A Study to Evaluate TAK-931 in Participants With Advanced Nonhematologic Tumors
Condition: Nonhematologic Neoplasms, Advanced
Intervention: TAK-931
Intervention description: TAK-931 oral capsules.
Phase: Phase 1
Study type: Interventional
Primary purpose: Other
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 80.0
Sex: All
Minimum age: 20 Years
Healthy volunteers: No
Keywords: Drug Therapy

Summary:

      The purpose of this study is to evaluate the safety, tolerability, pharmacokinetics (PK), and
      maximum tolerated dose (MTD) of TAK-931 in participants with advanced nonhematologic tumors.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Histologically confirmed diagnosis of an advanced, nonhematologic/solid tumor (with
             the exception of primary brain tumor).

          2. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 .

          3. For whom no effective standard therapy is available.

          4. Life expectancy of greater than or equal to (>=3) months.

          5. Female participants who:

               -  Are postmenopausal (natural amenorrhea and not due to other medical reasons) for
                  at least 1 year before the screening visit, OR

               -  Are surgically sterile, OR

               -  If they are of childbearing potential, agree to practice 2 effective methods of
                  contraception, at the same time, from the time of signing the informed consent
                  through 30 days after the last dose of study drug, OR

               -  Agree to practice true abstinence, when this is in line with the preferred and
                  usual lifestyle of the participant. (Periodic abstinence [example, calendar,
                  ovulation, symptothermal, postovulation methods] and withdrawal are not
                  acceptable methods of contraception.)

             Male participants, even if surgically sterilized (example, status postvasectomy), who:

               -  Agree to practice effective barrier contraception during the entire study
                  treatment period and through 120 days after the last dose of study drug, OR

               -  Agree to practice true abstinence, when this is in line with the preferred and
                  usual lifestyle of the participant. (Periodic abstinence [example, calendar,
                  ovulation, symptothermal, postovulation methods for the female partner] and
                  withdrawal are not acceptable methods of contraception.)

               -  Agree not to donate sperm during this study and for 120 days after receiving
                  their last dose of study drug.

          6. Voluntary written consent must be given before performance of any study-related
             procedure not part of standard medical care, with the understanding that consent may
             be withdrawn by the participant at any time without prejudice to future medical care.

          7. Ability to swallow oral medications, willingness to undergo serial skin punch
             biopsies, and suitable venous access for the study-required PK and pharmacodynamic
             sampling.

          8. Clinical laboratory values as specified below within 28 days before the first dose of
             study drug:

               -  Bone marrow reserve consistent with absolute neutrophil count (ANC) >=1500 per
                  millimeter cube (/mm˄3), platelet count >=100,000/mm˄3, and hemoglobin >=9 per
                  gram deciliter (g/dL).

               -  Total bilirubin must be less than (<) 1.5 times the upper limit of normal (ULN).

               -  Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) must be 3
                  <=ULN. AST and ALT may be elevated up to 5 times the ULN if their elevation can
                  be reasonably ascribed to the presence of hepatocellular carcinoma, biliary tract
                  cancer, or metastatic disease in liver.

               -  Serum albumin >=3.0 g/dL.

               -  Serum creatinine <1.5 times the institutional ULN or creatinine clearance based
                  on the Cockcroft-Gault estimate >=50 milliliter per minute (mL/minute) for
                  participants with serum creatinine concentrations above institutional limits.

          9. Left ventricular ejection fraction (LVEF) greater than (>) 50 percent (%) as measured
             by echocardiogram (ECHO) or multiple gated acquisition scan (MUGA) within 4 weeks
             before receiving the first dose of study drug.

         10. Recovered (that is, <=Grade 1 toxicity) from the reversible effects of prior
             anticancer therapy. Participants with ongoing toxicities at baseline may be eligible;
             however, any Grade 2 baseline toxicity (except for alopecia) should be discussed with
             the medical monitor.

        Exclusion Criteria:

          1. Who require continuous use of proton pump inhibitors (PPIs) or histamine-2 (H2)
             receptor antagonists and participants who are taking PPIs within 5 days before the
             first dose of study drug.

          2. Treatment with clinically significant enzyme inducers within 14 days before the first
             dose of study drug.

          3. Treatment with any investigational products within 30 days before the first dose of
             study drug.

          4. Female participants who are lactating and breastfeeding or have a positive serum
             pregnancy test during the screening period or a positive urine pregnancy test on Day 1
             before the first dose of study drug.

          5. Any serious medical or psychiatric illness that could, in the investigator's opinion,
             potentially interfere with the completion of treatment according to this protocol.

          6. History of any of the following within the last 3 months before administration of the
             first dose of study drug:

               -  Ischemic myocardial event including angina requiring therapy and artery
                  revascularization procedures, myocardial infarction, and unstable symptomatic
                  ischemic heart disease.

               -  Ischemic cerebrovascular event, including transient ischemic attack and artery
                  revascularization procedures.

               -  Thromboembolic events (example, deep vein thrombosis, pulmonary embolism, or
                  symptomatic cerebrovascular events).

               -  Significant, uncontrolled cardiac arrhythmia (including atrial
                  flutter/fibrillation, ventricular fibrillation, or ventricular tachycardia).

               -  Use of rate control drugs for arrhythmias (including beta blockers [such as
                  metoprolol],acetylcholine, digoxin, and non-dihydropyridine calcium channel
                  blockers diltiazem and verapamil).

               -  Placement of a pacemaker for control of cardiac rhythm.

               -  Requirement for inotropic support (including digoxin).

               -  New York Heart Association (NYHA) Class II to IV heart failure.

               -  Any other cardiac condition that in the opinion of the investigator could pose an
                  additional risk for the participation in the study (example, pericardial effusion
                  or restrictive cardiomyopathy).

               -  Baseline prolongation of the rate-corrected QT interval (QTc; example, repeated
                  demonstration of QTc interval >480 millisecond (msec), or history of congenital,
                  long QT syndrome, or torsades de pointes).

          7. With any of the following blood pressure conditions:

               -  History of orthostatic hypotension or syncope that required medical intervention.
                  Orthostatic hypotension is defined as a 20 millimeter of mercury (mmHg) fall in
                  systolic blood pressure and/or a 10 mmHg fall in diastolic blood pressure within
                  2 to 5 minutes of quiet standing immediately after a 5-minute period of supine
                  rest.

               -  Postural orthostatic tachycardia syndrome (POTS) or postural tachycardia syndrome
                  (defined as an increase in heart rate of >30 beats per minute over baseline after
                  10 minutes of quiet standing).

               -  Hypertension that is unstable or not controlled by medication.

          8. Seizures requiring antiepileptic treatment.

          9. History of uncontrolled brain metastasis unless:

               -  Previously treated with surgery, whole-brain radiation, or stereotactic
                  radiosurgery.

               -  Stable disease for ≥60 days, without steroid use (or stable steroid dose
                  established for ≥28 days before the first dose of TAK-931).

         10. Symptomatic and/or progressive central nervous system (CNS) metastases.

         11. Ongoing medical conditions, such as acute exacerbations of chronic illnesses, serious
             infections, or major surgery within 4 weeks before receiving the first dose of study
             drug.

         12. Known history of human immunodeficiency virus (HIV) infection.

         13. Known hepatitis B (HBV) surface antigen seropositive or detectable hepatitis C (HCV)
             infection viral load. Note: Participants who have positive hepatitis B core antibody
             or hepatitis B surface antibody can be enrolled but must have an undetectable
             hepatitis B viral load. Participants who have positive hepatitis C antibody must have
             an undetectable hepatitis C viral load.

         14. Known gastrointestinal (GI) disease or GI procedure that could interfere with the GI
             absorption of study drug, such as total gastrectomy or GI conditions that could
             substantially modify gastric pH.