stop_circleTerminated/Withdrawn

Advanced solid tumors

Bayer Identifier:

21343

ClinicalTrials.gov Identifier:

NCT04999202

EudraCT Number:

2020-003547-28

EU CT Number:

Not Available
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

Trial purpose

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.

Key Participants Requirements

Sex

All

Age

18 - N/A
  • - 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.
  • - 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

Trial summary

Enrollment Goal
47
Trial Dates
August 2021 - January 2025
Phase
Phase 1
Could I Receive a placebo
No
Products
BAY2416964
Accepts Healthy Volunteer
No

Where to participate

StatusInstitutionLocation
Completed
Brigette Harris Cancer Pavilion at Henry Ford Cancer Center - DetroitDetroit, 48202, United States
Withdrawn
Baptist Health South Florida Miami Cancer InstituteMiami, 33176, United States
Completed
Sarah Cannon Research InstituteNashville, 37203, United States
Active, not recruiting
Texas Oncology- Austin MidtownAustin, 78705, United States
Active, not recruiting
Freeman HospitalNewcastle, NE7 7DN, United Kingdom
Withdrawn
Clatterbridge Centre for OncologyBebington, CH63 4JY, United Kingdom
Withdrawn
Southampton General HospitalSouthampton, SO16 6YD, United Kingdom
Active, not recruiting
National University Hospital Medical CentreSingapore, 119074, Singapore
Withdrawn
National Cancer Center SingaporeSingapore, 168583, Singapore
Active, not recruiting
Belfast City HospitalBelfast, BT12 7AB, United Kingdom
Active, not recruiting
Florida Cancer Specialists & Research InstituteSarasota, 34232, United States
Completed
ASST Grande Ospedale Metropolitano NiguardaMilano, 20162, Italy
Completed
Humanitas Mirasole S.p.A. - Oncologia Medica ed EmatologiaRozzano, 20089, Italy
Completed
Istituto Europeo di Oncologia s.r.l - Sviluppo di nuovi farmaci per Terapie InnovativeMilano, 20141, Italy
Active, not recruiting
Fondazione IRCCS Istituto Nazionale dei Tumori - S. C. Oncologia Medica 1Milano, 20133, Italy
Active, not recruiting
IRCCS Istituto Nazionale Tumori Fondazione Pascale - S. C. Sperimentazioni ClinicheNapoli, 80131, Italy
Completed
Virginia Cancer Specialists, PCFairfax, 22031, United States
Completed
Florida Cancer SpecialistsAltamonte Springs, 32701, United States
Withdrawn
University College London Hospitals NHS Foundation TrustLondon, NW1 2BU, United Kingdom

Primary Outcome

  • The incidence of TEAEs including TESAEs
    TEAEs: treatment-emergent adverse events TESAEs: treatment-emergent serious adverse events
    date_rangeTime Frame:
    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
    date_rangeTime Frame:
    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
    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.
    date_rangeTime Frame:
    Cycle 1 (21 days) in dose escalation

Secondary Outcome

  • Cmax of BAY2416964 after single-dose in Cycle 1
    date_rangeTime Frame:
    Cycle 1 Day 1 (1 cycle is 21 days)
  • Cmax of BAY2416964 after multiple-dose in Cycle 1
    date_rangeTime Frame:
    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
    date_rangeTime Frame:
    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
    date_rangeTime Frame:
    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)
    ORR will be evaluated using RECIST 1.1 by investigator assessment.
    date_rangeTime 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

Trial design

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
Trial Type
Interventional
Intervention Type
Drug
Trial Purpose
Treatment
Allocation
Non-randomized
Blinding
N/A
Assignment
Sequential Assignment
Trial Arms
2

Additional Information

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