A Study of TAK-981 Given With Pembrolizumab in Participants With Select Advanced or Metastatic Solid Tumors

Inclusion Criteria:

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

   A. Non-squamous NSCLC for which prior standard first-line treatment containing an
   anti-programmed cell death protein 1/programmed cell death protein 1 ligand
   (PD-1/PD-L1) checkpoint inhibitor (CPI) alone or in combination has failed and that
   has progressed to no more than 1 prior systemic therapy. In Phase 2, participants with
   non-squamous NSCLC must have not received more than 1 prior systemic therapy and must
   not have presented with disease progression during the first 6 months of treatment
   with first-line CPI/anti-PD-(1/L1)-containing therapy.

   Note: In Phase 1, participants with non-squamous NSCLC and known driver
   mutations/genomic aberrations (e.g., 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. In Phase 2,
   participants with driver mutations are not eligible.

   B. CPI-naive cervical cancer (squamous cell carcinoma, adenosquamous carcinoma or
   adenocarcinoma of the cervix) participants for whom prior standard first-line
   treatment has failed and who have received no more than 1 prior systemic line of
   therapy for recurrent or Stage IVB cervical cancer. 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 (e.g., weekly cisplatin) is not
   counted as a systemic chemotherapy regimen.

   C. CPI-naïve microsatellite stable-colorectal cancer (MSS-CRC) participants for whom
   prior standard first-line treatment has failed and who have progressed on no more than
   3 chemotherapy regimens.

   Note: Participants must have received prior treatment with fluoropyrimidine-,
   oxaliplatin-, and irinotecan-containing regimens if indicated.

   D. Unresectable Stage III or Stage IV cutaneous melanoma that has not received prior
   therapy with a CPI in the metastatic setting.

   Note: Participants who have presented with disease relapse after ≥6 months of the last
   dose of CPI or BRAF-mitogen-activated protein kinase kinase (MEK) inhibitor in the
   adjuvant setting are eligible.

   E. Squamous NSCLC for which prior standard first-line treatment containing an
   anti-PD-(1/L1) checkpoint inhibitor alone or in combination has failed. Participant
   must have not received more than 1 prior systemic therapy and must not have presented
   with disease progression during the first 6 months of treatment with first-line
   CPI/anti-PD-(1/L1)-containing therapy.

   F. SCLC that has progressed during or after first-line platinum-based chemotherapy
   regimen or equivalent if platinum-based therapy is contraindicated.

   G. HNSCC (oral cavity, pharynx, larynx) not amenable to local therapy with curative
   intent that has progressed:

      - Within 6 months of the last dose of platinum therapy in the adjuvant (i.e., with
      radiation after surgery) or primary (i.e., with radiation) settings, or

      - On or after 1 prior systemic immune CPI/anti-PD-(1/L1)-containing therapy in the
      metastatic setting. HNSCC participant must have not received more than 1 prior
      systemic therapy and must not have presented with disease progression during the
      first 6 months of treatment with first-line CPI or anti-PD-(1/L1)-containing
      therapy.

   H. Treatment-naïve MSI-H/dMMR CRC.

   2. Has at least 1 radiologically measurable lesion based on RECIST, Version 1.1. Tumor
   lesions situated in a previously irradiated area are considered measurable if
   progression has been demonstrated in such lesions.

   3. Has a performance status of 0 or 1 on the Eastern Cooperative Group Oncology (ECOG)
   Performance Scale.

   4. Has left ventricular ejection fraction (LVEF) ≥40%; as measured by echocardiogram
   (ECHO) or multiple-gated acquisition (MUGA) scan.

   5. Has recovered to Grade 1 or baseline from all toxicity associated with previous
   therapy or have the toxicity established as sequela. Note: Has a neuropathy ≤Grade 2,
   any grade alopecia, or autoimmune endocrinopathies with stable replacement therapy are
   permitted.

   6. Demonstrate adequate organ function as described below:

A. Platelet count ≥75.0 × 10^9/L. B. Absolute neutrophil count (ANC) ≥1.0 × 10^9/L. C.
Hemoglobin ≥85 g/L (red blood cell [RBC] transfusion allowed ≥14 days before assessment).

D. Calculated creatinine clearance ≥30 mL/min using the Cockcroft-Gault formula.

E. Aspartate aminotransferase (AST, GOT) and alanine aminotransferase (ALT, GPT) ≤3.0 times
the upper limit of normal (ULN), <5.0 times the ULN if liver enzyme elevations are due to
liver metastases; bilirubin ≤1.5 times the ULN. Participants with Gilbert's syndrome may
have a bilirubin level >1.5 times the ULN, per discussion between the investigator and the
medical monitor.

Exclusion Criteria:

   1. Received extended field radiotherapy ≤4 weeks before the start of treatment (≤7 days
   for limited field radiation for palliation outside the chest or brain).

   2. History of uncontrolled brain metastasis (evidence of progression by imaging over a
   period of 4 weeks and/or neurologic symptoms that have not returned to baseline).
   Participant with treated brain metastases are allowed provided they are radiologically
   stable, without evidence of progression for at least 4 weeks by repeat imaging,
   clinically stable, and without requirement of steroid treatment for at least 14 days
   prior to first dose of study treatment. Note: For asymptomatic participants, screening
   brain imaging is not required.

   3. 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.

   4. Major surgery ≤14 days from the first dose of study drug and not recovered fully from
   any complications from surgery.

   5. History of immune-related AEs related to treatment with immune CPIs that required
   treatment discontinuation.

   6. Receiving or requires the continued use of medications that are known to be strong or
   moderate inhibitors and inducers of cytochrome P-450 (CYP) 3A4/5 and strong
   P-glycoprotein (Pgp) inhibitors.

   7. Baseline prolongation of the QT interval corrected using Fridericia's formula (QTcF)
   (e.g., repeated demonstration of QTcF interval >480 ms, history of congenital long QT
   syndrome, or torsades de pointes).

   8. Has a history of autoimmune disease requiring systemic immunosuppressive therapy with
   daily doses of prednisone >10 mg/day or equivalent doses, or any other form of
   immunosuppressive therapy. Hormone therapy (e.g., thyroxine, insulin, or physiologic
   corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not
   considered an excluded form of systemic treatment of an autoimmune disease.

   9. Has a history of noninfectious pneumonitis that required steroids or a history of
   interstitial lung disease.

10. Has an evidence of active, non-infectious pneumonitis.

11. Has a history of allogeneic tissue or solid organ transplant.

12. Has an active infection requiring systemic therapy.

13. Has a known history of human immunodeficiency virus (HIV) infection or any other
   relevant congenital or acquired immunodeficiency.

14. Has a known hepatitis B virus 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.

15. 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 >Grade 2,
   pulmonary embolism or symptomatic cerebrovascular events, or any other serious cardiac
   condition (e.g., pericardial effusion or restrictive cardiomyopathy). Chronic atrial
   fibrillation on stable anticoagulant therapy is allowed.

16. Psychiatric illness/social circumstances that would limit compliance with study
   requirements and substantially increase the risk of AEs or has compromised ability to
   provide written informed consent.