Clinical trial NCT04999202: 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
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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: Advanced Solid Tumors
Keywords: Non-small cell lung cancer (NSCLC)
Head and neck squamous cell carcinoma (HNSCC)
Urothelial Cancer
Advanced cancer
Immunotherapy
Immuno oncology
Aryl Hydrocarbon Receptor inhibitor(AhRi)
Aryl Hydrocarbon Receptor
Pembrolizumab
aPD1
Checkpoint inhibitor
Lead sponsor: Bayer
Sponsor class: INDUSTRY
First posted: 2021-08-10
Enrollment: 47
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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 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.


Eligibility criteria: 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

Primary outcomes:
measure: The incidence of TEAEs including TESAEs
timeFrame: After first administration of BAY2416964 in combination with pembrolizumab up to 90 days after the last dose of BAY2416964 in combination with pembrolizumab
measure: The severity of TEAEs including TESAEs
timeFrame: After first administration of BAY2416964 in combination with pembrolizumab up to 90 days after the last dose of BAY2416964 in combination with pembrolizumab
measure: Maximum tolerated dose (MTD) or maximum administered dose (MAD) of BAY2416964
timeFrame: Cycle 1 (21 days) in dose escalation
Secondary outcomes:
measure: Cmax of BAY2416964 after single-dose in Cycle 1
timeFrame: Cycle 1 Day 1 (1 cycle is 21 days)
measure: Cmax of BAY2416964 after multiple-dose in Cycle 1
timeFrame: Cycle 1 Day 15 (1 cycle is 21 days)
measure: AUC(0-t) (t depend on the dosing regimen) of BAY2416964 after single-dose in Cycle 1
timeFrame: Cycle 1 Day 1 (1 cycle is 21 days)
measure: AUC(0-t) (t depend on the dosing regimen) of BAY2416964 after multiple-dose in Cycle 1
timeFrame: Cycle 1 Day 15 (1 cycle is 21 days)
measure: Objective response rate (ORR) by Response Evaluation Criteria in Solid Tumors, version 1.1 (RECIST 1.1)
timeFrame: 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
Other outcomes:
Locations:
city: Altamonte Springs
country: United States
facility: Florida Cancer Specialists
state: Florida
city: Sarasota
country: United States
facility: Florida Cancer Specialists & Research Institute
state: Florida
city: Detroit
country: United States
facility: Brigette Harris Cancer Pavilion at Henry Ford Cancer Center - Detroit
state: Michigan
city: Nashville
country: United States
facility: Sarah Cannon Research Institute
state: Tennessee
city: Austin
country: United States
facility: Texas Oncology- Austin Midtown
state: Texas
city: Fairfax
country: United States
facility: Virginia Cancer Specialists, PC
state: Virginia
city: Napoli
country: Italy
facility: IRCCS Istituto Nazionale Tumori Fondazione Pascale - S. C. Sperimentazioni Cliniche
state: Campania
city: Milano
country: Italy
facility: Fondazione IRCCS Istituto Nazionale dei Tumori - S. C. Oncologia Medica 1
state: Lombardia
city: Milano
country: Italy
facility: Istituto Europeo di Oncologia s.r.l - Sviluppo di nuovi farmaci per Terapie Innovative
state: Lombardia
city: Milano
country: Italy
facility: ASST Grande Ospedale Metropolitano Niguarda
state: Lombardia
city: Rozzano
country: Italy
facility: Humanitas Mirasole S.p.A. - Oncologia Medica ed Ematologia
state: Lombardia
city: Singapore
country: Singapore
facility: National University Hospital Medical Centre
city: Belfast
country: United Kingdom
facility: Belfast City Hospital
state: North Ireland
city: Newcastle
country: United Kingdom
facility: Freeman Hospital
state: Tyne And Wear
Study officials:
References: