DS-6157a in Participants With Advanced Gastrointestinal Stromal Tumor (GIST)

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.