Inclusion Criteria:
- Male or female patients 18 years of age
- Patients with a histologically confirmed solid tumor:
- Tumor must harbor an IDH1-R132X mutation
- Disease must be evaluable as per RECIST 1.1 or RANO (for gliomas)
- Patients with advanced cancer who are refractory to, have demonstrated
intolerance to, or have refused access to, available standard therapies
- Glioma patients must have completed chemoradiotherapy at least 12 weeks prior to
screening and their baseline scan
- Patient must be able to provide a formalin-fixed and paraffin-embedded (FFPE) tumor
tissue specimen prior to treatment. The specimen may have been taken at any time
during the course of the disease and may be from the primary tumor or from a
metastasis.
- Patient must be able to take oral medication and comply with protocol procedures and
scheduled visits
- Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1 or 2
- Negative serum or urine pregnancy test must be obtained within 7 days prior to the
first dose of study drug in women of childbearing potential. Negative results must be
available prior to study drug administration.
- Sexually active women and men of reproductive potential must agree to use highly
effective contraception. This applies for the period between signing of the informed
consent and 3 months after the last administration of study drug. These procedures
should be documented in source documents. The investigator or a designated associate
is requested to advise the patient on how to achieve highly effective birth control.
Highly effective contraception includes:
- Established use of oral, injected or implanted hormonal methods of contraception
- Placement of certain intrauterine devices (IUD) or intrauterine systems (IUS)
- Hysterectomy, or vasectomy of the partner (provided that partner is the sole
sexual partner of the woman of childbearing potential trial participant and that
the vasectomized partner has received medical assessment of the surgical
success) In addition, the use of condoms for patients or their partners is
required
- Ability to understand and the willingness to sign a written informed consent. A
signed informed consent, including consent for biomarker analyses, must be obtained
prior to any study-specific procedures.
- Adequate blood clotting as defined by international normalized ratio (INR) and
partial thromboplastin time (PTT) 1.5 times ULN (patients on anticoagulation with
an agent such as Coumadin or heparin or Xarelto will be allowed to participate
provided that no prior evidence of underlying abnormality in these parameters
exists). For patients on warfarin, close monitoring of at least weekly evaluations
will be performed until INR is stable based on a measurement at pre-dose, as defined
by the local standard of care
- Adequate bone marrow, liver, and renal functions as assessed bythe following
laboratory requirements to be conducted within 7 days prior to the first dose of
study drug:
- Hemoglobin 9.0 g/dL;
- Absolute neutrophil count (ANC) 1.5*109/L;
- Platelet count 100*109/L.
- Total bilirubin 1.5 times the upper limit of normal (ULN). For intrahepatic
cholangiocarcinoma (IHCC) patients only, total bilirubin 2.5 times ULN is
acceptable.
- Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) 2.5 times
ULN ( 5 times ULN for patients with impaired liver function due to metastatic
disease)
- Estimated glomerular filtration rate (eGFR) 50 mL/min per 1.73 m2 according to
the Modification of Diet in Renal Disease Study Group (MDRD) formula
Exclusion Criteria:
- Known hypersensitivity to the study drug or excipients of the preparation or any
agent given in association with this study
- History of cardiac disease, including congestive heart failure of New York Heart
Association (NYHA) class >II, unstable angina (anginal symptoms at rest) or new-onset
angina (within 6 months prior to study entry), myocardial infarction within 6 months
prior to study entry, or cardiac arrhythmias requiring anti-arrhythmic therapy except
for beta-blockers and digoxin; evidence for uncontrolled coronary artery disease
(e.g. angina pectoris, myocardial infarction within 6 months prior to study entry,
major regional wall motion abnormalities upon baseline echocardiography). Patients
with a pacemaker are also excluded.
- Left ventricle ejection fraction (LVEF) < 40% as measured by echocardiography
performed at Screening
- Uncontrolled hypertension defined as systolic blood pressure 160 mmHg or diastolic
blood pressure 100 mmHg, despite medical management
- Patients who have an active clinically significant infection of the National Cancer
Institute Common Terminology Criteria for Adverse Events (CTCAE) grade 2
- Previous or coexisting cancer(s) distinct in primary site or histology from the
cancer evaluated in this study EXCEPT:
- Appropriately treated cervical cancer in-situ, non-melanoma skin cancers, or
superficial bladder tumors (Ta and Tis)
- Any cancer that was curatively treated at least 3 years before entry into this
study
- Unresolved specific chronic toxicity of previous treatment of grade > 1 except for
alopecia or hemoglobin 9.0 g/dL (or 5.6 mmol/L).
- Major surgery, significant trauma, wide-field radiotherapy, or therapy with
monoclonal antibodies within 4 weeks before the first dose of study drug
- Investigational drug treatment within 4 weeks before the start of BAY1436032
treatment and during the study (glioma patients must have completed chemoradiotherapy
at least 12 weeks prior to screening and their baseline scan; see inclusion criteria
#2)
- Pregnant women. Women of reproductive potential must have a negative serum or urine
pregnancy test performed within 7 day
- Prior treatment with any therapy targeting mutant IDH1 (including BAY1436032)
Minimum Eligible Age: 18 Years
Maximum Eligible Age: N/A
Eligible Gender: Both
