A Study to Evaluate the Safety, Tolerability, and Activity of TAK-931 in Participants With Metastatic Pancreatic Cancer, Metastatic Colorectal Cancer, and Other Advanced Solid Tumors
Condition: Metastatic Pancreatic Cancer; Colorectal Cancer; Esophageal Neoplasms; Carcinoma, Non-small-cell Lung
MeSH terms: Colorectal Neoplasms; Pancreatic Neoplasms; Carcinoma, Non-Small-Cell Lung; Esophageal Neoplasms
Intervention: TAK-931
Intervention description: TAK-931 hard gelatin capsules
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 101.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Drug therapy

Summary:

      The purpose of this study is to confirm the safety and tolerability of TAK-931 in a cohort of
      Western participants with metastatic solid tumors and to evaluate the anti-tumor activity of
      TAK-931 in participants with metastatic pancreatic cancer, colorectal cancer (CRC), squamous
      esophageal cancer (sqEC), and squamous non-small-cell lung cancer (sqNSCLC).
    

Eligibility criteria:

        Inclusion Criteria:

          1. Adult male or female participants aged >=20 years (Japan) or >=18 years (United
             States).

          2. Eastern Cooperative Oncology Group (ECOG) performance status of 0-1

          3. Has pathologically confirmed metastatic pancreatic adenocarcinoma that has progressed
             after, at least, a first line of standard systemic chemotherapy for the metastatic
             disease, OR participants with pathologically confirmed metastatic adenocarcinoma of
             the colon or rectum who have progressed to at least 2 lines of standard systemic
             chemotherapy for the metastatic disease, OR participants with pathologically confirmed
             locally advanced or metastatic sqEC that has progressed after at least a first line of
             standard systemic therapy for metastatic disease. First-line participants can be
             enrolled if a platinum doublet is contraindicated or refused by the participants, OR
             pathologically confirmed locally advanced or metastatic sqNSCLC that has progressed
             after at least 2 lines of standard systemic therapy for metastatic disease.

          4. For the Western safety cohort only: participants with locally advanced or metastatic
             solid tumor for whom no standard treatment with an established survival benefit is
             available or if the participant refuses other standard therapy.

          5. For disease-specific cohort participants: measurable disease per RECIST v. 1.1

          6. Left ventricular ejection fraction greater than (>) 50% as measured by ECHO or MUGA
             scan within 4 weeks before receiving the first dose of study drug.

          7. Recovered to Grade 1 or baseline from all toxic effects of previous therapy (except
             alopecia or neuropathy).

          8. Suitable venous access for the study-required blood sampling.

          9. For the Western safety cohort only: willingness to undergo serial skin tissue
             biopsies.

         10. For disease-specific cohort participants: Must have an archival (banked) tumor sample
             or agree to have a new (fresh) tumor biopsy during the screening period. If a new
             tumor sample is needed, the disease should be accessible for a nonsignificant risk
             biopsy procedure (those occurring outside the brain, lung/mediastinum, and pancreas,
             or obtained with endoscopic procedures not extending beyond the stomach or bowel). For
             participants in the Western safety cohort, this biopsy is optional.

        Exclusion Criteria:

          1. Participants 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, such as phenytoin,
             carbamazepine, phenobarbital, rifampin, rifabutin, rifapentine, or Saint John's wort
             within 14 days before the first dose of study drug.

          3. Treatment with any systemic anticancer treatment (including investigational products)
             within 30 days or 5 half-lives, whichever is shorter, before the first dose of study
             drug.

          4. 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.

               -  Significant, uncontrolled cardiac arrhythmia (including atrial
                  flutter/fibrillation, ventricular fibrillation, or ventricular tachycardia).

               -  New York Heart Association Class III to IV heart failure.

               -  Any other cardiac condition that, in the opinion of the investigator, could pose
                  an additional risk for participation in the study (example, pericardial effusion
                  or restrictive cardiomyopathy).

               -  Baseline prolongation of the QT interval corrected for heart rate (HR) using
                  Fridericia's formula [QT interval corrected for heart rate using Fridericia's
                  formula (QTcF); example, repeated demonstration of QTcF interval >480 millisecond
                  (ms), history of congenital long QT syndrome, or torsades de pointes].

          5. Hypertension that is unstable or not controlled by medication.

          6. History of uncontrolled brain metastasis unless:

               -  Previously treated with surgery, whole-brain radiation, or stereotactic
                  radiosurgery, and

               -  Stable disease (SD) for >=30 days, without steroid use (or stable steroid dose
                  established for >=14 days before the first dose of TAK-931).

          7. Known history of human immunodeficiency virus infection.

          8. Known hepatitis B virus (HBV) surface antigen seropositive or detectable hepatitis C
             virus (HCV) infection viral load. Note: Participants who have positive HBV core
             antibody or HBV surface antigen antibody can be enrolled but must have an undetectable
             HBV viral load.

          9. Prior treatment with radiation therapy involving >=25% of the hematopoietically active
             bone marrow within 3 months before the first dose of study drug.

         10. Participants with known microsatellite instability-high (MSI-H) genotype or known wild
             type tumor protein 53 (TP53) per local testing.

         11. Western Safety Cohort Only: Participants with Japanese heredity.