Trial Condition(s):

Advanced solid tumors

A First-in-Humans dose finding study for an Aryl Hydrocarbon Receptor Inhibitor (AhRi) in patients with advanced cancer

Bayer Identifier:

20201

ClinicalTrials.gov Identifier:

NCT04069026

EudraCT Number:

2019-000722-22

Recruiting

Trial Purpose

In this study researchers want to gather relevant information regarding the safety of BAY2416964 and how well the drug works in participants with a type of solid tumors that cannot be cured by currently available drugs. Researchers want to find the highest dose of BAY2416964 that participants could take without having too many side effects, how the drug is tolerated and the way the body absorbs, distributes and gets rid of the study dug. BAY2416964 is a small molecule which blocks the Aryl Hydrocarbon Receptor (a protein involved in immune cell reaction to tumor cells) allowing the body to use its immune response against the tumor cells.

Inclusion Criteria
- Participants 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 clinical benefit, or are intolerant to treatment, or refuse standard treatment. 
-- Dose Escalation: all solid tumor types
-- Tumor type-specific high-dose (MTD or MAD) Expansion cohorts: Will be grouped by tumor type:
--- NSCLC
--- HNSCC
- Have measurable disease per RECIST 1.1 as assessed by CT/MRI. At least one measurable lesion by RECIST 1.1 is required. Lesions situated in a previously irradiated area, or in an area subjected to other loco-regional therapy, are considered measurable if progression has been demonstrated in such lesions.
- Life expectancy at least 12 weeks.
- Eastern Cooperative Oncology Group (ECOG)performance status of 0 to 1.
- Adequate bone marrow and organ function as assessed by the following laboratory tests performed within 7 days before treatment initiation.
-- Bone marrow reserve:
--- Absolute neutrophil count (ANC) ≥ 1.5 x 10^9/L
--- Hemoglobin (Hb) ≥ 9.0g/dL, without erythropoietin dependency and without packed red blood cell (pRBC) transfusion within last 2 weeks. 
--- Platelet count ≥ 100 x 10^9/L. Transfusion to meet the inclusion criteria will not be allowed.
-- Hepatic:
--- Total bilirubin ≤ 1.5 x the upper limit of normal range (ULN). Known Gilbert syndrome is allowed if total bilirubin is ≤ 3 x ULN. 
--- Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2.5 x ULN (≤ 5 x ULN for participants with liver metastases). 
--- Albumin > 25 g/L.
-- Renal: 
--- eGFR ≥ 60 mL/min as calculated using the MDRD equation or creatinine level ≤ 1.5x ULN.
-- Lipase and amylase ≤ 1.5 x ULN.
-- Coagulation: 
--- International normalized ratio (INR) OR prothrombin time (PT) AND activated partial thromboplastin time (aPTT) ≤ 1.5 x ULN unless the participant is receiving anticoagulant therapy as long as PT or aPTT is within therapeutic range of intended use of anticoagulants. 
- Adequate cardiac function, measured by echocardiography within 28 days before start of study intervention (left ventricular ejection fraction within institutional normal range for age and gender).
Exclusion Criteria
- Severe (CTCAE v.5 Grade ≥ 3) infections within 4 weeks before the first BAY2416964 administration, including but not limited to hospitalization for complications of infection, bacteremia, or severe pneumonia. Clinically active infections (CTCAE v.5 > Grade 1) within 2 weeks before the first BAY2416964 administration.
- Active autoimmune disease that has required systemic treatment in past 2 years (i.e., with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered a form of systemic treatment and is allowed. 
- Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone or equivalent) or any other form of immunosuppressive therapy within 7 days prior the first dose of study intervention.
- Congestive heart failure New York Heart Association (NYHA) greater than Class I or cardiac arrhythmias requiring anti-arrhythmic therapy other than beta blockers or calcium channel blockers.
- Has active central nervous system (CNS) metastases and/or carcinomatous meningitis. 
Participants with previously treated brain metastases may participate provided they are radiologically stable, i.e., without evidence of progression for at least 4 weeks by repeat imaging (note that repeat imaging needs to be performed during study screening), clinically stable and without requirement of steroid treatment for at least 14 days prior to first dose of study intervention.
- Has a history of (non-infectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease.
- Significant acute gastrointestinal disorders with diarrhea as a major symptom, e.g. Crohn’s disease, malabsorption, or ≥ NCI-CTCAE v. 5.0 Grade 2 diarrhea of any etiology. 
- History of organ allograft transplantation, including allogeneic bone marrow transplantation.
- Has received prior radiotherapy within 2 weeks before start of BAY2416964 or received radiation therapy to the lung that is > 30 Gy within 6 months before start of study intervention. Participants must have recovered from all radiation-related toxicities, not require corticosteroids, and not have had radiation pneumonitis. A 1-week washout is permitted for palliative radiation (≤2 weeks of radiotherapy) to non-CNS disease.
- Treatment with systemic immunosuppressant medications (including but not limited to doses > 10 mg/day prednisone or equivalent, cyclophosphamide, azathioprine, methotrexate, thalidomide, and anti-tumor necrosis factor [anti-TNF] agents) within 2 weeks before the first BAY2416964 administration. 
The use of inhaled corticosteroids, or low doses of glucocorticoids (no more than 10 mg/day prednisone or equivalent; if a higher dose would be needed to maintain adrenal function investigator must obtain approval from sponsor), and mineralocorticoids (e.g. fludrocortisone for adrenal insufficiency) is allowed.

Trial Summary

Enrollment Goal
143
Trial Dates
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Phase
1
Could I receive a placebo?
No
Products
BAY2416964
Accepts Healthy Volunteers
No

Where to Participate

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Locations
Status
LocationsStatus
Locations

University of Texas MD Anderson Cancer Center

Houston, United States, 77030

Status
Recruiting
 
Locations

South Texas Accelerated Research Therapeutics, LLC

San Antonio, United States, 78229-3307

Status
Recruiting
 
Locations

Greenville Health System

Greenville, United States, 29605

Status
Recruiting
 
Locations

Yale University School of Medicine

New Haven, United States, 06520-8028

Status
Recruiting
 
Locations

Royal Marsden NHS Trust (Surrey)

Sutton, United Kingdom, SM2 5PT

Status
Recruiting
 
Locations

Universitätsklinikum Heidelberg

Heidelberg, Germany, 69120

Status
Recruiting
 
Locations

Hospital Universitario 12 de Octubre

Madrid, Spain, 28041

Status
Recruiting
 
Locations

Hospital Ramón y Cajal | Oncología

Madrid, Spain, 28034

Status
Recruiting
 
Locations

Hospital Clínico Universitario de Valencia

Valencia, Spain, 46010

Status
Recruiting
 
Locations

Institut Català d'Oncologia Hospitalet

L'Hospitalet de Llobregat, Spain, 08907

Status
Recruiting
 
Locations

Cancer Hospital, Chinese Academy of Medical Sciences

Beijing, China, 100021

Status
Not yet recruiting
 
Locations

Beatson West of Scotland Cancer Centre

Glasgow, United Kingdom, G12 0YN

Status
Recruiting
 
Locations

Christie Hospital

Manchester, United Kingdom, M20 4BX

Status
Recruiting
 
Locations

Princess Margaret Hospital-University Health Network

Toronto, Canada, M5G 2M9

Status
Recruiting
 
Locations

Cross Cancer Institute

Edmonton, Canada, T6G 1Z2

Status
Not yet recruiting
 
Locations

CHU de Québec-Hôpital de l'Enfant-Jésus

Québec, Canada, G1J 1Z4

Status
Recruiting
 
Locations

Universitätsklinikum Carl Gustav Carus Dresden

Dresden, Germany, 01307

Status
Recruiting
 
Locations

Charité Campus Benjamin Franklin (CBF)

Berlin, Germany, 12200

Status
Recruiting
 
Locations

Hospital Virgen de la Victoria

Málaga, Spain, 29010

Status
Not yet recruiting
 
Locations

Marienhospital Herne Universitätsklinik

Herne, Germany, 44625

Status
Not yet recruiting
 

Trial Design