A Study to Learn How Safe the Study Drug BAY 2416964 (AhR Inhibitor) in Combination With the Treatment Pembrolizumab is, How This Combination Affects the Body, the Maximum Amount That Can be Given, How it Moves Into, Through and Out of the Body and Its Action Against Advanced Solid Cancers in Adults

NCT ID: NCT04999202

Last Updated: 2025-02-10

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

TERMINATED

Clinical Phase

PHASE1

Total Enrollment

47 participants

Study Classification

INTERVENTIONAL

Study Start Date

2021-08-30

Study Completion Date

2025-01-20

Brief Summary

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Researchers are looking for a better way to treat advanced solid cancers including head and neck cancer, lung cancer and bladder cancer.

In some people with cancer a protein called Aryl Hydrocarbon Receptor (AhR) can prevent immune cells from fighting tumor cells. The study drug, BAY 2416964, is a small molecule which blocks the AhR allowing the body to use its immune response against the cancer cells. Researchers think that BAY 2416964 given together with a cancer treatment called pembrolizumab may help shrink tumors in people with cancer.

The main aims of this study are to find for BAY 2416964 in combination with pembrolizumab,

* how safe this drug combination is
* how it affects the body (also referred to as tolerability)
* the highest amount of BAY 2416964 that can be given in combination with pembrolizumab without too many side effects.

The researchers will also study the action of BAY 2416964 in combination with pembrolizumab against the cancer.

The participants in this study will get BAY 2416964 and pembrolizumab. BAY 2416964 will be given by mouth. Pembrolizumab will be given as an intravenous (IV) infusion. An IV infusion is given through a needle into a vein.

This study will have two parts. The first part will help find the most appropriate dose that can be given in the second part.

Each participant of the first, so called dose escalation part, will be assigned to one specific dose group for BAY 2416964. The amount of BAY 2416964 that is given changes step-wise from one group to the next. The dose of pembrolizumab will always be the same.

The participants of the second, so called dose expansion part, will receive the most appropriate dose of BAY 2416964 found in the first part.

During the study, the participants will receive the treatment in 3-week periods called cycles. In each cycle, the participants will in general get pembrolizumab once and BAY 2416964 in a daily schedule. These 3-week cycles will be repeated throughout the trial. The participants can take the study treatment until their cancer gets worse, until they have medical problems, or until they leave the trial. Participants will have around 4 visits in each cycle. Some of the visits can also be done via phone.

During the study, the study doctors and their team will:

* take blood and urine samples
* check if the participants' cancer has changed in size using computed tomography scans or magnetic resonance imaging scans of the participants' tumors
* check the participants' overall health
* ask the participants questions about how they are feeling and what adverse events they are having.

An adverse event is any medical problem that a participant has during a study. Doctors keep track of all adverse events that happen in studies, even if they do not think the adverse events might be related to the study treatments.

Detailed Description

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Conditions

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Advanced Solid Tumors

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

SEQUENTIAL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Dose escalation of BAY2416964

Six dose levels of BAY 2416964 (as determined in the first in human mono-therapy study of BAY2416964) are planned in combination with standard dose Pembrolizumab.

Group Type EXPERIMENTAL

BAY2416964

Intervention Type DRUG

Oral, twice or three times daily

Pembrolizumab

Intervention Type DRUG

Administered as a dose of 200 mg using a 30-minute IV infusion every 3 weeks

Dose expansion of BAY2416964 in tumor type specific cohort

To determine the RP2D of BAY2416964 in combination therapy with pembrolizumab. Participants will be enrolled in up to 3 tumor type-specific cohorts including relapsed/refractory non-small cell lung cancer (NSCLC), head and neck squamous cell carcinoma (HNSCC) and urothelial cancer.

Group Type EXPERIMENTAL

BAY2416964

Intervention Type DRUG

The highest dose determined safe in combination with pembrolizumab in the dose escalation part or a lower dose. More than one dose may be explored in the dose expansion.

Pembrolizumab

Intervention Type DRUG

Administered as a dose of 200 mg using a 30-minute IV infusion every 3 weeks

Interventions

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BAY2416964

Oral, twice or three times daily

Intervention Type DRUG

BAY2416964

The highest dose determined safe in combination with pembrolizumab in the dose escalation part or a lower dose. More than one dose may be explored in the dose expansion.

Intervention Type DRUG

Pembrolizumab

Administered as a dose of 200 mg using a 30-minute IV infusion every 3 weeks

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

* Participant must be ≥18 years of age inclusive, at the time of signing the informed consent.
* Participants with following histologically or cytologically confirmed advanced solid tumors that have progressed after treatment with all available therapies for metastatic disease that are known to confer clinically meaningful benefit, or are intolerant to treatment, or refuse standard treatment.

* Dose Escalation: all solid tumor types
* Tumor type-specific Expansion cohorts:

* NSCLC
* HNSCC with primary location in oropharynx, oral cavity, hypopharynx or larynx
* Urothelial Cancer
* Participants must have progressed on treatment with an anti-PD-1/L1 monoclonal antibody (mAb) administered either as monotherapy, or in combination with other checkpoint inhibitors or other therapies.
* Have measurable disease per RECIST 1.1
* Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1.

Exclusion Criteria

* Severe (Common terminology criteria for adverse events (CTCAE) v.5 Grade ≥ 3) infections within 4 weeks before the first study intervention administration
* Active autoimmune disease that has required systemic treatment in past 2 years
* Has a diagnosis of immunodeficiency or is receiving immunosuppressive therapy
* Has active Central nervous system (CNS) metastases and/or carcinomatous meningitis.
* Has a history of (non-infectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease.
* Cardiac disease as specified in the protocol
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Bayer

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Locations

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Florida Cancer Specialists

Altamonte Springs, Florida, United States

Site Status

Florida Cancer Specialists & Research Institute

Sarasota, Florida, United States

Site Status

Brigette Harris Cancer Pavilion at Henry Ford Cancer Center - Detroit

Detroit, Michigan, United States

Site Status

Sarah Cannon Research Institute

Nashville, Tennessee, United States

Site Status

Texas Oncology- Austin Midtown

Austin, Texas, United States

Site Status

Virginia Cancer Specialists, PC

Fairfax, Virginia, United States

Site Status

IRCCS Istituto Nazionale Tumori Fondazione Pascale - S. C. Sperimentazioni Cliniche

Napoli, Campania, Italy

Site Status

Fondazione IRCCS Istituto Nazionale dei Tumori - S. C. Oncologia Medica 1

Milan, Lombardy, Italy

Site Status

Istituto Europeo di Oncologia s.r.l - Sviluppo di nuovi farmaci per Terapie Innovative

Milan, Lombardy, Italy

Site Status

ASST Grande Ospedale Metropolitano Niguarda

Milan, Lombardy, Italy

Site Status

Humanitas Mirasole S.p.A. - Oncologia Medica ed Ematologia

Rozzano, Lombardy, Italy

Site Status

National University Hospital Medical Centre

Singapore, , Singapore

Site Status

Belfast City Hospital

Belfast, North Ireland, United Kingdom

Site Status

Freeman Hospital

Newcastle, Tyne and Wear, United Kingdom

Site Status

Countries

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United States Italy Singapore United Kingdom

Related Links

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https://clinicaltrials.bayer.com/

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Other Identifiers

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PN-A61

Identifier Type: OTHER

Identifier Source: secondary_id

2023-503547-33-00

Identifier Type: OTHER

Identifier Source: secondary_id

2020-003547-28

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

21343

Identifier Type: -

Identifier Source: org_study_id

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