Inclusion Criteria:

          -  Written informed consent

          -  At least 20 years old in Japan or 18 years old in other countries at the time of
             signature of the informed consent form (ICF), following local regulatory requirements

          -  Eastern Cooperative Oncology Group (ECOG) Performance Status score of 0 or 1

          -  Has histopathologically documented unresectable and/or metastatic GIST meeting the
             criteria below:

          -  Dose Escalation (Part 1): Participants should meet one of the following criteria:

               1. (For US sites only) Participants with GIST who have progressed on or are
                  intolerant to imatinib (IM) and at least one post-IM treatment or who are not
                  candidates for post-IM standard of care treatment

               2. (For Japan sites only) Participants with GIST who have received all the existing
                  standard of care treatments or who are not candidates for one or more available
                  post-IM standard of care treatments

               3. Participants with GIST who are not candidates for IM or curative intent surgical
                  treatment (i.e., participants without activating KIT or platelet-derived growth
                  factor receptor alpha (PDGFRa) mutations, with PDGFRa D842V mutations, or are KIT
                  negative by local results)

          -  Dose Expansion (Part 2) Cohort 1: Participants with GIST who have progressed on or are
             intolerant to IM and at least one post-IM treatment

          -  Dose Expansion (Part 2) Cohort 2: Participants with GIST who have progressed on IM and
             had not received a post-IM treatment (2nd line)

          -  Consents to provide fresh tumor biopsy tissue samples both before and on DS-6157a
             treatment for the measurement of GPR20 levels by immunohistochemistry and other
             biomarkers

          -  Has a left ventricular ejection fraction (LVEF) ≥50% by either echocardiogram (ECHO)
             or multi-gated acquisition scan (MUGA) within 28 days before study treatment

          -  Has at least 1 measurable lesion based on RECIST Version 1.1 as assessed by the
             Investigator

          -  Has adequate organ function within 7 days before the start of study treatment, defined
             as:

               1. Platelet count ≥100,000/mm^3

               2. Hemoglobin ≥8.5 g/dL

               3. Absolute neutrophil count ≥1,500/mm^3

               4. Creatinine clearance ≥50 mL/min

               5. Aspartate aminotransferase ≤3 × upper limit of normal (ULN) (if liver metastases
                  are present, ≤5 × ULN)

               6. Alanine aminotransferase ≤3 × ULN (if liver metastases are present, ≤5 × ULN)

               7. Total bilirubin ≤1.5 × ULN or ≤3.0 × ULN for participants with documented history
                  of Gilbert's Syndrome

          -  Has an adequate treatment washout period prior to start of study treatment, defined
             as:

               1. Major surgery: ≥4 weeks (or 2 weeks for minor surgeries)

               2. Radiation therapy: ≥3 weeks (or 2 weeks for palliative radiation excluding pelvic
                  radiation)

               3. Systemic anti-cancer therapy (except for anti-androgen for prostate cancer and
                  bisphosphonate, denosumab, or medroxyprogesterone acetate for bone metastases):

                    -  Cytotoxic chemotherapy: ≥3 weeks or 5 times the terminal elimination
                       half-life (t½) of the chemotherapeutic agent, whichever is shorter

                    -  Antibody and antibody-conjugates therapy: ≥3 weeks or 5 times the t½,
                       whichever is longer

                    -  Prior tyrosine kinase inhibitors (TKIs): washout period from 2 to 21 days
                       depending on the TKI

                    -  Immunotherapy: ≥4 weeks.

          -  Male participants with female partners of childbearing potential and female
             participants of child-bearing potential must agree to use a highly effective form of
             contraception, or avoid intercourse during and upon completion of the study and for at
             least 4 months (for males) and for at least 7 months (for females) after the last dose
             of study drug.

        Exclusion Criteria:

          -  History of an allogeneic bone marrow or solid organ transplant within 3 months before
             the start of study treatment

          -  Concomitant treatment with any medication that is classified as having a known risk of
             Torsades de pointes should be avoided from the start of study treatment through the
             end of Cycle 3

          -  Prophylactic administration of granulocyte colony-stimulating factor (G-CSF),
             filgrastim, pegfilgrastim, erythropoietin, or the transfusion of blood, red blood
             cells, or platelets within 14 days before the start of treatment and during Cycle 1.
             Chronic therapy with erythropoietin at stable dose that started at least 14 days
             before the first dose of DS-6157a may continue.

          -  Has unresolved toxicities from previous anticancer therapy, defined as toxicities
             (other than alopecia) not yet resolved to National Cancer Institute Common Terminology
             Criteria for Adverse Events version 5.0, Grade ≤1. Participants with chronic Grade 2
             toxicities may be eligible.

          -  Has spinal cord compression or clinically active central nervous system (CNS)
             metastases (including brain metastases), defined as untreated and symptomatic, or
             requiring therapy with steroids or anticonvulsants to control associated symptoms

          -  Has known hypersensitivity to either the drug substances or inactive ingredients in
             the drug product

          -  Has a prior or concurrent malignancy whose natural history or treatment has the
             potential to interfere with the safety, efficacy, or any other assessments of the
             investigational regimen

          -  Has a documented history of myocardial infarction or unstable angina within 6 months
             before study treatment

          -  Has a medical history of symptomatic congestive heart failure (New York Heart
             Association classes II-IV) or a serious cardiac arrhythmia requiring treatment

          -  Has a corrected QT by Fridericia's formula (QTcF), of >470 ms based on the average of
             triplicate 12-lead electrocardiogram (ECG) per local read

          -  Has a documented history of (non-infectious) interstitial lung disease
             (ILD)/pneumonitis that required corticosteroids, has current ILD/pneumonitis, or where
             suspected ILD/pneumonitis cannot be ruled out by imaging at screening

          -  Has clinically significant pulmonary compromise or requirement for supplemental oxygen

          -  Has clinically significant corneal disease

          -  Has an uncontrolled infection requiring IV antibiotics, antivirals, or antifungals

          -  Has active human immunodeficiency virus (HIV) infection as determined by plasma HIV
             RNA viral load.

          -  Has evidence of active hepatitis B virus (HBV) or hepatitis C virus (HCV) infection,
             as manifest by the detectable viral load (HBV-DNA or HCV-RNA, respectively)

          -  Is a lactating mother (women who are willing to temporarily interrupt breastfeeding
             will also be excluded), or pregnant as confirmed by pregnancy tests performed within 7
             days before study treatment

          -  Women who plan to become pregnant while in the study and for at least 7 months after
             the last administration of study treatment

          -  Men who plan to father a child while in the study and for at least 4 months after the
             last administration of study treatment

          -  Any evidence of severe or uncontrolled systemic diseases, including uncontrolled
             hypertension, uncontrolled diabetes mellitus, active bleeding diatheses, substance
             abuse, or other medical condition that would increase the risk of toxicity or
             interfere with participation of the participant or evaluation of the clinical study