account_circleRecruiting
Advanced solid tumors
Bayer Identifier:infoA unique number for a trial given by Bayer.
21820
ClinicalTrials.gov Identifier:infoA unique number for a trial given by United States government.
EudraCT Number:infoA unique reference for a trial given by European medical agency.
Not Available
EU CT Number:infoA unique reference for a trial given by European medical agency under EU Clinical Trial Regulation
2023-505594-32-00
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
Trial purpose
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.
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.
Key Participants Requirements
Sex
AllAge
18 - N/ATrial summary
Enrollment Goal info
354The overall number of participants needed for a trial.
Trial Dates info
October 2022 - May 2027Trial dates are when the trial starts and ends. If they are in the future, then they are estimates and can change before or during a trial.
Phase info
Phase 1A phase is a step in the research of a new treatment.
Could I Receive a placebo info
NoA “placebo” looks like a treatment but usually does not have any real treatment. A placebo is used to make sure the effects of a treatment that are seen in a trial are actually caused by that treatment.
Products info
BAY3375968A “product” can be any kind of drug, medical device, vaccine, or other treatment that is being studied in a trial.
Accepts Healthy Volunteer info
NoA healthy volunteer is a person who takes part in a trial but does not have a disease or condition. Usually, healthy volunteers are in Phase 1 trials.
Where to participate
Status | Institution | Location |
---|---|---|
Recruiting | Princess Margaret Cancer Centre | Toronto, M5G 2M9, Canada |
Recruiting | START | San Antonio | San Antonio, 78229-3307, United States |
Recruiting | The University of Chicago Medical Center (UCMC) | Chicago, 60637, United States |
Withdrawn | Ohio State University | Columbus, 43210, United States |
Recruiting | National Cancer Center Singapore | Singapore, 168583, Singapore |
Recruiting | National University Hospital Medical Centre | Singapore, 119074, Singapore |
Recruiting | South Texas Accelerated Research Therapeutics | START Rocky Mountain Region | West Valley City, 84119, United States |
Recruiting | Royal Marsden NHS Trust (Surrey) | Sutton, SM2 5PT, United Kingdom |
Recruiting | Ghent University Hospital | Drug Research Unit Department | Gent, 9000, Belgium |
Recruiting | Antwerp University Hospital | Oncology Department | Antwerpen, 2650, Belgium |
Recruiting | The Christie NHS Foundation Trust - Christie Hospital | Manchester, M204BX, United Kingdom |
Recruiting | Universitair Ziekenhuis Leuven | Gasthuisberg Campus - General Medical Oncology | Leuven, 3000, Belgium |
Not yet recruiting | CHU de Liège | Liege, 4000, Belgium |
Recruiting | Jilin Cancer Hospital | Changchun, 130000, China |
Recruiting | LinYi Cancer Hospital (Linyi Tumor Hospital) | Linyi, 276001, China |
Recruiting | Guangdong Provincial People's Hospital | Guangzhou, 510000, China |
Recruiting | Universidad de Navarra - Clinica Universidad de Navarra (CUN) - Madrid | Madrid, 28027, Spain |
Recruiting | Centro Integral Oncológico Clara Campal | Madrid, 28050, Spain |
Recruiting | Hospital Universitari Vall d'Hebron - Vall d'Hebron Institut d'Oncologia (VHIO) | Barcelona, 8035, Spain |
Not yet recruiting | OncoCare Cancer Centre | Gleneagles Medical Centre | Singapore, 258499, Singapore |
Not yet recruiting | University of North Carolina | Chapel Hill, 27514, United States |
Recruiting | Institut Bergonie - Unicancer Nouvelle Aquitaine - Service Oncologie medicale | Bordeaux, 33000, France |
Recruiting | Institut de Cancerologie Ouest - Saint Herblain - Oncologie medicale | Saint Herblain, 44800, France |
Recruiting | Institut Gustave Roussy - Departement d’Innovation Therapeutique et d’Essais Precoces (DITEP) | Villejuif Cedex, 94805, France |
Recruiting | Centre Oscar Lambret - Service Oncologie | Lille, 59000, France |
Not yet recruiting | Cross Cancer Institute, Clinical Trials Unit | Edmonton, T6G 1Z2, Canada |
Recruiting | Universidad de Navarra - Clinica Universidad de Navarra (CUN) - Pamplona | Pamplona, 31008, Spain |
Not yet recruiting | Zhejiang Cancer Hospital | Hangzhou, 310022, China |
Not yet recruiting | The Sixth Affiliated Hospital, Sun Yat-sen University | Guangzhou City, 510655, China |
Primary OutcomeinfoA primary outcome is the most important effect of a treatment that is measured in a trial. Most trials have one primary outcome measure, but some have more than one.
- Number of participants with treatment-emergent adverse events (TEAEs) categorized by severitydate_rangeTime Frame:First administration of study treatment up to 90 days after the last dose of study treatment
- Maximum tolerated dose (MTD) or Maximum administered dose (MAD)date_rangeTime Frame:Up to 21 days
- Number of participants experiencing dose-limiting toxicity (DLTs) at each dose level in the dose-escalation part of the studydate_rangeTime Frame:Up to 21 days
- Recommended dose for expansion (RDE)date_rangeTime Frame:Approximately 34 months
- Peak plasma concentration after drug administration (Cmax) of BAY3375968date_rangeTime Frame:Up to 21 days after first drug administration
- Area under the concentration–time curve (AUC) of BAY3375968date_rangeTime Frame:Up to 21 days after first drug administration
Secondary OutcomeinfoA secondary outcome is an effect of a treatment that is measured in a trial. A secondary outcome is less important than a primary outcome. But secondary outcomes are still important since they help researchers learn more about the effects of a treatment. Most clinical trials have more than one secondary outcome measure.
- Objective response rate (ORR)ORR (RECIST [Response Evaluation Criteria in Solid Tumors]) is defined as the proportion of participants with best overall response rating over the whole duration of the study of CR (complete response) or PR (partial response) according to RECIST 1.1 by Investigator assessment.date_rangeTime Frame:From start of treatment up to end of safety follow-up (90 days (±7 days) after the last administration of study treatment)
- Fold change in serum IFN (Interferon)-γ in on-treatment compared with baseline serum samplesdate_rangeTime Frame:Approximately 60 months
- Fold change in intratumor CD8+ T cell/Treg ratio in on-treatment compared with baseline tumor biopsiesdate_rangeTime Frame:Approximately 60 months
- Recommended Phase 2 dose (RP2D)date_rangeTime Frame:Approximately 60 months
Trial design
Trial Type info
InterventionalDescribes the nature of the clinical study.
Intervention Type info
DrugAn intervention is a drug, medical device, vaccine, or other treatment that is being studied in a trial or is already approved for all patients to use. An intervention can also include treatments like changing diet and exercise, or educating people about a health topic.
Trial Purpose info
TreatmentThe main reason the clinical trial is being done.
Allocation info
Non-randomizedAllocation is the way treatments are assigned to the people in the trial.
Blinding info
N/A“Blinding” means a person in a trial does not know what treatment they are using. Everyone in the trial knows which treatments they might get if they join the trial, but they do not always know which treatment they use during the trial.
Assignment info
Sequential AssignmentAn “assignment” is the way that people in a trial are assigned to use a treatment.
Trial Arms info
4A “trial arm” is a group of people in a trial. Each trial arm is assigned to use a specific treatment. Types of trial arms are: Experimental arm is a group assigned to use the treatment being studied in the trial Active comparator arm is a group assigned to use a treatment considered to be effective. The results of this group are compared to the results of the experimental arm. Placebo arm is a group assigned to use a placebo. A “placebo” looks like a treatment but usually does not have any real treatment. The results of this group are compared to the experimental arm. This helps make sure any effects that are seen in the experimental arm are actually caused by the main treatment being studied. No intervention arm is a group that is not assigned to use a treatment. The people in this group do not use any treatment during the trial.