A Study of TAK-981 in People With Advanced Solid Tumors or Cancers in the Immune System

Inclusion Criteria:

1. Adult male or female participants ≥18 years old.
2. Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1.
3. Population for Phase 1 dose escalation:

   * Has histologically or cytologically confirmed advanced (local regionally recurrent not amenable to curative therapy) or metastatic solid tumors who 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 FL, 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. Population for Phase 2 dose expansion cohorts:

   o Has histologically or cytologically documented, advanced (metastatic and/or unresectable) cancer as listed below, that is incurable and for which prior standard first-line treatment has failed: Note: Prior neoadjuvant or adjuvant therapy included in initial treatment may not be considered first- or later-line SOC treatment unless such treatments were completed less than 12 months before the current tumor recurrence.

   o Nonsquamous NSCLC that has progressed to 1 prior systemic immune checkpoint inhibitors (CPI)/anti-PD-(1/L1)-containing therapy and no more than 2 lines of therapy. Participants must have not shown evidence of tumor progression during the first 5 months of treatment with first-line CPI/anti-PD-(1/L1)-containing therapy (cohort A).

   Note: Participants with known driver mutations/genomic aberrations (example- epidermal growth factor receptor \[EGFR\], B-Raf proto-oncogene mutation V600E \[BRAF V600E\], and ROS proto-oncogene 1 \[ROS1\] sensitizing mutations, neurotrophic receptor tyrosine kinase \[NRTK\] gene fusions, and anaplastic lymphoma kinase \[ALK\] rearrangements) must have also shown progressive disease after treatment with a commercially available targeted therapy.

   o CPI-naïve cervical cancer (squamous cell carcinoma, adenosquamous carcinoma or adenocarcinoma of the cervix) participants who have received no more than 1 prior systemic line of therapy for recurrent or Stage IVB cervical cancer (cohort B).

   Note: The following cervical tumors are not eligible: minimal deviation/adenoma malignum, gastric-type adenocarcinoma, clear-cell carcinoma, and mesonephric carcinoma. Histologic confirmation of the original primary tumor is required via pathology report.

   Note: First-line treatment must have consisted of platinum-containing doublet. Chemotherapy administered concurrently with primary radiation (example- weekly cisplatin) is not counted as a systemic chemotherapy regimen.

   o CPI-naïve MSS-CRC participants who have progressed on no more than 3 chemotherapy regimens (cohort C).

   Note: Participants must have received prior treatment with fluoropyrimidine-, oxaliplatin-, and irinotecan-containing regimens if indicated.
   * Relapsed/refractory DLBCL progressed or relapsed after prior CAR T cell therapy that has received approval by a health authority for the treatment of DLBCL (cohort D).
   * Relapsed/refractory DLBCL that has progressed or relapsed after at least 2 but no more than 3 prior lines of systemic therapy and has not received prior cellular therapy. At least one prior line of therapy must have included a CD20-targeted therapy (cohort E).
   * Relapsed/refractory FL that has progressed or relapsed after at least 2 but no more than 3 prior lines of systemic therapy. At least 1 prior line of therapy must have included a CD20-targeted therapy (cohort F).
5. In Phase 2 only, have at least 1 radiologically measurable lesion based on RECIST v1.1 for participants with solid tumors or Lugano criteria for lymphoma. Tumor lesions situated in a previously irradiated area are considered measurable if progression has been demonstrated in such lesions.

   Note: In Phase 2 stage 1, have an additional lesion for pretreatment and on-treatment biopsy.
6. In Phase 2 stage 1, willing to consent to mandatory pretreatment and on-treatment tumor biopsy.

   Note: For fresh tumor biopsies, the lesion must be accessible for a biopsy procedure as assessed by the investigator.
7. Is willing to provide archival tumor tissue sample, if available.
8. Adequate bone marrow reserve and renal and hepatic function.
9. Recovered to Grade 1 or baseline or established as sequelae from all toxic effects of previous therapy (except alopecia, neuropathy, or autoimmune endocrinopathies with stable endocrine replacement therapy, bone marrow parameters \[any of Grade 1 or 2 permitted if directly related to bone marrow involvement).
10. Consented to undergo serial skin punch biopsies (dose escalation only).
11. Suitable venous access for safe drug administration and the study-required PK and pharmacodynamics sampling.
12. Women of childbearing potential participating in this study should avoid becoming pregnant, and male participants should avoid impregnating a female partner. Nonsterilized female participants of reproductive age and male participants should use effective methods of contraception through defined periods during and after study treatment as specified below. Female participants must meet 1 of the following:

    * Postmenopausal for at least 1 year before the screening visit, or
    * Surgically sterile, or
    * If they are of childbearing potential, agree to practice 1 highly effective method and 1 additional effective (barrier) method of contraception at the same time, from the time of signing of the informed consent form (ICF) through 6 months 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 \[example, calendar, ovulation, symptothermal, postovulation methods\], withdrawal, spermicides only, and lactational amenorrhea are not acceptable methods of contraception. Female and male condoms should not be used together.)
13. Male participants, even if surgically sterilized (that is, status post vasectomy) must agree to 1 of the following:

    * Agree to practice effective barrier contraception during the entire study treatment period and through 6 months 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 \[example, calendar, ovulation, symptothermal, postovulation methods\], withdrawal, spermicides only, and lactational amenorrhea are not acceptable methods of contraception. Female and male condoms should not be used together.)

Exclusion Criteria:

1. Phase 1 dose escalation and Phase 2 cancer treatment expansion cohorts:

   o Has received 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.

   Note: Low-dose steroids (oral prednisone or equivalent ≤20 mg per day), hormonal therapy for prostate cancer or breast cancer (as adjuvant treatment), and treatment with bisphosphonates and receptor activator of nuclear factor kappa-Β ligand (RANKL) inhibitors are allowed.

   o Has received extended field radiotherapy ≤4 weeks before the start of treatment (≤2 weeks for limited field radiation for palliation), and who has not recovered to grade 1 or baseline from related side effects of such therapy (except for alopecia).
2. 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, severe noncompensated hypertension despite appropriate medical therapy, ongoing symptomatic cardiac arrhythmias of \>Grade 2, pulmonary embolism, or symptomatic cerebrovascular events, or any other serious cardiac condition (example, pericardial effusion or restrictive cardiomyopathy). Chronic atrial fibrillation on stable anticoagulant therapy is allowed.
3. Baseline prolongation of the QT interval with Fridericia correction method (QTcF) (example, repeated demonstration of QTcF interval \>480 milliseconds (ms), history of congenital long QT syndrome, or torsades de pointes).
4. Psychiatric illness/social circumstances that would limit compliance with study requirements and substantially increase the risk of adverse events (AEs) or has compromised ability to provide written informed consent.
5. Admission or evidence of illicit drug use, drug abuse, or alcohol abuse.
6. History of autoimmune disease requiring systemic immunosuppressive therapy.
7. History of immune-related AEs related to treatment with immune checkpoint inhibitors that required treatment discontinuation.
8. History of noninfectious pneumonitis that required steroids or a history of interstitial lung disease.
9. Has evidence of active, noninfectious pneumonitis.
10. Have a significant active infection.
11. Known history of human immunodeficiency virus (HIV) infection or any other relevant congenital or acquired immunodeficiency.
12. 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.
13. Receiving or requiring the continued use of medications that are known to be strong or moderate inhibitors and inducers of cytochrome P-450 3A4/5 (CYP3A4/5) or are strong permeability glycoprotein (P-gp) inhibitors. To participate in this study, participants should discontinue use of such agents for at least 2 weeks (1 week for CYP3A4/5 and P-gp inhibitors) before receiving a dose of TAK-981.
14. Participant requires the use of drugs known to prolong QTc interval (during Phase 1 only).
15. History of allogeneic tissue or solid organ transplant.
16. Second malignancy within the previous 3 years, except treated basal cell or localized squamous skin carcinomas, localized prostate cancer, cervical carcinoma in situ, resected colorectal adenomatous polyps, breast cancer in situ, or other malignancy for which the participant is not on active anticancer therapy.
17. 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.