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

February 7, 2025 updated by: Bayer

An Open-label, Phase 1b, Dose Escalation and Expansion Study to Evaluate the Safety, Tolerability, Maximum Tolerated or Administered Dose, Pharmacokinetics, Pharmacodynamics and Efficacy of the Aryl Hydrocarbon Receptor Inhibitor (AhRi) BAY 2416964 in Combination With Pembrolizumab in Participants With Advanced Solid Tumors

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.

Study Overview

Status

Terminated

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

47

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Italy
    • Campania
      • Napoli, Campania, Italy, 80131
        • IRCCS Istituto Nazionale Tumori Fondazione Pascale - S. C. Sperimentazioni Cliniche
    • Lombardia
      • Milano, Lombardia, Italy, 20162
        • ASST Grande Ospedale Metropolitano Niguarda
      • Milano, Lombardia, Italy, 20133
        • Fondazione IRCCS Istituto Nazionale dei Tumori - S. C. Oncologia Medica 1
      • Milano, Lombardia, Italy, 20141
        • Istituto Europeo di Oncologia s.r.l - Sviluppo di nuovi farmaci per Terapie Innovative
      • Rozzano, Lombardia, Italy, 20089
        • Humanitas Mirasole S.p.A. - Oncologia Medica ed Ematologia
  • Singapore
      • Singapore, Singapore, 119074
        • National University Hospital Medical Centre
  • United Kingdom
    • North Ireland
      • Belfast, North Ireland, United Kingdom, BT12 7AB
        • Belfast City Hospital
    • Tyne And Wear
      • Newcastle, Tyne And Wear, United Kingdom, NE7 7DN
        • Freeman Hospital
  • United States
    • Florida
      • Altamonte Springs, Florida, United States, 32701
        • Florida Cancer Specialists
      • Sarasota, Florida, United States, 34232
        • Florida Cancer Specialists & Research Institute
    • Michigan
      • Detroit, Michigan, United States, 48202
        • Brigette Harris Cancer Pavilion at Henry Ford Cancer Center - Detroit
    • Tennessee
      • Nashville, Tennessee, United States, 37203
        • Sarah Cannon Research Institute
    • Texas
      • Austin, Texas, United States, 78705
        • Texas Oncology- Austin Midtown
    • Virginia
      • Fairfax, Virginia, United States, 22031
        • Virginia Cancer Specialists, PC

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Sequential Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: 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.
Drug: Pembrolizumab
Administered as a dose of 200 mg using a 30-minute IV infusion every 3 weeks
Drug: BAY2416964
Oral, twice or three times daily
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.
Experimental: 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.
Drug: Pembrolizumab
Administered as a dose of 200 mg using a 30-minute IV infusion every 3 weeks
Drug: BAY2416964
Oral, twice or three times daily
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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
The incidence of TEAEs including TESAEs
Time Frame: After first administration of BAY2416964 in combination with pembrolizumab up to 90 days after the last dose of BAY2416964 in combination with pembrolizumab
TEAEs: treatment-emergent adverse events TESAEs: treatment-emergent serious adverse events
After first administration of BAY2416964 in combination with pembrolizumab up to 90 days after the last dose of BAY2416964 in combination with pembrolizumab
The severity of TEAEs including TESAEs
Time Frame: After first administration of BAY2416964 in combination with pembrolizumab up to 90 days after the last dose of BAY2416964 in combination with pembrolizumab
After first administration of BAY2416964 in combination with pembrolizumab up to 90 days after the last dose of BAY2416964 in combination with pembrolizumab
Maximum tolerated dose (MTD) or maximum administered dose (MAD) of BAY2416964
Time Frame: Cycle 1 (21 days) in dose escalation
The MTD/MAD is the dose level that can be safely given, defined as the occurrence of dose-limiting toxicities (DLTs) below a certain threshold.
Cycle 1 (21 days) in dose escalation

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Cmax of BAY2416964 after single-dose in Cycle 1
Time Frame: Cycle 1 Day 1 (1 cycle is 21 days)
Cycle 1 Day 1 (1 cycle is 21 days)
Cmax of BAY2416964 after multiple-dose in Cycle 1
Time Frame: Cycle 1 Day 15 (1 cycle is 21 days)
Cycle 1 Day 15 (1 cycle is 21 days)
AUC(0-t) (t depend on the dosing regimen) of BAY2416964 after single-dose in Cycle 1
Time Frame: Cycle 1 Day 1 (1 cycle is 21 days)
Cycle 1 Day 1 (1 cycle is 21 days)
AUC(0-t) (t depend on the dosing regimen) of BAY2416964 after multiple-dose in Cycle 1
Time Frame: Cycle 1 Day 15 (1 cycle is 21 days)
Cycle 1 Day 15 (1 cycle is 21 days)
Objective response rate (ORR) by Response Evaluation Criteria in Solid Tumors, version 1.1 (RECIST 1.1)
Time Frame: At the end of Cycle 2 (-7 days, each cycle is 21 days), Cycle 4 (-7 days) and at the end of every third cycle (-7 days) from Cycle 5 onwards
ORR will be evaluated using RECIST 1.1 by investigator assessment.
At the end of Cycle 2 (-7 days, each cycle is 21 days), Cycle 4 (-7 days) and at the end of every third cycle (-7 days) from Cycle 5 onwards

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Bayer

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

August 30, 2021

Primary Completion (Actual)

June 28, 2024

Study Completion (Actual)

January 20, 2025

Study Registration Dates

First Submitted

August 5, 2021

First Submitted That Met QC Criteria

August 5, 2021

First Posted (Actual)

August 10, 2021

Study Record Updates

Last Update Posted (Actual)

March 25, 2025

Last Update Submitted That Met QC Criteria

February 7, 2025

Last Verified

February 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 21343
  • PN-A61 (Other Identifier: Merck)
  • 2020-003547-28 (EudraCT Number)
  • 2023-503547-33-00 (Other Identifier: CTIS (EU))

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

IPD Plan Description

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.vivli.org 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 member section of the portal.

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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