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
- Participants must be ≥18 years of age inclusive, at the time of signing the informed
- 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. Note: there is no limit to the number of
prior treatment regimens. Immune checkpoint inhibitors are also allowed in
- Dose Escalation: all solid tumor types
- Tumor type-specific high-dose (MTD or MAD) Expansion cohorts: Will be grouped by
tumor type, but no specific biomarker selection will be applied:
- Colorectal cancer MSS
- Urothelial cancer
- Tumor type-specific low-dose Expansion cohort: Any tumor type based on data from
dose escalation and expansion indicating pharmacodynamics effect and/or clinical
response from the tumor type-specific high-dose(MTD or MAD) expansion.
- 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 109/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 109/L. Transfusion to meet the inclusion criteria
will not be allowed.
- 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.
--- eGFR ≥ 60 mL/min as calculated using the MDRD equation or creatinine level ≤
- Lipase and amylase ≤ 1.5 x ULN.
- 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).
- 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 known active central nervous system (CNS) metastases and/or carcinomatous
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 should 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.
- Interstitial lung disease or chronic obstructive pulmonary disease (COPD) with ongoing
signs and symptoms at the time of screening. Has a history of (non-infectious)
pneumonitis that required steroids or has current pneumonitis.
- 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
- History of organ allograft transplantation, including allogeneic bone marrow
- 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.