Phase I Study of BAY1436032 in IDH1-mutant Advanced Solid Tumors

• Register: ClinicalTrials.gov
• Last refreshed on: 6 May 2024
• Main ID: NCT02746081
• Date of registration: 08/04/2016
• Prospective Registration: Yes
• Primary sponsor: Bayer
• Public title: Phase I Study of BAY1436032 in IDH1-mutant Advanced Solid Tumors
• Scientific title: An Open-label, Non-randomized, Multicenter Phase I Study to Determine the Maximum Tolerated or Recommended Phase II Dose of Oral Mutant IDH1 Inhibitor BAY1436032 and to Characterize Its Safety, Tolerability, Pharmacokinetics and Preliminary Pharmacodynamic and Anti-tumor Activity in Patients With IDH1-R132X-mutant Advanced Solid Tumors
• Date of first enrolment: May 26, 2016
• Target sample size: 81
• Recruitment status: Active, not recruiting
• URL: https://clinicaltrials.gov/ct2/show/NCT02746081
• Study type: Interventional
• Study design: Allocation: N/A. Intervention model: Single Group Assignment. Primary purpose: Treatment. Masking: None (Open Label).
• Phase: Phase 1

Countries of recruitment

Denmark, Germany, Japan, United States

Contacts

• Name: Bayer Study Director
• Affiliation: Bayer

Key inclusion & exclusion criteria

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). At least one
measurable target lesion is required in expansion cohort patients

- 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 or 1

- 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. Pregnancy tests will be repeated
regularly during treatment

- 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
activated partial thromboplastin time (aPTT) = 1.5 times ULN (patients on
anticoagulation with an agent such as warfarin or heparin or rivoraxaban 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 by the 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) = 1.5x10^9/L;

- Platelet count = 100x10^9/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 primary tumor or
metastatic disease)

- Estimated glomerular filtration rate (eGFR) = 40 mL/min per 1.73 m^2 according to
the Modification of Diet in Renal Disease Study Group (MDRD) formula

- Minimum life expectancy of 3 months per the judgment of the investigator

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 or multiple-gated
acquisition [MUGA] scan). Patients with a pacemaker are also excluded

- Left ventricular ejection fraction (LVEF) < 40% as measured by echocardiography or
MUGA scan 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

- Treatment with investigational or approved anti-cancer drugs 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)



Age minimum: 18 Years
Age maximum: N/A
Gender: All

Health Condition(s) or Problem(s) studied

Solid Tumors

Intervention(s)

Drug: BAY1436032

Primary Outcome(s)

Number of participants with adverse events as a measure of safety and tolerability of BAY1436032 [Time Frame: Up to 30 months]

Maximum tolerated dose (MTD) of BAY1436032 [Time Frame: 21 days]

Recommended Phase II Dose (RP2D) of BAY1436032 [Time Frame: Up to 20 months]

Secondary Outcome(s)

AUC(0-24) of BAY1436032 [Time Frame: on C1D-2 and C1D1]

Change of 2-hydroxyglutarate (2-HG) concentration in plasma from baseline [Time Frame: Up to 30 months]

AUC(0-12) of BAY1436032 [Time Frame: on C1D-2 and C1D1]

C(max,md) of BAY1436032 [Time Frame: on C1D15]

AUC(0-12)md of BAY1436032 [Time Frame: on C1D15]

Change of 2-hydroxyglutarate (2-HG) concentration in urine from baseline [Time Frame: Up to 30 months]

Duration of response [Time Frame: Up to 30 months]

Objective response rate (partial and complete response) [Time Frame: Up to 30 months]

Cmax of BAY1436032 [Time Frame: on C1D-2 and C1D1]

Progression free survival (PFS) [Time Frame: Up to 30 months]

Secondary ID(s)

18239

2015-003483-37

Source(s) of Monetary Support

Please refer to primary and secondary sponsors