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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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. Identifier: NCT04999202
Recruitment Status : Recruiting
First Posted : August 10, 2021
Last Update Posted : July 15, 2022
Information provided by (Responsible Party):

Brief Summary:

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 in tablet form 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 increases 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 spread 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.

Condition or disease Intervention/treatment Phase
Advanced Solid Tumors Drug: BAY2416964 Drug: Pembrolizumab Phase 1

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 78 participants
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: 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
Actual Study Start Date : August 30, 2021
Estimated Primary Completion Date : March 20, 2024
Estimated Study Completion Date : March 20, 2024

Resource links provided by the National Library of Medicine

Arm Intervention/treatment
Experimental: Dose escalation of BAY2416964
Up to four dose levels of BAY2416964 (as determined in the first in human mono-therapy study of BAY2416964) will be given in combination with standard dose Pembrolizumab.
Drug: BAY2416964
Oral, twice daily in dose level 1 and dose level 2, three times daily in dose level 3 and dose level 4.

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

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: BAY2416964
Oral, the highest dose determined safe in combination with pembrolizumab in the dose escalation part.

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

Primary Outcome Measures :
  1. 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

  2. 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 ]
  3. 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.

Secondary Outcome Measures :
  1. Cmax of BAY2416964 after single-dose in Cycle 1 [ Time Frame: Cycle 1 Day 1 (1 cycle is 21 days) ]
  2. Cmax of BAY2416964 after multiple-dose in Cycle 1 [ Time Frame: Cycle 1 Day 15 (1 cycle is 21 days) ]
  3. 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) ]
  4. 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) ]
  5. 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 every 9 weeks (-7 days) thereafter ]
    ORR will be evaluated using RECIST 1.1 by investigator assessment.

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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. Note: there is no limit to the number of prior treatment regimens.

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

      • NSCLC
      • HNSCC
      • 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT04999202

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Contact: Bayer Clinical Trials Contact (+)1-888-84 22937

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United States, Florida
Florida Cancer Specialists & Research Institute Recruiting
Sarasota, Florida, United States, 34232
United States, Michigan
Henry Ford Hospital Recruiting
Detroit, Michigan, United States, 48202
United States, Tennessee
Sarah Cannon Research Institute Recruiting
Nashville, Tennessee, United States, 37203
United States, Texas
Texas Oncology- Austin Midtown Not yet recruiting
Austin, Texas, United States, 78705
United States, Virginia
Virginia Cancer Specialists, PC Not yet recruiting
Fairfax, Virginia, United States, 22031
Istituto Nazionale Tumori IRCCS Fondazione G.Pascale Not yet recruiting
Napoli, Campania, Italy, 80131
Istituto Clinico Humanitas - Humanitas Mirasole S.p.A. Not yet recruiting
Milano, Lombardia, Italy, 20089
Fondazione IRCCS Istituto Nazionale dei Tumori Not yet recruiting
Milano, Lombardia, Italy, 20133
IRCCS Istituto Europeo di Oncologia s.r.l. (IEO) Not yet recruiting
Milano, Lombardia, Italy, 20141
ASST Grande Ospedale Metropolitano Niguarda Not yet recruiting
Milano, Lombardia, Italy, 20162
National University Hospital Recruiting
Singapore, Singapore, 119228
National Cancer Center Singapore Not yet recruiting
Singapore, Singapore, 169610
United Kingdom
Southampton General Hospital Withdrawn
Southampton, Hampshire, United Kingdom, SO16 6YD
Clatterbridge Centre for Oncology Not yet recruiting
Bebington, Merseyside, United Kingdom, CH63 4JY
Belfast City Hospital Not yet recruiting
Belfast, North Ireland, United Kingdom, BT12 7AB
Freeman Hospital Not yet recruiting
Newcastle Upon Tyne, Tyne And Wear, United Kingdom, NE7 7DN
Sponsors and Collaborators
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Responsible Party: Bayer Identifier: NCT04999202    
Other Study ID Numbers: 21343
PN-A61 ( Other Identifier: Merck )
2020-003547-28 ( EudraCT Number )
First Posted: August 10, 2021    Key Record Dates
Last Update Posted: July 15, 2022
Last Verified: July 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Plan Description: Availability of this study's data will 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 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.

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Bayer:
Non-small cell lung cancer (NSCLC)
Head and neck squamous cell carcinoma (HNSCC)
Urothelial Cancer
Advanced cancer
Immuno oncology
Aryl Hydrocarbon Receptor inhibitor(AhRi)
Aryl Hydrocarbon Receptor
Checkpoint inhibitor
Additional relevant MeSH terms:
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Antineoplastic Agents, Immunological
Antineoplastic Agents