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

The drug being tested in this study is called TAK-931. TAK-931 blocks function of a specific
protein called CDC7 kinase in the human body. TAK-931 is being tested in participants with
metastatic cancer (colorectal, pancreatic, sqNSCLC and sqEC) in the United States and Japan
and also in the participants with any type of metastatic cancer with no standard therapeutic
alternative in the United States only. This study will look at the safety, tolerability and
pharmacokinetics of TAK-931.

The study will enroll approximately 160 participants. Participants will be enrolled in 5
cohorts: 1) Western safety cohort, to be enrolled in the United States only, will include
non-Japanese participants with metastatic solid tumors and no standard therapeutic
alternative, 2) Metastatic pancreatic cancer cohort, 3) Metastatic colorectal cancer cohort,
4) Metastatic sqNSCLC cohort, and 5) Metastatic sqEC cohort. All participants will receive:

• TAK-931 50 mg capsules

All participants will be asked to take one 50 mg capsule at the same time of the day every
day for 14 days, followed by 7 days break in 21-day cycles throughout the study.

This multi-center trial will be conducted in the United States and Japan. The overall time to
participate in this study is approximately 24 months. Participants will make multiple visits
to the clinic. Participants in both Western cohort and disease specific cohorts will be
followed for progression-free survival every 12 weeks after the last dose of the study drug
until the occurrence of disease progression, loss to follow up, consent withdrawal, death,
start of subsequent antineoplastic therapy, study termination, or until 6 months after
discontinuation of the study treatment, whichever occurs first. Once disease progression is
confirmed, participants in the disease-specific cohorts will be followed for overall survival
every 12 weeks until death, loss to follow up, consent withdrawal, study termination, or
transfer of a participant to a long term safety study, single participant investigational new
drug application, or similar program after the last dose of the study drug.

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 reate (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.