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 and colorectal cancer (CRC).
The drug being tested in this study is called TAK-931. TAK-931 blocks the function of a
specific protein in the body called CDC7 kinase. TAK-931 is being tested in participants with
metastatic pancreatic cancer or metastatic colorectal cancer plus a cohort of US patients
with metastatic cancer with no other standard therapeutic alternative. This study will look
at safety, tolerability and pharmacokinetics of TAK-931 in people who take TAK-931.
The study will enroll approximately 88 patients. Participants will be enrolled in 3 cohorts:
1) Western safety cohort to be enrolled in the US only which will include non-Japanese
participants who have metastatic solid tumors with no standard therapeutic alternative, 2)
Participants with metastatic pancreatic cancer 3) Participants with metastatic colorectal
cancer. All participants will receive:
• TAK-931 50 mg
All participants will be asked to take one capsule at the same time each day throughout the
This multi-center trial will be conducted in United States and Japan. The overall time to
participate in this study is approximately 24 months. Participants will make multiple visits
to the clinic, and participants in both Western cohort and disease specific cohort will be
followed-up for up to 12 weeks for progression-free survival. Once disease progression is
confirmed, participants in disease-specific cohort will be followed for overall survival for
up to 12 weeks after last dose of study drug.
1. Adult male or female patients aged ≥20 years (Japan) or ≥18 years (US).
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.
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 >50% as measured by echocardiogram (ECHO) or
multiple gated acquisition (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
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.
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
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,
- Significant, uncontrolled cardiac arrhythmia (including atrial
flutter/fibrillation, ventricular fibrillation, or ventricular tachycardia).
- Current use of rate control drugs for arrhythmias or to control cardiac frequency
(including β-blockers [e.g., metoprolol], acetylcholine, digoxin, and
nondihydropyridine calcium channel blockers [e.g., diltiazem and verapamil).
Patients will not be excluded if these drugs are used for other indications other
than arrhythmia control.
- Placement of a pacemaker for control of cardiac rhythm.
- New York Heart Association Class II 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 (e.g., pericardial effusion or
- Baseline prolongation of the QT interval corrected for HR using Fridericia's
formula (QTcF; e.g., repeated demonstration of QTcF interval >480 ms, history of
congenital long QT syndrome, or torsades de pointes).
5. Participants with any of the following blood pressure (BP) conditions:
- History of orthostatic hypotension or syncope that required medical intervention.
- Orthostatic hypotension is defined as a 20-mmHg decrease in systolic BP and/or a
10-mmHg decrease in diastolic BP within 2 to 5 minutes of quiet standing
immediately after 5 minutes of supine rest.
- Postural orthostatic tachycardia syndrome or postural tachycardia syndrome
(defined as an increase in HR of >30 beats per minute over baseline after 10
minutes of quiet standing).
- 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
- 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. Western Safety Cohort Only: Participants with Japanese heredity.
11. Colorectal cancer (CRC) Cohort Only: Participants with known microsatellite
instability-high (MSI-H) genotype.