A Study to Evaluate the Safety, Tolerability and Pharmacokinetics (PK) of TAK-981 in Adult Participants With Metastatic Solid Tumors or Lymphomas.

The drug being tested in this study is called TAK-981. TAK-981 is being tested to evaluate
safety, tolerability, and PK in participants who have locally advanced or metastatic solid
tumors or relapsed or refractory lymphomas for whom there is no standard therapeutic
alternative with established clinical benefit is available. The study will include a dose
escalation phase and a dose expansion phase.

The study will enroll approximately 80 participants, approximately 40 to 50 participants in
the dose escalation phase and approximately 15 participants in each of the 2 cohorts of dose
expansion phase.

In the dose escalation phase, dose levels will be escalated based on safety, and available PK
and pharmacodynamic data. This study will also determine the single agent recommended phase 2
dose (RP2D). Participants in dose expansion phase will be enrolled, once maximum tolerated
dose (MTD) or biological effective dose (BED) is determined. One of the 2 cohorts in dose
expansion phase will consist of participants with relapsed/refractory lymphomas, and other
cohort will consist of participants with solid tumors with no standard therapeutic option
available with established clinical benefit.

This multi-center trial will be conducted in the United States and Canada. The overall time
to participate in this study is approximately 3 years. The overall time to receive treatment
in this study is approximately 1 year. Based on decision of sponsor, participants with
demonstrated clinical benefit can continue treatment beyond 1 year. Participants will make
multiple visits to the clinic, and will make a final visit 30 days after receiving their last
dose of drug or before the start of subsequent anticancer therapy, whichever occurs first for
a follow-up assessment.

Inclusion Criteria:

1. Adult male or female participants greater than or equal to (>=)18 years old.

2. Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1.

3. Population for dose escalation and expansion.

- Has histologically confirmed advanced (local regionally recurrent not amenable to
curative therapy) or metastatic solid tumors that have no standard therapeutic
option with a proven clinical benefit, are intolerant or have refused them, OR

- Has relapsed/refractory lymphoma not amenable to therapies with proven clinical
benefit or who are intolerant or who refuse them. Participants with low grade
lymphomas such as follicular lymphoma, small lymphocytic lymphoma,
lymphoplasmacytoid lymphoma, and marginal zone lymphomas, may not need to exhaust
all available therapy. These participants can be enrolled after failure of at
least 2 prior systemic therapies, provided that there is not an immediate need
for cytoreduction. In these cases, participants who need immediate therapy for
tumor bulk are not eligible for this trial.

4. If enrolled before the dose level for which there is consistent evidence of TAK-981
pharmacodynamic effect (DLx) will not be required to have measurable disease. Once
evidence of pharmacodynamics effect at a dose level, is determined, participants
enrolling in dose escalation and expansion cohorts are required to have measurable
disease per RECIST version 1.1 for participants with solid tumors or RECIL 2017 for
participants with lymphoma.

5. Screening and post-dose tumor biopsies are required from all participants in the
expansion cohorts and are optional during dose escalation, however once a DLx is
identified at which there is clear evidence of TAK-981 biological effect (that is,
observation of peripheral lymphopenia, induction of cytokines/chemokines, type 1
interferon (IFN) signature in blood, drug-related toxicity or antitumor effect),
subsequent participants must agree in providing a fresh tumor biopsy during the
screening period and a second tumor biopsy as requested in the schedule of events
(SOE). The screening biopsy can be replaced by an archival one if it was taken within
60 days before the calculated enrollment date, and no anticancer or immunosuppressive
or immunomodulatory treatment was administered in between. The lesion accessible for
biopsy may not be the only target lesion and should not be located in a previously
irradiated field (unless this index lesion has progressive disease >=20% post
radiation).

6. Adequate bone marrow reserve and renal and hepatic function.

7. Recovered to Grade 1, baseline or established as sequela, from all toxic effects of
previous therapy (except alopecia, neuropathy, or autoimmune endocrinopathies with
stable endocrine replacement therapy).

8. Left ventricular ejection fraction (LVEF) >=40 percent (%); as measured by
echocardiogram or multiple gated acquisition scan (MUGA).

9. Consent to undergo serial skin punch biopsies.

10. Suitable venous access for safe drug administration and the study-required PK and
pharmacodynamics sampling.

Exclusion Criteria:

1. Treatment with systemic anticancer treatments or investigational products within 14
days before the first dose of study drug or 5 half-lives, whichever is shorter.

2. History of uncontrolled brain metastasis.

3. Is receiving any live vaccine (example, varicella, pneumococcus) within 4 weeks of
initiation of study treatment.

4. Has received extended field radiotherapy less than or equal to (<=) 4 weeks before the
start of treatment (<=2 weeks for limited field radiation for palliation), and who has
not recovered to grade 1 or better from related side effects of such therapy (except
for alopecia).

5. History of any of the following <=6 months before first dose: congestive heart failure
New York Heart Association Grade III or IV, unstable angina, myocardial infarction,
unstable symptomatic ischemic heart disease, uncontrolled hypertension despite
appropriate medical therapy, ongoing symptomatic cardiac arrhythmias of >Grade 2,
pulmonary embolism, or symptomatic cerebrovascular events, or any other serious
cardiac condition.

6. Admission or evidence of illicit drug use, drug abuse, or alcohol abuse.

7. History of autoimmune disease requiring systemic immunosuppressive therapy.

8. Active infection.

9. Known hepatitis B virus (HBV) surface antigen seropositive or detectable hepatitis C
infection viral load. Note: Participants who have positive hepatitis B core antibody
or hepatitis B surface antigen antibody can be enrolled but must have an undetectable
hepatitis B viral load.

10. Known history of human immunodeficiency virus infection or any other relevant
congenital or acquired immunodeficiency.

11. Receiving or requiring the continued use of medications that are known to be strong or
moderate inhibitors and inducers of CYP3A4/5 as well as strong permeability
glycoprotein (P-gp) inhibitors. To participate in this study, such participants should
discontinue use of such agents for at least 2 weeks before receiving a dose of
TAK-981.

12. Lymphomas with leukemic expression.

13. 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 first dose of study drug.

14. Patient requires the use of drugs known to prolong QTc interval.