Study of RET Inhibitor TAS0953/HM06 in Patients With Advanced Solid Tumors With RET Gene Abnormalities

Inclusion Criteria:

Phase I - Common inclusion criteria for Dose-Escalation / Dose-Expansion:

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

   - Available RET-gene abnormalities determined on tissue or liquid biopsy

   - Documented progression of disease following existing therapies deemed by the
   Investigator to have demonstrated clinical benefit or unable to receive such
   therapies.

   - Adequate hematopoietic, hepatic and renal function

Phase I Dose-Escalation - Specific inclusion criteria:

   - Advanced solid tumors

   - Measurable and/or non-measurable disease as determined by RECIST 1.1

   - If patient has brain and/or leptomeningeal metastases, (s)he should be asymptomatic.

Phase I Dose-Expansion - Specific inclusion criteria:

   - Locally advanced or metastatic non small cell lung cancer (NSCLC) patients with
   primary RET gene fusion and prior exposure to RET selective inhibitors

   - Measurable disease as determined by RECIST 1.1

   - If patient has brain and/or leptomeningeal metastases,(s)he should have:

      - asymptomatic untreated brain/leptomeningeal metastases off steroids and
      anticonvulsant for at least 7 days or

      - asymptomatic brain metastases already treated with local therapy and be
      clinically stable on steroids and anticonvulsant for at least 7 days before study
      drug administration.

Phase II :

   - Available RET-gene abnormalities determined on tissue or liquid biopsy

   - Locally advanced or metastatic:

      - NSCLC patients with primary RET gene fusion and prior exposure to RET selective
      inhibitors;

      - NSCLC patients with RET gene fusion and without prior exposure to RET selective
      inhibitors

      - patients with advanced solid tumors that harbour RET gene abnormalities (other
      than NSCLC patients with primary RET gene fusions) and has failed all the
      available therapeutic options

   - Eastern Cooperative Oncology Group (ECOG) performance score of 0-2

   - Measurable disease as determined by RECIST 1.1

   - If patient has brain and/or leptomeningeal metastases,(s)he should have:

      - asymptomatic untreated brain/leptomeningeal metastases off steroids and
      anticonvulsant for at least 7 days or

      - asymptomatic brain metastases already treated with local therapy and be
      clinically stable on steroids and anticonvulsant for at least 7 days before study
      drug administration.

   - Adequate hematopoietic, hepatic and renal function

Exclusion Criteria:

Common exclusion criteria for Phase 1 and Phase 2

   - Investigational agents or anticancer therapy within 5 half-lives prior to the first
   dose of study drug

   - Major surgery (excluding placement of vascular access) within 4 weeks prior to the
   first dose of study drug or planned major surgery during the course of study
   treatment.

   - Whole Brain Radiotherapy within 14 days or other palliative radiotherapy within 7 days
   prior to the first dose of study drug, or persisting side effects of such therapy, in
   the opinion of the Investigator.

   - Clinically significant, uncontrolled, cardiovascular disease including myocardial
   infarction within 3 months prior to Day 1 of Cycle 1, unstable angina pectoris,
   significant valvular or pericardial disease, history of ventricular tachycardia,
   symptomatic Congestive Heart Failure (CHF) New York Heart Association (NYHA) class
   III-IV, and severe uncontrolled arterial hypertension, according to the Investigator's
   opinion.

   - QT interval corrected using Fridericia's formula (QTcF) >470 msec; personal or family
   history of prolonged QT syndrome or history of Torsades de pointes (TdP). History of
   risk factors for TdP

   - Treatment with strong CYP3A4 inhibitors within 1 week prior to the first dose of study
   drug or strong CYP3A4 inducers within 3 weeks prior to the first dose of study drug.

Phase I Dose-Expansion - and Phase II specific exclusion criteria:

   - Presence of known EGFR, KRAS, ALK, HER2, ROS1, BRAF and METex14 activating mutations.