Not Available

  • Centro Integral Oncológico Clara Campal

    Madrid, 28050
    Spain

    Active - Recruiting

  • Universidad de Navarra - Clinica Universidad de Navarra (CUN) - Madrid

    Madrid, 28027
    Spain

    Active - Recruiting

  • Royal Marsden NHS Trust (Surrey)

    Sutton, Surrey SM2 5PT
    United Kingdom

    Active - Recruiting

  • The Christie NHS Foundation Trust - Christie Hospital

    Manchester, M204BX
    United Kingdom

    Active - Recruiting

  • The University of Chicago

    Chicago, Illinois 60637
    United States

    Active - Recruiting

  • The University of Chicago Medical Center (UCMC)

    Chicago, Illinois 60637
    United States

    Active - Recruiting

  • The University of Chicago Medical Center - Hyde Park - Hematology & Oncology

    Chicago, Illinois 60637
    United States

    Active - Recruiting

  • University of Chicago

    Chicago, Illinois 60637
    United States

    Active - Recruiting

  • University of North Carolina

    Chapel Hill, North Carolina 27514
    United States

    Site Not Available

  • Ohio State University

    Columbus, Ohio 43210
    United States

    Site Not Available

  • The Ohio State University - Arthur G James Cancer Hospital and Richard J Solove Research Institute

    Columbus, Ohio 43210
    United States

    Site Not Available

  • START | San Antonio

    San Antonio, Texas 78229
    United States

    Active - Recruiting

  • South Texas Accelerated Research Therapeutics | START San Antonio

    San Antonio, Texas 78229-3307
    United States

    Active - Recruiting

  • South Texas Accelerated Research Therapeutics | START Rocky Mountain Region

    West Valley City, Utah 84119
    United States

    Active - Recruiting

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