Trial Title:
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
NCT ID:
NCT05537740
Condition:
Advanced Solid Tumors
Conditions: Official terms:
Neoplasms
Pembrolizumab
Conditions: Keywords:
Relapse
Immunooncology treatment
Non small cell lung cancer
NSCLC
HNSCC
Head and neck squamous cell carcinomas
Melanoma
TNBC
Triple negative breast cancer
Study type:
Interventional
Study phase:
Phase 1
Overall status:
Recruiting
Study design:
Allocation:
Non-Randomized
Intervention model:
Sequential Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
BAY3375968
Description:
Intravenous (IV) infusion
Arm group label:
Dose escalation - Arm 1A
Arm group label:
Dose escalation - Arm 1B
Arm group label:
Dose expansion - Arm 2A
Arm group label:
Dose expansion - Arm 2B
Intervention type:
Drug
Intervention name:
Pembrolizumab
Description:
IV infusion
Arm group label:
Dose escalation - Arm 1B
Arm group label:
Dose expansion - Arm 2B
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, 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.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
- Capable of giving signed informed consent.
- Has received, been intolerant to, or been ineligible for all treatment options
proven 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 in
heterosexual intercourse must agree to use methods of contraception.
- Female participants are eligible if they are not pregnant, not breastfeeding or not
a Woman of childbearing potential (WOCBP).
- Inclusion criterion for the dose-escalation: Individuals with histologically or
cytologically confirmed, advanced or metastatic solid tumors.
- Inclusion criteria for disease-specific combination expansion: Individuals with
histologically or cytologically confirmed Triple-negative breast cancer (TNBC),
Non-small cell lung cancer (NSCLC), Head and neck squamous cell carcinoma (HNSCC),
or melanoma.
- Inclusion criterion for the monotherapy-MoA expansion: Individuals with
histologically or cytologically confirmed NSCLC.
- Willingness and medical feasibility (as per Investigator assessment) to undergo
paired tumor biopsies with a non-significant risk.
Exclusion Criteria:
- A known additional malignancy that is progressing or has required active treatment
within 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 eligibility
criteria, from previous anticancer treatment, except for alopecia and skin
pigmentation.
- Uncontrolled intercurrent illness requiring systemic treatment or solid organ
transplant.
- Known hypersensitivity to study treatment or any drugs similar in structure or
class, including severe hypersensitivity (≥ Grade 3) to pembrolizumab and/or any of
its excipients.
- Any toxicity (Grade 3 or 4) related to prior immunotherapy leading to prior
treatment discontinuation.
- 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 any
evidence of clinically-active pneumonitis/ILD.
- HIV-infection with a history of Kaposi sarcoma and/or Multicentric Castleman
Disease.
- Known psychiatric or substance abuse disorder that would interfere with the
participant's ability to cooperate with the requirements of the study.
- History or current evidence of any condition, therapy, laboratory abnormality, or
other circumstance that might confound the results of the study or interfere with
the participant's participation for the full duration of the study, such that it is
not in the best interest of the participant to participate, in the opinion of the
treating Investigator.
- Any other history, condition, therapy, or uncontrolled intercurrent illness which
could in the opinion of the Investigator affect compliance with study requirements.
- New brain metastases on screening brain MRI/CT; previously treated brain metastases
that 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 of
study treatment.
- Diagnosis of immunodeficiency or current chronic systemic steroid therapy (in dosing
exceeding 10 mg daily of prednisone equivalent).
- Active autoimmune disease that has required systemic treatment in the past 2 years.
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
The University of Chicago Medical Center (UCMC)
Address:
City:
Chicago
Zip:
60637
Country:
United States
Status:
Recruiting
Facility:
Name:
University of North Carolina
Address:
City:
Chapel Hill
Zip:
27514
Country:
United States
Status:
Not yet recruiting
Facility:
Name:
Ohio State University
Address:
City:
Columbus
Zip:
43210
Country:
United States
Status:
Withdrawn
Facility:
Name:
START | San Antonio
Address:
City:
San Antonio
Zip:
78229-3307
Country:
United States
Status:
Recruiting
Facility:
Name:
South Texas Accelerated Research Therapeutics | START Rocky Mountain Region
Address:
City:
West Valley City
Zip:
84119
Country:
United States
Status:
Recruiting
Facility:
Name:
Antwerp University Hospital | Oncology Department
Address:
City:
Antwerpen
Zip:
2650
Country:
Belgium
Status:
Recruiting
Facility:
Name:
Ghent University Hospital | Drug Research Unit Department
Address:
City:
Gent
Zip:
9000
Country:
Belgium
Status:
Recruiting
Facility:
Name:
Universitair Ziekenhuis Leuven | Gasthuisberg Campus - General Medical Oncology
Address:
City:
Leuven
Zip:
3000
Country:
Belgium
Status:
Not yet recruiting
Facility:
Name:
CHU de Liège
Address:
City:
Liege
Zip:
4000
Country:
Belgium
Status:
Not yet recruiting
Facility:
Name:
Cross Cancer Institute
Address:
City:
Edmonton
Zip:
T6G 1Z2
Country:
Canada
Status:
Not yet recruiting
Facility:
Name:
Princess Margaret Cancer Centre
Address:
City:
Toronto
Zip:
M5G 2M9
Country:
Canada
Status:
Recruiting
Facility:
Name:
Guangdong Provincial People's Hospital
Address:
City:
Guangzhou
Zip:
510000
Country:
China
Status:
Not yet recruiting
Facility:
Name:
Jilin Cancer Hospital
Address:
City:
Changchun
Zip:
130000
Country:
China
Status:
Not yet recruiting
Facility:
Name:
LinYi Cancer Hospital (Linyi Tumor Hospital)
Address:
City:
Linyi
Zip:
276001
Country:
China
Status:
Not yet recruiting
Facility:
Name:
Institut Bergonié - Unicancer Nouvelle Aquitaine
Address:
City:
Bordeaux
Zip:
33076
Country:
France
Status:
Not yet recruiting
Facility:
Name:
Centre Oscar Lambret - Lille
Address:
City:
Lille Cedex
Zip:
59020
Country:
France
Status:
Not yet recruiting
Facility:
Name:
Institut de Cancérologie de l'Ouest - Saint Herblain
Address:
City:
Saint-Herblain
Zip:
44800
Country:
France
Status:
Not yet recruiting
Facility:
Name:
Institut Gustave Roussy - Hematologie
Address:
City:
Villejuif cedex
Zip:
94805
Country:
France
Status:
Not yet recruiting
Facility:
Name:
National University Hospital
Address:
City:
Singapore
Zip:
119074
Country:
Singapore
Status:
Recruiting
Facility:
Name:
National Cancer Center Singapore
Address:
City:
Singapore
Zip:
168583
Country:
Singapore
Status:
Recruiting
Facility:
Name:
OncoCare Cancer Centre | Gleneagles Medical Centre
Address:
City:
Singapore
Zip:
258499
Country:
Singapore
Status:
Not yet recruiting
Facility:
Name:
Universidad de Navarra - Clinica Universidad de Navarra (CUN) - Pamplona
Address:
City:
Pamplona
Zip:
31008
Country:
Spain
Status:
Not yet recruiting
Facility:
Name:
Hospital Universitari Vall d'Hebron - Vall d'Hebron Institut d'Oncologia (VHIO)
Address:
City:
Barcelona
Zip:
8035
Country:
Spain
Status:
Not yet recruiting
Facility:
Name:
Universidad de Navarra - Clinica Universidad de Navarra (CUN) - Madrid
Address:
City:
Madrid
Zip:
28027
Country:
Spain
Status:
Not yet recruiting
Facility:
Name:
Centro Integral Oncológico Clara Campal
Address:
City:
Madrid
Zip:
28050
Country:
Spain
Status:
Recruiting
Facility:
Name:
Royal Marsden NHS Trust (Surrey)
Address:
City:
Sutton
Zip:
SM2 5PT
Country:
United Kingdom
Status:
Recruiting
Facility:
Name:
The Christie NHS Foundation Trust - Christie Hospital
Address:
City:
Manchester
Zip:
M204BX
Country:
United Kingdom
Status:
Recruiting
Start date:
October 11, 2022
Completion date:
May 4, 2027
Lead sponsor:
Agency:
Bayer
Agency class:
Industry
Source:
Bayer
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05537740
https://clinicaltrials.bayer.com/
