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Dose escalation of BAY3375968 as monotherapy

Dose escalation of BAY 3375968 in combination with pembrolizumab

BAY3375968 monotherapy-mode-of-action (monotherapy-MoA) expansion in subjects with one of the following tumor types: NSCLC (PD-L1 tumor proportion score \[TPS\] ≥50%), TNBC (PD-L1 combined positive score \[CPS\] ≥10), HNSCC (PD-L1 CPS ≥20), or melanoma (no PD-L1 cut-off). The tumors should have primary (ICI-refractory) or secondary (ICI-relapsed) resistance to prior ICI-therapy. The final decision on the enrolled tumor type is at the discretion of the Sponsor.

Disease-specific combination expansion with separate cohorts in 4 ICI-relapsed tumor types (NSCLC, TNBC, HNSCC, and melanoma)

BAY3375968

Bayer Clinical Trials Contact

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, 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 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

First-in-human Dose-escalation and Expansion Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of the Anti-CCR8 Antibody BAY 3375968 as Monotherapy and in Combination With Pembrolizumab in Participants With Selected Advanced Solid Tumors

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.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.

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.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
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	NCT05537740	Advanced Solid ...	BAY3375968 Pembrolizumab	18 Years -	Bayer
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	NCT05537740	Advanced Solid ...	BAY3375968 Pembrolizumab	18 Years -	Bayer

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