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Participants must be ≥18 years of age inclusive, at the time of signing the informed consent |
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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 pretreatment |
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Dose Escalation: all solid tumor types |
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Tumor type-specific high-dose (MTD or MAD) Expansion cohorts: Will be grouped by tumor type, but no specific biomarker selection will be applied |
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NSCLC |
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HNSCC |
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Colorectal cancer MSS |
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Urothelial cancer |
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Tumor type-specific low-dose Expansion cohort: Any tumor type based on data from |
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Life expectancy at least 12 weeks |
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dose escalation and expansion indicating pharmacodynamics effect and/or |
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Eastern Cooperative Oncology Group (ECOG)performance status of 0 to 1 |
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clinical response from the tumor type-specific high-dose(MTD or MAD) |
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expansion |
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Bone marrow reserve |
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Have measurable disease per RECIST 1.1 as assessed by CT/MRI. At least one measurable |
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lesion by RECIST 1.1 is required. Lesions situated in a previously irradiated |
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area, or in an area subjected to other loco-regional therapy, are considered |
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measurable if progression has been demonstrated in such lesions |
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Hepatic |
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Adequate bone marrow and organ function as assessed by the following laboratory tests |
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Albumin > 25 g/L |
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performed within 7 days before treatment initiation |
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Renal |
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Absolute neutrophil count (ANC) ≥ 1.5 x 109/L |
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Hemoglobin (Hb) ≥ 9.0g/dL, without erythropoietin dependency and without packed red blood cell (pRBC) transfusion within last 2 weeks |
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Platelet count ≥ 100 x 109/L. Transfusion to meet the inclusion criteria will not be allowed |
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Coagulation |
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Total bilirubin ≤ 1.5 x the upper limit of normal range (ULN). Known Gilbert syndrome is allowed if total bilirubin is ≤ 3 x ULN |
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Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2.5 x ULN (≤ 5 x ULN for participants with liver metastases) |
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\--- eGFR ≥ 60 mL/min as calculated using the MDRD equation or creatinine |
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level ≤ 1.5x ULN |
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Lipase and amylase ≤ 1.5 x ULN |
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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 |
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Adequate cardiac function, measured by echocardiography within 28 days before start of |
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study intervention (left ventricular ejection fraction within institutional |
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normal range for age and gender) |
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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
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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
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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
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Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis
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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
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Participants with previously treated brain metastases may participate provided they are
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radiologically stable, i.e., without evidence of progression for at least 4 weeks by repeat
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imaging (note that repeat imaging should be performed during study screening), clinically
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stable and without requirement of steroid treatment for at least 14 days prior to first
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dose of study intervention
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Interstitial lung disease or chronic obstructive pulmonary disease (COPD) with ongoing
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signs and symptoms at the time of screening. Has a history of (non-infectious)
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pneumonitis that required steroids or has current pneumonitis
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Significant acute gastrointestinal disorders with diarrhea as a major symptom, e.g
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Crohn's disease, malabsorption, or ≥ NCI-CTCAE v. 5.0 Grade 2 diarrhea of any
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etiology
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History of organ allograft transplantation, including allogeneic bone marrow
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transplantation
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Has received prior radiotherapy within 2 weeks before start of BAY2416964 or received
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radiation therapy to the lung that is > 30 Gy within 6 months before start of study
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intervention. Participants must have recovered from all radiation-related toxicities
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not require corticosteroids, and not have had radiation pneumonitis. A 1-week washout
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is permitted for palliative radiation (≤2 weeks of radiotherapy) to non-CNS disease
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Treatment with systemic immunosuppressant medications (including but not limited to
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doses > 10 mg/day prednisone or equivalent, cyclophosphamide, azathioprine
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methotrexate, thalidomide, and anti-tumor necrosis factor [anti-TNF] agents) within 2
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weeks before the first BAY2416964 administration
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The use of inhaled corticosteroids, or low doses of glucocorticoids (no more than 10 mg/day
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prednisone or equivalent; if a higher dose would be needed to maintain adrenal function
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investigator must obtain approval from sponsor), and mineralocorticoids (e.g
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fludrocortisone for adrenal insufficiency) is allowed
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